Sex differences in the risk of stroke and HbA1c among diabetic patients

Zhao, Weigang; Katzmarzyk, Peter T.; Horswell, Ronald; Wang, Yujie; Johnson, Jolene; Hu, Gang

doi:10.1007/s00125-014-3190-3

Cited by 49 publications

(41 citation statements)

References 39 publications

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“…This highlights the significance of the augmented increases in BP and MSNA that were observed in T2D patients and attributable in part to a heightened muscle metaboreflex activation. These findings are of vital importance given the incidence of myocardial infarction and stroke among T2D patients (5,26,28,57), and the number of common daily activities that involve an isometric muscle contraction component. Given our findings of a significant contribution of the muscle metaboreflex to greater pressor and sympathetic responses to isometric contractions in patients with T2D, future studies to identify the mechanism(s) responsible to target and reduce such hyperresponses are needed.…”

Section: Discussionmentioning

confidence: 96%

“…Likewise, exaggerated increases in exercise BP are related to adverse cardiovascular and cerebrovascular events both during and after physical activity (19,27,33). Indeed, the incidence of cardiovascular and cerebrovascular events such as myocardial infarction and stroke are significantly elevated among T2D patients (5,26,28,57). An augmented pressor response to exercise is also a predictor for the development of hypertension (HTN) (10,47), a common comorbidity among T2D patients (1,3,49,50).…”

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confidence: 99%

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Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

Holwerda

Restaino

Manrique

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Holwerda SW, Restaino RM, Manrique C, Lastra G, Fisher JP, Fadel PJ. Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients. Am J Physiol Heart Circ Physiol 310: H300 -H309, 2016. First published November 13, 2015; doi:10.1152/ajpheart.00636.2015.-Previous studies have reported exaggerated increases in arterial blood pressure during exercise in type 2 diabetes (T2D) patients. However, little is known regarding the underlying neural mechanism(s) involved. We hypothesized that T2D patients would exhibit an augmented muscle metaboreflex activation and this contributes to greater pressor and sympathetic responses during exercise. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured in 16 patients with T2D (8 normotensive and 8 hypertensive) and 10 healthy controls. Graded isolation of the muscle metaboreflex was achieved by postexercise ischemia (PEI) following static handgrip performed at 30% and 40% maximal voluntary contraction (MVC). A cold pressor test (CPT) was also performed as a generalized sympathoexcitatory stimulus. Increases in MAP and MSNA during 30 and 40% MVC handgrip were augmented in T2D patients compared with controls (P Ͻ 0.05), and these differences were maintained during PEI (MAP: 30% MVC PEI: T2D, ⌬16 Ϯ 2 mmHg vs. controls, ⌬8 Ϯ 1 mmHg; 40% MVC PEI: T2D, ⌬26 Ϯ 3 mmHg vs. controls, ⌬16 Ϯ 2 mmHg, both P Ͻ 0.05). MAP and MSNA responses to handgrip and PEI were not different between normotensive and hypertensive T2D patients (P Ͼ 0.05). Interestingly, MSNA responses were also greater in T2D patients compared with controls during the CPT (P Ͻ 0.05). Collectively, these findings indicate that muscle metaboreflex activation is augmented in T2D patients and this contributes, in part, to augmented pressor and sympathetic responses to exercise in this patient group. Greater CPT responses suggest that a heightened central sympathetic reactivity may be involved.exercise; hypertension; muscle sympathetic nerve activity; postexercise ischemia; blood pressure TYPE 2 DIABETES (T2D) patients exhibit exaggerated increases in arterial blood pressure (BP) during exercise (23,25,39,44).Augmented BP responses have been observed even during moderate-intensity handgrip (38), a level of isometric forearm muscle contraction that is equivalent to many activities of daily living such as opening jars, or carrying groceries. This is important because repeated surges in BP throughout the day have been related to increased cardiovascular risk (11, 37). Likewise, exaggerated increases in exercise BP are related to adverse cardiovascular and cerebrovascular events both during and after physical activity (19,27,33). Indeed, the incidence of cardiovascular and cerebrovascular events such as myocardial infarction and stroke are significantly elevated among T2D patients (5,26,28,57). An augmented pressor response to exercise is also a predictor for the development of hypertension (HTN) (10, 47), a common comorbidity amon...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

Holwerda

Restaino

Manrique

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…The intervention, however, lowered HbA 1c in women but not men ( Table 1). The HbA 1c level has been shown to have a graded positive association with risk of stroke in women [21] and mortality increases with HbA 1c in type 2 diabetes [22]. The lowering of HbA 1c could therefore contribute to explaining the positive outcome for women.…”

