Sex Differences in the Burden and Complications of Diabetes

Purpose of the Review: To review the latest evidence on sex differences in the burden and complications of diabetes and discuss the potential explanations for the sex differences described. Recent Findings: Diabetes is a strong risk factor for vascular disease, with compelling evidence that the relative risks of vascular diseases conferred by diabetes are considerably greater in women than men. The mechanisms underpinning women’s excess relative risk of vascular disease from diabetes are unknown. Sex differences in the health care provided for the prevention, management, and treatment of diabetes and its complications could contribute to women’s greater excess relative risks of diabetes complications. However, since the excess risk of vascular disease is not seen for other major vascular risk factors, inherent biological factors may be more likely to be involved. In addition to other cardiometabolic pathways, the sex dimorphism in body composition and fat distribution may be particularly important in explaining women’s greater excess risk of the vascular complications of diabetes. Summary: There is strong evidence to suggest that diabetes is a stronger risk factor for vascular disease in women than men. Although several mechanisms may be involved, further research is needed to provide new and deeper insights into the mechanisms underpinning sex differences in the association between diabetes and vascular diseases. Such research will inform patients, health care professionals, and policy makers to ensure that women are not disproportionately affected by diabetes, and will help to reduce the burden in both sexes

Obesity as a risk factor for COVID-19 mortality in women and men in the UK biobank: Comparisons with influenza/pneumonia and coronary heart disease

Obesity is associated with severe COVID-19 outcomes, yet, it is unclear whether the risk of COVID-19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID-19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502 493 individuals (54% women), of whom 410 (36% women) died from COVID-19, 549 (36% women) died from influenza/pneumonia and 3355 (19% women) died from CHD. A higher body mass index (BMI), waist circumference, waist-to-hip ratio and waist-to-height ratio were each associated with a greater risk of death from COVID-19, influenza/pneumonia and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID-19 mortality in women than men; the women-to-men ratio of hazard ratios was 1.20 (95% confidence interval 1.00; 1.43). This study demonstrates the role of obesity in COVID-19 mortality and shows that the relative effects of a higher BMI on COVID-19 mortality may be stronger in women than men

Social deprivation as a risk factor for COVID-19 mortality among women and men in the UK Biobank: nature of risk and context suggests that social interventions are essential to mitigate the effects of future pandemics

Objectives To investigate sex differences in the effects of social deprivation on COVID-19 mortality and to place these effects in context with other diseases. Design Prospective population-based study. Setting UK Biobank. Participants 501 865 participants (54% women). Main outcome measure COVID-19 as the underlying cause of death. Results Of 472 946 participants alive when COVID-19 was first apparent in the UK (taken as 1 February 2020), 217 (34% women) died from COVID-19 over the next 10 months, resulting in an incidence, per 100 000 person years, of 100.65 (95% CI 79.47 to 121.84) for women and 228.59 (95% CI 194.88 to 262.30) for men. Greater social deprivation, quantified using the Townsend Deprivation Score, was associated with greater risk of fatal COVD-19. Adjusted for age and ethnicity, HRs for women and men, comparing those in the most with the least deprived national fifths, were 3.66 (2.82 to 4.75) for women and 3.00 (2.46 to 3.66) for men. Adjustments for key baseline lifestyle factors attenuated these HRs to 2.20 (1.63 to 2.96) and 2.62 (2.12 to 3.24), respectively. There was evidence of a log-linear trend in the deprivation–fatal COVID-19 association, of similar magnitude to the equivalent trends for the associations between deprivation and fatal influenza or pneumonia and fatal cardiovascular disease. For all three causes of death, there was no evidence of a sex difference in the associations. Conclusions Higher social deprivation is a risk factor for death from COVID-19 on a continuous scale, with two to three times the risk in the most disadvantaged 20% compared with the least. Similarities between the social gradients in COVID-19, influenza/pneumonia and cardiovascular disease mortality, the lack of sex differences in these effects, and the partial mediation of lifestyle factors suggest that better social policies are crucial to alleviate the general medical burden, including from the current, and potential future, viral pandemics

Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events

Aims/hypothesis: Diabetes has been shown to be a risk factor for some cancers. Whether diabetes confers the same excess risk of cancer, overall and by site, in women and men is unknown. Methods: A systematic search was performed in PubMed for cohort studies published up to December 2016. Selected studies reported sex-specific relative risk (RR) estimates for the association between diabetes and cancer adjusted at least for age in both sexes. Random-effects meta-analyses with inverse-variance weighting were used to obtain pooled sex-specific RRs and women-to-men ratios of RRs (RRRs) for all-site and site-specific cancers. Results: Data on all-site cancer events (incident or fatal only) were available from 121 cohorts (19,239,302 individuals; 1,082,592 events). The pooled adjusted RR for all-site cancer associated with diabetes was 1.27 (95% CI 1.21, 1.32) in women and 1.19 (1.13, 1.25) in men. Women with diabetes had ~6% greater risk compared with men with diabetes (the pooled RRR was 1.06, 95% CI 1.03, 1.09). Corresponding pooled RRRs were 1.10 (1.07, 1.13) for all-site cancer incidence and 1.03 (0.99, 1.06) for all-site cancer mortality. Diabetes also conferred a significantly greater RR in women than men for oral, stomach and kidney cancer, and for leukaemia, but a lower RR for liver cancer. Conclusions/interpretation: Diabetes is a risk factor for all-site cancer for both women and men, but the excess risk of cancer associated with diabetes is slightly greater for women than men. The direction and magnitude of sex differences varies by location of the cancer

Obesity as a risk factor for COVID-19 mortality in women and men in the UK Biobank: comparisons with influenza/pneumonia and coronary heart disease

