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Type 2 diabetes linked to metabolic health in obesity

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November 10, 2017

The risk for type 2 diabetes is increased in adults with obesity, whether they were metabolically healthy or unhealthy, and in those with normal weight who were metabolically unhealthy, according to findings published in Obesity Research & Clinical Practice.

Dongsheng Hu, MD, of the department of epidemiology and health statistics at the College of Public Health, Zhengzhou University in China, and colleagues evaluated data from a cluster random sample of adults recruited from a rural Chinese population during July to August 2007 and July to August 2008 to determine whether risk for type 2 diabetes is associated with metabolically healthy obesity or metabolically unhealthy overweight or obesity.

Participants were divided into groups based on their weight status and metabolic health status. Normal weight was defined as BMI of 18.5 kg/m2 to 23.9 kg/m2, and overweight or obesity as BMI of at least 24 kg/m2.

The 6-year incidence of type 2 diabetes was 3.38 per 1,000 person-years for participants with baseline metabolically healthy normal weight, 5.53 for those with baseline metabolically healthy overweight or obesity, 9.89 for those with baseline metabolically unhealthy normal weight and 19.25 for those with metabolically unhealthy overweight or obesity. Participants with overweight or obesity had a higher risk for type 2 diabetes than those with normal weight (adjusted HR = 2.82; 95% CI, 2.32-3.44). The risk for type 2 diabetes was increased 1.4- to 5.3-fold in participants with metabolic disorder components of fasting plasma glucose, blood pressure, triglycerides and HDL cholesterol compared with participants without the conditions; FPG was the strongest risk factor (aHR = 5.33; 95% CI, 4.42-6.43).

The risk for type 2 diabetes was higher in all participants who were metabolically unhealthy compared with those who were metabolically healthy (aHR = 2.96; 95% CI, 2.38-3.7); risk was also increased in participants with metabolically healthy overweight or obesity (aHR = 1.94; 95% CI, 1.33-2.81), metabolically unhealthy normal weight (aHR = 3.1; 95% CI, 2.19-4.39) and metabolically unhealthy overweight or obesity (aHR = 6.63; 95% CI, 4.94-8.9).

Participants who went from metabolically healthy overweight or obesity to metabolically unhealthy overweight or obesity had an increased risk for type 2 diabetes (aHR = 4.52; 95% CI, 2.42-8.47) compared with stable metabolically healthy normal weight. Compared with stable metabolically healthy normal weight, the risk for type 2 diabetes was increased by nine- and 15-fold in participants who maintained metabolically unhealthy normal weight or metabolically unhealthy overweight or obesity status. – by Amber Cox

Disclosures: The authors report no relevant financial disclosures.

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W. Timothy Garvey

Wang and colleagues have shown in a large rural Chinese cohort that a predominant factor conferring risk of future diabetes is an unhealthy metabolic status (ie, presence of metabolic syndrome) regardless of whether individuals are lean or obese. For example, compared with healthy normal weight, the 6-year diabetes incidence was increased by 1.6-fold in healthy obese, by 3.4 in unhealthy lean and by 5.7 in unhealthy obese. While the authors appropriately used a lower BMI threshold to define obesity in this Asian population, these results generally parallel results of studies in the United States and Europe. Another important insight gained by Wang and colleagues, who conducted longitudinal follow-up, is that when individuals convert from healthy to unhealthy status, their diabetes risk is markedly increased regardless of BMI.

However, it is also important to consider the authors’ definition of metabolic health. The term metabolic health is used often in the literature and essentially reflects relative degrees of insulin resistance. Metabolic syndrome traits represent the clinical manifestations of insulin resistance. As many, but not all, authors have done previously, Wang and colleagues classify metabolically healthy individuals as having two or fewer metabolic syndrome traits, and metabolically unhealthy subjects are defined as having metabolic syndrome (ie, three or more traits). The problem is that individuals with one or two traits are insulin resistant (Liao Y, et al. Diabetes Care. 2004;doi:10.2337/diacare.27.4.978) and have increased risk for diabetes and cardiovascular disease (Guo F, et al. Obesity. 2014;doi:10.1002/oby.20585; Guo F, et al. Obesity. 2016;doi:10.1002/oby.21344). The authors demonstrate this in their paper where subjects with isolated abnormal FPG, BP, triglyceride or HDL cholesterol exhibit an increased HR for diabetes. Thus, it can be misleading to classify these individuals as healthy.

True metabolically healthy individuals, whether lean or obese, have a complete absence of metabolic syndrome traits and are insulin sensitive. With this definition of metabolic health, BMI adds nothing to CVD risk in healthy subjects and the risk for diabetes is only minimally increased by obesity (Guo F, et al. Obesity. 2016;doi:10.1002/oby.21344). If the authors had considered healthy status as the absence of any metabolic syndrome traits, the fold increase in diabetes risk when comparing unhealthy lean with that in healthy obese would have been much greater than what was reported. In any event, in high-risk individuals when obesity is present in conjunction with insulin resistance, the most effective approach for diabetes prevention is weight-loss therapy achieving 10% loss of body weight (Garvey WT, et al. Endocr Pract. 2016;doi: 10.4158/EP161356.ESGL), which is accompanied by an increase in insulin sensitivity.

W. Timothy Garvey, MD, FACE

Professor and Chair, Department of Nutrition Sciences
University of Alabama at Birmingham
Director, UAB Diabetes Research Center

Disclosure: Garvey reports he serves on advisory boards for Alexion, Eisai, Merck, Novo Nordisk, Takeda and Vivus, and receives research support from AstraZeneca, Elcelyx, Lexicon, Merck, Novo Nordisk, Pfizer and Weight Watchers.