Bimodal distribution of glucose is not universally useful for diagnosing diabetes

Abstract

Objective: Bimodality in the distribution of glucose has been used to define the cut point for the diagnosis of diabetes. Previous studies on bimodality have primarily been in populations with a high prevalence of type 2 diabetes, including one study in a white Caucasian population. All studies included participants with known diabetes. The aim of this study was to assess whether a bimodal structure is a general phenomenon in fasting plasma glucose (FPG) and 2-h plasma glucose that is useful for deriving a common cut point for diabetes in populations of different origin, both including and excluding known diabetes.

Research design and methods: The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project is an international collaboration pooling surveys from all continents. These studies include surveys in which plasma glucose was measured during an oral glucose tolerance test; in total, 43 studies (135,383 participants) from 27 countries were included. A mixture of two normal distributions was fitted to plasma glucose levels, and a cut point for normal glycemia was estimated as their intersection. In populations with a biologically meaningful cut point, bimodality was tested for significance.

Results: Distributions of FPG and 2-h plasma glucose did not, in general, produce bimodal structures useful for deriving cut points for diabetes. When present, the cut points produced were inconsistent over geographical regions.

Conclusions: Deriving cut points for normal glycemia from distributions of FPG and 2-h plasma glucose does not appear to be suitable for defining diagnostic cut points for diabetes.

Figure 1

Distribution of FPG in Korea (A) and Nauru (B) and 2-h plasma glucose in Egypt (C) and Taiwan (D). Patients with known diabetes are excluded. The histograms represent data (intervals of 0.2 mmol/l). The superimposed solid curve is the fitted mixture model, and the dotted curves are the two underlying distributions.

Figure 2

Cut points (95% CI) for normal glycemia in glucose. The gray and black lines represent analyses with and without individuals with known diabetes. The dotted vertical line is the WHO 1999 cut point for diabetes. *Statistically significant mixture model.