THE ANTIDIABETOGENIC EFFECT OF GLP-1 IS MAINTAINED DURING A 7-DAY TREATMENT PERIOD AND IMPROVES DIABETIC DYSLIPOPROTEINEMIA IN NIDDM PATIENTS

OBJECTIVE - To investigate the long-term antidiabetogenic effect of gl ucagon-like peptide I (GLP-1) and its influence on diabetic dyslipopro teinemia, patients with NIDDM were treated with GLP-1 subcutaneously f or 1 week. RESEARCH DESIGN AND METHODS - Twelve patients participated in the study. The 1st week of the study, all of them were on intensive insulin treatment and from day 8, four were randomized to a control g roup continuing with insulin, and eight to a treatment group where GLP -1 was given at meals together with regular insulin from day 8 to 12. On days 13 and 14, they were only given GLP-1 at meals. NPH insulin at bedtime was given throughout the study. RESULTS - In the GLP-1-treate d patients, the doses of regular insulin, given to keep a satisfactory blood glucose control, were reduced compared with treatment with insu lin only. GLP-1 virtually inhibited the early increase in blood glucos e after the meals, whereas an increase of similar to 2 mmol was seen d uring an optimized insulin treatment. In agreement with the short half -life of the peptide, 2-h postprandial plasma insulin levels were sign ificantly decreased both at day 12 and 14, suggesting that there was n ot enough GLP-1 left to stimulate endogenous insulin release and compe nsate for the decrease in the dose of exogenous insulin. Therefore, th e effect of GLP-1 was lost before the next meal, resulting in increase d preprandial blood glucose values at lunch and dinner. The concentrat ion of VLDL triglycerides decreased already during the Ist week. This decrease persisted during the 2nd week when GLP-1 was included in the treatment. No changes were observed in the levels of LDL and HDL chole sterol. The LDL particle diameter increased from a mean of 22.3 to 22. 6 nm (P < 0.01) in response to insulin treatment. A further increment to 22.9 nm (P < 0.05) was seen after GLP-1 treatment. The LDL particle size did not change in the control group. Lipoprotein lipase activity was decreased by 27% and hepatic lipase was reduced by 13% in the GLP -1-treated group. CONCLUSIONS - We confirm the antidiabetogenic effect of GLP-1 in NIDDM patients. This effect was maintained during 7 days, which implies that the patients did not develop tolerance during this treatment period. Intensive insulin treatment, leading to normotrigly ceridemia, increased the mean IDL particle diameter, which is likely t o lower the risk of future coronary heart disease in patients with NID DM. Furthermore, an additive effect of GLP-1 is indicated. Hence, this study gives additional evidence that GLP-1 may be useful as an agent for treating NIDDM.