Thinner May Not Always Be Better for People With Diabetes

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http://www.medscape.com/viewarticle/768771?src=wnl_edit_specol

Thinner May Not Always Be Better for People With Diabetes

Norra MacReady

Aug 07, 2012

 

 Researchers call it the "obesity paradox": the finding that obese patients with certain illnesses, such as heart failure or chronic kidney disease, live longer than their leaner counterparts.

Now it appears that the paradox may also apply to people with diabetes. In a study of patients who developed incident diabetes, mortality was higher among normal-weight than obese subjects, according to an article published in the August 8 issue of JAMA.

Lead author Mercedes R. Carnethon, PhD, from the Department of Preventive Medicine at the Feinberg School of Medicine, Northwestern University, Chicago, and colleagues conducted a pooled analysis of 5 longitudinal cohort studies: the Atherosclerosis Risk in Communities study, Cardiovascular Health Study, Coronary Artery Risk Development in Young Adults study, Framingham Offspring Study, and Multi-Ethnic Study of Atherosclerosis. A total of 2625 participants were included in the analysis.

Unlike studies in which the patients had diabetes at the time of enrolment, this study focused on people who were diabetes-free at baseline to "minimize the influence of diabetes duration and unintentional or intentional weight loss secondary to diabetes development and diagnosis," the authors write. They selected studies that "had repeated measures of body weight, fasting glucose level, and medication use; a comprehensive set of commonly measured covariates; and longitudinal follow-up for events and mortality."

Patients were considered to have diabetes if they had a fasting glucose level of 126 mg/dL or higher or reported use of hypoglycemic agents or insulin. Body mass index (BMI) was used to determine weight status, with normal weight defined as a BMI of between 18.5 kg/m² and 24.9 kg/m², overweight as between 25 kg/m² and 29.9 kg/m², and obese as 30 kg/m² or more. Starting from the examination at which diabetes was first identified, the patients were followed-up until they died, came to the end of their cohort surveillance, or were lost to follow-up.

Study Findings

Across the cohorts, 293 participants (11.2%) had normal-weight diabetes. A total of 449 deaths (17.1% of the combined cohorts; 165.5 per 10,000 person-years) occurred during follow-up: 178 (6.8% of the cohorts; 66.1 per 10,000 person-years) from cardiovascular causes and 253 (9.6%; 99.0 per 10,000 person-years) from noncardiovascular causes, with 18 causes of death remaining unidentified.

Total, cardiovascular, and noncardiovascular mortality among the normal-weight participants was 284.8, 99.8, and 198.1 per 10,000 person-years, respectively, compared with obese patients, among whom the rates were 152.1, 67.8, and 87.9 per 10,000 person-years, respectively. After covariate adjustment for sex, age, race, education level, waist circumference, lipid levels, and smoking status, normal-weight participants had significantly elevated hazard ratios (HRs) for total mortality (HR, 2.08; 95% confidence interval [CI], 1.52 - 2.85; P < .001) and noncardiovascular mortality (HR, 2.32; 95% CI, 1.55 - 3.48; P < .001) compared with the heavier patients. Normal-weight patients also had a higher HR for cardiovascular mortality (HR, 1.52; 95% CI, 0.89 - 2.58), but it was not statistically significant (P = .06).

Potential study limitations included the use of BMI to define weight status, rather than direct measures of adiposity, the authors write. People with higher BMI may have more lean tissue, which is more insulin-sensitive than fat tissue. Inconsistencies across the studies in capturing smoking status was another limitation, as was lack of information on the participants' use of medications such as antidepressants, which promote the onset of diabetes and are also associated with higher mortality.

Still, the study "adds an important dimension to evidence supporting the obesity paradox in diabetes, as it is the first to measure [BMI] at the time of onset of diabetes, eliminating the potential confounding effects of diabetes duration," Hermes Florez, MD, MPH, PhD, and Sumaya Castillo-Florez, MD, MPH, from the Department of Medicine and Epidemiology and the Department of Public Health, University of Miami Miller School of Medicine, Florida, write in an editorial accompanying the study. They conclude that the study is a "wake-up call" for preventive efforts for all patients with diabetes, including those they term "metabolically obese normal-weight" individuals, who may be lulled into a false sense of security because they are not overweight.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Disease. Dr. Florez and Dr. Castillo-Florez receive research support from the Department of Veterans Affairs Geriatrics Research, Education, and Clinical Center program and from the National Institutes of Health and Department of Health and Human Services. The authors and editorialists have disclosed no relevant financial relationships.

JAMA. 2012;308:581-590, 619-620. Abstract

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