Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study

Megumi Oshima; Yasunori Iwata; Tadashi Toyama; Shinji Kitajima; Akinori Hara; Norihiko Sakai; Miho Shimizu; Kengo Furuichi; Masakazu Haneda; Tetsuya Babazono; Hiroki Yokoyama; Kunitoshi Iseki; Shinichi Araki; Toshiharu Ninomiya; Shigeko Hara; Yoshiki Suzuki; Masayuki Iwano; Eiji Kusano; Tatsumi Moriya; Hiroaki Satoh; Hiroyuki Nakamura; Hirofumi Makino; Takashi Wada

doi:10.1111/1753-0407.13367

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study

J Diabetes. 2023 Mar;15(3):246-254. doi: 10.1111/1753-0407.13367. Epub 2023 Feb 13.

Authors

Megumi Oshima¹, Yasunori Iwata¹, Tadashi Toyama^{1

2}, Shinji Kitajima¹, Akinori Hara^{1

3}, Norihiko Sakai¹, Miho Shimizu¹, Kengo Furuichi⁴, Masakazu Haneda⁵, Tetsuya Babazono⁶, Hiroki Yokoyama⁷, Kunitoshi Iseki⁸, Shinichi Araki⁹, Toshiharu Ninomiya¹⁰, Shigeko Hara^{11

12}, Yoshiki Suzuki¹³, Masayuki Iwano¹⁴, Eiji Kusano¹⁵, Tatsumi Moriya¹⁶, Hiroaki Satoh¹⁷, Hiroyuki Nakamura², Hirofumi Makino¹⁸, Takashi Wada¹

Affiliations

¹ Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan.
² Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan.
³ Department of Environmental and Preventive Medicine, Kanazawa University, Kanazawa, Japan.
⁴ Department of Nephrology, Kanazawa Medical University, Uchinada, Japan.
⁵ Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.
⁶ Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
⁷ Jiyugaoka Medical Clinic, Internal Medicine, Obihiro, Japan.
⁸ Okinawa Heart and Renal Association, Naha, Japan.
⁹ Division of Nephrology, Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
¹⁰ Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹¹ Center of Health Management, Toranomon Hospital, Tokyo, Japan.
¹² Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
¹³ Niigata University Medical and Dental Hospital, Niigata, Japan.
¹⁴ Department of Nephrology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
¹⁵ Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Tochigi, Japan.
¹⁶ Health Care Center, Kitasato University, Sagamihara, Japan.
¹⁷ Department of Diabetes and Endocrinology, Juntendo University Urayasu Hospital, Chiba, Japan.
¹⁸ Okayama University, Okayama, Japan.

Abstract
in English, Chinese

Background: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes.

Methods: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models.

Results: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups.

Conclusions: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

背景: 本研究调查了2型糖尿病患者中性别差异对终末期肾脏疾病(ESKD)和死亡风险的影响, 以及性别对相关因素的调节效应。方法: 这项多中心观察性队列研究包括4,328名2型糖尿病患者。使用Cox比例风险回归模型调整基线协变量, 估计性别对ESKD和死亡的风险比(HR)和95%置信区间(CI)。为评估风险调节, 使用Cox比例风险回归和泊松回归模型比较性别在患者特征上对ESKD和死亡的风险比和发生率。结果: 在中位随访7年期间, 276名患者(男性70%)出现了ESKD, 而241名患者(男性68%)死亡。在调整多个协变量后, 男性相比女性患ESKD(HR 1.34; 95% CI 1.02, 1.75; p = 0.034)和死亡(HR 1.64; 95% CI 1.24, 2.16; p = 0.001)的风险更高。在微量白蛋白尿患者中, 相比于无蛋白尿和高度蛋白尿的患者, 男性相比女性患ESKD的风险要高得多(交互作用p值为0.04)。在约为300 mg/g的蛋白尿患者中, 男性的发病率也比女性高。在基线患者亚组中, 没有发现性别和死亡的关联差异。结论:在2型糖尿病患者中, 男性相比女性患ESKD和死亡的风险更高。中度增加的蛋白尿与性别在发展ESKD方面的差异密切相关。.

Keywords: 2型糖尿病; albuminuria; death; end-stage kidney disease; sex difference; type 2 diabetes; 性别差异; 死亡; 白蛋白尿; 终末期肾脏疾病.

Publication types

Multicenter Study
Observational Study

MeSH terms

Albuminuria / complications
Albuminuria / etiology
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / epidemiology
Female
Humans
Kidney Failure, Chronic* / epidemiology
Kidney Failure, Chronic* / etiology
Male
Retrospective Studies
Risk Factors
Sex Characteristics

Abstract in English, Chinese

Publication types

MeSH terms

Abstract
in English, Chinese