Diabetes

A scoring system that predicts risk for new heart failure over 5 years that is based solely on a few familiar, readily available biomarkers could potentially help steer patients with diabetes or even prediabetes toward HF-preventive therapies, researchers proposed based on a new study.

They foresee the risk-stratification tool, based on data pooled from three major community-based cohort studies but not independently validated, as a way to select patients with diabetes and prediabetes for treatment with SGLT2 inhibitors.

Several members of that drug class, conceived as antidiabetic agents, have been shown to help in prevention or treatment of HF in patients with diabetes and those without diabetes but at increased cardiovascular (CV) risk. Yet their uptake in practice has been lagging, the group noted.

Most HF benefits in the SGLT2 inhibitor trials “were seen in patients who have established cardiovascular disease – basically a history of heart attack or stroke,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“So we wanted to see how we can identify high-risk patients without a history of cardiovascular disease using these biomarkers, as an approach to targeting SGLT2 inhibitors, which are fairly expensive therapies,” he said. Without such risk stratification, “you end up treating so many more patients to get very modest returns.”

The group developed a scoring system based on four biomarkers that are “easily measured with inexpensive tests,” Dr. Pandey said: high-sensitivity-assay cardiac troponin T (hs-cTnT) and C-reactive protein (hs-CRP) levels, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels, and electrocardiography for evidence of left-ventricular hypertrophy (ECG-LVH).

The derivation cohort consisted of participants in the Atherosclerosis Risk in Communities RIC, Dallas Heart Study, and Multi-Ethnic Study of Atherosclerosis Multi-Ethnic Study of Atherosclerosis epidemiologic studies who were free of coronary heart disease, stroke, or HF for whom there were sufficient data on CV risk factors and the four biomarkers. None were taking SGLT2 inhibitors at enrollment in their respective studies, the researchers noted.

Members of the pooled cohorts who had diabetes or prediabetes were assigned 1 point for each abnormal biomarker. The 5-year risk for incident HF went up continuously along with the score in people with diabetes and in those with prediabetes, the latter defined as a fasting plasma glucose level from 100 mg/dL to less than 126 mg/dL.

For those with a score of 1, compared with 0, for example, the risk for HF went up 82% with diabetes and 40% with prediabetes. But for those with a score of 3 or 4, the risk went up more than four and a half times with diabetes and more than three and a half times for those with prediabetes. Risk increases were independent of other likely HF risk factors and consistently significant.

The analysis was published Jan. 6 in JACC: Heart Failure.

The biomarker score should be especially useful in patients considered at low to intermediate risk, based on clinical characteristics, as a means to identify residual HF risk and, potentially, select candidates for SGLT2-inhibitor therapy, Dr. Pandey said.

“The other purpose of the study was to broaden the scope of heart failure prevention in dysglycemia by looking also at prediabetes, not just diabetes,” he said. There isn’t much high-quality evidence supporting SGLT2-inhibitor therapy in prediabetes, but it follows that the drugs may be helpful in prediabetes because they are protective in patients with and without diabetes.

“Our work suggests that prediabetes patients who have elevated biomarkers are at a higher risk of heart failure,” Dr. Pandey said, suggesting that the HF risk score could potentially help select their drug therapy as well.

The current study seems “to provide a proof of concept that one can use circulating biomarkers to more precisely identify patients in whom therapies might be expected to exert greatest benefit,” which is especially important for potentially expensive agents like the SGLT2 inhibitors, James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Importantly in the analysis, a greater number of biomarker abnormalities not only corresponded to rising levels of risk, the risk increases were “dramatic,” and therefore so was the supposed potential benefit of SGLT2-inhibitor therapy, said Dr. Januzzi, who isn’t a coauthor but was an editor for its publication in JACC: Heart Failure.

The uptake of SGLT2 inhibitors for heart failure in practice has been less rapid than hoped, he observed, so if “this hypothetical construct holds up” for the drug class, “it might actually help kick-start focusing on who might optimally receive the drugs.”

Elevated levels of hs-cTnT, hs-CRP, and NT-proBNP, as well as presence of ECG-LVH, were each independently associated with a significantly increased 5-year risk for HF in unadjusted and adjusted analyses of the 6,799 people in the pooled cohort, 33.2% of whom had diabetes and 66.8% of whom had prediabetes, the group writes.

The scoring system would require validation in other cohorts before it could be used, Dr. Pandey observed; once there is “robust validation,” it might be applied first to patients with dysglycemia at intermediate CV risk by standard clinical measures.

Certainly the HF risk-stratification scoring system requires validation in other studies, Dr. Januzzi agreed. But it is intuitively appealing, and the study’s results are consistent with “data that we’re submitting for publication imminently” based on the CANVAS CV-outcomes trial of the SGLT2 inhibitor canagliflozin (Invokana) in patients with diabetes.

Dr. Pandey disclosed receiving support from the Gilead Sciences Research Scholar Program and serving on an advisory board of Roche Diagnostics. Dr. Januzzi disclosed receiving grant support from Novartis, Applied Therapeutics, and Innolife; consulting for Abbott Diagnostics, Janssen, Novartis, Quidel, and Roche Diagnostics; and serving on end-point committees or data safety monitoring boards for trials supported by Abbott, AbbVie, Amgen, CVRx, Janssen, MyoKardia, and Takeda.

A version of this article first appeared on Medscape.com.

A scoring system that predicts risk for new heart failure over 5 years that is based solely on a few familiar, readily available biomarkers could potentially help steer patients with diabetes or even prediabetes toward HF-preventive therapies, researchers proposed based on a new study.

They foresee the risk-stratification tool, based on data pooled from three major community-based cohort studies but not independently validated, as a way to select patients with diabetes and prediabetes for treatment with SGLT2 inhibitors.

Several members of that drug class, conceived as antidiabetic agents, have been shown to help in prevention or treatment of HF in patients with diabetes and those without diabetes but at increased cardiovascular (CV) risk. Yet their uptake in practice has been lagging, the group noted.

Most HF benefits in the SGLT2 inhibitor trials “were seen in patients who have established cardiovascular disease – basically a history of heart attack or stroke,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“So we wanted to see how we can identify high-risk patients without a history of cardiovascular disease using these biomarkers, as an approach to targeting SGLT2 inhibitors, which are fairly expensive therapies,” he said. Without such risk stratification, “you end up treating so many more patients to get very modest returns.”

