Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors

Meloni, Antonella; Dessalvi, Christian Cadeddu; Cugusi, Lucia; Donataccio, Maria Pia; Deidda, Martino; Sciomer, Susanna; Gallina, Sabina; Vassalle, Cristina; Moscucci, Federica; Mercuro, Giuseppe; Maffei, Silvia

doi:10.3390/ijms24021588

Cited by 24 publications

(17 citation statements)

References 166 publications

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“…The Atherosclerosis Risk in Communities study showed that metabolic disorders have higher levels of prognostic significance for CVD in women than in men, 48 a finding that is consistent with the greater impact of the components of metabolic syndrome in women than in men. 49 Thus, careful identification of sexspecific risk factors is not a mere formality but a vital cornerstone of full comprehension of atherosclerosis and cardiometabolic diseases.…”

Section: Discussionmentioning

confidence: 99%

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Huang,

Liu,

Wei

et al. 2024

Diabetes Metabolism Res

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BackgroundEvidence of the effects of metabolically healthy obesity (MHO) on atherosclerosis is limited; the transition effects of metabolic health and obesity phenotypes have been ignored. We examined the association between metabolic health and the transition to atherosclerosis risk across body mass index (BMI) categories in a community population.MethodsThis cross‐sectional study was based on a national representative survey that included 50,885 community participants aged ≥40 years. It was conducted from 01 December 2017 to 31 December 2020, in 13 urban and 13 rural regions across Hunan China. Metabolic health was defined as meeting less than three abnormalities in blood pressure, glucose, high‐density lipoprotein cholesterol, triglycerides, or waist circumference. The participants were cross‐classified at baseline based on their metabolic health and obesity. In addition, the relationship between atherosclerosis and transitions in metabolic health status based on 4733 participants from baseline to the second survey after 2 years was considered. The relationship between metabolic health status and the risk of transition to Carotid atherosclerosis (CA) was assessed using logistic regression and Cox proportional hazards regression analyses.ResultsIn this study, the mean age of the participants was 60.7 years (standard deviation [SD], 10.91), 53.0% were female, and 51.2% had CA. As compared with metabolically healthy normal weight (MHN), those with MHO phenotype (odd ratio [OR] 1.10, 95% confidence interval [CI] 1.02–1.21), metabolically unhealthy normal weight (OR 1.27, 95% CI 1.19–1.35), metabolically unhealthy overweight (OR 1.41, 95% CI 1.33–1.48), and metabolically unhealthy obese (OR 1.54, 95% CI 1.44–1.64) had higher risk for CA. However, during the follow‐up of 2 years, almost 33% of the participants transitioned to a metabolically unhealthy status. As compared with stable healthy normal weight, transition from metabolically healthy to unhealthy status (hazard ratios [HR] 1.21, 95% [CI] 1.02–1.43) and stable metabolically unhealthy overweight or obesity (MUOO) (HR 1.32, 95% CI 1.17–1.48) were associated with higher risk of CA.ConclusionsIn the community population, obesity remains a risk factor for CA despite metabolic health. However, the risks were highest for metabolically unhealthy status across all BMI categories. A large proportion of metabolically healthy overweight or participants with obesity converts to an unhealthy phenotype over time, which is associated with an increased risk of CA.

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Section: Discussionmentioning

confidence: 99%

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Huang,

Liu,

Wei

et al. 2024

Diabetes Metabolism Res

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“…Diabetes represents one of the most widespread conditions today, affecting ∼10% of the adult population of the United States 96 . Dysglycemia is central to the pathology of diabetes, resulting in a significant proportion of the morbidity and mortality associated with the illness 97, 98 . Treatment with APDs, some of the most widely prescribed psychiatric medications today, is a key contributor to the development of dysglycemia and T2D 99, 100 .…”

Section: Discussionmentioning

confidence: 99%

Development of novel tools for dissection of central versus peripheral dopamine D₂-like receptor signaling in dysglycemia

