Sex Differences in Diabetic Kidney Disease

Abstract

While the global prevalence of both type 1 and type 2 diabetes mellitus is similar in men and women, the consequences of diabetes on associated end-organ complications, including diabetic kidney disease appear to be more sex-specific. Particularly, women with diabetes have higher mortality rates for diabetes-related deaths, and higher prevalence of diabetic kidney disease risk factors such as hypertension, hyperglycemia, obesity, and dyslipidemia. However, the evidence for the impact of sex on diabetic kidney disease prevalence and disease progression is limited and inconsistent. Although most studies agree that the protective effect of the female sex against the development of kidney disease is diminished in the setting of diabetes, the reasons for this observation are unclear. Whether or not sex differences exist in the risk of diabetic kidney disease is also unclear, with studies reporting either higher risk in men, women, or no sex differences. Despite the remaining controversies, some of the factors that associate with sex differences in the risk of diabetic kidney disease are age at onset, and type and duration of diabetes. There is growing appreciation of the importance of sex hormones in the regulation of renal function, with estrogens generally considered to be renoprotective. Although some progress has been made towards better understanding of the mechanisms by which sex hormones play a role in the pathophysiology of diabetic kidney disease, the translational potential

Understanding the opposite effects of sex hormones in mediating renal injury

“…Although the prevalence of DM appears to be similar between both sexes, women with DM have a higher residual lifetime risk at all ages; a higher mortality rate from diabetes‐related deaths, including diabetic nephropathy; and a higher prevalence of risk factors for diabetic nephropathy 51 . However, there are controversial studies regarding the risk of diabetic nephropathy according to sex, such as if there is a greater risk in men, 52 or in women, and even in other studies, no differences by sex have been found, as was clearly detailed by Maric‐Bilkan 51 . The reasons for these inconsistent findings include different populations of patients studied, age, type of diabetes, hormonal status, hormone replacement and the proportion of menopausal women vs young women.…”

Sex Differences in Biopsy-confirmed Diabetic Kidney Disease

“…An increasing amount of studies have investigated the effect of sex differences on DKD development and progression, however, but different cohorts have reported conflicting findings. In studies that enrolled patients with type 2 diabetes, it seems that more results indicated female has greater risk of DKD progression [8] . A study from Japan [12] (247 male and 97 female)…”

The Association Between Leucine and Diabetic Nephropathy in Different Gender: A Cross-Sectional Study in Chinese Patients With Type 2 Diabetes

“…However, noninvasive available markers for accurate prediction and diagnoses of DN in diabetic patients are lacking now ( 8 ). It is worth noting that many studies have found the burden of diabetes is different in different genders ( 9 , 10 ). For example, women have higher mortality rate for diabetes-related deaths, including DN ( 9 ).…”

“…It is worth noting that many studies have found the burden of diabetes is different in different genders ( 9 , 10 ). For example, women have higher mortality rate for diabetes-related deaths, including DN ( 9 ). One may speculate that there is maybe something different in pathology and predictors of DN between men and women.…”