1. Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with type 2 diabetes uncontrolled by oral agents.
- Author
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Sakharova OV, Lleva RR, Dziura JD, Spollett GR, Howell SK, Beisswenger PJ, and Inzucchi SE
- Subjects
- Administration, Oral, Aged, Body Weight, Cross-Over Studies, Diabetes Mellitus, Type 2 blood, Fasting blood, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemic Agents administration & dosage, Insulin Glargine, Male, Middle Aged, Treatment Failure, Treatment Outcome, Blood Glucose metabolism, Diabetes Mellitus, Type 2 drug therapy, Glycation End Products, Advanced blood, Hypoglycemic Agents therapeutic use, Insulin Lispro therapeutic use, Insulin, Long-Acting therapeutic use, Postprandial Period
- Abstract
Objective: Progressive β-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs., Research Design and Methods: This was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90-110 mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups., Result: Both insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P=0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P=0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P=0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations., Conclusion: In type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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