S Bioletto1, A Golay, R Munger, B Kalix, R W James. 1. Clinical Diabetes Unit, Division of Endocrinology and Diabetology, and the Division for Treatment of Chronic Diseases, University Hospital, Geneva, Switzerland.
Abstract
BACKGROUND: The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified. OBJECTIVE: We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp. DESIGN: Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patients with type 2 diabetes, and nonobese control subjects. RESULTS: Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obese patients but had a minor effect on VLDL(2) and VLDL(3). Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes. CONCLUSIONS: Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.
BACKGROUND: The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified. OBJECTIVE: We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp. DESIGN: Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obesepatients, obesepatients with type 2 diabetes, and nonobese control subjects. RESULTS:Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obesepatients but had a minor effect on VLDL(2) and VLDL(3). Placing obesepatients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes. CONCLUSIONS:Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obesepatients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.
Authors: Xuewen Wang; Gordon I Smith; Bruce W Patterson; Dominic N Reeds; Janine Kampelman; Faidon Magkos; Bettina Mittendorfer Journal: Am J Physiol Endocrinol Metab Date: 2012-01-17 Impact factor: 4.310
Authors: Mehmet Emre Taşcılar; Tolga Özgen; Murat Cihan; Ayhan Abacı; Ediz Yeşilkaya; Ibrahim Eker; Muhiddin Serdar Journal: J Clin Res Pediatr Endocrinol Date: 2010-05-02