Obesity is associated with severe COVID-19 outcomes, yet, it unclear whether the risk of COVID-19 mortality associated with obesity is similar between the sexes. We used data from the UK Biobank to assess the risk of COVID-19 mortality associated with various anthropometric measures in women and men. To put these results in context, we also compared these estimates with those for mortality from influenza/pneumonia and coronary heart disease (CHD). The analyses included 502,493 individuals (54% women), of whom 410 (36% women) died of COVID-19, 549 (36% women) died of influenza/pneumonia, and 3355 (19% women) died of CHD. A higher BMI, waist circumference, waist-to-hip ratio, and waist-to-height ratio were each associated with a greater risk of death from COVID-19, influenza/pneumonia, and CHD in both sexes, with the exception of the association between higher BMI and the risk of influenza/pneumonia death in men. A higher BMI was associated with a stronger risk of COVID-19 mortality in women than men; the women-to-men ratio of hazard ratios was 1.20 (95% confidence interval: 1.00; 1.43). This study demonstrates the role of obesity in COVID-19 mortality and shows that the relative effects of a higher BMI on COVID-19 mortality may be stronger in women than men. This article is protected by copyright. All rights reserved

Duration of diabetes and the risk of major cardiovascular events in women and men: A prospective cohort study of UK Biobank participants

Aims: Diabetes has been associated with a greater excess risk of cardiovascular disease (CVD) in women than men. We investigated whether there are also sex differences in the association of diabetes duration and the risk of CVD. Methods: Data were used from 18,961 (40% women) individuals with type 2 diabetes, without a history of CVD, in the UK Biobank. Sex-specific incidence rates were calculated by diabetes duration. Cox proportional hazards analyses estimated multiple-adjusted sex-specific hazard ratios (HR) and women-to-men ratio of HRs (RHR). Results: Over a median follow-up of 11 years, 1,506 (29% women) CVD events were documented. Compared with men, women had lower multiple-adjusted incidence rates of CVD per 10,000 person-years for all categories of diabetes duration. Duration of diabetes was associated with an increased risk of CVD in both sexes. A 5-year increase in diabetes duration was associated with an approximately similar excess risk of about 20% for each of the three endpoints, in both sexes. Conclusions/Interpretation: The increased risk of CVD associated with longer duration of diabetes is similar in women and men, and thus cannot explain the higher excess risk from diabetes in women in this study population

Sex differences in the association between major cardiovascular risk factors in midlife and dementia: a cohort study using data from the UK Biobank

Background: Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods: Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results: 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions: Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference

Intimate partner violence during the COVID-19 pandemic in Western and Southern European countries

Background: Intimate partner violence (IPV) is a significant problem with several negative health outcomes. Disasters are linked to increased IPV, but little is known about reporting of and strategies to address IPV during the COVID-19 pandemic. This review maps the IPV reporting during the pandemic and interventions to prevent and respond to IPV in 11 Western and Southern European countries. Methods: Government websites, news articles and pre-prints were searched using the terms 'domestic violence' or 'violence' in combination with 'Covid' or 'Corona'. Embase, PubMed, Scopus and Google Scholar were searched using the terms 'domestic violence' and 'partner violence' and 'interventions'. Results: Six countries showed an increase in domestic violence reports (Austria, Belgium, France, Ireland, Spain and UK), two countries a drop (Italy and Portugal), two countries showed no change (The Netherlands and Switzerland) and one country did not provide comparative data (Germany). Common measures to address IPV were starting a campaign (nine countries), creating online support (seven), more funding for alternative accommodation (seven) and support (eight) and use of a code word (four). Conclusions: IPV reports or helpline calls in Western and Southern European countries in the first weeks of COVID-19 measures increased in six countries, remained the same in two countries and showed a decrease in two countries. While this review cannot ascertain the impact of the measures taken by the countries during the pandemic and beyond, this mapping provides a foundation for future research, and an opportunity to trace the efficacy of these strategies

Serum lipid traits and the risk of dementia: A cohort study of 254,575 women and 214,891 men in the UK Biobank

Background: Serum lipid traits are associated with cardiovascular disease, but uncertainty remains regarding their associations with dementia. Methods: From 2006 to 2010, 254,575 women and 214,891 men were included from the UK Biobank. Cox regression estimated overall and sex-specific hazard ratios (HRs) for apolipoprotein A (ApoA), apolipoprotein B (ApoB), HDL, LDL, total cholesterol, triglycerides, lipoprotein A, and various lipid ratios, by quarters and standard deviation (SD) higher, associated with all-cause dementia, Alzheimer's disease (AD) and vascular dementia (VaD). Subgroup analyses by age and social deprivation were conducted. Findings: Over 11·8 years (median), 3734 all-cause dementia (1,716 women), 1231 AD and 929 VaD were recorded. Compared to respective lowest quarters, highest quarter of ApoA was associated with lower dementia risk (HR, [95% confidence interval (95% CI)]: 0·77 [0·69, 0·86]) while the highest quarter of ApoB was associated with greater risk (HR, 1·12 [1·01, 1·24]). Higher HDL/ApoA and ApoB/ApoA, were associated with greater risk of dementia (HR, 1·12 [1·00, 1·25], per standard deviation (SD), 1.23 [1·11, 1·37], per SD, respectively), LDL/ApoB was inversely associated (HR, 0·85 [0·76, 0·94], per SD. Higher triglycerides was associated with higher dementia risk in <60 years, but the inverse was observed for ≥60 years. Similar associations were observed for VaD and AD. Interpretation: Apolipoproteins, and their ratios, were associated with the risk of dementia. It may be prudent to consider apolipoproteins, along with circulating cholesterol, when assessing dementia risk. Funding: University of New South Wales, UK Medical Research Council, and the Australian National Health and Medical Research Council