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. Naveed Sattar1,
  2. Alex McConnachie2,
  3. Ian Ford2,
  4. Allan Gaw3,
  5. Stephen J. Cleland4,
  6. Nita G. Forouhi5,
  7. Peter McFarlane6,
  8. James Shepherd1,
  9. Stuart Cobbe6 and
  10. Chris Packard1
  1. 1Department of Vascular Biochemistry, University of Glasgow, Glasgow, Scotland
  2. 2Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland
  3. 3Clinical Trials Unit, University of Glasgow, Glasgow, Scotland
  4. 4Department of Medicine, Stobhill Hospital, Glasgow, Scotland
  5. 5MRC Epidemiology Unit, Cambridge, U.K
  6. 6Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland
  1. 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

Abstract

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.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 19, 2006.
    • Received September 6, 2006.
| Table of Contents