Screening and Diagnosis of Prediabetes and Metabolic Syndrome

Prediabetes

Type 2 diabetes is a serious and costly disease currently affecting more than 16 million people in the US.[1] Type 2 diabetes, which has devastating consequences on life expectancy, morbidity, and quality of life, imposes significant healthcare costs to society.[1,2] Despite advancing therapeutic options utilized in the treatment of diabetes, type 2 diabetes remains a chronic degenerative condition that is difficult to treat.[3] Prevention of diabetes is thus a worthy public health goal, especially since the diabetes pandemic is closely correlated with the contemporary lifestyle.[4] Prediabetes, also referred to as impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) (Table 1), is a major risk for the development of type 2 diabetes (Table 2).[5] The American Diabetes Association (ADA) recommends targeting prevention efforts to the population of people with prediabetes (either IGT or IFG).[6] Impaired glucose tolerance is thought to arise from peripheral insulin resistance, whereas IFG may be secondary to increased hepatic gluconeogenesis and decreasing or impaired pancreatic β-cell function.[5,7] It is estimated that nearly 12 million overweight individuals aged 45 to 74 years have prediabetes.[1] The predicted cumulative 5- to 6-year incidence of development of type 2 diabetes for patients with either IGT or IFG is 20% to 34%.[6] It is also estimated that nearly 60% of patients with type 2 diabetes had prediabetes 5 years before diagnosis.[8] To aid in the identification of people with prediabetes, the ADA has recommended diabetes screening during a healthcare visit for men and women who are ≥45 years, particularly those with BMI ≥25 kg/m.[6] A recent clinical study evaluated the effectiveness, costs, and efficiency of 5 strategies to identify people with prediabetes based on a one-time screening of the US population. Results are depicted in Table 3. Overall, A1C testing produced the highest cost, followed by OGTT and FPG testing; CBG screening produced the lowest cost. Currently, FPG and OGTT remain the “gold standards” for defining prediabetes.[9]

Table 1. ADA's classification of prediabetes[10]

Table 2. Risk factors for type 2 diabetes mellitus[11]

Table 3. Analysis of screening methods[9]

Four recent, randomized, controlled trials, performed across diverse countries, settings and populations, have provided evidence that the progression from IGT to type 2 diabetes can be delayed or prevented. A brief summary including results from these clinical trials is illustrated in Table 4. The most compelling evidence has been reported from the Diabetes Prevention Program (DPP). The DPP trial found that modest weight loss and changes in lifestyle reduced the 3-year incidence of type 2 diabetes by 58%, and that drug therapy consisting of metformin reduced the risk by 31%.[6] Based on the results from the listed clinical trials, the ADA recommends screening for prediabetes in patients ≥45 years, especially with BMI ≥25 kg/m², using either IGT or IFG testing, as well as overweight younger individuals with prediabetes and other risk factors.[12] Patients with either IGT or IFG should be screened every 1-2 years to check for development of type 2 diabetes; those with normal values should be screened again in 3 years.[6]

The ADA treatment of choice for patients with prediabetes is lifestyle modification consistent with a 5% to 10% weight reduction and increased physical activity (30 minutes/day, most days of week). At this time, the ADA does not recommend drug therapy for initial prevention of prediabetes based on the limited efficacy of treatment with oral agents versus lifestyle modifications, the potential for adverse drug reactions, the lack of data showing a reduction in the microvascular complications of diabetes in this patient population, and insufficient assessment of cost effectiveness of drug treatment.[6] More clinical studies are needed to determine the role of drug therapy (usually reserved for patients with clinically diagnosed diabetes) with lifestyle modifications to assess long-term safety, cost, and their potential to reduce cardiovascular risk. Several studies are currently underway to help provide more information regarding lifestyle modifications and drug therapy limiting progression from IGT to diabetes. A summary of these trials is listed in Table 5.

High-risk patients should be counseled regarding the potential benefits of increased activity and weight loss based on the trials previously mentioned. Due to the high prevalence of other cardiovascular risk factors, identification and potential treatment of tobacco use, dyslipidemia, and hypertension also should be considered.[5]

Table 4. Summary of clinical studies

*Defined as cumulative sum of the OGTT plasma glucose levels drawn at 0, 30, 60, 90, and 120 minutes.

ILI = intensive lifestyle modification

Table 5. Summary of currently enrolled clinical trials[5]

DREAM = Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication

NAVIGATOR = The Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research

Metabolic syndrome

Individuals with prediabetes (impaired IGT) and diabetes are at increased risk for the development of cardiovascular disease.[17,18] Also, many individuals with prediabetes and diabetes have certain metabolic disturbances that, when grouped together in a single individual patient, comprise the cluster known as metabolic syndrome[19]:

• Abdominal obesity
• Atherogenic dyslipidemia
• Sustained elevated blood pressure (>140/90 mm Hg)
• Insulin resistance ± glucose intolerance
• Prothrombotic state
• Proinflammatory state

The diagnostic criteria, adapted from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III), are illustrated in Table 6. According to this definition, >20% of adults have metabolic syndrome.[20] The metabolic syndrome can result from increased glucose intolerance and decreased insulin sensitivity and resistance, which is thought to precede the development of the metabolic syndrome.[21] The prevalence of metabolic syndrome appears to increase with increasing glucose intolerance. Insulin resistance subsequently leads to elevations in triglyceride and glucose levels and in systolic and diastolic blood pressure and to reduced HDL cholesterol levels.[20] Furthermore, all 5 metabolic syndrome criteria are established cardiovascular risk factors, which correlates with a 3-fold increased risk in coronary artery disease and stroke.[22]

Table 6. ATP III Diagnostic criteria for metabolic syndrome[19]

The evaluation of patients with 2 or more indications of metabolic syndrome should include measurement of vital signs and body weight, measurement of waist circumference, measurement of fasting blood sugar, and a complete lipid profile. Increased weight loss has a positive impact on all components of the metabolic syndrome. The FDP and the DDP (previously mentioned) found that a mean weight loss of 7% reduces the risk of developing type 2 diabetes by 58%. Thus, weight loss can prevent prediabetes from developing into type 2 diabetes as well as aid in the prevention of metabolic syndrome.

References

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2. Hogan P, Dall T, Nikolov P; American Diabetes Association. Economic costs of diabetes in the US in 2002. Diabetes Care. 2003;26:917-932.
3. Knowler WC, Narayan KM, Hanson RL, et al. Preventing non-insulin-dependent diabetes. Diabetes. 1995;44:483-488.
4. Narayan KM, Bowman BA, Engelgau ME. Prevention of type 2 diabetes. BMJ. 2001;323:63-64.
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19. US Department of Health and Human Services. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. National Cholesterol Education Program National Heart, Lung, and Blood Institute National Institutes of Health. NIH Publication No. 02-5215. September 2002. II-26.
20. Palaniappan L, Carnethon MR, Wang Y, et al, and the Insulin Resistance Atherosclerosis Study. Predictors of the incident metabolic syndrome in adults: the Insulin Resistance Atherosclerosis Study. Diabetes Care. 2004;27:788-793.
21. Kendall DM, Harmel AP. The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. Am J Manag Care. 2002;8(20 suppl):S635-S653.
22. Somaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683-689.