The group developed a scoring system based on four biomarkers that are “easily measured with inexpensive tests,” Dr. Pandey said: high-sensitivity-assay cardiac troponin T (hs-cTnT) and C-reactive protein (hs-CRP) levels, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels, and electrocardiography for evidence of left-ventricular hypertrophy (ECG-LVH).

The derivation cohort consisted of participants in the Atherosclerosis Risk in Communities RIC, Dallas Heart Study, and Multi-Ethnic Study of Atherosclerosis Multi-Ethnic Study of Atherosclerosis epidemiologic studies who were free of coronary heart disease, stroke, or HF for whom there were sufficient data on CV risk factors and the four biomarkers. None were taking SGLT2 inhibitors at enrollment in their respective studies, the researchers noted.

Members of the pooled cohorts who had diabetes or prediabetes were assigned 1 point for each abnormal biomarker. The 5-year risk for incident HF went up continuously along with the score in people with diabetes and in those with prediabetes, the latter defined as a fasting plasma glucose level from 100 mg/dL to less than 126 mg/dL.

For those with a score of 1, compared with 0, for example, the risk for HF went up 82% with diabetes and 40% with prediabetes. But for those with a score of 3 or 4, the risk went up more than four and a half times with diabetes and more than three and a half times for those with prediabetes. Risk increases were independent of other likely HF risk factors and consistently significant.

The analysis was published Jan. 6 in JACC: Heart Failure.

The biomarker score should be especially useful in patients considered at low to intermediate risk, based on clinical characteristics, as a means to identify residual HF risk and, potentially, select candidates for SGLT2-inhibitor therapy, Dr. Pandey said.

“The other purpose of the study was to broaden the scope of heart failure prevention in dysglycemia by looking also at prediabetes, not just diabetes,” he said. There isn’t much high-quality evidence supporting SGLT2-inhibitor therapy in prediabetes, but it follows that the drugs may be helpful in prediabetes because they are protective in patients with and without diabetes.

“Our work suggests that prediabetes patients who have elevated biomarkers are at a higher risk of heart failure,” Dr. Pandey said, suggesting that the HF risk score could potentially help select their drug therapy as well.

The current study seems “to provide a proof of concept that one can use circulating biomarkers to more precisely identify patients in whom therapies might be expected to exert greatest benefit,” which is especially important for potentially expensive agents like the SGLT2 inhibitors, James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Importantly in the analysis, a greater number of biomarker abnormalities not only corresponded to rising levels of risk, the risk increases were “dramatic,” and therefore so was the supposed potential benefit of SGLT2-inhibitor therapy, said Dr. Januzzi, who isn’t a coauthor but was an editor for its publication in JACC: Heart Failure.

The uptake of SGLT2 inhibitors for heart failure in practice has been less rapid than hoped, he observed, so if “this hypothetical construct holds up” for the drug class, “it might actually help kick-start focusing on who might optimally receive the drugs.”

Elevated levels of hs-cTnT, hs-CRP, and NT-proBNP, as well as presence of ECG-LVH, were each independently associated with a significantly increased 5-year risk for HF in unadjusted and adjusted analyses of the 6,799 people in the pooled cohort, 33.2% of whom had diabetes and 66.8% of whom had prediabetes, the group writes.

The scoring system would require validation in other cohorts before it could be used, Dr. Pandey observed; once there is “robust validation,” it might be applied first to patients with dysglycemia at intermediate CV risk by standard clinical measures.

Certainly the HF risk-stratification scoring system requires validation in other studies, Dr. Januzzi agreed. But it is intuitively appealing, and the study’s results are consistent with “data that we’re submitting for publication imminently” based on the CANVAS CV-outcomes trial of the SGLT2 inhibitor canagliflozin (Invokana) in patients with diabetes.

Dr. Pandey disclosed receiving support from the Gilead Sciences Research Scholar Program and serving on an advisory board of Roche Diagnostics. Dr. Januzzi disclosed receiving grant support from Novartis, Applied Therapeutics, and Innolife; consulting for Abbott Diagnostics, Janssen, Novartis, Quidel, and Roche Diagnostics; and serving on end-point committees or data safety monitoring boards for trials supported by Abbott, AbbVie, Amgen, CVRx, Janssen, MyoKardia, and Takeda.

A version of this article first appeared on Medscape.com.

A scoring system that predicts risk for new heart failure over 5 years that is based solely on a few familiar, readily available biomarkers could potentially help steer patients with diabetes or even prediabetes toward HF-preventive therapies, researchers proposed based on a new study.

They foresee the risk-stratification tool, based on data pooled from three major community-based cohort studies but not independently validated, as a way to select patients with diabetes and prediabetes for treatment with SGLT2 inhibitors.

Several members of that drug class, conceived as antidiabetic agents, have been shown to help in prevention or treatment of HF in patients with diabetes and those without diabetes but at increased cardiovascular (CV) risk. Yet their uptake in practice has been lagging, the group noted.

Most HF benefits in the SGLT2 inhibitor trials “were seen in patients who have established cardiovascular disease – basically a history of heart attack or stroke,” Ambarish Pandey, MD, MSCS, University of Texas Southwestern Medical Center, Dallas, said in an interview.

“So we wanted to see how we can identify high-risk patients without a history of cardiovascular disease using these biomarkers, as an approach to targeting SGLT2 inhibitors, which are fairly expensive therapies,” he said. Without such risk stratification, “you end up treating so many more patients to get very modest returns.”

The group developed a scoring system based on four biomarkers that are “easily measured with inexpensive tests,” Dr. Pandey said: high-sensitivity-assay cardiac troponin T (hs-cTnT) and C-reactive protein (hs-CRP) levels, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) levels, and electrocardiography for evidence of left-ventricular hypertrophy (ECG-LVH).

The derivation cohort consisted of participants in the Atherosclerosis Risk in Communities RIC, Dallas Heart Study, and Multi-Ethnic Study of Atherosclerosis Multi-Ethnic Study of Atherosclerosis epidemiologic studies who were free of coronary heart disease, stroke, or HF for whom there were sufficient data on CV risk factors and the four biomarkers. None were taking SGLT2 inhibitors at enrollment in their respective studies, the researchers noted.

Members of the pooled cohorts who had diabetes or prediabetes were assigned 1 point for each abnormal biomarker. The 5-year risk for incident HF went up continuously along with the score in people with diabetes and in those with prediabetes, the latter defined as a fasting plasma glucose level from 100 mg/dL to less than 126 mg/dL.

