Trajectories of Glycemia, Insulin Sensitivity and Insulin Secretion Preceding the Diagnosis of Type 2 Diabetes: The Whitehall II Study
By Á. Tabák, M. Jokela, T. Akbaraly, E. Brunner, M. Kivimaki, D. Witte. The Lancet, 2009
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Background Little is known about the timing of changes in glucose metabolism prior to type 2 diabetes development. We aimed to characterize trajectories of fasting and postload glucose, insulin sensitivity and insulin secretion in individuals developing type 2 diabetes. Methods Prospective occupational cohort study of 6538 (70.7% male, 91.3% Caucasian) British civil servants free of diabetes mellitus at baseline. During a median follow-up of 8.2 years, 505 incident diabetes cases were diagnosed (49.1% based on oral glucose tolerance test). Trajectories of fasting and 2-hour postload glucose, homeostasis model assessment (HOMA) insulin sensitivity, and β-cell function until diabetes diagnosis (the diabetic group) or the end of follow-up (the non-diabetic controls) were determined. Findings Multilevel models adjusted for age, sex and ethnicity confirmed that all metabolic measures followed linear trends in the controls except for insulin secretion that did not change during the follow-up. In the diabetic group a linear increase in fasting glucose was followed by a steep quadratic increase starting 3 years prior to the diagnosis of diabetes. For 2-hour postload glucose levels a fast elevation started 3 years prior to the diagnosis and for HOMA insulin sensitivity a steeper decrease was seen during the last 5 years before the diagnosis. HOMA β-cell function showed an increase between years 4 and 3 prior to the diagnosis and then a decrease until the diagnosis. Interpretation In this large cohort of British adults changes in glucose levels, insulin sensitivity, and insulin secretion were evident already 3–6 years before the diabetes diagnosis.
Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Genetics
View Paper: https://www.semanticscholar.org/paper/6abaf949a3e12e74d8b395cb356b3d3abb03afbe
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Citations in the corpus
- Metabolite Profiles and the Risk of Developing Diabetes (2011, neutral): “For instance, by the time relative insulin deficiency manifests as hyperglycemia and a diagnosis of type 2 diabetes is made, considerable pancreatic beta cell insufficiency has already occurre”
- The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives (2018, background): “Although the relative contribution of beta cell dysfunction and insulin resistance can vary in people with T2D, it is generally accepted that abnormal insulin sensitivity precedes the clinical diagnosis of diabetes by up to 15 years.(62) Therefore, along with mechanistic studies investigating mechan”