Fat distribution, lipid accumulation in the liver, and exercise capacity do not explain the insulin resistance in healthy males with a family history for type 2 diabetes.
To explore the mechanisms for the insulin resistance associated with a family history of type 2 diabetes, we studied 16 healthy men with at least two first-degree relatives with type 2 diabetes and 16 control subjects without known heredity. They were pair-wise matched for age, body mass index, and fasting triglycerides and underwent an oral glucose tolerance test, iv glucose infusion to measure the early insulin secretion, euglycemic hyperinsulinemic clamp, computed tomography scan, 7-d food record, and a cardiopulmonary exercise test to measure peak oxygen uptake. Insulin sensitivity index was 30% lower (P = 0.02) in relatives, compared with controls, but fasting and 2-h blood glucose and first-phase insulin secretion were similar. There were no differences in mean fasting free fatty acid levels, amount of sc or visceral adipose tissue, or fat accumulation in the liver. Dietary intake and peak oxygen uptake were also similar. However, multiple regression analysis of both groups showed that fat in the liver and physical capacity were, like known heredity for type 2 diabetes, independent predictors of insulin sensitivity. Thus, lipid accumulation in the liver and physical capacity are related to insulin sensitivity, but neither of these factors nor the amount and distribution of the body fat can explain the insulin resistance associated with a family history for type 2 diabetes.
Johanson
Else H
EH
Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska Academy at Göteborg University, SE-413 45 Göteborg, Sweden. else@medic.gu.se
Jansson
Per-Anders
PA
Lönn
Lars
L
Matsuzawa
Yuji
Y
Funahashi
Tohru
T
Taskinen
Marja-Riitta
MR
Smith
Ulf
U
Axelsen
Mette
M
D052242:Adiponectin; D000273:Adipose Tissue / Q000033:anatomy & histology*; D000328:Adult; D015308:Anaerobic Threshold / Q000502:physiology; D000886:Anthropometry; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004032:Diet; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011506:Proteins / Q000378:metabolism; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D014280:Triglycerides