Insulin resistance, beta-cell dysfunction start several years before diabetes diagnosis

Metabolic changes occur well before an actual diagnosis of type 2 diabetes, providing opportunities for screening and prevention, say British researchers.

Results of the WHITEHALL II study suggest "that at a population level, both insulin resistance and beta-cell dysfunction are likely present years before a diabetes diagnosis," says lead investigator Adam Tabák, MD, University College, London.

In studying 6,538 metabolically normal civil servants from the United Kingdom, investigators discovered elevated levels of fasting glucose, postload glucose, and insulin secretion and declining insulin sensitivity starting 3 to 6 years before the diagnosis of type 2 diabetes.

They followed British civil servants who were 35 to 55 years old for a median of 9.7 years. Over this time, 505 of the participants were diagnosed with diabetes, most often based on oral glucose tolerance tests. The trajectories of fasting and 2-hour postload glucose, homeostasis model assessment (HOMA) of insulin sensitivity, and HOMA beta-cell function were analyzed from up to 13 years before their diagnosis of diabetes (or at the end of follow-up for nondiabetics).

Thirteen years before a diagnosis of diabetes, "these individuals already show an elevated fasting plasma glucose" and postload glucose as well, says Dr. Tabák.

In those without an eventual diagnosis of diabetes, the trajectories for metabolic measures followed linear trends, except for insulin secretion, which did not change during the follow-up. In contrast, in those diagnosed with diabetes, fasting glucose increased linearly until 3 years before their diagnosis, at which time it started to increase steeply. The same pattern also applied to postload glucose levels.

An increase in beta-cell function was observed between the fourth and third years before a diagnosis of diabetes, followed by a decline at year 3. The transient increase in beta-cell function was a result of beta-cell adaptation to raised glucose levels.

"For insulin resistance, there was a steeper increase during the last 5 years prior to diagnosis," says Dr. Tabák.

Prevention of diabetes may be more successful before the unstable period during which persons with prediabetes are on the steep portion of the glucose trajectory, he concludes.