For those with a score of 1, compared with 0, for example, the risk for HF went up 82% with diabetes and 40% with prediabetes. But for those with a score of 3 or 4, the risk went up more than four and a half times with diabetes and more than three and a half times for those with prediabetes. Risk increases were independent of other likely HF risk factors and consistently significant.

The analysis was published Jan. 6 in JACC: Heart Failure.

The biomarker score should be especially useful in patients considered at low to intermediate risk, based on clinical characteristics, as a means to identify residual HF risk and, potentially, select candidates for SGLT2-inhibitor therapy, Dr. Pandey said.

“The other purpose of the study was to broaden the scope of heart failure prevention in dysglycemia by looking also at prediabetes, not just diabetes,” he said. There isn’t much high-quality evidence supporting SGLT2-inhibitor therapy in prediabetes, but it follows that the drugs may be helpful in prediabetes because they are protective in patients with and without diabetes.

“Our work suggests that prediabetes patients who have elevated biomarkers are at a higher risk of heart failure,” Dr. Pandey said, suggesting that the HF risk score could potentially help select their drug therapy as well.

The current study seems “to provide a proof of concept that one can use circulating biomarkers to more precisely identify patients in whom therapies might be expected to exert greatest benefit,” which is especially important for potentially expensive agents like the SGLT2 inhibitors, James L. Januzzi, MD, Massachusetts General Hospital, Boston, said in an interview.

Importantly in the analysis, a greater number of biomarker abnormalities not only corresponded to rising levels of risk, the risk increases were “dramatic,” and therefore so was the supposed potential benefit of SGLT2-inhibitor therapy, said Dr. Januzzi, who isn’t a coauthor but was an editor for its publication in JACC: Heart Failure.

The uptake of SGLT2 inhibitors for heart failure in practice has been less rapid than hoped, he observed, so if “this hypothetical construct holds up” for the drug class, “it might actually help kick-start focusing on who might optimally receive the drugs.”

Elevated levels of hs-cTnT, hs-CRP, and NT-proBNP, as well as presence of ECG-LVH, were each independently associated with a significantly increased 5-year risk for HF in unadjusted and adjusted analyses of the 6,799 people in the pooled cohort, 33.2% of whom had diabetes and 66.8% of whom had prediabetes, the group writes.

The scoring system would require validation in other cohorts before it could be used, Dr. Pandey observed; once there is “robust validation,” it might be applied first to patients with dysglycemia at intermediate CV risk by standard clinical measures.

Certainly the HF risk-stratification scoring system requires validation in other studies, Dr. Januzzi agreed. But it is intuitively appealing, and the study’s results are consistent with “data that we’re submitting for publication imminently” based on the CANVAS CV-outcomes trial of the SGLT2 inhibitor canagliflozin (Invokana) in patients with diabetes.

Dr. Pandey disclosed receiving support from the Gilead Sciences Research Scholar Program and serving on an advisory board of Roche Diagnostics. Dr. Januzzi disclosed receiving grant support from Novartis, Applied Therapeutics, and Innolife; consulting for Abbott Diagnostics, Janssen, Novartis, Quidel, and Roche Diagnostics; and serving on end-point committees or data safety monitoring boards for trials supported by Abbott, AbbVie, Amgen, CVRx, Janssen, MyoKardia, and Takeda.

A version of this article first appeared on Medscape.com.

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

A version of this article first appeared on Medscape.com.

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

A version of this article first appeared on Medscape.com.

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has determined that data collected on the dual SGLT1/2 inhibitor sotagliflozin (Zynquista) for treating patients with type 2 diabetes in the SOLOIST and SCORED pivotal trials can help support a New Drug Application (NDA) submission, according to a statement released on Jan. 14 by Lexicon Pharmaceuticals, the company developing this drug. Lexicon concurrently said that it hopes to potentially file this NDA later in 2021.

The statement said the FDA’s decision related to an NDA for “an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.”

Results from SOLOIST and SCORED, first reported in November 2020 at the American Heart Association scientific sessions, showed statistically significant benefits for their respective primary endpoints.

The findings also demonstrated several novel benefits from the first advanced clinical trials of an SGLT inhibitor that blocks both the SGLT2 protein in kidneys as well as the SGLT1 protein, which resides primarily in the gastrointestinal system and is the main route for glucose out of the gut.

In both SOLOIST and SCORED, patient outcomes on sotagliflozin tracked the benefits and adverse effects previously seen with several SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), but in addition showed several unprecedented benefits: An ability to lower hemoglobin A1c in patients with severely depressed renal function, safe initiation in patients recently hospitalized for heart failure, the first prospective data to show improvements in patients with heart failure with preserved ejection fraction, and a higher level of protection against MIs and strokes than the SGLT2 inhibitors.

The FDA’s willingness to consider data from both trials in an NDA was not a given, as the primary endpoints for both trials underwent tweaking while they were underway to compensate for an unexpectedly early end to patient enrollment and follow-up caused by changes in drug company sponsorship and challenges introduced by the COVID-19 pandemic.

In 2019, the FDA denied the NDA for sotagliflozin as a treatment for patients with type 1 diabetes, but this indication received approval in Europe.

SOLOIST and SCORED were sponsored initially by Sanofi, and more recently by Lexicon.

mzoler@mdedge.com

The Food and Drug Administration has determined that data collected on the dual SGLT1/2 inhibitor sotagliflozin (Zynquista) for treating patients with type 2 diabetes in the SOLOIST and SCORED pivotal trials can help support a New Drug Application (NDA) submission, according to a statement released on Jan. 14 by Lexicon Pharmaceuticals, the company developing this drug. Lexicon concurrently said that it hopes to potentially file this NDA later in 2021.

The statement said the FDA’s decision related to an NDA for “an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.”

Results from SOLOIST and SCORED, first reported in November 2020 at the American Heart Association scientific sessions, showed statistically significant benefits for their respective primary endpoints.

The findings also demonstrated several novel benefits from the first advanced clinical trials of an SGLT inhibitor that blocks both the SGLT2 protein in kidneys as well as the SGLT1 protein, which resides primarily in the gastrointestinal system and is the main route for glucose out of the gut.

