Improved glucose disposal after repeated intravenous (IV) glucose loads, known as the Staub effect, is absent in both type I and type II diabetes. Acute decrements of insulin secretion (AID) are observed following the early phase of insulin release on IV glucose stimulation in non-insulin-dependent diabetes mellitus (NIDDM). The AID cannot be corrected by acute infusions of glyburide or glipizide, or phentolamine, or by glycemic control after 2 weeks of intensive insulin treatments. Fifteen male subjects had 3 hourly successive IV glucose tolerance tests before and after 6 months of glipizide, at a final maintenance dose of 30 ± 3 mg/d. Before treatment, AID, defined as the difference of the lowest of post IV glucose 7- or 10-minute samples from the preceding baseline insulin levels, was detected in the three loads: -6.4 ± 1.9 μU/mL in the first, and then more consistently in the second and third loads, -11 ± 2 μU/mL, and -17 ± 9 μU/mL, respectively. There was a stepwise increase in insulin sums after each load. After glipizide therapy, the AIDs following all three IV glucose loads were no longer demonstrable; both insulin values, as well as insulin sums, were significantly elevated after all three glucose loads. While in the untreated state, the Staub effect was absent: serum glucose disappearances (K), corrected for glycosuria, were K1 = 0.52 ± 0.02, K2 = 0.50 ± 0.04, and K3 = 0.52 ± 0.03. After glipizide, fasting glucose decreased from 215 ± 12 mg/dL to 132 ± 9 mg/dL, glucose values during the triple IV tolerance tests were significantly lower, and the glycohemoglobin decreased from 9.9% ± 0.5% to 8.2% ± 0.03%. Furthermore, glucose disappearance rates were improved: K1 = 0.62 ± 0.02, K2 = 0.68 ± 0.02, and K3 = 0.77 ± 0.04, also defining a positive Staub effect. There was a positive correlation between the glucose disappearance rates and the treatment-induced improvement of early insulin release in the second and third glucose loads (the difference from baseline of the higher of either the 3-minute or the 5-minute post IV samples). There was also a positive correlation between improvement in glucose disappearance rates in the third load with the total insulin sums. Mean AID in untreated overt NIDDM is potentiated by IV glucose priming, even while insulin levels increase. After treatment with glipizide, the AID is either reverted or insignificant, and the Staub effect is restored, along with post IV glucose improvement in insulin levels. Chronic sulfonylurea administration appears at present to be the only known conventional treatment restoring post IV glucose Staub effect and ameliorating the AID of NIDDM.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism