Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts Type II diabetes independent of insulin resistance

Abstract

Epidemiological studies have firmly established that obesity is a major risk factor for the development of Type II (non-insulin-dependent) diabetes mellitus [1±4]. Obesity does not, however, invariably result in diabetes and many people who are very obese are able to maintain normal glucose tolerance. The reason why some people with obesity develop Type II diabetes and others do not is largely not known.There is good evidence that differences in body fat distribution play a part [3±9]. A large number of cross-sectional studies have shown that obese people with an abdominal pattern of fat accumulation are Diabetologia (2000) Abstract Aims/hypothesis. Cross-sectional studies indicate that enlarged subcutaneous abdominal adipocyte size is associated with hyperinsulinaemia, insulin resistance and glucose intolerance. To further explore the pathophysiological significance of these associations, we examined prospectively whether enlarged subcutaneous abdominal adipocyte size predicts Type II (non-insulin-dependent) diabetes mellitus. Methods. Body composition (hydrodensitometry), mean subcutaneous abdominal adipocyte size (fat biopsy), insulin sensitivity (hyperinsulinaemic clamp) and the acute insulin secretory response (25-g i. v. GTT) were assessed in 280 Pima Indians with either normal (NGT), impaired (IGT) or diabetic glucose tolerance (75-g OGTT). Subjects with NGT were then followed prospectively. Results. After adjusting for age, sex and per cent body fat, mean subcutaneous abdominal adipocyte size was 19 % and 11 % higher in subjects with diabetes and IGT, compared with those with NGT (p < 0.001). Insulin sensitivity was inversely correlated with mean subcutaneous abdominal adipocyte size (r = ±0.53, p < 0.0001), even after adjusting for per cent body fat (r = ±0.31, p < 0.001). In 108 NGT subjects followed over 9.3 4.1 years (33 of whom developed diabetes), enlarged mean subcutaneous abdominal adipocyte size but not high per cent body fat, was an independent predictor of diabetes, in addition to a low insulin sensitivity and acute insulin secretory response [relative hazard 10 th vs 90 th centile (95 % CI): 5.8 (1.7±19.6), p < 0.005]. In 28 NGT subjects with a 9 % weight gain over 2.7 1.3 years, changes in insulin sensitivity were inversely and independently related to changes in mean subcutaneous abdominal adipocyte size and per cent body fat. Conclusion/interpretation. Although enlarged mean subcutaneous abdominal adipocyte size is associated with insulin resistance cross-sectionally, prospectively, both abnormalities are independent and additive predictors of Type II diabetes. [Diabetologia (2000

Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue

“…2b). Insulin action was previously shown to be dependent on fat cell size: large adipocytes correlate well with insulin resistance [12][13][14] and show decreased insulinstimulated glucose uptake [15]. Interestingly, the transplanted fat depot exhibited features reminiscent of those induced in adipose tissue by thiazolidinediones.…”

Adipose tissue distribution and risk of metabolic disease: does thiazolidinedione-induced adipose tissue redistribution provide a clue to the answer?

“…Compared with small adipocytes, large cells are more insulin-resistant and lipolytic, release more inflammatory cytokines and less adiponectin [24,28], and are more frequently found in people with obesity-related metabolic disorders [29,30]. Therefore, adipose tissue cell composition, expressed as the relative number of large adipose cells in a given fat depot, is an important determinant of the metabolic activity and response to environmental changes of that depot.…”

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients

“…It has also been shown that the transcription factor sterol regulatory element binding protein-1 (SREBP1), which activates the expression of several genes involved in fatty acid synthesis, is overexpressed in animal models of insulin resistance and obesity (Shimomura et al 2000). It has been suggested that the increased expression of lipogenic genes in adipocytes leading to fat accretion and adipocyte hypertrophy exerts an antagonistic effect on insulin action, due to substrate competition with glucose or to a lipotoxic effect, or both (Schmitz-Peiffer 2000), which finally contribute to the development of type 2 diabetes mellitus (T2DM) (Weyer et al 2000).…”