Current evidence on gender-related risk factors for type 1 diabetes, type 2 diabetes and prediabetes: a reappraisal of the Italian study group on gender difference in endocrine diseases

Diabetes is a chronic disease with a significant socio-economic burden. Recognizing its risk factors and gender differences within its physio-pathological mechanisms may allow early diagnosis. This review aims to summarize the current evidence on gender differences in terms of prevalence, risk factors and pathogenesis for Type 1 Diabetes (T1D), Type 2 Diabetes (T2D) and prediabetes. A comprehensive search of English-language articles was conducted in PubMed, EMBASE and Cochrane Library until July 2024. We selected all studies that assessed gender differences on risk factors for diabetes and prediabetes. T1D is an autoimmune disease, with a multifactorial pathogenesis. Contrary to most autoimmune diseases, it has a male gender bias, with a male predominance incidence after puberty, for which the involvement of hormones has been hypothesized in addition to genetic predisposition. In T2D, the accumulation of visceral adipose tissue is recognized as the main predisposing factor for insulin resistance and consequent β-cells loss and dysfunction. Sex hormones influence fat disposition resulting in different body composition between males and females and different metabolic impact. Gender differences in dietary patterns and socio-cultural determinants also influence the risk of T2D. Also, a gender-related risk factor has been detected in prediabetes; indeed, females are at greater risk of impaired glucose tolerance than males. Evidence shows the existence of gender differences in risk factors for T1D, T2D and prediabetes. This suggests that gender should be considered in prevention and screening programs, with the goal of reducing incidence or making an early diagnosis.