Bonifazi,

Ellenberger,

Farino

et al. 2024

Preprint

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Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D2-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D2-like receptors including D2(D2R) and D3(D3R) receptors remain poorly understood. To address this, we developed new pharmacological tools, D2-like receptor agonists with diminished and delayed blood-brain barrier capability, to selectively manipulate D2R/D3R signaling in the periphery. We designated bromocriptine methiodide (BrMeI), a quaternary methiodide analogue of D2/3R agonist and diabetes drug bromocriptine, as our lead compound based on preservation of D2R/D3R binding and functional efficacy. We then used BrMeI and unmodified bromocriptine to dissect relative contributions of CNS versus peripheral D2R/D3R signaling in treating dysglycemia. Systemic administration of bromocriptine, with unrestricted access to CNS and peripheral targets, significantly improved both insulin sensitivity and glucose tolerance in obese, dysglycemic micein vivo. In contrast, metabolic improvements were attenuated when access to bromocriptine was restricted either to the CNS through intracerebroventricular administration or delayed access to the CNS via BrMeI. Our findings demonstrate that the coordinated actions of both CNS and peripheral D2-like receptors are required for correcting dysglycemia. Ultimately, the development of a first-generation of drugs designed to selectively target the periphery provides a blueprint for dissecting mechanisms of central versus peripheral DA signaling and paves the way for novel strategies to treat dysglycemia.

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“…Another study showed that earlier age at menarche was associated with obesity and poor glycemic control in patients with type 2 diabetes [ 49 ]. Menopause transition and its incidental hormonal changes have also been associated with unfavorable changes in lipids, accumulation of abdominal adiposity, and increased blood glucose [ 50 ], and may contribute to the observed sex differences. Sex-related differences in lifestyle behaviors and psychological factors could also contribute to the sex difference in cardiovascular risk factor control.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in cardiovascular risk, lifestyle, and psychological factors in patients with type 2 diabetes: the Fukuoka Diabetes Registry

et al. 2023

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Background The excess risk of cardiovascular diseases associated with diabetes is greater in women than in men. The present study aimed to examine sex differences in the control of cardiovascular risk factors, as well as lifestyle and psychological factors, in patients with type 2 diabetes. Methods A total of 4923 Japanese patients with type 2 diabetes were included in this cross-sectional study. Female/male differences in cardiovascular risk factor levels, and corresponding odds ratios for achieving recommended ranges for preventing cardiovascular diseases and having unhealthy lifestyle and psychological factors were computed by linear and logistic regression models. Results Women were less likely than men to achieve recommended ranges for glycated hemoglobin, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and obesity-related anthropometric indices such as body mass index and waist circumference, but were more likely than men to be on target for high-density lipoprotein cholesterol and triglycerides. Women were also more likely than men to have an unhealthy lifestyle and psychological factors, including less dietary fiber intake, less leisure-time physical activity, shorter sleep duration, more constipation, and more depressive symptoms. Similar findings were observed when the participants were subgrouped by age (< 65 and ≥ 65 years) and past history of cardiovascular disease. Conclusions We observed significant sex differences for a range of cardiovascular risk factors, as well as lifestyle and psychological factors, suggesting the importance of adopting a sex-specific approach for the daily clinical management of diabetes.

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Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors

Cited by 24 publications

References 166 publications

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Development of novel tools for dissection of central versus peripheral dopamine D₂-like receptor signaling in dysglycemia

Sex differences in cardiovascular risk, lifestyle, and psychological factors in patients with type 2 diabetes: the Fukuoka Diabetes Registry

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Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors

Cited by 24 publications

References 166 publications

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis

Development of novel tools for dissection of central versus peripheral dopamine D2-like receptor signaling in dysglycemia

Sex differences in cardiovascular risk, lifestyle, and psychological factors in patients with type 2 diabetes: the Fukuoka Diabetes Registry

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Development of novel tools for dissection of central versus peripheral dopamine D₂-like receptor signaling in dysglycemia