A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM.
To assess the role of fasting plasma non-esterified fatty acids (NEFA) in the development of non-insulin-dependent diabetes mellitus (NIDDM), data were analysed from annual examinations of 190 non-diabetic Pima Indians. Glucose tolerance was measured by a 75-g oral glucose tolerance test, insulin action by a euglycaemic hyperinsulinaemic (40 mU x m-2 x min-1) clamp and in vitro lipolysis using isolated abdominal fat cells. After a mean follow-up period of 4.0 +/- 2.4 years (mean +/- SD), 47 subjects developed NIDDM. Risk factors for NIDDM were estimated by proportional-hazards analysis and risk ratios (RR) with 95% confidence intervals (95% CI) calculated at the 90th and 10th percentile of the predictor variables. A large average fat-cell volume was predictive of NIDDM (RR=2.4; 95% CI=1.2-4.8) independent of age, sex, percent body and body fat distribution. A high fasting plasma NEFA concentration was also a risk factor for NIDDM (RR=2.3; 95% CI=1.1-4.7) independent of sex, percent body fat, waist/thigh ratio, insulin-mediated glucose uptake and fasting triglyceride concentration. We conclude that large fat cells and the resulting increased plasma NEFA concentrations are risk factors for the development of NIDDM.
Paolisso
G
G
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
Tataranni
P A
PA
Foley
J E
JE
Bogardus
C
C
Howard
B V
BV
Ravussin
E
E
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D001130:Arizona; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism; D015994:Incidence; D007198:Indians, North American; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007545:Isoproterenol