Department of Medicine, Karolinska Institute at Karolinska Hospital, Huddinge, Stockholm, Sweden.
PLoS One. 2011 Apr 12;6(4):e18284. doi: 10.1371/journal.pone.0018284.
Development of Type 2 diabetes, like obesity, is promoted by a genetic predisposition. Although several genetic variants have been identified they only account for a small proportion of risk. We have asked if genetic risk is associated with abnormalities in storing excess lipids in the abdominal subcutaneous adipose tissue.
METHODOLOGY/PRINCIPAL FINDINGS: We recruited 164 lean and 500 overweight/obese individuals with or without a genetic predisposition for Type 2 diabetes or obesity. Adipose cell size was measured in biopsies from the abdominal adipose tissue as well as insulin sensitivity (HOMA index), HDL-cholesterol and Apo AI and Apo B. 166 additional non-obese individuals with a genetic predisposition for Type 2 diabetes underwent a euglycemic hyperinsulinemic clamp to measure insulin sensitivity. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, was associated with inappropriate expansion of the adipose cells, reduced insulin sensitivity and a more proatherogenic lipid profile in non-obese individuals. However, obesity per se induced a similar expansion of adipose cells and dysmetabolic state irrespective of genetic predisposition.
CONCLUSIONS/SIGNIFICANCE: Genetic predisposition for Type 2 diabetes, but not obesity, is associated with an impaired ability to recruit new adipose cells to store excess lipids in the subcutaneous adipose tissue, thereby promoting ectopic lipid deposition. This becomes particularly evident in non-obese individuals since obesity per se promotes a dysmetabolic state irrespective of genetic predisposition. These results identify a novel susceptibility factor making individuals with a genetic predisposition for Type 2 diabetes particularly sensitive to the environment and caloric excess.
2 型糖尿病的发生和肥胖一样，是由遗传易感性所促进的。尽管已经确定了一些遗传变异，但它们只占风险的一小部分。我们曾询问过遗传风险是否与腹部皮下脂肪组织中储存多余脂肪的异常有关。
方法/主要发现：我们招募了 164 名瘦人和 500 名超重/肥胖者，他们有无 2 型糖尿病或肥胖的遗传易感性。在腹部脂肪组织活检中测量脂肪细胞大小，以及胰岛素敏感性（HOMA 指数）、HDL-胆固醇和载脂蛋白 AI 和载脂蛋白 B。另外 166 名无肥胖但有 2 型糖尿病遗传易感性的非肥胖者接受了正葡萄糖高胰岛素钳夹试验，以测量胰岛素敏感性。2 型糖尿病的遗传易感性，但不是超重/肥胖，与脂肪细胞的不适当扩张、胰岛素敏感性降低以及非肥胖个体更具动脉粥样硬化倾向的脂质谱有关。然而，肥胖本身会导致脂肪细胞扩张和代谢紊乱，而不论遗传易感性如何。
结论/意义：2 型糖尿病的遗传易感性与不能招募新的脂肪细胞来储存皮下脂肪组织中多余的脂肪有关，从而促进异位脂质沉积。这在非肥胖个体中尤为明显，因为肥胖本身会促进代谢紊乱，而不论遗传易感性如何。这些结果确定了一个新的易感因素，使有 2 型糖尿病遗传易感性的个体对环境和热量过剩特别敏感。
