The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial

• Published in: Journal of diabetes and its complications Vol. 25; no. 6; pp. 355 - 361
• Main Authors: Duckworth, William C, Abraira, Carlos, Moritz, Thomas E, Davis, Stephen N, Emanuele, Nicholas, Goldman, Steven, Hayward, Rodney, Huang, Grant D, Marks, Jennifer B, Reaven, Peter D, Reda, Domenic J, Warren, Stuart R, Zieve, Franklin J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2011; Elsevier Limited
• Subjects: Body Mass Index; C-Peptide - blood; Cardiovascular Diseases - complications; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - physiopathology; Endocrinology & Metabolism; Female; Hospitals, Veterans; Humans; Hyperglycemia - prevention & control; Hypoglycemia - prevention & control; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - therapeutic use; Intensive glucose control; Intention to Treat Analysis; Macrovascular risk and events; Male; Middle Aged; Obesity - complications; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Single-Blind Method; Time Factors; Type 2 diabetes; United States; Veterans; United States; Type 2 diabetes; Intensive glucose control; Macrovascular risk and events
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/j.jdiacomp.2011.10.003

Abstract Background The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population. Methods This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat. Findings Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P <.0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR >1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77–3.320, P <.01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently. Interpretation In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration.