Insulin and Sulfonylurea Therapy in NIDDM Patients: Are the Effects on Lipoprotein Metabolism Different Even With Similar Blood Glucose Control?

Abstract

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 +/- 3 years, BMI 26.5 +/- 0.9 kg/m2) (means +/- SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1e, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2, HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 +/- 0.3 vs. 7.9 +/- 0.3 mmol/l; HbA1c 7.4 +/- 0.3 vs. 7.0 +/- 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05), VLDL triglycerides (50.1 +/- 12.2 vs. 63.6 +/- 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 +/- 7.5 vs. 39.9 +/- 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 +/- 1.6 vs. 20.3 +/- 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 +/- 3.0 vs. 37.8 +/- 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 +/- 3.8 vs. 37.3 +/- 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 +/- 22.3 vs. 263.5 +/- 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.

Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control

“…particles and a lowered activity of hepatic lipase during insulin treatment [15]. Although VLDL subfractions and hepatic lipase activity were not measured in our study, it seems reasonable that similar changes explain the differences we found in postprandial lipaemia between insulin aspart and repaglinide treatment as both repaglinide and sulphonylureas are considered to exclusively act as insulin secretagogues [44].…”

“…This goal was achieved as the 24-h blood glucose profiles obtained were similar and there was no significant difference in A1c. While a few studies have been performed comparing effects of insulin treatment with oral hypoglycaemic agents during similar glycaemic control [15,16], this is the first study comparing these rapid-acting treatments with main effects in the postprandial phase. We found differences in a number of variables including lipid metabolism and the IGF-system.…”

“…During insulin treatment lowering of postprandial triglyceride levels and of apolipoprotein B was found when compared to treatment with repaglinide. While there is no previous study that has compared fasting and postprandial lipaemia between insulin aspart and repaglinide, the effect by insulin and sulphonylurea on fasting lipoprotein levels were studied by Romano and et al [15]. They found lower fasting triglycerides and higher HDL 2 cholesterol during insulin therapy than during treatment with glyburide and related these differences to lower production of large VLDL1…”

“…Improving glycaemic control by exogenous insulin in patients with type 2 diabetes and insufficient glycaemic control on treatment with oral hypoglycaemic agent alters the lipoprotein profile towards a less atherogenic pattern [13,14]. Independent of glycaemic control the mode of treatment, insulin secretagogue versus exogenous insulin, may alter the lipoprotein profile possibly by affecting portal insulin delivery to the liver [15][16][17]. This can also have importance for the GH-IGF axis [18], since insulin up regulates the GHR and GHBP level in the liver and down regulates the production of IGFBP-1 [19][20][21][22].…”

Insulin or sulfonylurea treatments of the diabetics differentially affect erythrocyte membrane and serum enzymes and extent of protein glycosylation

“…Insulin therapy or treatment with sulfonylurea type drugs (13) have differential effect on lipof,-otein metabolism at least in the NIDDM patients (14). In view of the above it was of interest to find out if the extent of glycosylation of erythrocyte membrane proteins and serum proteins, aswell asthe activities (DTNB) and vanadium ttee adenoine 5' ldplx~l~t~le, sodium salt (A'I'F)) were purchased from SRL, India.…”