Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β-cell protection in individuals with type 2 diabetes
ABSTRACT 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.
Full-textDOI: · Available from: Andreas Pfützner, Aug 19, 2014
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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.Diabetes Technology & Therapeutics 08/2011; 14(1):35-42. DOI:10.1089/dia.2011.0123 · 2.29 Impact Factor
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ABSTRACT: Our objective was to investigate how postprandial processing of intact proinsulin is influenced by different pharmacological strategies in type 2 diabetes mellitus (T2DM). This exploratory, nonrandomized, cross-sectional study recruited T2DM patients and healthy subjects. Upon recruitment, eligible T2DM patients had been treated for ≥6 months with insulin glargine (GLA) plus metformin (MET), sulfonylureas (SU) plus MET, or dipeptidyl-peptidase-4 inhibitors (DPP-4-I) plus MET. Blood samples were drawn from study participants after an 8 h fast and at regular intervals for up to 5 h after consumption of a standardized meal. Study endpoints included postprandial intact proinsulin and insulin levels and the insulin/proinsulin ratio. As expected, postprandial secretion of proinsulin was greater in all T2DM treatment groups than in healthy subjects (p < .01 for all comparisons). Postprandial release of proinsulin was significantly greater in T2DM patients treated with SU plus MET than in those treated with GLA plus MET (p = .003). Treatment with DPP-4-I plus MET was associated with reduced proinsulin secretion versus SU plus MET and an increased insulin/proinsulin ratio versus the other T2DM groups. Treatment of T2DM with GLA plus MET or DPP-4-I plus MET was associated with a more physiological postprandial secretion pattern of the β cell compared with those treated with SU plus MET.Journal of diabetes science and technology 05/2012; 6(3):634-40. DOI:10.1177/193229681200600318
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ABSTRACT: PURPOSE: Evolving practice recommendations on the use of insulin analogs versus other forms of insulin therapy in adults with type 2 diabetes are reviewed, with an emphasis on supporting evidence from practice guidelines and clinical trials published over the last six years. SUMMARY: Current consensus guidelines call for aggressive pharmacotherapy to attain specific glycosylated hemoglobin (HbA(1c)) targets as a means of reducing the risk of macrovascular events (e.g., myocardial infarction, stroke, cardiovascular [CV] death) and the tailoring of HbA(1c)-lowering regimens according to patient-specific factors such as the duration of diabetes, life expectancy, and comorbid conditions. Joint guidelines issued in 2009 by two leading organizations of endocrinology specialists recommend the use of insulin analogs (e.g., detemir, glargine) versus neutral protamine Hagedorn insulin, citing a more predictable time course and a lower potential for hypoglycemia; growing evidence indicates that the use of insulin analogs may offer other advantages such as enhanced dosing flexibility (with the possibility of self-titration by some patients) and less weight gain. Some evidence from trials published since 2007 indicates that early or intensive insulin analog therapy and very aggressive glycemic goals (e.g., HbA(1c) of <6%) may be associated with an increased mortality risk, especially in patients with longstanding diabetes and major CV comorbidities. Ongoing research is expected to help elucidate the comparative merits of intensive and standard HbA(1c)-lowering regimens and optimal strategies for individualized treatment of diabetic and prediabetic patients. CONCLUSION: Published evidence suggests that insulin analogs may ofer advantages over other insulins as part of individualized pharmacotherapy regimens for appropriately selected patients with type 2 diabetes. Am J Health-Syst Pharm. 2013; 70:320-34.American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists 02/2013; 70(4):320-334. DOI:10.2146/ajhp110381 · 2.21 Impact Factor