Ravi Retnakaran, Jiajie Pu, Chang Ye, Alexandra Emery, Stewart B. Harris, Sonja M. Reichert, Hertzel C. Gerstein, Natalia McInnes, Caroline K. Kramer, Bernard Zinman
{"title":"2型糖尿病早期β细胞功能和血糖的改善在胰岛素治疗后放大的血糖阈值:葡萄糖毒性的逆转","authors":"Ravi Retnakaran, Jiajie Pu, Chang Ye, Alexandra Emery, Stewart B. Harris, Sonja M. Reichert, Hertzel C. Gerstein, Natalia McInnes, Caroline K. Kramer, Bernard Zinman","doi":"10.2337/dc24-1375","DOIUrl":null,"url":null,"abstract":"OBJECTIVE Alleviation of unrecognized glucotoxicity, with resultant recovery of β-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 β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-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 β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-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 β-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 β-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.","PeriodicalId":11140,"journal":{"name":"Diabetes Care","volume":null,"pages":null},"PeriodicalIF":14.8000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Glycemic Threshold Above Which the Improvement of β-Cell Function and Glycemia in Response to Insulin Therapy Is Amplified in Early Type 2 Diabetes: The Reversal of Glucotoxicity\",\"authors\":\"Ravi Retnakaran, Jiajie Pu, Chang Ye, Alexandra Emery, Stewart B. Harris, Sonja M. Reichert, Hertzel C. Gerstein, Natalia McInnes, Caroline K. Kramer, Bernard Zinman\",\"doi\":\"10.2337/dc24-1375\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"OBJECTIVE Alleviation of unrecognized glucotoxicity, with resultant recovery of β-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 β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-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 β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-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 β-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 β-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.\",\"PeriodicalId\":11140,\"journal\":{\"name\":\"Diabetes Care\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.8000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes Care\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2337/dc24-1375\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2337/dc24-1375","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
A Glycemic Threshold Above Which the Improvement of β-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 β-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 β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-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 β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-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 β-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 β-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.
期刊介绍:
The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes.
Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.