Project: Research project

Project Details


DESCRIPTION (Adapted from applicant's abstract): 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.
Effective start/end date6/15/984/30/03


  • Endocrinology, Diabetes and Metabolism


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