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Diabetes and BMI

Diabetic patients with normal weight have higher mortality

Total mortality and cardiovascular and non-cardiovascular mortality were higher in normal weight subjects
Mechanisms are unknown but could indicate a genetic predisposition

Patients who are normal weight at the time of a diagnosis of diabetes experienced higher rates of total and non-cardiovascular death, compared with those who were overweight or obese at diabetes diagnosis, according to a study in the Journal of the American Medical Association.

“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,” the authors stated in the paper. “It is not known 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.”

Dr Mercedes R Carnethon, Feinberg School of Medicine, Northwestern University, Chicago, and colleagues conducted a study to compare mortality between participants who were normal weight and overweight or obese at the time of new adult-onset diabetes.

The study consisted of a pooled analysis of five longitudinal studies with a total of 2,625 participants with new diabetes. Included were men and women (older than 40 years of age) who developed incident diabetes based on fasting glucose 126mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI.

Participants were classified as normal weight (BMI 18.5 to 24.99) or overweight/obese (BMI>25). Fifty percent of 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% (overall 12%). During follow-up, 449 participants died: 178 (6.8%) from cardiovascular causes and 253 (10.4%) from non-cardiovascular causes. Eighteen causes of death were unidentified.

In the pooled sample, total mortality and cardiovascular and non-cardiovascular mortality were higher in normal-weight participants, compared with rates among overweight or obese participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively, vs. 152.1, 67.8, and 87.9 per 10 000 person-years, respectively).

After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and non-cardiovascular mortality were 2.08 (95% CI, 1.52-2.85), 1.52 (95% CI, 0.89-2.58), and 2.32 (95% CI, 1.55-3.48), respectively.

“These findings are relevant to segments of the US population, including older adults and non-white persons who are more likely to experience normal-weight diabetes,” the authors noted.

The researchers write that mechanisms to explain their findings are unknown, but could indicate a genetic predisposition: “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.”

The researchers add that 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.


In an accompanying editorial, Dr Hermes Florez, University of Miami Miller School of Medicine, and Miami Veterans Affairs Healthcare System, noted that the study addresses an emerging challenge regarding diabetes and weight status.

“This could be a wake-up call for timely prevention and management to reduce adverse outcomes in all patients with type 2 diabetes, particularly in those metabolically obese normal-weight at diagnosis, who may have a false sense of protection because they are not overweight or obese,” the editorial stated. “Standards of diabetes care recommend weight loss for all overweight or obese individuals who have diabetes. Low carbohydrate, low-fat, calorie-restricted, or Mediterranean diets may be effective weight-loss strategies in these individuals.”

Hermes adds that the additional benefits of increased physical activity and behaviour modification strategies may lead to the successful implementation of weight management and healthy living programs for all patients with diabetes.

“It is important to understand how diabetes duration relates to the benefits of intentional weight loss, as well as the clinical consequence associated with sarcopenic obesity and bone loss in older adults with or at high risk for diabetes.”

The research was funded by a National Institute of Diabetes and Digestive and Kidney Disease grant.

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