Non-insulin dependent diabetes is the most common form of diabetes and afflicts some 20 million people in the U.S. alone. The disease, which is generally associated with obesity, results in serious complications and is a major cause of premature death. It's public health and social costs are enormous. NIDDM is a polygenic disorder, which in its early stages is characterized by insulin resistance and hyperinsulinemia. In genetically susceptible individuals the pancreatic B-cell eventually becomes compromised, insulin output stagnates and the full blow picture of diabetes appears. It is generally believed that the underlying problem in the etiology of obesity/NIDDM syndromes is an inherited defect in muscle causing insulin resistance, and this in turn elicits compensatory hyperinsulinemia. The investigator believes the available evidence is more compatible with one or other of two alternative views; namely, that (i) both hyperinsulinemia and insulin resistance arise simultaneously from other primary defect; (ii) hyperinsulinemia is the earlier derangement and that this gives rise to insulin resistance. In either case, it is evident that hyperinsulinemia is a very early event. Recent data suggest that the availability of free fatty acids (FFA) is an important determinant of insulin secretion. They propose that excess FFA flux potentiates hyperinsulinemia and promotes excessive delivery of fat from liver to adipose tissue and muscle beds, resulting in hyperlipidemia, obesity and buildup of triglyceride in muscle. They further propose that elevated levels of fatty acyl-CoA and of fatty acid oxidation in muscle impair insulin-mediated glucose uptake, oxidation and storage as glycogen at this site. The investigators have recently develop a technique to specifically measure intramuscular glyceride content in humans and have validate the procedure in experimental animal models. The method, proton spectroscopy, is non- invasive and rapid. Previous studies have not found a relationship between muscle triglyceride content and insulin sensitivity. However, these measurements likely were confounded by contaminating adipose tissue. Using proton spectroscopy, the investigators plan to correlate insulin sensitivity with intramuscular triglyceride and rates of lipid oxidation in (lean and obese) normal and diabetic individuals genetically at risk for NIDDM. If the expected associations are confirmed, it is entirely possible that subjects at high risk for the development of NIDDm can be identified early and treated in such a way as to limit weight gain, improve insulin sensitivity, control hyperlipidemia and potentially forestall progression to frank diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK053358-05
Application #
6381065
Study Section
Metabolism Study Section (MET)
Program Officer
Laughlin, Maren R
Project Start
1998-06-15
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
5
Fiscal Year
2001
Total Cost
$137,325
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Szczepaniak, Lidia S; Dobbins, Robert L; Stein, Daniel T et al. (2002) Bulk magnetic susceptibility effects on the assessment of intra- and extramyocellular lipids in vivo. Magn Reson Med 47:607-10
Hwang, J H; Pan, J W; Heydari, S et al. (2001) Regional differences in intramyocellular lipids in humans observed by in vivo 1H-MR spectroscopic imaging. J Appl Physiol 90:1267-74
Szczepaniak, L S; Babcock, E E; Schick, F et al. (1999) Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol 276:E977-89