Incidence and correlated factors of beta cell failure in a 4-year follow-up of patients with type 2 diabetes: a longitudinal analysis of the BETADECLINE study
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Type 2 diabetes is associated with progressive deterioration of beta cell function and loss of glycemic control, with increased morbidity and mortality from microvascular and macrovascular complications. Factors predictive of beta cell decline are needed.
We have conducted a prospective evaluation of baseline predictors of beta cell dysfunction and insulin initiation in a cohort of outpatients with type 2 diabetes receiving stable treatment with oral hypoglycemic agents or dietary intervention, over a 4-year follow-up period.
Of 507 patients enrolled, 56 (10.8 %) experienced the study endpoint of initiation of insulin therapy. Univariate and multivariate Cox proportional hazard regression analyses revealed that the likelihood of initiating insulin therapy during follow-up increased with longer diabetes duration and with higher baseline values for hemoglobin A1c, fasting plasma glucose, triglycerides, proinsulin, interleukin-6, Homeostatic Model Assessment-IR and lower values for Homeostatic Model Assessment-B. The likelihood of initiating insulin therapy increased by 46 % for each 1 % increase (10.9 mmol/mol) in baseline hemoglobin A1c and by 6 % for each unit increase (1 ng/l) in baseline IL-6 level. The risk was fourfold higher in the lowest versus highest Homeostatic Model Assessment-B quartile. Treatment with metformin plus a secretagogue increased the risk by fourfold.
Our results show that commonly measured parameters may predict treatment failure in type 2 diabetes and suggest that early treatment with metformin plus secretagogues may foretell this failure.
KeywordsType 2 diabetes Secondary failure Beta cell function
The BETADECLINE Group includes S. Leotta, A. Arcangeli, M. Calabrese, G. Vespasiani, A. Corda, L. Gentile, M. A. Pellegrini.
All the authors contributed to study conception and design, acquisition of data, analysis and interpretation of data, drafting of manuscript and critical revision.
Compliance with ethical standards
Conflict of interest
This study was organized by AMD Foundation Rome, in part supported by Chaira Medica Association (non-profit organization for the study of endocrine and metabolic disorders), Chieri, Italy, and was funded by MSD Italia Srl. There is no one outside of the author SC who is employed or has relationships with Merck Sharp & Dohme Corp. Inc. SC’s contribution is in data analysis and interpretation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Medical writing assistance was provided by Editamed srl, Turin, Italy.
This study was conducted in conformance with good clinical practice standards. Written informed consent was obtained from all participants before enrollment; the study was conducted in accordance with the Declaration of Helsinki and was approved on 30/06/2008 by the Ethics Committee of the University Hospital Saint Luigi Gonzaga of Orbassano, Turin, Italy.
Human and animal rights
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
Informed consent was obtained from all patients for being included in the study.
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