Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β-cell protection in individuals with type 2 diabetes

Institute for Clinical Research and Development, Clinical Department, Mainz, Germany.
Diabetes Obesity and Metabolism (Impact Factor: 6.36). 05/2010; 12(5):437-41. DOI: 10.1111/j.1463-1326.2010.01209.x
Source: PubMed


Postprandial release of intact proinsulin (IP) is an independent marker for beta-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the beta-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin.
Overall, 28 insulin-naive type 2 diabetes subjects (mean +/- SD age, 61.5 +/- 6.7 years; diabetes duration, 9.8 +/- 6.5 years; HbA1c, 7.1 +/- 0.5%; BMI, 30.7 +/- 4.3 kg/m(2)) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG).
Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 +/- 13.4 vs. 23.3 +/- 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 +/- 19 to 121 +/- 23 mg/dl; NPH: 156 +/- 34 to 119 +/- 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups.
Adding basal insulin to metformin reduces postprandial beta-cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces beta-cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.

Download full-text


Available from: Andreas Pfützner, Aug 19, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin therapy has been suggested to preserve beta-cell mass in patients with diabetes through the mechanisms of beta-cell rest as well as direct effects on beta-cell proliferation. However, data about the effects of hyperinsulinism on beta-cell mass and turnover in humans are sparse. Pancreatic tissue specimens from five patients with pancreatic insulinomas and ten non-diabetic control subjects were examined. Pancreatic sections were stained for insulin, Ki67 (replication) and TUNEL (apoptosis), and quantitative morphometric analyses were performed. Fractional beta-cell area was 1.11%±0.67% in the tumor-free pancreatic tissue of the insulinoma patients and 0.78%±0.26% in the control group (p=0.19). There also were no differences in islet size (p=0.62) or beta-cell nuclear diameter (p=0.20). Beta-cell replication and apoptosis were infrequently detected, without any measurable differences between the groups. There were also no differences in percentage of duct cells expressing insulin (p=0.47), a surrogate marker for islet neogenesis. Beta-cell area and turnover are not significantly altered in the proximity of intra-pancreatic insulinomas. Future in vivo studies, ideally employing larger animal models, are warranted to further evaluate the impact of exogenous insulin on beta-cell turnover.
    Full-text · Article · Dec 2010 · Regulatory Peptides
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine the long-term effects of combination insulin glargine/exenatide treatment on glycemic control. We conducted a 24-month retrospective US chart review of patients with inadequately controlled type 2 diabetes (T2DM) and hemoglobin A1c (A1C) levels >7.0% for whom glargine and exenatide were coprescribed in differing order (glargine added after exenatide [exenatide/glargine]; exenatide added after glargine [glargine/exenatide]). Treatment order groups were combined to form a pooled treatment group. Changes from baseline in A1C, patients with A1C ≤7.0%, body weight, glargine/exenatide daily dose, oral antidiabetic drug (OAD) use, and hypoglycemia were evaluated. Treatment groups were similar at baseline; however, patients in the glargine/exenatide group (n = 121) (vs exenatide/glargine group [n = 44]) had longer disease duration (11.8 vs 8.0 years) and took fewer OADs (1.7 vs 2.3). Overall, baseline A1C was 8.8 ± 1.3% and weight was 109.5 ± 25.3 kg. Significant A1C reductions emerged at month 6 and persisted throughout 24 months (vs baseline) in both treatment groups (pooled: -0.7 ± 1.6; P<.001), and 33.0% of patients achieved an A1C level ≤7.0%. After 24 months of exenatide/glargine, body weight remained unchanged (0.7 ± 8.3 kg; P = .640). With glargine/exenatide, body weight decreased (-2.5 ± 6.7 kg; P = .001). At month 24, daily glargine dose was 0.40 ± 0.23 units/kg for the exenatide/glargine group and 0.47 ± 0.30 units/kg for the glargine/exenatide group. Hypoglycemia frequency was similar in both treatment groups. Regardless of treatment order, long-term combined therapy with glargine and exenatide for up to 24 months in patients with inadequately controlled T2DM suggests reduction of A1C without significant weight gain or increased hypoglycemia risk.
    No preview · Article · Jul 2011 · Endocrine Practice
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In newly diagnosed type 2 diabetes mellitus (T2DM) patients, short-term insulin therapy might improve β-cell function and glycemic control. This study aimed to compare the effects of basal insulin monotherapy with continuous subcutaneous insulin infusion (CSII) treatment. Fifty-nine cases of newly diagnosed T2DM patients with fasting plasma glucose of 9.0-16.7 mmol/L were recruited into this study. They were hospitalized and randomly assigned to a basal insulin monotherapy group (n=27) or a CSII group (n=32). Insulin dosage was titrated according to fasting capillary blood glucose levels, and treatment was stopped after 2 weeks. Intravenous glucose tolerance tests were performed, and blood glucose, insulin, C-peptide, and lipid profiles were measured before therapy and 2 days after therapy withdrawal. Both treatments reduced fasting and postprandial blood glucose levels (after treatment vs. baseline, both P<0.05). Fasting glycemic control target was achieved in 52 cases (88.14%) with 2 weeks of insulin treatment, and there were no significant differences between the glargine and CSII groups (P=0.059). The time to achieve fasting glycemic target in the CSII group was shorter than that in the glargine group (P<0.01). Plasma lipid profiles such as triglycerides and total cholesterol also decreased significantly after the intervention. Overall β-cell function improved significantly after insulin intervention (P<0.01). Variation did not differ between two groups, nor did the effects on insulin and C-peptide secretion (P>0.05). The effect of basal insulin monotherapy was similar to that of CSII, and thus basal insulin monotherapy might be a reasonable alternative to CSII for initial insulin therapy in newly diagnosed T2DM patients.
    Full-text · Article · Aug 2011 · Diabetes Technology & Therapeutics
Show more