In both SOLOIST and SCORED, patient outcomes on sotagliflozin tracked the benefits and adverse effects previously seen with several SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), but in addition showed several unprecedented benefits: An ability to lower hemoglobin A1c in patients with severely depressed renal function, safe initiation in patients recently hospitalized for heart failure, the first prospective data to show improvements in patients with heart failure with preserved ejection fraction, and a higher level of protection against MIs and strokes than the SGLT2 inhibitors.

The FDA’s willingness to consider data from both trials in an NDA was not a given, as the primary endpoints for both trials underwent tweaking while they were underway to compensate for an unexpectedly early end to patient enrollment and follow-up caused by changes in drug company sponsorship and challenges introduced by the COVID-19 pandemic.

In 2019, the FDA denied the NDA for sotagliflozin as a treatment for patients with type 1 diabetes, but this indication received approval in Europe.

SOLOIST and SCORED were sponsored initially by Sanofi, and more recently by Lexicon.

mzoler@mdedge.com

The Food and Drug Administration has determined that data collected on the dual SGLT1/2 inhibitor sotagliflozin (Zynquista) for treating patients with type 2 diabetes in the SOLOIST and SCORED pivotal trials can help support a New Drug Application (NDA) submission, according to a statement released on Jan. 14 by Lexicon Pharmaceuticals, the company developing this drug. Lexicon concurrently said that it hopes to potentially file this NDA later in 2021.

The statement said the FDA’s decision related to an NDA for “an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.”

Results from SOLOIST and SCORED, first reported in November 2020 at the American Heart Association scientific sessions, showed statistically significant benefits for their respective primary endpoints.

The findings also demonstrated several novel benefits from the first advanced clinical trials of an SGLT inhibitor that blocks both the SGLT2 protein in kidneys as well as the SGLT1 protein, which resides primarily in the gastrointestinal system and is the main route for glucose out of the gut.

In both SOLOIST and SCORED, patient outcomes on sotagliflozin tracked the benefits and adverse effects previously seen with several SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin), but in addition showed several unprecedented benefits: An ability to lower hemoglobin A1c in patients with severely depressed renal function, safe initiation in patients recently hospitalized for heart failure, the first prospective data to show improvements in patients with heart failure with preserved ejection fraction, and a higher level of protection against MIs and strokes than the SGLT2 inhibitors.

The FDA’s willingness to consider data from both trials in an NDA was not a given, as the primary endpoints for both trials underwent tweaking while they were underway to compensate for an unexpectedly early end to patient enrollment and follow-up caused by changes in drug company sponsorship and challenges introduced by the COVID-19 pandemic.

In 2019, the FDA denied the NDA for sotagliflozin as a treatment for patients with type 1 diabetes, but this indication received approval in Europe.

SOLOIST and SCORED were sponsored initially by Sanofi, and more recently by Lexicon.

mzoler@mdedge.com

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

Cardiologist Ethan J. Weiss, MD, followed an intermittent-fasting diet for 7 years. He lost about 3.6 kg (8 lb) and began recommending the approach to friends and patients who wanted to lose weight.

“I liked the way the diet was so simple,” said Dr. Weiss, an associate professor at the Cardiovascular Research Institute, University of California, San Francisco. But he also felt “it was too good to be true because you can eat what you want as long as it’s within a narrow window.”

So when, last year, he conducted a randomized, controlled trial, TREAT, testing such an approach – eating during just 8 hours a day, fasting for the remaining 16 hours – versus an eating plan of three meals a day without restrictions, he was somewhat dismayed to find the group of people who fasted didn’t lose any more weight than the other group.

The approach used in this study is known as time-restricted eating. It involves designating periods of time within the day when people can consume whatever they want; they then “fast” at times outside those eating windows. Other methods include alternate-day fasting, or the well-known 5:2 diet. In the latter, people eat a “normal” amount of around 2,000 calories per day on 5 days of the week, but for the other 2 days, they restrict caloric intake to 500 calories per day.

Intermittent fasting is an umbrella term encompassing all of these different approaches.

Dr. Weiss’s work builds on more than a decade of research into this type of eating plan by scientists, including Krista Varady, PhD, professor of nutrition at the University of Illinois at Chicago, who presented an overview of her own studies last fall at the virtual annual meeting of the European Association for the Study of Diabetes.

Although much of the work has suggested that the shorter duration of eating period in this type of diet leads to lower calorie intake and weight loss while avoiding the need for the tedious calorie-counting of conventional diets, Dr. Weiss’s data – published last year – throws a spanner in the works and now complicates the evidence base.
 

A promise of simplicity: ‘All you have to do is watch the clock’

Dr. Varady said she, too, is intrigued by the simplicity of intermittent-fasting diets.

In 2018, Dr. Varady and colleagues tested the weight-loss efficacy of 12 weeks of time-restricted feeding in a pilot study of 23 people with obesity.

Participants were permitted an 8-hour eating window (10 a.m. to 6 p.m.) followed by water-only fasting of 16 hours (6 p.m. to 10 a.m.) the next day (sometimes referred to as the 16:8 diet). Researchers measured weight loss and fat mass, as well as metabolic parameters, and compared the active group with 23 matched-control participants who ate freely.

There were no restrictions on type or quantity of food consumed by the control group during the 8-hour period, but individuals in the time-restricted feeding group consumed around 350 calories less than the comparator group.

Dr. Varady thinks this is most likely because of the fact that people normally eat during a 14-hour window and time-restricted feeding cuts that down by 6 hours.

“One of the most beautiful things about time-restricted feeding is that it doesn’t require calorie monitoring,” she explained. “People get burnt out with having to constantly monitor calories. All you have to do is watch the clock.”

Adherence was quite high, she reported, although most people skipped 1 day, often a Saturday, likely because of social engagements.

Weight loss in the time-restricted feeding group was mild to moderate. After 3 months, mean body weight decreased by 2.6%, or approximately 3 kg (7-8 lb), relative to those who ate freely, but this was a significant difference (P  < .05).

But the researchers observed little change in metabolic disease risk factors between the groups.

In the time-restricted feeding group, systolic blood pressure dropped from 128 mm Hg to 121 mm Hg over the 12-week period, which was significant relative to the control group (P  <  .05) but there were no significant changes in fasting glucose, fasting lipids, fasting insulin, or insulin resistance relative to the comparator group.

