Objective: To assess clinical efficacy and tolerability of cholestyramine therapy in patients with dyslipidemia and non-insulin-dependent diabetes mellitus (NIDDM).
Design: A randomized, double-blind, crossover study of cholestyramine (8 g twice daily) compared with placebo for a period of 6 weeks each.
Setting: Metabolic Unit and the Lipid and Diabetes Clinics at the Department of Veterans Affairs Medical Center, Dallas, Texas.
Patients: 21 patients with NIDDM that was well controlled using either glyburide or insulin therapy and with low-density lipoprotein (LDL) cholesterol levels more than 3.36 mmol/L (130 mg/dL) and fasting plasma triglyceride levels less than 3.4 mmol/L (300 mg/dL).
Measurements: During the last week of each period, for 5 consecutive days fasting plasma lipids and lipoproteins were measured, and plasma glucose levels were determined at 3, 7, and 11 a.m. and at 4 and 8 p.m. Daily urinary glucose excretion was measured for 3 days and glycosylated hemoglobin concentrations were determined on days 28 and 38 of the study periods.
Results: In this short-term study, when compared with placebo, cholestyramine reduced total cholesterol by 18% (95% CI, 14% to 22%) and LDL cholesterol by 28% (CI, 21% to 35%). Although cholestyramine therapy increased plasma triglyceride levels by 13.5% (CI, 1% to 26%), very-low density lipoprotein cholesterol and high-density lipoprotein cholesterol levels remained unchanged. Cholestyramine therapy improved glycemic control; mean plasma glucose values were lower by 13% (CI, 5% to 21%), a median reduction in urinary glucose excretion of 0.22 g/d was observed (P < 0.001), and a tendency to lower glycosylated hemoglobin concentration was noted. The doses of glyburide and insulin did not change during the study, and body weight remained stable. Constipation was the main side effect, and two patients dropped out of the study because of cholestyramine intolerance.
Conclusions: In carefully selected male patients with NIDDM and high LDL cholesterol and normal triglyceride levels, cholestyramine therapy effectively reduces LDL levels and also may improve glycemic control. The long-term efficacy of cholestyramine therapy in patients with NIDDM needs further evaluation.