Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with Type 2 diabetes uncontrolled by oral agents

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• 作者：Olga V. Sakharova ; Ranee R. Lleva ; James D. Dziura ; Geralyn R. Spollett ; Scott K. Howell ; Paul J. Beisswenger ; Silvio E. Inzucchi
• 关键词：Diabetes ; Post-prandial glucose ; AGE precursors ; Insulin
• 刊名：Journal of Diabetes and its Complications
• 出版年：2012
• 出版时间：July-August, 2012
• 年：2012
• 卷：26
• 期：4
• 页码：333-338
• 全文大小：257 K

文摘

Objective

Progressive ¦Â-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 90-110mg/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 ¦Á-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 ¡À 36 vs. 199 ¡À 49 mg/dL, respectively; <em>Pem> = 0.001). Likewise, there was a reduction in both fasting (48 ¡À 13 vs. 57 ¡À 19, <em>Pem> = 0.047) and post-prandial (53 ¡À 19 vs. 63 ¡À 23; <em>Pem> = 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.