Researchers in the UK found that changes in glucose concentrations, insulin sensitivity, and insulin secretion can be detected as early as 3 to 6 years before diagnosis of diabetes and hope that the discovery will lead to more accurate risk prediction as part of regular check ups.
The study was led by a team at University College London and was published in the 8 June early online issue of The Lancet. It was also presented at the 69th Scientific Sessions of the American Diabetes Association that took place in New Orleans, Louisiana earlier this week.
Although we know quite a lot about glucose metabolism and insulin, the hormone that helps us use glucose for energy and goes awry in diabetes, we don’t know very much about the timing of the changes that lead up to diabetes, wrote the researchers.
For this study they followed changes in glucose (before fasting and after eating), insulin sensitivity, and insulin secretion in 6,538 British civil servants who took part in the Whitehall II study.
71 per cent of the participants were white, 91 per cent were male, and none had diabetes at the start of the investigation, which followed them for a median of 9.7 years.
Over the course of the study, 505 of the participants developed diabetes (about half of them diagnosed using an oral glucose tolerance test), so the researchers looked back at the data that had been collected on those individuals from up to 13 years earlier and plotted the changes in levels of particular metabolic markers. They also looked at the same data for those who did not develop diabetes during the study.
The metabolic markers included: fasting and postload glucose (the latter taken 2 hours after eating), insulin sensitivity and beta-cell function. The last two were assessed using a method called HOMA (short for Homeostatic Model Assessment), a way of calculating insulin resistance which is often used in larger studies instead of the “gold standard” Hyperinsulinemic Glucose Clamp. Beta-cells are the cells in the pancreas that produce and release insulin.
After adjustment for age, sex and ethnic origin, the results showed that:
- All the metabolic markers (nearly 11,000 measurements) showed a steady linear increase in the non-diabetic group, except insulin secretion which did not change during the period of the study.
- However, in the diabetic group (over 800 measurements) fasting glucose went up in a linear fashion at first but was then followed by a steep quadratic (upward curved) increase that started about 3 years before diagnosis of diabetes.
- In this group, the 2-hour postload glucose measure also showed a rapid increase that started about 3 years before diagnosis, and HOMA insulin sensitivity fell sharply during 5 years before diagnosis.
- Also, in this group, the HOMA beta-cell function went up between 4 and 3 years prior to diagnosis (from 85 to 92.6 per cent) and then fell until diagnosis (to 62.4 per cent).
The study suggests that changes in the biomarkers of diabetes such as glucose concentrations, insulin sensitivity, and insulin secretion take place between 3 to 6 years before diagnosis.
The researchers wrote that:
“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.”
“Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study.”
Adam G Tabák, Markus Jokela, Tasnime N Akbaraly, Eric J Brunner, Mika Kivimäki, Daniel R Witte.
doi:10.1016/S0140-6736(09)60619-X
Additional sources: diabetesincontrol.com..
Written by: Catharine Paddock, PhD