Sex differences in diabetes and kidney disease: mechanisms and consequences

Shepard, Blythe D.

doi:10.1152/ajprenal.00249.2019

Cited by 92 publications

(90 citation statements)

References 71 publications

(92 reference statements)

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“…67,68 Classical risk factors for DKD, including glycemic control, hypertension, obesity, and dyslipidemia have also been reported to differentially contribute to disease pathophysiology according to sex. [67][68][69] As we strive to better understand the pathophysiology of DKD, studies addressing how sex contributes to and affects disease development and progression may provide important clues.…”

Section: Mechanisms Underlying Sex Differ-ences In Dkdmentioning

confidence: 99%

Sex Differences in Diabetic Kidney Disease

Maric‐Bilkan

2020

Mayo Clinic Proceedings

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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

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Section: Mechanisms Underlying Sex Differ-ences In Dkdmentioning

confidence: 99%

Sex Differences in Diabetic Kidney Disease

Maric‐Bilkan

2020

Mayo Clinic Proceedings

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“…HUA is just one of many conditions that have observable sex differences, as differing pathologies based on sex have been observed in a variety of fields [14][15][16][17] including cardiovascular [18][19][20][21], neurological [22][23][24][25], immunological [26][27][28], and renal diseases [29][30][31][32][33]. The architecture of the female kidney is likely distinct from that of the male kidney [34], given women have a lower blood pressure than men [35], women are less likely to develop acute kidney injury than men [36,37], women demonstrate improved tolerance to renal ischemia [38,39], and women are protected from renal and cardiovascular disease before menopause as compared to men [40,41].…”

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

Sex Differences in Urate Handling

Kuhns

Woodward

2020

IJMS

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Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.

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“…In animal studies, female rats preferentially use SGLT1 and SGLT2 transporters over other channels for Na + reabsorption compared to male rats. While increased reliance on these glucose transporters in female animals is often linked to a higher incidence of glomerular hyperfiltration, whether these differences extend to humans is still unclear 24 . There also exists conflicting.…”

Section: Discussionmentioning

confidence: 99%

Gender differences in adverse event reports associated with antidiabetic drugs

Joung

Jung

Park

et al. 2020

Sci Rep

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Little is known about gender-specific reporting of adverse events (AEs) associated with antidiabetic drugs. This study was to assess the gender-related difference in AEs reporting associated with antidiabetic agents. The number of antidiabetic drug-AE pairs associated was identified using the Korea Adverse Event Reporting System database. Prevalence of diabetes was estimated using the Health Insurance Review and Assessment Service-National Patients Sample database. Reporting rate per 10,000 people was calculated by dividing drug-AE pairs with the number of antidiabetic drug users by gender. Gender difference was presented with risk ratio (reporting rate ratio) of women to men. Antidiabetic agent-associated AEs were more frequently reported by women than men throughout body organs and drug classes. 13 out of 17 system organ class level disorders with significant gender differences were reported more often by women than men. By drug class, gender-specific reporting rates were observed in most of the drug classes, especially in newer classes such as glucagon-like peptide-1 analog (GLP1-RA), sodium glucose co-transporter-2 inhibitor (SGLT2i), and thiazolidinedione (TZD). Looking into preferred term level for each drug class, women dominated the reports of class-specific AEs of newer antidiabetic drugs such as urinary tract/genital infection (all reported by women) in SGLT2i, edema in TZD (risk ratio (RR) 12.56), and hyperglycemia in insulin users (RR 15.35). Gender differences in antidiabetic-associated AE reporting often attributed to women. Explanations for these different report levels by gender should be further investigated.

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Sex differences in diabetes and kidney disease: mechanisms and consequences

Cited by 92 publications

References 71 publications

Sex Differences in Diabetic Kidney Disease

Sex Differences in Diabetic Kidney Disease

Sex Differences in Urate Handling

Gender differences in adverse event reports associated with antidiabetic drugs

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