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

Abstract

Aims/hypothesis We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA 1c 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 HbA 1c criteria overlapped with the current OGTT-based criteria of glucose intolerance. Methods We used cross-sectional data from 6,006 nondiabetic men and women. HbA 1c 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 HbA 1c 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 HbA 1c levels were not explained by anthropometric measures. Among individuals with HbA 1c 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 HbA 1c levels are likely to have a true physiological basis. In clinical practice, the HbA 1c 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

Effect of time of day and fasting duration on measures of glycaemia: analysis from the Whitehall II Study

“…Models for 2hPG were also adjusted for height, as previously suggested [9]. To handle the within-person correlation arising from the longitudinal structure of the dataset, random effects were included for the intercept in each model.…”

Sex Differences in Obesity-Related Glucose Intolerance and Insulin Resistance

“…Further analysis using anthropometric measures (e.g., weights, heights and waist-hip circumferences) indicated that the differences in plasma glucose levels 2 hours after oral glucose tolerance tests, but not fasting plasma glucose levels, could be explained by differences in body size and/or body composition between men and women (113,115,118,121). Consequently, women are more commonly diagnosed with diabetes on the basis of glucose level 2-hour post glucose tolerance test compared with fasting plasma glucose levels (112,115).The risk of gestational diabetes is also higher in shorter compared with taller women (122).…”

“…Several epidemiological investigations from European countries (111)(112)(113), Australia (114)(115)(116), Asian countries (117), and Mauritius (118) report that men have higher fasting plasma glucose levels and plasma glucose levels during the early course of the oral glucose tests than women, indicating that the prevalence of impaired fasting glycaemia is higher in men than in women; and women have higher plasma glucose levels 2 hours after oral glucose tolerance tests than men, suggesting that the prevalence of impaired glucose tolerance is higher in women than in men. The pre-diabetic condition of impaired fasting glycaemia is characterized by hepatic insulin resistance, elevated hepatic glucose production and beta cell dysfunction.…”

“…Consequently, women are more commonly diagnosed with diabetes on the basis of glucose level 2-hour post glucose tolerance test compared with fasting plasma glucose levels (112,115).The risk of gestational diabetes is also higher in shorter compared with taller women (122). Women do not have higher glucose levels following glucose test than men when differences in height and high-waist circumference (113) or absolute amount of fatfree mass (121) are taken into account. This notion is supported by the observation that there is a higher risk of developing type 2 diabetes in men than in women with impaired glucose tolerance (123), suggesting that women with impaired glucose tolerance may be healthier than their male counterparts.…”

“…Indeed, higher fasting plasma glucose in men compared with women reflects differences in insulin sensitivity and pancreatic cell function between men and women (113), suggesting that the sex difference in fasting plasma glucose has a true physiological basis.…”