Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, is associated with a restricted adipogenesis

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 sub...

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Bibliographic Details
Published in:PloS one 2011-04, Vol.6 (4), p.e18284-e18284
Main Authors: Arner, Peter, Arner, Erik, Hammarstedt, Ann, Smith, Ulf
Format: Article
Language:English
Subjects:
Abnormalities
Adipogenesis
Adipose tissue
Adipose Tissue - pathology
Body weight
Cell size
Cholesterol
Clinical Medicine
Diabetes mellitus
Diabetes Mellitus, Type 2 - genetics
Disease susceptibility
Genetic aspects
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Glucose
High density lipoprotein
Humans
Insulin
Insulin resistance
Klinisk medicin
Laboratories
Lipids
Medicin och hälsovetenskap
Medicine
Obesity
Obesity - genetics
Overweight
Overweight - genetics
Risk factors
Sensitivity
Type 2 diabetes
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Summary: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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0018284