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Serial Metabolic Measurements and Conversion to Type 2 Diabetes in the West of Scotland Coronary Prevention Study

Specific Elevations in Alanine Aminotransferase and Triglycerides Suggest Hepatic Fat Accumulation as a Potential Contributing Factor

¹ Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland
² Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland
³ Clinical Trials Unit, University of Glasgow, Glasgow, Scotland
⁴ Department of Medicine, Stobhill Hospital, Glasgow, Scotland
⁵ MRC Epidemiology Unit, Cambridge, U.K
⁶ Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland

Address correspondence and reprint requests to Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, 4th Floor QEB, Glasgow Royal Infirmary. E-mail: nsattar{at}clinmed.gla.ac.uk

Abbreviations: ADA, American Diabetes Association; ALT, alanine aminotransferase; AST, aspartate aminotransferase; OGTT, oral glucose tolerance testing; SBP, systolic blood pressure; WOSCOPS, West of Scotland Coronary Prevention Study

To examine metabolic changes (lipids, liver enzymes, blood pressure, and weight) potentially associated with conversion to diabetes, we analyzed serial glucose and other metabolic measures obtained every 6 months within the West of Scotland Coronary Prevention Study trial. Changes in parameters for 86 men who converted to new-onset diabetes ("converters": two consecutive glucose levels 7 mmol/l) were compared with 860 "nonconverters" matched for age and treatment allocation. Eighteen months before the diagnosis, converters to diabetes had elevated (P < 0.01) fasting glucose, weight, triglyceride, alanine aminotransferase (ALT), blood pressure, and white cell count and lower HDL cholesterol compared with nonconverters. The mean (SD) increase in fasting glucose over 18 months in converters was 1.80 (1.52) mmol/l, compared with 0.10 (0.57) in nonconverters. Of parameters measured, only ALT (P = 0.0005) and triglyceride (P = 0.030) increased significantly more over the 18 months in converters compared with nonconverters, but neither parameter increased significantly in nonconverters with high baseline glucose concentrations (>6.1 mmol/l). Finally, only sustained increases in ALT predicted a higher risk for diabetes. We conclude that a relatively rapid rise in fasting glucose levels is frequent in converters to diabetes and that associated increases over time in ALT and potentially triglyceride suggest hepatic fat accumulation as a contributing factor for conversion to diabetes in men at risk.

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