Study participants who were normal weight at the time of a diagnosis of diabetes experienced higher rates of total and noncardiovascular death compared with those who were overweight or obese at diagnosis.
“Type 2 diabetes in normal-weight adults is an understudied representation of the metabolically obese normal-weight phenotype that has become increasingly common over time,” researchers wrote in background information for the study, which appears in the Aug. 8 issue of the Journal of the American Medical Association. “Whether the ‘obesity paradox that has been observed in chronic diseases such as heart failure, chronic kidney disease and hypertension extends to adults who are normal weight at the time of incident diabetes” has been unclear, the authors wrote.
Mercedes R. Carnethon, PhD, of the Feinberg School of Medicine at Northwestern University in Chicago, and colleagues conducted an analysis to compare mortality between participants who were normal weight and overweight/obese at the time of new adult-onset diabetes. The analysis consisted of five longitudinal studies with a total of 2,625 participants with new diabetes. Included were men and women (older than 40) who developed incident diabetes based on fasting glucose of 126 milligrams per deciliter or greater or newly initiated diabetes medication, and who had concurrent measurements of body mass index. Participants were classified as normal weight if their BMI was 18.5 to 24.99 and overweight/obese if BMI was 25 or greater. Half the participants were women and 36% were non-white.
The proportion of adults who were normal weight at the time of incident diabetes ranged from 9% to 21% in the pooled studies. During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes, with 18 causes unidentified.
In the pooled sample, total mortality and cardiovascular and noncardiovascular mortality were higher in normal-weight participants as compared with rates among overweight or obese participants. Following adjustment for certain variables, the researchers found that participants with normal-weight diabetes had significantly elevated more than twice as high total and noncardiovascular mortality risk. Although cardiovascular mortality was elevated, the association was not statistically significant.
“These findings are relevant to segments of the U.S. population, including older adults and nonwhite persons (e.g. Asian, black), who are more likely to experience normal-weight diabetes,” the authors wrote.
Although mechanisms to explain the findings are unknown, “previous research suggests that normal-weight persons with diabetes have a different genetic profile than overweight or obese persons with diabetes. If those same genetic variants that predispose to diabetes are associated with other illnesses, these individuals may be ‘genetically loaded toward experiencing higher mortality.
“Future research in normal-weight persons with diabetes should test these genetic hypotheses, along with other plausible mechanisms to account for higher mortality, including inflammation, the distribution and action of adipose tissue, atherosclerosis burden and the composition of fatty plaques, and pancreatic beta-cell function.”
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