In contrast to Dr. Varady’s findings, Dr. Weiss’s randomized TREAT trial, which used a similar 16:8 period of time-restricted versus unrestricted eating in 116 individuals with overweight or obesity, did not find greater weight loss in the group restricted to eating within the 8-hour window.

As previously reported by this news organization, those who fasted for 16 hours of each day (n = 59) did lose some weight, compared with the control group (n = 57) over 12 weeks, but the difference in weight loss between the groups was not significant (−0.26 kg; P = .63).

And there were no significant differences in any of the secondary outcomes of fat mass, fasting insulin, fasting glucose, hemoglobin A1c levels, estimated energy intake, total energy expenditure, and resting energy expenditure between the time-restricted eating and regular feeding groups.

“I don’t claim time-restricted eating is dead,” Dr. Weiss said, “but the hope that you can eat for a limited time each day and solve metabolic disease is not there.”

Does the length of the eating window matter?

Following her pilot study of an 8-hour eating window, Dr. Varady conducted further research with 4- or 6-hour eating windows to see if even shorter periods would precipitate greater weight loss, ideally a clinically significant loss of 5% of body weight.

She ran a 2-month randomized, controlled study in people with obesity, published in 2020, which was the first to examine both a 4-hour (3 p.m. to 7 p.m.; n = 19) or 6-hour (1 p.m to 7 p.m.; n = 20) eating window versus a diet without any food restrictions as a control (n = 19) (Cell Metab. 2020;32:366-78.e3).

Dr. Varady explained that they decided to shift the eating window to later in the day for this trial (in contrast to the earlier 8-hour study) to allow people to eat dinner at a sociable time, and thereby hopefully reduce dropouts from the study. 

“Unlike with alternate-day fasting, most people find time-restricted feeding easy to incorporate into their lifestyles,” she remarked.

Both the 4- and 6-hour eating window groups experienced a mean 3.2% body weight loss, compared with controls, and this correlated with a 550-calorie reduction in their daily consumption, compared with their baseline calorie intake.

In terms of other outcomes – and in contrast to the 8-hour window study which showed very little changed other than a minor decrease in blood pressure – researchers saw some changes in metabolic risk factors with the 4- and 6-hour eating windows, Dr. Varady reported.

Compared with the control group, fasting insulin decreased in both time-restricted feeding groups by a mean of 15% (P < .05). Insulin resistance also decreased by 25% in the 4-hour group and by 15% in the 6-hour group, compared with the control group. Fasting glucose did not change in either group, however.

The researchers did not observe any effect on blood pressure or plasma lipids in the 4- or 6-hour eating window groups, compared with controls. However, measures of oxidative stress and inflammation decreased in both groups versus controls by approximately 35% (P < .05).

“These findings suggest that this form of severe time-restricted feeding is achievable and can help adults with obesity lose weight, without having to count calories,” Dr. Varady and colleagues conclude.
 

Is intermittent fasting better for weight loss than calorie restriction?

Ultimately, if weight loss is the primary goal, many want to know how time-restricted feeding compares with conventional daily calorie restriction.

Back in 2017, Dr. Varady published a year-long randomized, controlled study that compared alternate-day fasting with a calorie-restriction diet and a conventional/usual diet among 100 participants with obesity who were otherwise healthy.  

Participants on the alternate-day fasting plan (n = 34) consumed 500 calories on fasting days for the first 6 months for weight loss (approximately 25% of energy needs) followed by 125% of energy needs on alternating “feast days”. For an additional 6 months, they ate 1,000 calories on fasting days – aimed at weight maintenance.

Those following the calorie-restriction diet (n = 35) reduced energy intake by 25% (approximately 500 kcal) for the first 6 months for weight loss, followed by enough calories sufficient for weight maintenance (so no further loss nor gain).

However, the study showed alternate-day fasting did not produce better weight loss than conventional calorie counting.

“Over the first 6 months [during the weight-loss period] both groups lost an average of 6% body weight. After 12 months it crept back to 5% weight loss,” reported Dr. Varady.

“Realistically, if the study continued for 2 or 3 years, they probably would have regained much of their weight,” she admitted.

Dr. Varady suspects it might be better for the alternate-day fasting participants to continue eating only 500 calories on their fast day during the weight-loss maintenance period rather than increasing calorie intake during this phase.

Heart rate and blood pressure did not change in either group, while triglycerides decreased in the alternate-day fasting group, and LDL cholesterol decreased in the calorie-restriction group.

Glucose level decreased in the calorie-restriction group but not the alternate-day fasting group, and insulin and HOMA-IR were unaffected in both groups, reported Dr. Varady, noting that these findings were in healthy people with obesity.

In people with obesity and insulin resistance – evaluated as a subgroup in a separate study by Dr. Varady of alternate-day fasting versus daily calorie restriction published in 2019 – she noted that when insulin levels and HOMA-IR were measured, there was a greater reduction in both variables in the fasting group, compared with the calorie-restriction group.

“For people at risk of diabetes, maybe fasting produces more potent effects on glycemic control?” she ventured.
 

Who fares best with which fasting diets?

Summing up, Dr. Varady provided some practical pointers regarding who she feels is best suited to intermittent fasting and who should avoid it.

Those who binge eat, shift-workers, and frequent snackers do not do well with fasting, she said.

The first 10 days of intermittent fasting are rough, she pointed out, with the most common complaint being headaches.

“Eventually, people do feel an energy boost on fast days, and they say they concentrate better and have lots of energy. People won’t feel lethargic. Also, eating protein on fast days has been shown to keep hunger at bay.”

She cautiously concluded that weight loss with “alternate-day fasting” is quicker than some other methods, at 4.5-7 kg (10-15 lb) in 3 months, but is harder to follow and requires some calorie counting.

“In comparison, with time-restricted feeding, for which there have been very few ... studies to date, weight loss is slower at 2-4.5 kg (5-10 lb) in 3 months, but it is easier to follow and tolerable because you don’t need to count calories.”

Dr. Weiss has reported no relevant financial relationships. Dr. Varady has reported receiving author fees from Hachette for her book, “Every Other Day Diet.” (New York: Hachette, 2013)

A version of this article first appeared on Medscape.com.

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

A version of this article first appeared on Medscape.com.

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

A version of this article first appeared on Medscape.com.

The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.

“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.

“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.  

This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.

And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”

The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.

The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.

“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.

“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.

The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.  

For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.

Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.

