RE: "CHANGES IN BODY WEIGHT AND BODY FAT DISTRIBUTION AS RISK FACTORS FOR CLINICAL DIABETES IN US MEN"

Marieke B. Snijder1,2, Marjolein Visser1,2, Jacqueline M. Dekker2 and Jaap C. Seidell1,2

1 Department of Nutrition and Health, Faculty of Earth and Life Sciences, Vrije Universiteit, 1081 HV Amsterdam, the Netherlands
2 Institute for Research in Extramural Medicine, VU University Medical Center, 1081 HV Amsterdam, the Netherlands

We read with great interest the paper recently published in the Journal by Koh-Banerjee et al. (1), who prospectively studied the relations between changes in body weight and body fat distribution (1986–1996) and subsequent risk of diabetes mellitus (1996–2000) among 22,171 Caucasian men. Weight gain was associated with increased risk of type 2 diabetes, whereas weight loss was related to decreased risk, independently of baseline body mass index, changes in fat distribution, and potential lifestyle confounders. Even more interesting were the relations with changes in fat distribution. As expected, an increase in waist circumference was associated with increased risk of diabetes independently of weight changes. However, increased risk was also observed for persons with a decrease in hip circumference.

Koh-Banerjee et al. assumed the higher risk of diabetes associated with decreased hip circumference to be caused by wasting of leg muscle mass (1). Indeed, a decrease in peripheral muscle mass is a well-known phenomenon of aging. We would like to emphasize another possible underlying mechanism which is in line with several studies that also found an independent relation of smaller hip circumference with more unfavorable glucose and lipid levels (2, 3) and future risk of diabetes (46).

Until recently, it was not clear whether the relation between smaller hips and increased health risk was due to smaller muscle mass at the hips, smaller fat mass, or both. A number of recent investigations used dual-energy x-ray absorptiometry to distinguish muscle and fat mass in the legs (710). These studies showed that, apart from lower muscle mass, a lower fat mass in the legs was independently related to unfavorable glucose and lipid levels (79) and progression of aortic calcification (10).

Several mechanisms may explain why leg fat seems to confer protection against metabolic disturbances. First, because the femoral fat depot is relatively insensitive to lipolytic stimuli and highly sensitive to antilipolytic stimuli, the femoral-gluteal fat depot may play a protective role by acting as a "sink" for circulating free fatty acids (11). This uptake of free fatty acids prevents ectopic fat storage in the liver, skeletal muscle, and pancreas, which causes insulin resistance and beta-cell dysfunction. In other words, if a person is more capable of storing lipids in femoral-gluteal adipose tissue (which results in larger hips), circulatory lipid levels will be lower and therefore cause less damage to organs, resulting in a lower risk of diabetes. Second, adipose tissue secretes many signaling proteins and cytokines with broad biologic activity and critical functions. Some of these adipokines may be involved in the development of insulin resistance in obesity (12). Because the secretory functions of adipose tissue are probably subject to regional variation (13), the different associations of abdominal and femoral fat with metabolic variables may be mediated by differential secretion of adipokines by these fat depots.

We think these considerations are relevant additional explanations for the intriguing findings of Koh-Banerjee et al. (1).

REFERENCES

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