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Dr. Keenan is associate professor, department of medicine, University of California, Davis.
Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD
- Screen annually for type 2 diabetes mellitus (T2DM), prediabetes, weight gain, and lipid abnormalities in all patients taking atypical antipsychotics.
- Screen annually psychiatric patients age ≥30 who do not take atypicals for T2DM and prediabetes.
- For patients age <30, regularly review your patients’ risk factors for diabetes to determine whom to screen for T2DM or prediabetes.
- Screening is done most simply by ordering a fasting plasma glucose test.
Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.
Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.
Screening recommendations
Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.1 The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.1 For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.
The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.2 Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.
The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.3 The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.
AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.4
European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.5 The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.
Table 1
General population screening recommendations for type 2 diabetes mellitus or prediabetes
Organization | Year | Whom to screen | How to screen |
---|---|---|---|
U.S. Preventive Services Task Force (USPSTF) | 2008 | Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated) | FPG or OGTT every 3 years |
American Diabetes Association (ADA) | 2009 | All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2) | FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks |
American Association of Clinical Endocrinologists (AACE) | 2007 | All adults age ≥30 with risk factors for diabetes (Table 2) | FPG or 2-hour OGTT (frequency not specified) |
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC) | 2007 | All adults with elevated risk score* | OGTT (frequency not indicated) |
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index | |||
*Risk scoring tool available at www.diabetes.fi/english/risktest |
Discussion
Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.
Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.
Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.
Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.
Table 2
Risk factors identified for diabetes or prediabetes
American Diabetes Association (ADA) |
|
American Association of Clinical Endocrinologists |
|
Clinical presentation
Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.
Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.6 Metformin also was effective, but less so than lifestyle measures alone.
Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.
Drug brand names
- Aripiprazole • Abilify
- Metformin • Glucophage
- Ziprasidone • Geodon
Related resources
- American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
- Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.
Disclosure
Dr. Keenan reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
2. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.
3. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13-61.
4. Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):1-68.
5. Rydén L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardio-vascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28(1):88-136.
6. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
Dr. Keenan is associate professor, department of medicine, University of California, Davis.
Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD
- Screen annually for type 2 diabetes mellitus (T2DM), prediabetes, weight gain, and lipid abnormalities in all patients taking atypical antipsychotics.
- Screen annually psychiatric patients age ≥30 who do not take atypicals for T2DM and prediabetes.
- For patients age <30, regularly review your patients’ risk factors for diabetes to determine whom to screen for T2DM or prediabetes.
- Screening is done most simply by ordering a fasting plasma glucose test.
Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.
Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.
Screening recommendations
Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.1 The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.1 For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.
The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.2 Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.
The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.3 The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.
AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.4
European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.5 The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.
Table 1
General population screening recommendations for type 2 diabetes mellitus or prediabetes
Organization | Year | Whom to screen | How to screen |
---|---|---|---|
U.S. Preventive Services Task Force (USPSTF) | 2008 | Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated) | FPG or OGTT every 3 years |
American Diabetes Association (ADA) | 2009 | All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2) | FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks |
American Association of Clinical Endocrinologists (AACE) | 2007 | All adults age ≥30 with risk factors for diabetes (Table 2) | FPG or 2-hour OGTT (frequency not specified) |
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC) | 2007 | All adults with elevated risk score* | OGTT (frequency not indicated) |
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index | |||
*Risk scoring tool available at www.diabetes.fi/english/risktest |
Discussion
Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.
Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.
Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.
Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.
Table 2
Risk factors identified for diabetes or prediabetes
American Diabetes Association (ADA) |
|
American Association of Clinical Endocrinologists |
|
Clinical presentation
Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.
Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.6 Metformin also was effective, but less so than lifestyle measures alone.
Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.
Drug brand names
- Aripiprazole • Abilify
- Metformin • Glucophage
- Ziprasidone • Geodon
Related resources
- American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
- Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.
Disclosure
Dr. Keenan reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Keenan is associate professor, department of medicine, University of California, Davis.
Principal Source: U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.—Discussant: Craig R. Keenan, MD
- Screen annually for type 2 diabetes mellitus (T2DM), prediabetes, weight gain, and lipid abnormalities in all patients taking atypical antipsychotics.
- Screen annually psychiatric patients age ≥30 who do not take atypicals for T2DM and prediabetes.
- For patients age <30, regularly review your patients’ risk factors for diabetes to determine whom to screen for T2DM or prediabetes.
- Screening is done most simply by ordering a fasting plasma glucose test.
Psychiatric patients—especially those with schizophrenia or taking atypical antipsychotics—are at risk for developing type 2 diabetes mellitus (T2DM) and prediabetes conditions. T2DM can be present for years without significant symptoms and even asymptomatic conditions increase the risk of cardiovascular, renal, retinal, and neurologic complications.
Despite a need for T2DM screening and treatment, expert guidelines disagree on who and how to screen (Table 1). Although testing patients who have diabetes symptoms—including polyuria, polydipsia, and weight loss—is indicated, some medical groups advocate screening asymptomatic persons for T2DM.
Screening recommendations
Consensus guidelines. In 2004, the American Diabetes Association (ADA), American Psychiatric Association (APA), American Association of Clinical Endocrinologists (AACE), and North American Association for the Study of Obesity (NAASO) created consensus guidelines for screening psychiatric patients receiving atypical antipsychotics. In addition to diabetes risk, psychiatric patients are at higher risk for metabolic syndrome, dyslipidemia, obesity, and hypertension.1 The ADA, APA, AACE, and NAASO recommend regularly screening for weight gain and dyslipidemia, obtaining baseline values of fasting plasma glucose (FPG), rechecking FPG after 3 months, and then screening annually for diabetes or prediabetes. For patients with risk factors for diabetes and those who develop diabetes or prediabetes while taking an atypical antipsychotic, consider an atypical with a lower risk of diabetes—specifically aripiprazole or ziprasidone.1 For psychiatric patients who do not take atypicals, there is no consensus on who and how to screen for T2DM.
