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A Glycemic Threshold Above Which the Improvement of b-Cell Function and Glycemia in Response to Insulin Therapy Is Amplified in Early Type 2 Diabetes: The Reversal of Glucotoxicity
OBJECTIVE Alleviation of unrecognized glucotoxicity, with resultant recovery of b-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve b-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated baseline fasting glucose threshold above which the post-IIT improvement in both b-cell function and glycemia is amplified. RESEARCH DESIGN AND METHODS IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of b-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 t o 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in b-cell function between those at/above the indicated glucose level and those below it. RESULTS The relationship between baseline fasting glucose and the differential change in b-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified. CONCLUSIONS The respective improvements in b-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity. © 2024 by the American Diabetes Association.
Authors : Retnakaran R.; Pu J.; Ye C.; Emery A.; Harris S.B.; Reichert S.M.; Gerstein H.C.; McInnes N.; Kramer C.K.; Zinman B.
Source : American Diabetes Association Inc.
Article Information
| Year | 2024 |
| Type | Article |
| DOI | 10.2337/dc24-1375 |
| ISSN | 01495992 |
| Volume | 47 |
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