Sex differences in the clinical profile of individuals with prediabetes and type 2 diabetes mellitus in the general population - results from the Gutenberg Health Study
Authors: Schmitt V , Prochaska J , Schulz A , Hahad O , Keller K , Hobohm L , Troebs S O , Koeck T , Michal M , Schuster A , Mueller-Nurasyid M , Lackner K , Munzel T , Wild P 
Published: November 2023

Abstract

Introduction
The rising prevalence of type 2 diabetes mellitus (T2DM) and concomitant diseases accompany mounting evidence of clinically significant sex differences. T2DM is more frequently diagnosed at lower ages in men, differences in biology and lifestyle affect risk and complications differently in both sexes, and risk for vascular disease was shown to be higher in women. Also, in prediabetes, sex differences were detected, but only a few studies exist.

Purpose
To investigate the sex-related prevalence of prediabetes and T2DM in the general population, the clinical profile regarding asymptomatic organ damage (AOD) and prevalent cardiovascular disease (CVD), and its influence on CVD risk prediction and mortality.

Methods
The Gutenberg Health Study sample (15,010 subjects, 35-74 years) was stratified regarding sex and glucose state. Euglycemia, prediabetes, and T2DM were categorized based on clinical information and HbA1c level. CVD included the prevalence of coronary artery disease, myocardial infarction, stroke or transient ischemic attack, heart failure, atrial fibrillation, and peripheral artery disease. AOD was assessed in individuals without prevalent CVD as an indicator of early, subclinical CVD according to current guidelines and included left ventricular mass index, carotid intima-media thickness and plaque, ankle-brachial index, and renal function. Ten years of CVD risk prediction was assessed using the Framingham score. Clinical outcome was assessed by structured follow-up.

Results
Overall, 14,870 individuals were included in the present analysis, 7,352 women and 7,518 men. Among them, 4,784 (65.1%) women and 4,642 (61.7%) men revealed euglycemia, 2,065 (28.1%) women and 2,063 (27.4%) men had prediabetes, and in 503 (6.8%) women and 813 (10.8%) men T2DM was present. Except for obesity, cardiovascular risk factors were more prevalent in prediabetic and diabetic men than in women. Female sex was associated with a reduced risk for AOD (prevalence ratio (PR) 0.92, 95% confidence interval (CI) 0.89 to 0.94, P&lt;0.0001) and CVD (PR 0.65, 95%CI 0.59 to 0.71, P&lt;0.0001). The 10-year risk for CVD was about doubled in men compared to women in euglycemia (women 6.8±6.2% vs. men 14.9±11.3%), prediabetes (women 11.6±7.8% vs. men 21.6±12.6%) and T2DM (women 24.7±12.9% vs. men 42.6±17.9%). Regarding all-cause mortality, female sex was favorable (hazard ratio 0.58, 95%CI 0.51 to 0.66, P&lt;0.0001).

Conclusions
In the general population, euglycemia and prediabetes were more prevalent in women, T2DM was more prevalent in men. Distinct differences were found in risk between both sexes, with a more favorable profile in women. Particularly the high prevalence of the primarily unrecognized prediabetes in the general population highlights the necessity for prevention and early detection. Investigating sex-associated differences may help to elucidate the pathophysiology and improve prevention and treatment by more individualized therapy concepts.