The U.S. Preventive Services Task Force (USPSTF) recommends screening only adults with hypertension.2 Its review found insufficient evidence that early detection and treatment leads to improved clinical outcomes in asymptomatic adults.
The ADA recommends more liberal screening, including individuals age ≥45 or anyone age <45 who is overweight and has any other diabetes risk factors.3 The ADA admits that no trials show a benefit of screening asymptomatic patients but notes that the duration of glycemic burden predicts adverse outcomes and effective interventions for diabetes and prediabetes are available.
AACE guidelines recommend screening starting at age 30 if the patient has risk factors for T2DM. This is the only group that includes psychiatric illness as a risk factor.4
European Association for the Study of Diabetes (EASD) guidelines calculate a risk score based on common risk factors to determine who should be screened and recommend using the oral glucose tolerance test (OGTT) rather the FPG.5 The OGTT identifies more cases of diabetes and pre-diabetes but takes >2 hours to administer.
Table 1
General population screening recommendations for type 2 diabetes mellitus or prediabetes
Organization | Year | Whom to screen | How to screen |
---|---|---|---|
U.S. Preventive Services Task Force (USPSTF) | 2008 | Asymptomatic adults with sustained blood pressure >135/80 mmHg (treated or untreated) | FPG or OGTT every 3 years |
American Diabetes Association (ADA) | 2009 | All adults age ≥45 Adults of any age with BMI >25 kg/m2 and ≥1 risk factors for diabetes (Table 2) | FPG or 2-hour OGTT every 3 years or more frequently, depending on initial results and risks |
American Association of Clinical Endocrinologists (AACE) | 2007 | All adults age ≥30 with risk factors for diabetes (Table 2) | FPG or 2-hour OGTT (frequency not specified) |
European Association for the Study of Diabetes (EASD) and European Society of Cardiology (ESC) | 2007 | All adults with elevated risk score* | OGTT (frequency not indicated) |
FPG: fasting plasma glucose; OGTT: oral glucose tolerance test (75 gm glucose load); BMI: body mass index | |||
*Risk scoring tool available at www.diabetes.fi/english/risktest |
Discussion
Despite a lack evidence showing benefit to the screened population, treating diabetes and its comorbidities improves outcomes, and the potential risks of therapy are low. Therefore, it seems reasonable to screen more patients than the USPSTF recommends.
Using the EASD risk score is intriguing, but difficult to implement in a busy practice. Therefore, I recommend following the AACE guidelines, which recognize psychiatric illness as a risk factor, for screening psychiatric patients who are not receiving atypicals.
Annually screen psychiatric patients age ≥30, especially those with schizophrenia or affective disorders. I also follow the ADA guidelines and screen overweight adults age ≤30 if they have any of the other risk factors listed in Table 2. The most common risk factors seen in practice are being a member of a high-risk ethnic group, hypertension, lipid abnormalities, and cardiovascular disease. For overweight adults without other risk factors, I start screening at age 30.
Other practitioners can be more or less conservative and still be within accepted guidelines. The FPG—glucose level drawn from a vein after at least 8 hours of fasting—is probably the easiest screening test in practice. Any patient with a value >100mg/dL should be referred to the patient’s primary care physician. Any patient who develops diabetes symptoms—including polyuria, polydipsia, and weight loss—should be tested immediately. The hemoglobin A1C test is not recommended for screening.
Table 2
Risk factors identified for diabetes or prediabetes
American Diabetes Association (ADA) |
|
American Association of Clinical Endocrinologists |
|
Clinical presentation
Screening detects overt diabetes and can identify prediabetes. Prediabetes includes conditions of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). IFG is defined as a fasting glucose of 100 to 125 mg/dL, and IGT is defined as having a 2-hour glucose of 140 to 199 mg/dL on an OGTT.
Approximately one-quarter of the adult population has prediabetes, and interventions can prevent the progression of prediabetes to overt diabetes and reverse prediabetes. The Diabetes Prevention Trial found that lifestyle measures—including exercise and diet—were most effective, with a 53% reduction in the rate of progression to diabetes.6 Metformin also was effective, but less so than lifestyle measures alone.
Treatment slows the development or progression of microvascular complications, such as retinopathy, nephropathy, and neuropathy. Aggressive treatment of comorbid conditions, including hyperlipidemia and hypertension, also reduces the risk of cardiovascular events.
Drug brand names
- Aripiprazole • Abilify
- Metformin • Glucophage
- Ziprasidone • Geodon
Related resources
- American Diabetes Association. Diabetes risk calculator. www.diabetes.org/risk-test.jsp.
- Dagogo-Jack S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(1):22-23. Quick, up-to-date review of the association between atypical antipsychotics and diabetes mellitus.
Disclosure
Dr. Keenan reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
2. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.
3. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13-61.
4. Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):1-68.
5. Rydén L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardio-vascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28(1):88-136.
6. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
1. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, et al. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601.
2. U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.
3. American Diabetes Association. Standards of medical care in diabetes—2009. Diabetes Care. 2009;32(suppl 1):S13-61.
4. Rodbard HW, Blonde L, Braithwaite SS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):1-68.
5. Rydén L, Standl E, Bartnik M, et al. Guidelines on diabetes, pre-diabetes and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardio-vascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J. 2007;28(1):88-136.
6. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.