Chronic reduction of fasting glycemia with insulin glargine improves first- and second-phase insulin secretion in patients with type 2 diabetes

Abstract

Objective: Insulin secretion is often diminished in hyperglycemic patients with type 2 diabetes. We examined whether chronic basal insulin treatment with insulin glargine improves glucose-induced insulin secretion.

Research design and methods: Fourteen patients with type 2 diabetes on metformin monotherapy received an add-on therapy with insulin glargine over 8 weeks. Intravenous glucose tolerance tests (IVGTTs) were performed before and after the intervention, with and without previous adjustment of fasting glucose levels using a 3-h intravenous insulin infusion.

Results: Fasting glycemia was lowered from 179.6 ± 7.5 to 117.6 ± 6.5 mg/dL (P < 0.001), and HbA(1c) levels declined from 8.4 ± 0.5 to 7.1 ± 0.2% (P = 0.0046). The final insulin dose was 59.3 ± 10.2 IU. Acute normalization of fasting glycemia by intravenous insulin reduced C-peptide levels during the IVGTT (P < 0.0001). In contrast, insulin and C-peptide responses to intravenous glucose administration were significantly greater after the glargine treatment period (P < 0.0001, respectively). Both first- and second-phase insulin secretion increased significantly after the glargine treatment period (P < 0.05, respectively). These improvements in insulin secretion were observed during both the experiments with and without acute adjustment of fasting glycemia.

Conclusions: Chronic supplementation of long-acting basal insulin improves glucose-induced insulin secretion in hyperglycemic patients with type 2 diabetes, whereas acute exogenous insulin administration reduces the β-cell response to glucose administration. These data provide a rationale for basal insulin treatment regiments to improve postprandial endogenous insulin secretion in hyperglycemic patients with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01249677.

Figures

Figure 1

Plasma concentrations of glucose (A and B), insulin (C and D), and C-peptide (E and F) as well as insulin secretion rates (G and H) in 14 patients with type 2 diabetes before (filled symbols) and after (open symbols) 8 weeks of insulin glargine treatment. Intravenous glucose was administered at 0 min. The experiments were performed without (A, C, E, and G) and with (B, D, F, and H) prior adjustment of fasting glycemia using a 3-h intravenous insulin infusion. Data are presented as means ± SEM. Statistics were carried out using paired repeated-measures ANOVA and denote (A) differences between the experiments, (B) differences over the time course, and (AB) differences due to the interaction of experiment and time. Asterisks indicate significant differences at individual time points (P < 0.05).

Figure 2

First-phase insulin secretion (A and B; insulin secretion rates at t = 0–10 min minus basal levels) and second-phase insulin secretion (C and D; insulin secretion rates from t = 10 to 120 min minus basal levels) in response to intravenous glucose administration in 14 patients with type 2 diabetes before and after 8 weeks of insulin glargine treatment. The experiments were performed without (A and C) and with (B and D) prior adjustment of fasting glycemia using a 3-h intravenous insulin infusion. Data are presented as means ± SEM. Statistics were carried out using paired t tests.