Predictors of and Longitudinal Changes in Insulin Sensitivity and Secretion Preceding Onset of Type 2 Diabetes
- Valeriya Lyssenko1,
- Peter Almgren1,
- Dragi Anevski12,
- Roland Perfekt1,
- Kaj Lahti3,
- Michael Nissén4,
- Bo Isomaa5,
- Björn Forsen6,
- Nils Homström7,
- Carola Saloranta89,
- Marja-Riitta Taskinen8,
- Leif Groop1,
- Tiinamaija Tuomi89 and
- for the Botnia Study Group
- 1Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, Lund University, Malmö, Sweden
- 2Fraunhofer Chalmers Centre, Gothenburg, Sweden
- 3Vasa Health Care Center, Vasa, Finland
- 4Vasa Central Hospital, Vasa, Finland
- 5Jakobstad Hospital, Jakobstad, Finland
- 6Närpes Care Health Center, Närpes, Finland
- 7Korsholm Health Care Center, Korsholm, Finland
- 8Department of Medicine, Helsinki University Hospital, Helsinki, Finland
- 9Folkhälsan Research Center, Helsinki, Finland
- Address correspondence and reprint requests to Valeriya Lyssenko, MD, PhD, Department of Endocrinology, Wallenberg Laboratory, University Hospital MAS, 205 02 Malmö, Sweden. E-mail: valeri.lyssenko{at}endo.mas.lu.se
Abstract
Identification of individuals at high risk of developing type 2 diabetes is a prerequisite for prevention of the disease. We therefore studied risk factors predicting type 2 diabetes in the Botnia Study in western Finland. A total of 2,115 nondiabetic individuals were prospectively followed with repeated oral glucose tolerance tests. After a median follow-up of 6 years, 127 (6%) subjects developed diabetes. A family history of diabetes (hazard ratio [HR] 2.2, P = 0.008), BMI (HR for comparison of values below or above the median 2.1, P < 0.001), waist-to-height index (2.3, P < 0.001), insulin resistance (2.1, P = 0.0004), and β-cell function adjusted for insulin resistance (2.7, P < 0.0001) predicted diabetes. Marked deterioration in β-cell function with modest changes in insulin sensitivity was observed during the transition to diabetes. The combination of FPG ≥5.6 mmol/l, BMI ≥30 kg/m2, and family history of diabetes was a strong predictor of diabetes (3.7, P < 0.0001). Of note, using FPG ≥6.1 mmol/l or 2-h glucose ≥7.8 mmol/l did not significantly improve prediction of type 2 diabetes. In conclusion, a marked deterioration in β-cell function precedes the onset of type 2 diabetes. These individuals can be identified early by knowledge of FPG, BMI, and family history of diabetes.
- DPS, Diabetes Prevention Study
- FFA, free fatty acid
- FPG, fasting plasma glucose
- HOMA, homeostasis model assessment
- HOMAIR, HOMA of insulin resistance
- IFG, impaired fasting glucose
- IGT, impaired glucose tolerance
- NCEP, National Cholesterol Education Program
- NGT, normal glucose tolerance
- OGTT, oral glucose tolerance test
- ROC, receiver operator curve
- WHO, World Health Organization
- WHR, waist-to-hip ratio
Footnotes
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M.-R.T. has received honoraria and consulting fees from Merk, Sharp and Dome, Pfizer, Fournier, and GlaxoSmithKline and research and support from Fournier and Novartis. L.G. has received honoraria and consulting fees from Bristol-Myers Squibb and Roche.
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- Accepted September 22, 2004.
- Received July 12, 2004.
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