Effect of 6 months' gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial CSII-induced normoglycemia

Abstract

In 10 obese, newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (group A) continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia over a period of 14 days. Fasting blood glucose was 4.61 +/- 0.22 mmol/l and mean daily blood glucose 5.83 +/- 0.27 mmol/l at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 h. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 56 +/- 0.35 to 24 +/- 0.76 micrograms/24 h. Thus, physiological insulin replacement induced normoglycemia in NIDDM, indicating that insulin resistance is not clinically important. Gliclazide was given to group A following CSII and to 5 obese NIDDM patients (group B) in their habitual hyperglycemic state. Gliclazide maintained in group A and induced in group B excellent metabolic control. This was accompanied by the appearance of a small first-phase insulin response to iv glucose and by significant increases in the mean daily insulin to mean daily blood glucose ratio and in the 24-h urinary C-peptide to glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on sensitivity to endogenous insulin (slope of disappearance of blood glucose as function of insulin response to glucose infusion). During the 6 months of gliclazide treatment, excellent glycemic control was obtained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose as well as mean by 48-h insulin to glucose and urinary C-peptide to glucose ratios. Again, sensitivity to endogenous insulin was not augmented. We conclude that gliclazide has a beta-cell-stimulating action which is maintained quantitatively unchanged for at least 6 months. The therapeutic effect of gliclazide in NIDDM seems to be mainly, if not exclusively, the result of its beta-cytotrophic action. Initial normoglycemia, induced here by CSII, may have a lasting enhancing effect on gliclazide action.