Study examines heterogeneity of type 2 diabetes

Type 2 diabetes appears to have different subtypes based on how it is diagnosed, according to a recent study.

Researchers used prospectively collected data from the Whitehall II study and performed a retrospective analysis of the trajectory of cardiovascular risk factors and 10-year cardiovascular risk in patients identified as diabetic by a 75-g oral glucose tolerance test (OGTT). The Whitehall II study is a longitudinal study done in the United Kingdom in adults who were 35 to 55 years of age in 1985-1988 and have undergone eight phases of follow-up through 2009. For this study, participants who were diagnosed with type 2 diabetes on the OGTT were divided into three subgroups: those who at time of diagnosis had fasting hyperglycemia, those who had elevated 2-hour glucose concentrations and those who had both fasting hyperglycemia and elevated 2-hour glucose concentrations. The goal of the study was to determine whether patients diagnosed with type 2 diabetes by these three methods differed in pathogenesis or in cardiovascular risks. The results were published online Feb. 21 by The Lancet Diabetes & Endocrinology.

Patients were followed for a median of 14.2 years from 1991 to 2009, with 15,826 person-examinations. Of 10,308 individuals in the Whitehall II study, 6,843 met criteria for inclusion in this analysis (patients with diabetes diagnosed before the OGTT and diagnosed outside the study were excluded). A total of 274 patients developed type 2 diabetes, and of these, 55 had high fasting glucose concentrations, 148 had high 2-hour glucose concentrations and 71 had both. Patients with high concentrations on both measures had a higher mean body mass index at diagnosis than those who had only high fasting glucose concentrations (P=0.0009) or high 2-hour concentrations (P<0.0001). The first group also had higher mean glycated hemoglobin A1c levels (7.4% vs. 5.9% vs. 5.9%; P<0.0001 for both comparisons), a larger proportion of patients with moderate to high risk for cardiovascular disease and a more substantial acceleration of glucose levels and insulin resistance, plus classic β-cell compensation before diagnosis.

The authors noted that their results may not be generalizable to all patients and that their study included few women (<30%) and few minorities, among other limitations. However, they concluded that the natural history and pathogenesis of type 2 diabetes appear to differ depending on how the disorder is diagnosed. For example, patients with high concentrations on only the fasting or two-hour glucose test showed no increase in β-cell function before diagnosis, as has been considered typical in type 2 diabetes. “Future studies should establish whether glycaemic control, drug needs, and the incidence of cardiovascular disease and microvascular complications differ between patients with different subgroups of disease,” the authors wrote.