Risk Factors for Type 2 Diabetes

Sylvia H. Ley, Matthias B. Schulze, Marie-France Hivert, James B. Meigs, Frank B. Hu, Catherine C. Cowie, Sarah Stark Casagrande, Andy Menke, Michelle A. Cissell, Mark S. Eberhardt, James B. Meigs, Edward W. Gregg, William C. Knowler, Elizabeth Barrett-Connor, Dorothy J. Becker, Frederick L. Brancati, Edward J. Boyko, William H. Herman, Barbara V. Howard, K. M. Venkat Narayan, Marian Rewers, Judith E. Fradkin, Sylvia H. Ley, Matthias B. Schulze, Marie-France Hivert, James B. Meigs, Frank B. Hu, Catherine C. Cowie, Sarah Stark Casagrande, Andy Menke, Michelle A. Cissell, Mark S. Eberhardt, James B. Meigs, Edward W. Gregg, William C. Knowler, Elizabeth Barrett-Connor, Dorothy J. Becker, Frederick L. Brancati, Edward J. Boyko, William H. Herman, Barbara V. Howard, K. M. Venkat Narayan, Marian Rewers, Judith E. Fradkin

Excerpt

Type 2 diabetes is a heterogeneous disease involving multiple behavioral, metabolic, and genetic factors. The occurrence of diabetes is characterized by progressive deterioration of glucose tolerance, but not all individuals in the intermediate states of glucose intolerance progress to a diagnosis of diabetes. Data suggest the onset of type 2 diabetes can be prevented and delayed through improved understanding of underlying susceptibility to diabetes and intervening on modifiable risk factors.

Over 29 million people in the United States were estimated to have diabetes in 2012. The type 2 diabetes epidemic has been attributed to urbanization and environmental transition leading to lifestyle changes. Prospective studies have uncovered roles for individual nutrients, foods, and dietary patterns in type 2 diabetes prevention. Diets favoring higher intake of whole grains, green leafy vegetables, and coffee; lower intake of refined grains, red and processed meat, and sugar-sweetened beverages; and moderate intake of alcohol have been linked with reduced risk of type 2 diabetes. In a randomized trial after 4-year follow-up, a Mediterranean diet with extra virgin olive oil supplementation reduced diabetes risk by 40% compared to a low-fat control diet. Physical inactivity is another behavioral risk factor for type 2 diabetes. A lifestyle that includes physical activity, from brisk walking to higher intensity endurance or resistance training, can reduce the risk of developing type 2 diabetes. For example, regular brisk walking of ≥2.5 hours per week has been associated with 30% reduction in type 2 diabetes risk compared to almost no walking. Many benefits of a healthy lifestyle appear to be mediated through maintenance of a healthy distribution of body fat. Central obesity, which can be assessed by measuring waist circumference, is a strong predictor of type 2 diabetes. A large, international meta-analysis suggested that the relative risk (RR) of type 2 diabetes per standard deviation in obesity indicators was slightly more pronounced for higher waist circumference (1.87, 95% confidence interval [CI] 1.58–2.20) than higher body mass index (1.72, 95% CI 1.47–2.02).

With the increased prevalence of obesity at a population level, more women are experiencing metabolic abnormalities during pregnancy. Children who experienced intrauterine exposure to maternal diabetes are more likely to have childhood overweight, followed by impaired glucose tolerance in early adulthood. For example, intrauterine exposure to maternal diabetes was associated with type 2 diabetes in youth age 10–22 years (odds ratio 5.7, 95% CI 2.4–13.4). Therefore, the vicious cycle of diabetes may continue to the next generation, as they enter childbearing age in the absence of early-life intervention.

Novel biomarkers and intermediate conditions associated with diabetes risk have been identified. Type 2 diabetes is increasingly considered to be a subclinical pro-inflammatory condition derived from accumulation of excess adipose tissue leading to impaired secretion of adipokines and inflammatory cytokines by adipocytes. Endothelial dysfunction markers have been associated with type 2 diabetes. In addition, the metabolic syndrome, a phenomenon of metabolic risk traits clustering, including central obesity, elevated fasting glucose, triglyceride, and blood pressure levels, and/or low high-density lipoprotein cholesterol levels, has emerged as a powerful risk factor for developing type 2 diabetes (RR averaging 5.1 in one meta-analysis).

Prospective studies have identified modifiable risk factors for type 2 diabetes, which offer the potential to predict and detect diabetes risk before the onset of the disease. Although type 2 diabetes cannot be cured at the present time, development of the disease can be prevented or delayed by intervening on modifiable risk factors at an early stage.

Conflict of interest statement

DUALITY OF INTEREST

Drs. Ley, Schulze, Hivert, Meigs, and Hu reported no conflicts of interest.

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