Learning about diabetes through epidemiology

This month’s issue of Diabetic Medicine is devoted to a number of recently accepted articles on the epidemiology of diabetes, covering the definitions used to diagnose diabetes, prevalence, incidence over time, characteristics, and complications associated with diabetes, including retinopathy, cardiovascular disease and early mortality. We start with two papers that highlight the increasing burden of diabetes in Europe. Combining a number of Polish data sources, Topor-Madry et al. [1] found higher crude prevalence rates of diagnosed diabetes in women than in men, 6.1% vs 5.1%, but after age standardization, the prevalence rates were higher in men, at 4.3% and 4.7%, respectively. If undiagnosed diabetes is included, the overall crude prevalence was 7.0%. Using a modelling approach based on constant mortality and incidence rates, T€ onnies et al. [2] project that the number of people with diagnosed type 2 diabetes in Germany will increase by 21% over the period 2015 to 2040. However, using different scenarios with decreasing mortality and increasing or decreasing incidence rates, the authors estimate the relative increase to be between 54% and 77%. The current prevalence of diagnosed diabetes in Germany is 9.9%. The actual thresholds for defining diabetes have changed over the past decades, and there are now three identifiers: fasting glucose, 2-h glucose after an oral glucose tolerance test, as well as HbA1c [3]. For gestational diabetes, controversies about diagnosis continue; the WHO recommendations are based in part on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study results, but they state that the quality of evidence is ‘very low’ for the given thresholds for fasting, 1-h and 2-h plasma glucose [4]. The criteria recommended by the National Institute for Health and Care Excellence (NICE) [5] differ from those of the WHO: NICE do not include a 1-h glucose criterion, and have a higher fasting glucose and a lower 2-h glucose threshold than the WHO recommendations. Although well recognized in the biochemical research literature, one important issue that is too rarely discussed is the type of sample and the handling of samples before the assay of glucose or HbA1c [6,7]. The current recommendations and thresholds for diagnosing gestational diabetes are based on the HAPO study where the pre-analytical sampling methodology was ‘left to the discretion of local sites’ [8]. In some settings, it is likely that the pre-analytical sampling methodology in the HAPO study did not prevent glycolysis, which could render the levels of these current diagnostic recommendations too low. Song et al. [8] studied 892 pregnant women, of whom 14% had gestational diabetes, using samples collected in sodium fluoride/potassium oxalate tubes, stored at room temperature [8]. Using lyophilized citrate tubes reduces glycolysis and so measurements are higher than samples using sodium fluoride/potassium oxalate tubes stored for a similar time. The authors applied a modelled correction to correspond to the use of lyophilized citrate tubes and estimated that the prevalence would increase to 39%. The diagnostic levels need to be revisited for clinics using the recommended pre-analytical plasma glucose methods. Although it is pragmatic to define diabetes by the same thresholds in both sexes, all age groups and all ethnicities, this can be debated. For example, women have higher 2-h glucose concentrations than men [9]. In the cross-sectional US National Health and Nutrition Examination Survey (NHANES) 2005–2014, Ford et al. [10] compared the use of HbA1c to define diabetes, with the fasting and 2-h plasma glucose criteria as the gold standard [10]. This yielded different ‘optimal’ HbA1c thresholds for defining diabetes in the two ethnic groups studied: 42mmol/mol (6.0%) for people of African ancestry and 39 mmol/mol (5.7%) for people of white European ancestry. The confidence intervals for these thresholds are not given, and it is possible that the thresholds might not differ using statistical tests. There may also be differences in the mean fasting and 2-h glucose levels between these two ethnic groups, and these glucose levels were used to define diabetes. Ideally, thresholds should be defined by the specific consequences of hyperglycaemia, such as retinopathy, according to a continuous measure of glucose or HbA1c [11]. Cover image: Doughnut and tape measure. Credit: IAN HOOTON / SCIENCE PHOTO LIBRARY.