Other policy recommendations for relevant stakeholders include:

• Limit future insulin list price increases to the rate of inflation.
• Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
• Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
• Expedite approval of insulin biosimilars to create market competition.
• Include real-time benefit information in electronic medical records.
• Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.

For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.   

Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.

A version of this article first appeared on Medscape.com.

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

A version of this article first appeared on Medscape.com.

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

A version of this article first appeared on Medscape.com.

Nostrum Laboratories has voluntarily recalled another lot of metformin HCl extended-release tablets 750-mg dosage, expanding their initial announcement in November 2020. According to the new notice, issued by the Food and Drug Administration earlier this week, the recalled tablets are off-white and oblong with a debossed ID “NM7.”

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The lot number, NDC, and expiration dates can be found on the FDA website.

Nostrum noted that the tablets were distributed across the United States to wholesalers; these distributors are being notified of the recall and the company is arranging for the drug to be returned.

Metformin is the most prescribed medication worldwide for the treatment of type 2 diabetes.

Nostrum said that anyone in possession of any of the affected lots should consult their physician or pharmacist to obtain a replacement treatment option because it can be dangerous for patients with type 2 diabetes to stop taking metformin.

This new announcement expands further the number of metformin HCl extended-release tablets recalled in the United States because they contain potentially high levels of nitrosamines, also known as N-nitrosodimethylamine (NDMA), which are possible carcinogens.

The risks of nitrosamines are not clear. The FDA said they may increase the risk of cancer in people who are exposed to high levels over a long period of time, “but we do not anticipate that shorter-term exposure at levels above the acceptable intake limit would lead to an increase in the risk of cancer.”

As well as the November recall of 2 lots of metformin by Nostrum, 76 more lots of metformin extended-release tablets were flagged in October 2020 from various manufacturers for possible contamination with NDMA, on top of an earlier recall for the same problem in May 2020.

More than 175 different drug combinations, all extended release with either 500 mg or 750 mg of metformin, have now been recalled since late May 2020, and a list of those recalled to November 2020 is available here.

A version of this article first appeared on Medscape.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have brown fat detected on imaging seem to be at reduced risk of cardiac and metabolic conditions, ranging from type 2 diabetes to hypertension and coronary artery disease, with a notably strong effect in people with obesity, according to a new study of more than 52,000 individuals who had PET/CT scans as part of cancer evaluation.

Although this has been studied for decades in newborns and animals, only in the past decade have scientists appreciated that some adults have brown fat, typically around the neck and shoulders.

The new study, by far the largest of its kind in humans, appears to confirm the health benefits of brown fat suggested by previous studies, Tobias Becher, MD, and colleagues from The Rockefeller University, New York, wrote in their article published online Jan. 4 in Nature Medicine.

“Our study indicates an important contribution of brown adipose tissue to cardiometabolic health and suggests ... [it] has therapeutic potential in humans,” they stated.

But Caroline M. Apovian, MD, Center for Weight Management and Wellness, Brigham and Women’s Hospital, Boston, is more cautious in her interpretation of the findings.

“It’s nice to see that what we believe about this is correct, and it’s great to see that with obesity and more brown fat there is reduced diabetes and hypertension, but it’s only an association,” she said in an interview.

“This is a good study, but I don’t think we have an understanding of exactly why some people have more brown fat than others, how white fat becomes brown fat, the role of therapeutics, or if it’s important to try to create more brown fat.

“We don’t know if it’s a matter of exercise or something like living in a colder environment, so we need to find out whether or not brown fat is, for instance, a genetic issue, and if it is, if there is a way to increase it in humans,” she added.

And the fact that the study included patients with or being screened for cancer is one of the most important limitations of the study, Dr. Apovian noted.
 

Brown fat detected in 10% of participants

Contrary to white fat, which stores energy, brown fat is thermogenic, activated by cold conditions, and instead burns energy. And although animal studies have shown a link between brown fat and improvements in glucose and lipid homeostasis, the effects of brown fat in humans are not well understood.

Dr. Becher and colleagues explained that large-scale studies of brown fat have been practically impossible because the tissue only shows up on medical imaging and it would be unethical to expose people to radiation just to study brown fat.  

But they realized that, across the street from their lab, many thousands of people visit Memorial Sloan Kettering Cancer Center each year to undergo PET/CT scans for cancer evaluation.

Because radiologists routinely take note when brown adipose tissue is detected to prevent its misinterpretation as a tumor, the information was readily available with the scan data.

“We realized this could be a valuable resource to get us started with looking at brown fat at a population scale,” Dr. Becher said in a press statement from The Rockefeller University.

So they reviewed 134,529 PET/CT scans from 52,487 individuals attending Memorial Sloan Kettering between June 2009 and March 2018 for indications ranging from cancer diagnosis to treatment or surveillance.

Participants were classified by the presence or absence of brown adipose tissue and researchers were able to use electronic health records to comprehensively examine associations between brown fat and rates of disease.

Overall, brown adipose tissue was identified in 5,070 (9.7%) of patients, with higher rates of brown fat among women than men (13.8% vs. 4.9%; P < .0001) and reduced rates with advancing age (P < .0001), as has been observed in previous studies.

The researchers noted, however, that this rate of around 10% of people having brown fat is likely an underestimate because the patients had been instructed to avoid cold exposure, exercise, and caffeine – all of which are thought to increase brown adipose tissue – prior to having their scans.
 

Does brown fat mitigate some harms of obesity?

Among those with brown fat, the rate of type 2 diabetes was 4.6% compared with 9.5% in those with no detected brown fat (P < .0001), and in a multivariate analysis, the odds ratio (OR) for type 2 diabetes in the presence of brown fat was 0.44.

The occurrence of coronary artery disease was significantly lower in those with brown fat (OR, 0.68; P = .0002), as was cerebrovascular disease (OR, 0.77; P = .0317), heart failure (OR, 0.62; P = .0043), and hypertension (OR, 0.85; P = .0014).

Brown fat also was associated with notable improvements in glucose, triglycerides, and HDL-C levels (all P < .0001), while no differences were seen in measures of LDL-Cs or total cholesterol.

Leukocyte and platelet counts were significantly decreased in individuals with brown fat (both P < .0001).

The findings “suggest potential roles for brown adipose beyond regulation of lipid and glucose metabolism,” the authors wrote.

Most notably, the effects were more pronounced in people with obesity. For example, the prevalence of type 2 diabetes in those with obesity and brown fat was less than half the rate in those with obesity without brown fat (7.5% vs. 20.3%; P < .0001).

