Sex and gender-specific aspects in prediabetes and diabetes mellitus-clinical recommendations (Update 2023)

Metabolic diseases dramatically affect the life of men and women from infancy up to old age in different and manifold ways and are a major challenge for the healthcare system. The treating physicians are confronted with the different needs of women and men in the clinical routine. Gender-specific differences affect pathophysiology, screening, diagnostic and treatment strategies of diseases as well as the development of complications and mortality rates. Impairments in glucose and lipid metabolism, regulation of energy balance and body fat distribution and therefore the associated cardiovascular diseases, are greatly influenced by steroidal and sex hormones. Furthermore, education, income and psychosocial factors play an important role in the development of obesity and diabetes differently in men and women. Males appear to be at greater risk of diabetes at a younger age and at a lower body mass index (BMI) compared to women but women feature a dramatic increase in the risk of diabetes-associated cardiovascular diseases after the menopause. The estimated future years of life lost owing to diabetes is somewhat higher in women than men, with a higher increase in vascular complications in women but a higher increase of cancer deaths in men. In women prediabetes or diabetes are more distinctly associated with a higher number of vascular risk factors, such as inflammatory parameters, unfavourable changes in coagulation and higher blood pressure. Women with prediabetes and diabetes have a much higher relative risk for vascular diseases. Women are more often morbidly obese and less physically active but may have an even greater benefit in health and life expectation from increased physical activity than men. In weight loss studies men often showed a higher weight loss than women; however, diabetes prevention is similarly effective in men and women with prediabetes with a risk reduction of nearly 40%. Nevertheless, a long-term reduction in all cause and cardiovascular mortality was so far only observed in women. Men predominantly feature increased fasting blood glucose levels, women often show impaired glucose tolerance. A history of gestational diabetes or polycystic ovary syndrome (PCOS) as well as increased androgen levels and decreased estrogen levels in women and the presence of erectile dysfunction or decreased testosterone levels in men are important sex-specific risk factors for the development of diabetes. Many studies showed that women with diabetes reach their target values for HbA(1c), blood pressure and low-density lipoprotein (LDL)-cholesterol less often than their male counterparts, although the reasons are unclear. Furthermore, sex differences in the effects, pharmacokinetics and side effects of pharmacological treatment should be taken more into consideration.