Journal
LANCET
Volume 373, Issue 9682, Pages 2215-2221Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(09)60619-X
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Funding
- Medical Research Council New Investigator Award [G0501184]
- Medical Research Council, Economic and Social Research Council
- British Heart Foundation
- Health and Safety Executive, and Department of Health (UK)
- National Heart Lung and Blood institute [HL36310]
- National Institute on Aging [AG13196]
- Agency for Health Care Policy Research [HS06516]
- The John D and Catherine T MacArthur Foundation (USA)
- Academy of Finland
- MRC [G0501184] Funding Source: UKRI
- AGENCY FOR HEALTHCARE RESEARCH AND QUALITY [R01HS006516] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL036310] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R37AG013196, R01AG013196] Funding Source: NIH RePORTER
- British Heart Foundation [RG/07/008/23674] Funding Source: researchfish
- Medical Research Council [G0501184, G0100222, G19/35, G8802774] Funding Source: researchfish
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Background Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and posdoad glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. Methods We analysed data from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). Findings Multilevel models adjusted for age, sex, and ethnic origin confirmed that all metabolic measures followed linear trends in the group of non-diabetics (10989 measurements), except for insulin secretion that did not change during follow-up. In the diabetic group (801 measurements), a linear increase in fasting glucose was followed by a steep quadratic increase (from 5.79 mmol/L to 7.40 mmol/L) starting 3 years before diagnosis of diabetes. 2-h postload glucose showed a rapid increase starting 3 years before diagnosis (from 7.60 mmol/L to 11.90 mmol/L), and HOMA insulin sensitivity decreased steeply during the 5 years before diagnosis (to 86.7%). HOMA beta-cell function increased between years 4 and 3 before diagnosis (from 85.0% to 92.6%) and then decreased until diagnosis (to 62.4%). Interpretation In this study, we show changes in glucose concentrations, insulin sensitivity, and insulin secretion as much as 3-6 years before diagnosis of diabetes. The description of biomarker trajectories leading to diabetes diagnosis could contribute to more-accurate risk prediction models that use repeated measures available for patients through regular check-ups. Funding Medical Research Council (UK); Economic and Social Research Council (UK); British Heart Foundation (UK); Health and Safety Executive (UK); Department of Health (UK); National Institute of Health (USA); Agency for Health Care Policy Research (USA); the John D and Catherine T MacArthur Foundation (USA); and Academy of Finland (Finland).
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