Section: Discussionmentioning

confidence: 99%

The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study

et al. 2015

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Aims/hypothesis The aim of this study was to assess gender differences in mortality and morbidity during 13 follow-up years after 6 years of structured personal care in patients with type 2 diabetes mellitus. Methods In the Diabetes Care in General Practice (DCGP) multicentre, cluster-randomised, controlled trial (ClinicalTrials.gov registration no. NCT01074762), 1,381 patients newly diagnosed with type 2 diabetes were randomised to receive 6 years of either structured personal care or routine care. The intervention included regular follow-up, individualised goal setting and continuing medical education of general practitioners participating in the intervention. Patients were re-examined at the end of intervention. This observational analysis followed 970 patients for 13 years thereafter using national registries. Outcomes were all-cause mortality, incidence of diabetes-related death, any diabetes-related endpoint, myocardial infarction, stroke, peripheral vascular disease and microvascular disease. Results In women, but not men, a lower HR for structured personal care vs routine care emerged for any diabetes-related endpoint (0.65, p=0.004, adjusted; 73.4 vs 107.7 events per 1,000 patient-years), diabetes-related death (0.70, p=0.031; 34.6 vs 45.7), all-cause mortality (0.74, p = 0.028; 55.5 vs 68.5) and stroke (0.59, p=0.038; 15.6 vs 28.9). This effect was different between men and women for diabetesrelated death (interaction p=0.015) and all-cause mortality (interaction p=0.005). Conclusions/interpretation Compared with routine care, structured personal diabetes care reduced all-cause mortality and diabetes-related death in women but not in men. This gender difference was also observed for any diabetes-related outcome and stroke but was not statistically significant after extensive multivariate adjustment. These observational results from a post hoc analysis of a randomised controlled trial cannot be explained by intermediate outcomes like HbA 1c alone, but involves complex social and cultural issues of gender. There is a need to rethink treatment schemes for both men and women to gain benefit from intensified treatment efforts.

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“…98 Importantly, strict blood glucose control has not been shown to decrease the incidence of stroke among people with DM. 99 …”

Section: Type Of Dm and Diabetic Controlmentioning

confidence: 99%

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

et al. 2015

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Currently, ≈1 in 13 people living in the United States has DM, and 90% to 95% of these individuals have type 2 DM (T2DM).2 Overall, the prevalence of T2DM is similar in women and men. In the United States, ≈12.6 million women (10.8%) and 13 million men (11.8%) ≥20 years of age are currently estimated to have T2DM. 2 Among individuals with T2DM, cardiovascular disease (CVD) is the leading cause of morbidity and mortality and accounts for >75% of hospitalizations and >50% of all deaths.3 Although nondiabetic women have fewer cardiovascular events than nondiabetic men of the same age, this advantage appears to be lost in the context of T2DM. 4,5 The reasons for this advantage are not entirely clear but are likely multifactorial with contributions from inherent physiological differences, including the impact of the sex hormones, differences in cardiovascular risk factors, and differences between the sexes in the diagnosis and treatment of DM and CVD. 6 In addition, there are racial and ethnic factors to consider because women of ethnic minority backgrounds have a higher prevalence of DM than non-Hispanic white (NHW) women.This scientific statement was designed to provide the current state of knowledge about sex differences in the cardiovascular consequences of DM, and it will identify areas that would benefit from further research because much is still unknown about sex differences in DM and CVD. Areas that are discussed include hormonal differences between the sexes and their possible effects on the interaction between DM and CVD, sex differences in epidemiology, ethnic and racial differences and risk factors for CVD in DM across the life span, sex differences in various types of CVD and heart failure, and sex differences in the effects of treatments for DM, including both medications and lifestyle. In addition, there is discussion about risk factors that are specific to women, including gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS), which affect CVD risk. Table 1 focuses on sex differences in CVD risk factors and outcomes in DM, and Table 2 provides information about sex differences in CVD treatments and interventions in DM. Table 3 contains some of the important ideas for research in sex differences in the cardiovascular consequences of DM. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on July 31, 2015, and the American Heart Association Executive Committee on September 5, 2015. A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By...

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Sex differences in the risk of stroke and HbA1c among diabetic patients

Cited by 49 publications

References 39 publications

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

Augmented pressor and sympathetic responses to skeletal muscle metaboreflex activation in type 2 diabetes patients

The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

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