Study Challenges Notion of 'Metabolically Healthy Obese'

Miriam E. Tucker

August 28, 2014

The absence of additional metabolic risk factors does not protect overweight or obese young men from developing type 2 diabetes, a new study finds.

Gilad Twig, MD, PhD, of the department of medicine at Sheba Medical Center, Tel Hashomer, Israel, and colleagues published the results from the Metabolic, Lifestyle and Nutrition Assessment in Young Adults (MELANY) study online August 19 in Diabetes Care.

"Our findings primarily suggest that obesity, even when accompanied by an intact metabolic profile, is not a benign condition. Physicians should be aware of this, especially among young adults," Dr. Twig told Medscape Medical News.

The researchers enrolled 33,939 men aged 25 and older who were in the Israel Defense Forces (IDF). They followed the participants from 1995 through 2011. At baseline, 49% were of normal weight (body mass index [BMI] < 25 kg/m2), 38% were overweight (BMI 25 to 30 kg/m2), and 13% were obese (BMI > 30 kg/m2).

Over a median 6-year follow-up, 734 (2.2%) were diagnosed with type 2 diabetes.

Dr. Twig and colleagues also divided the subjects according to how many baseline metabolic abnormalities they had, including:

  • Triglyceride level of 150 mg/dL or greater or use of lipid-lowering drugs.

  • Glucose level of 100 mg/dL or greater.

  • Systolic blood pressure 130 mm Hg or greater or diastolic blood pressure 85 mm Hg or above or use of antihypertensive drugs.

  • HDL cholesterol less than 40 mg/dL.

Only 14.7% of the obese group were "metabolically healthy," defined as having none of the additional risk factors, compared with 55% of the normal-weight group and 32% of the overweight group.

The investigators found that each 1-unit increase in BMI was associated with a 10.6% increased risk of developing diabetes (P < .001), after adjusting for age, family history of diabetes, country of origin, physical activity, fasting plasma glucose, triglycerides, and white blood cell count.

Among the "metabolically healthy," the hazard ratios for development of diabetes compared with normal-weight subjects were 1.89 for overweight individuals and 3.88 for obese ones ( P < .001). The rates for development of diabetes among the metabolically healthy were 4.34 cases per 1000 per person-years for the obese group vs 1.15/1000 person-years for the normal-weight group (P < .001).

The increase in risk for each additional risk factor was far greater among those who were obese than those of normal weight. Among those with at least 3 risk factors, the difference in diabetes incidence was 19.17 per 1000 person-years for the obese group vs 3.17 for the normal-weight group.

When the risk factors were analyzed as continuous variables, diabetes risk increased by more than 3-fold in the obese group both among the "metabolically healthy" and among those with 3 metabolic abnormalities.

This study differs from others that identified a "metabolically healthy obese" group in that "metabolically healthy" was defined as having no additional risk factors. By contrast, other studies have included those with 1 or 2 risk factors in the metabolically healthy group, Dr. Twig and colleagues note.

In addition, the subjects in this study were younger at baseline and were thus likely to develop more risk factors in the future. Moreover, previous studies have not carefully adjusted for the various risk factors as continuous variables, which is particularly important in young adults, the authors note.

While they acknowledge one limitation of this study is that it was only done in men, Dr. Twig told Medscape Medical News that the findings should be extrapolatable to other populations. "The MELANY cohort of the IDF has been shown to be similar to many European and US cohorts of young adults....We analyzed these results by country of origin and show that our findings are independent of this variable."

Dr. Twig was partially supported by a grant from the Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel Hashomer, Israel. Disclosures for the coauthors are listed in the article.

Diabetes Care. Published online August 19, 2014. Abstract

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