This could indicate that brown adipose tissue “might play a role in mitigating the deleterious effects of obesity,” the researchers stated.

“Future research should aim to improve our understanding of brown adipose tissue regulation in humans and to develop mechanisms to safely modulate [its activity],” they concluded.

The study received funding from the American Diabetes Association, the Sinsheimer Foundation, and the National Center for Advancing Translational Sciences of the U.S. Department of Health & Human Services. The authors and Dr. Apovian have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Yet another study has linked the consumption of ultraprocessed, or “junk,” foods to bad health outcomes.

In a longitudinal analysis of more than 22,000 men and women from southern Italy, those who consumed the most ultraprocessed food (UPF) had the highest risk for cardiovascular disease (CVD) and all-cause mortality, likely mediated through a diet high in sugar, researchers said.

High consumption of UPF in this Mediterranean cohort was associated with a 58% increased risk for CVD mortality and 52% higher risk of dying from ischemic heart disease (IHD) and cerebrovascular causes, independently of known risk factors for CVD, even among individuals who otherwise adhered to the Mediterranean diet.

The findings “should serve as an incentive for limiting consumption of UPF and encouraging natural or minimally processed foods, as several national nutritional policies recommend,” Marialaura Bonaccio, PhD, department of epidemiology and prevention, IRCCS Neuromed, Pozzilli, Italy, and colleagues wrote. The results were published online Dec. 18 in the American Journal of Clinical Nutrition.

Earlier this year, as reported by this news organization, researchers found mounting evidence that the obesity epidemic and the increase in incidence of related chronic conditions corresponded with an increase in the intake of UPF.

A study that was conducted in a European cohort found that adults whose diet included more UPF and beverages, such as ice cream, soda, and hamburgers, were more likely to develop CVD or die sooner than others who had a more wholesome diet.

As reported previously by this news organization, among adults in France who had a 10% higher intake of UPF and beverages, the rate of CVD, coronary heart disease, and cerebrovascular disease was 11% to 13% higher over a period of about 5 years.

Similarly, university graduates in Spain who consumed more than four servings of UPF and beverages a day were 62% more likely to die of any cause over about a decade than those who consumed less than two servings per day.
 

Where’s the food?

There is very little actual food in UPF. “The NOVA classification provides 4 main classes of food and beverages, the last of which is represented by the ultraprocessed food group. This comprises products (e.g., snacks, drinks, and ready meals, ‘created mostly or entirely from substances extracted from foods or derived from food constituents with little, if any intact food, which often contain flavors, colors, and other additives that imitate or intensify the sensory qualities of foods or culinary preparations made from foods,’ ” Dr. Bonaccio and colleagues wrote.

Such foods are very convenient, tasty, inexpensive, and have a long shelf life. They are highly competitive with foods that are naturally ready to consume and freshly prepared dishes and meals, the authors add.

The researchers conducted a longitudinal analysis on 22,475 men and women (mean age, 55 years; range, 43-67 years) who were recruited from the Moli-sani Study, a population-based cohort of men and women aged 35 years and older in the Molise region of southern Italy, between 2005 and 2010. Participants were followed for 8.2 years.

Food intake was assessed with the Food Frequency Questionnaire; UPF was defined using the NOVA classification according to degree of processing.

UPF intakes were categorized as quartiles of the ratio of UPF to total food consumed.

Overall, study participants reported a median of 10% (interquartile range, 6.6%-14.6%) of dietary intake as UPF and a total of 181.5 g/d of UPF intake.

The foods that contributed most to total UPF consumed were processed meat, which accounted for 19.8% of UPF intake; pizza (16.8%); and cakes and pies (13.4%).

High consumers of UPF, defined as those for whom UPF constituted more than 14.6% of their total diet, were more likely to be women, to be younger, and to have a higher educational level. They also reported fewer risk factors and fewer baseline chronic diseases and health conditions than persons who consumed UPF less frequently.

In addition, high consumption of UPF was associated with lower adherence to the Mediterranean diet; higher intake of fat, sugar, dietary cholesterol, and sodium; and lower intake of fiber.

During a median follow-up of 8.2 years, 1,216 all-cause deaths occurred. Of these, 439 were attributed to CVD, 255 to IHD/cerebrovascular disease, 477 to cancer, and 300 to other causes.
 

The more UPF, the higher the risk for CVD, death

The researchers found a direct linear dose-response relation between a 5% increase in the proportion of UPF in the diet and risk for all-cause and CVD mortality.

Individuals who reported the highest intake of UPF (fourth quartile, 14.6% of total food) as opposed to the lowest (first quartile, UPF <6.6%) experienced increased risks for CVD mortality (hazard ratio, 1.58; 95% CI, 1.23-2.03), death from IHD/cerebrovascular disease (HR, 1.52, 95% CI, 1.10-2.09), and all-cause mortality (HR, 1.26; 95% CI, 1.09-1.46).

High sugar content accounted for 36.3% of the relation of UPF with IHD/cerebrovascular mortality. Other nutritional factors, such as saturated fats, were unlikely to play a role, the researchers wrote.

Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality and 12.0% for that of UPF with CVD mortality.

Subgroup analyses indicated that the magnitude of the association between UPF and all-cause mortality risk was greater among high-risk individuals, such as those with a history of CVD or diabetes. UPF was also likely to be more strongly associated with CVD mortality among those high-risk groups.

The interesting finding that the association between UPF and CVD mortality was greater among individuals with good adherence to the Mediterranean diet, which is known to have health benefits, could be explained by the fact that people who may benefit from a Mediterranean diet are more susceptible to losing health advantages when they also include “detrimental dietary behavior,” whereas those who consume a poor-quality diet are less likely to be harmed by an additional unhealthy behavior such as eating UPF regularly, wrote Dr. Bonaccio and colleagues.

“This is an interesting study confirming that consumption of highly processed foods such as pizza, processed meats, and soda are associated with greater risks of cardiovascular disease,” Walter Willett, MD, professor of epidemiology and nutrition, Harvard School of Public Health, Boston, said in an interview.

“These higher risks appear to be mediated in part by high intakes of saturated fat and sugar, but lower intakes of health-promoting aspects of diet also likely contribute to the findings,” Dr. Willett said.

