Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance.

Abstract

We tested the hypothesis that Insulin resistance, rather than high Insulin level, is associated with lipid and lipoprotein changes favoring atherosclerosis Independently of the glucose tolerance status. To this aim, 50 subjects with normal glucose tolerance, 28 subjects with Impaired glucose tolerance, and 54 subjects with nonlnsulln-dependent diabetes (NIDDM) were studied. Subjects wtth low glucose disposal rate (GDR) or a high degree of Insulin resistance as measured by the euglycemlc hyperinsullnemlc damp technique had lower high density lipoprotein (HDL) cholesterol and higher total and very low density lipoprotein (VLDL) triglycerldea than did subjects wtth high GDR (highest GDR fertile). These associations were Independent of fasting insulin level and other confounding factors. In stepwlse multiple linear regression analysis, GDR was the most important single variable associated with HDL cholesterol and VLDL trigh/ceride level Independently of age, obesity, distribution of obesity (waist/hip ratio), 2-hour glucose level, and free fatty acid concentration. 12 Three prospective population studies, the Helsinki Policemen Study, the Paris Prospective Study, and the Busselton Study, have independently shown that high plasma insulin level is associated with an increased risk of coronary heart disease in nondiabetic male subjects.345 Information on the relationship of plasma insulin to atherosclerosis in noninsulin-dependent diabetes (NIDDM) is scanty. 6 The mechanisms by which hyperinsulinemia promotes atherosclerosis are, however, unknown. Several studies indicate that high insulin concentration is associated with adverse changes in serum lipid and lipoprotein levels, characterized by elevated total and very low density lipoprotein (VLDL) triglyceride and decreased high density lipoprotein (HDL) cholesterol levels in subjects with normal glucose tolerance (NGT) concentration Is only an indirect indicator of the link between insulin resistance and adverse changes in lipid and lipoprotein levels. Indeed, two recent studies in subjects with NGT have demonstrated that low insulinmediated glucose uptake is associated with lipid and lipoprotein changes favoring atherosclerosis.1314 Subjects with impaired glucose tolerance (IGT) and NIDDM are more insulin-resistant than are subjects with NGT,16 and in both there is an increased risk of atherosclerosis.2 Therefore, if insulin resistance is a general risk factor for atherosclerosis, low insulin-mediated glucose uptake should be associated with adverse lipid and lipoprotein changes irrespective of the glucose tolerance status. To test this hypothesis, we studied lipid and lipoprotein levels and their association with insulin-mediated glucose uptake in a total of 132 subjects with varying degrees of glucose tolerance. Methods SubjectsThe subjects for this study, ages 50 years and older, were recruited from the previous population studies done by our department. 1617 Random samples of 50 subjects with NGT, 28 subjects with IGT, and 54 patients with NIDDM (duration of diab...

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery

“…A high prevalence of these abnormalities has also been reported by Laakso and Barrett-Connor [29]. These abnormalities have been suggested to result from insulin resistance or hyperinsulinaemia [37,38] which may lead to a high CHD mortality rate, termed syndrome X [39] or the deadly quartet [40]. Another possibility, suggested by Laakso et al [41], is that insulin resistance rather than hyperinsulinaemia causes the progression of atherosclerosis.…”

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes

“…An insulinogenic index was calculated as a ratio between changes in insulin and glucose during the first 30 min of the OGTT. Lipoprotein fractionation was performed by ultracentrifugation and selective precipitation, as previously described [23]. Cholesterol and triglyceride levels from whole serum and lipoprotein fractions were assayed by automated enzymatic methods (Boehringer-Mannheim, Mannheim, Germany).…”

Impaired Insulin-Stimulated Glucose Oxidation and Free Fatty Acid Suppression in Patients with Familial Combined Hyperlipidemia

“…Lipoprotein fractionation was performed by ultracentrifugation and selective precipitation 21 as previously described. 22 Cholesterol and triglyceride levels from whole serum and lipoprotein fractions were assayed by automated enzymatic methods (Boehringer-Mannheim). ApoB and apolipoprotein A1 were determined by a commercial immunoturbidimetric method (Kone Instruments) and serum FFAs from fresh frozen samples by an enzymatic method (Wako Chemicals GmbH).…”