Sex Differences in the Progression of Metabolic Risk Factors in Diabetes Development

Yoshida, Yilin; Chen, Zhipeng; Baudier, Robin L.; Krousel‐Wood, Marie; Anderson, Amanda H.; Fonseca, Vivian; Mauvais-Jarvis, Franck

doi:10.1001/jamanetworkopen.2022.22070

Cited by 24 publications

(18 citation statements)

References 5 publications

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“…Importantly, sex differences have been observed for the aetiology and progression of cardiometabolic risk factors ( Gerdts and Regitz-Zagrosek, 2019 , Yoshida et al, 2022 ) and their relation to the brain ( Alqarni et al, 2021 , Subramaniapillai et al, 2021 , Subramaniapillai et al, 2022 , Than et al, 2022 ), illustrating the critical need for sex-specific studies ( Miller and Spencer, 2014 , Shansky and Murphy, 2021 , Taylor et al, 2019 ). Further research is necessary to understand the complex interplay of mechanisms that contribute to risk for cardiometabolic and neurodegenerative diseases in post-menopausal females ( Christensen and Pike, 2015 ), and how preventive measures such as physical exercise and hormone replacement therapy can be optimised to moderate risk.…”

Section: Discussionmentioning

confidence: 99%

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Schindler

Subramaniapillai

Barth

et al. 2022

NeuroImage: Clinical

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Section: Discussionmentioning

confidence: 99%

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Schindler

Subramaniapillai

Barth

et al. 2022

NeuroImage: Clinical

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Section: Discussionmentioning

confidence: 99%

“…50 Analysis of data from the ARIC Study (Atherosclerosis Risk in Communities) revealed that women experienced a greater increase in metabolic syndrome severity, central adiposity, and triglycerides than men in the prediabetes state, which may explain women's disadvantage in diabetic cardiovascular disease risk. 51 No-reflow after recanalization therapy has been reported in many clinical trials. [16][17][18] Our present data, on the other hand, show that the capillary reperfusion in penumbra in control mice did not differ from baseline at 24 hours post-MCAO.…”

Section: Go Red For Womenmentioning

confidence: 99%

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Zhu

Davis

Allen

et al. 2023

Stroke

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Background: Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO). Methods: Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography–based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining. Results: Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 ( P <0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls ( P <0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 ( P <0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls ( P <0.05). Conclusions: DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

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“…The factors contributing to sex-related differences in relative risk of CV events is still a subject of debate. It has been suggested that deterioration in glucose homeostasis from normal glucose tolerance to prediabetes to overt T2DM is associated with worsening in metabolic risk pro le and target organ damage in women than men (5,(11)(12)(13)(14)(15). CV risk factors progress during menopausal transition, determining greater accumulation of fat in visceral and ectopic tissues and aggravating insulin resistance, in ammation and dyslipidemia in women with T2DM (16).…”

Section: Introductionmentioning

confidence: 99%

“…CV risk factors progress during menopausal transition, determining greater accumulation of fat in visceral and ectopic tissues and aggravating insulin resistance, in ammation and dyslipidemia in women with T2DM (16). Moreover, it has been hypothesized that hyperglycaemia has a stronger effect on CV risk factors in women than men (5,(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects

Succurro,

Vizza,

Cicone

et al. 2023

Preprint

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Background Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects. Methods we aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26). Results Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% decrease in myocardial MRGlu (P = 0.04) and women with T2DM a 74% decrease (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% reduction in myocardial MRGlu (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association. Conclusions Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.

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Sex Differences in the Progression of Metabolic Risk Factors in Diabetes Development

Abstract: This cohort study uses data from the Atherosclerosis Risk in Communities (ARIC) Study to investigate whether the increase in metabolic syndrome severity is more pronounced in women than men and whether the sex difference varies by race.

Cited by 24 publications

References 5 publications

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice

Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects

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