“Some processing of food can be useful for preservation and control of infectious agents, but in general, a diet emphasizing minimally processed fruits and vegetables, whole grains, nuts, legumes, and plant sources of fat will be best for long-term well-being,” he said.

The study was supported in part by the Italian Ministry of Health and the HYPERCAN Study Italian Association for Cancer Research. Dr. Bonaccio and Dr. Willett reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.

They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.

Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).

“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.

Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.

Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
 

Large dataset: Use age at diagnosis to risk stratify patients

Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.

But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.

Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).

Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).

Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.

Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”

Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.

They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”

Dr. Nanayakkara disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.

They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.

Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).

“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.

Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.

Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
 

Large dataset: Use age at diagnosis to risk stratify patients

Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.

But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.

Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).

Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).

Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.

Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”

Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.

They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”

Dr. Nanayakkara disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Those who are found to have type 2 diabetes at a younger age face “hidden” dangers. The issue is becoming more and more important, “since new diagnoses in this younger age group continue to rise,” said the authors of a new study, led by Natalie Nanayakkara, MD.

They believe clinical approaches should be based on age at diagnosis. The results of their new meta-analysis, published online in Diabetologia, reveal the extent of the problem.

Believed to be the first systematic review of its kind, the study showed that the younger the age at diagnosis of type 2 diabetes, the greater the risks of dying and of having either microvascular or macrovascular complications each subsequent year (adjusted for current age).

“This difference in risk between younger and older people in terms of absolute versus lifetime risks of type 2 diabetes complications should perhaps be recognized in diabetes management guidelines,” wrote Dr. Nanayakkara, an endocrinologist at Monash University, Melbourne, and colleagues.

Those diagnosed at younger ages are more likely to develop complications that cause greater disability and lead to loss of productivity compared with people diagnosed at an older age, they stressed.

Hence, they suggested “a greater emphasis on preventive measures for younger people with type 2 diabetes,” with “early intensive multifactorial risk factor intervention ... sustained long term to minimize risks over time.”
 

Large dataset: Use age at diagnosis to risk stratify patients

Rates of type 2 diabetes have increased in all age groups and virtually all countries over the past 3 decades. Particularly worrying is a trend toward increased rates among adults aged 20-44 years. The increases are associated with higher rates of overweight and obesity, poor diet, and decreasing levels of physical activity, numerous studies have shown.

But few studies have examined the association between age at diagnosis and subsequent complications from type 2 diabetes, the authors noted.

Their review included 26 observational studies involving more than one million individuals from 30 countries in the Asia Pacific, Europe, and North America. The investigators found that each 1-year increase in age at diabetes diagnosis was significantly associated with a 4%, 3%, and 5% decreased risk for all-cause mortality, macrovascular disease, and microvascular disease, respectively, adjusted for current age (all P < .001).

Similar decreases in risk per 1-year increase in age at diabetes diagnosis were seen for coronary heart disease (2%), cerebrovascular disease (2%), peripheral vascular disease (3%), retinopathy (8%), nephropathy (6%), and neuropathy (5%); all associations were significant (P < .001).

Dr. Nanayakkara and colleagues noted that current treatment guidelines are limited in that they’re related to the management of patients with suboptimal blood glucose control, and there is no way to predict which people require intensified treatment.

Therefore, they said, “refined stratification using age at diagnosis may provide a method of identifying, at diagnosis, those at greatest risk of complications who would most benefit from targeted, individualized treatment regimens.”

Awareness of this “hidden” danger to younger adults with type 2 diabetes is becoming more and more important, because such cases continue to rise, they reiterated.

They also advised that “public health measures to delay and/or prevent the onset of type 2 diabetes until older age may yield benefits by reducing the duration of diabetes and the burden of complications.”

Dr. Nanayakkara disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the first-ever generic glucagon injection kit for the treatment of severe hypoglycemia in patients with diabetes and as a diagnostic aid.

The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.

Both require a multistep mixing process that means they are complicated to use.

In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).

The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.

“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.

As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.

According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.

Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.

Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”

Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.

Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the first-ever generic glucagon injection kit for the treatment of severe hypoglycemia in patients with diabetes and as a diagnostic aid.

The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.

Both require a multistep mixing process that means they are complicated to use.

In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).

The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.

“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.

As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.

According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.

Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.

Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”

Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.

Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the first-ever generic glucagon injection kit for the treatment of severe hypoglycemia in patients with diabetes and as a diagnostic aid.

The FDA determined that Amphastar’s Glucagon for Injection Emergency Kit, 1 mg, a synthetic peptide product, is bioequivalent and therapeutically equivalent to Eli Lilly’s recombinant DNA Glucagon Emergency Kit for Low Blood Sugar.

Both require a multistep mixing process that means they are complicated to use.

In 2019, FDA approved two branded, easier-to-use formulations of glucagon – one nasally administered (Baqsimi, Eli Lilly & Co) and the other a prefilled pen or syringe (Gvoke HypoPen and Gvoke PFS, respectively, Xeris Pharmaceuticals).

The new generic will have the advantage of lower cost, Amphastar spokesman Dan Dischner said in an interview.

“Our generic glucagon will be priced as a generic product so that patients will benefit from a lower price. As we are just at the beginning of the commercialization of the product, we are unable to discuss our specific product price,” he wrote.

As with the branded Lilly injectable glucagon, the new generic is also indicated as a diagnostic aid in gastrointestinal radiologic imaging, as glucagon slows gastric motility.

According to an FDA statement, glucagon is a “complex product” that has been difficult to manufacture generically despite the lifting of patent protection. This approval was the result of the FDA’s efforts to encourage the development and submission of applications for such drugs.

Amphastar specializes in “developing, manufacturing, marketing, and selling technically-challenging generic and proprietary injectable, inhalation, and intranasal products,” the company website says.

Mr. Dischner said, “Glucagon is a complex product that requires R&D and manufacturing capabilities to develop a highly purified synthetic peptide product bioequivalent and therapeutically equivalent to the recombinant DNA origin Glucagon. Given that this product has been through various review cycles, its complexity, and the technological capabilities required to manufacture, it is no surprise that there hasn’t been a generic of glucagon until now.”

Side effects of injected glucagon include nausea, vomiting, transient increase in heart rate, and redness/swelling of the injection site.

Mr. Dischner added, “We are confident that our generic to Lilly’s time-tested glucagon will provide a favorable option, at a reasonable price, to patients who rely on this product.”

A version of this article first appeared on Medscape.com.