title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Metabolism and Diabetes Unit ASL TO5, Regione Piemonte, Via De Maria, 10023, Chieri (TO), Italy. giordaca@tin.it.
authors.forename: Carlo B
authors.initials: CB
authors.lastname: Giorda
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Giuseppina T
authors.initials: GT
authors.lastname: Russo
authors.affiliation: MSD, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cercone
authors.affiliation: Unit of Internal Medicine, Department of Medical Sciences, IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Cosmo
authors.affiliation: Center for Outcomes Research and Clinical Epidemiology (CORE), Pescara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Nicolucci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Cucinotta
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: Beta cell function; Secondary failure; Type 2 diabetes