Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia.
In 10 obese, new-onset non-insulin-dependent diabetes mellitus (NIDDM) patients (group A), continuous subcutaneous insulin infusion (CSII) was used to induce normoglycemia during 14 days. Fasting blood glucose was 4.6 +/- 0.2 mmol/L and mean daily blood glucose 5.8 +/- 0.2 mmol/L at the end of the CSII period. This excellent glycemic control was obtained with 35 +/- 4.8 U of insulin per day, corresponding to 0.47 +/- 0.06 U/kg/24 hours. Endogenous insulin production was markedly suppressed, since urinary C-peptide was reduced from 18.5 +/- 0.12 to 7.9 +/- 0.25 nmol/24 hours. Gliclazide was given to group A following CSII, and to five 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 intravenous glucose, and significant increases in the mean-daily-insulin to mean-daily-blood-glucose ratio, as well as in the 24-hour urinary C-peptide-to-glucose ratio. The gliclazide effects tended to be more pronounced in group A. No significant effect was seen on efficacy of endogenous insulin (slope of disappearance of blood glucose divided by insulin levels). During 6 months of gliclazide treatment, excellent glycemic control was maintained in all patients. This was paralleled by unchanged stimulation by gliclazide of first-phase insulin response to glucose, and augmented mean 48-hour insulin-to-glucose and urinary C-peptide-to-glucose ratios. No change in the ratio of glucose disposal to endogenous insulin was noted. We conclude that physiologic insulin replacement may induce normoglycemia in NIDDM, indicating that insulin resistance is not of clinical significance; gliclazide has a beta-cell-stimulating action that 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 the gliclazide action.
Della Casa
L
L
Department of Metabolic Diseases, University of Modena Health Science Center, Italy.
del Rio
G
G
Glaser
B
B
Cerasi
E
E
D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005500:Follow-Up Studies; D005907:Gliclazide / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007332:Insulin Infusion Systems; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects; D008875:Middle Aged
D001786:Blood Glucose; D007328:Insulin; D005907:Gliclazide