Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study

Aims/hypothesis We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA₁c could be explained by differences in body size and/or body composition between men and women in a general non-diabetic Danish population. Moreover, we aimed to study to what degree the newly suggested high-risk HbA₁c criteria overlapped with the current OGTT-based criteria of glucose intolerance. Methods We used cross-sectional data from 6,006 non-diabetic men and women. HbA₁c and FPG levels were measured and a 75 g OGTT was performed in all individuals. Height, weight and waist and hip circumferences were measured and BMI was calculated. Data were analysed in age-adjusted linear regression models. Results Men had higher FPG and HbA₁c levels than women, and women had higher 2hPG levels than men. Sex differences in 2hPG levels were explained by differences in height and FPG levels, but sex differences in FPG or HbA₁c levels were not explained by anthropometric measures. Among individuals with HbA₁c in the high-risk range (6.0-6.5%), 73% had normal glucose tolerance. Conclusions/interpretation Sex differences in 2hPG levels after an OGTT may to some extent be a consequence of giving the same amount of glucose to individuals with different body size. In contrast, sex differences in FPG and HbA₁c levels are likely to have a true physiological basis. In clinical practice, the HbA₁c assay may be more convenient than the OGTT, but it is important to note that different populations are identified by the two methods. Trial registration ClinicalTrials.gov NCT00289237 Funding Supported by grants from the Danish Diabetes Association, the Danish Medical Research Council, the Danish Centre for Evaluation and Health Technology Assessment, Novo Nordisk, GlaxoSmithKline, Copenhagen County, The Danish Heart Foundation, The Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, and the Becket Foundation.