Combination insulin/glyburide therapy in type II diabetes mellitus. Effects on lipoprotein metabolism and glucoregulation.
A randomized double-blind, placebo-controlled trial of insulin plus glyburide was carried out in 22 insulin-treated patients with poorly controlled type II diabetes mellitus. Glycemic control and lipoprotein responses were assessed for 16 weeks. Oral glucose tolerance testing was performed at weeks 0, 4, and 16. Clinical characteristics and glycemic control were similar at week 0 in the placebo/insulin group (n = 12) and the glyburide/insulin group (n = 10). Throughout the study, the dose of insulin was fixed. The placebo group had no change in any metabolic parameter throughout the protocol period. After four weeks, glyburide significantly lowered fasting blood glucose and integrated glucose areas (p less than 0.01) after oral glucose testing compared with week 0 (fasting blood glucose 225 +/- 20 mg/dl versus 286 +/- 27 mg/dl, p less than 0.02). Associated with this were mean fasting, stimulated, and integrated C-peptide levels that were significantly higher (p less than 0.02) at week 4 versus week 0. After 16 weeks, mean fasting blood glucose remained significantly lower compared with baseline values (252 +/- 25 mg/dl versus 286 +/- 27 mg/dl, p less than 0.05). Glycosylated hemoglobin (hemoglobin A1c) levels decreased significantly (p less than 0.05) at weeks 4 to 16 compared with the baseline value. Although integrated areas were no different after oral glucose, fasting and stimulated C-peptide levels were significantly higher (p less than 0.05) at week 16 versus week 0. Total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol did not change during the study. After the code was broken, comparisons were made between those with response to combination therapy (reduction of fasting blood glucose by at least 50 mg/dl or fasting blood glucose of 140 mg/dl or less at the end of the first week of treatment that persisted for four consecutive weeks) and those without response. Baseline clinical and laboratory characteristics were identical in both groups. Mean fasting and stimulated serum C-peptide levels after oral glucose, however, were significantly higher in the patients with response at week 4 compared with the patients without response. The mean maximal incremental C-peptide level was 1.50 +/- 0.19 ng/ml at week 0 in the patients with response compared with 0.67 +/- 0.28 ng/ml in the patients without response (p less than 0.01). Lipoproteins were not different in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)
D001786:Blood Glucose / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis; D002096:C-Peptide / Q000032:analysis; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos
D001786:Blood Glucose; D001798:Blood Proteins; D002096:C-Peptide; D005905:Glyburide; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D010919:Placebos