Due to population growth and ageing, diabetes is now among the 8 leading causes of death [1]. Thus, type 2 diabetes comprising the majority of diabetic patients is one of the most important NCDs and its steep rise and associated complications go along with mounting evidence of clinically important sex and gender differences [2]. Genetic background, lifestyle, epigenetics, and environment contribute to the pandemic increase with important biological and psychosocial risk factors of men and women. Overall, globally, more men are diagnosed with diabetes as there were 15.7 million more men than women with diabetes in 2015 [3]. There are large sex-ratio differences regarding diabetes across countries which parallel those of obesity, the most prominent risk factor in both sexes. Type 2 diabetes is more frequently and at a younger age and lower body-mass-index (BMI) diagnosed in males as men usually feature more visceral fat and higher degree of insulin resistance compared to women of comparable age and BMI. However, waist is a better predictor of diabetes and cardiovascular disease in women who also have a greater relative risk of cardiovascular complications and mortality in the presence of prediabetes, the metabolic syndrome, or overt diabetes [4, 5]. Altogether, diabetic women bear a greater risk to suffer and die from myocardial infarction or stroke than men in comparison to same sex nondiabetic subjects [6].
Diversities in biology, culture, lifestyle, and socioeconomic status impact sex dimorphism in clinical presentation of type 2 diabetes. Biological differences comprise differences in body composition, glucose and fat metabolism, energy balance, and neuroendocrine regulation [2]. In particular, reproductive history and reproductive factors are important for evaluation of diabetes and cardiovascular risk. Thus, women with early menarche, irregular cycles, or the PCOS were shown to be at higher risk. However, the most important risk factor in women appears to be gestational diabetes which affects approximately 10% of all pregnant women and is associated with both acute and long-term complications in mothers and offspring. Therefore, sex-specific guidelines for stroke prevention in women were recently released outlining the importance of gestational diabetes and preeclampsia as sex-specific risk factors and the impact of diabetes, depression, and psychosocial stress as risk factors particularly in females [7]. Differences in therapy and interventions further contribute to different outcomes in diabetic patients with greater disparities in women [8].
Therefore, the issue of prevention and therapy of cardiovascular disease is of utmost importance for health-related quality of life of diabetic women. To this end, this special series will cover interesting papers on this important topic summarizing current evidence and further expanding our present knowledge.
One paper describes the incidence of stroke and stroke subtypes derived from the stroke and diabetes surveillance system in China. L. Guo et al. report almost fourfold excess risk in diabetic patients, especially in females and particularly regarding the subtype cerebral infarction.
Another study by M. Leutner et al. analysed metabolic and vascular characteristics of treated hyperlipidemic men and women. Overall, vascular morphology, insulin sensitivity, and glucose tolerance did not differ between sexes although women had a more favourable lipid profile and better liver enzymes.
In addition, a review by G. T. Russo et al. will address the important topic of osteoporosis and fracture risk based on experimental and clinical evidence in men and women with diabetes. Both sex differences in pathophysiology and lifestyle and gender implications including the side effects of glucose-lowering drug therapies will be discussed.
Further, a review by S. Burlina et al. will present and discuss the current evidence of cardiovascular risk in women with gestational diabetes. This is important as this growing number of women could present an ideal group for sex-specific diabetes and cardiovascular prevention programs. Early identification of those women at the highest risk could reduce the burden of transgenerational diabetes.
We hope that this special series will further highlight the importance of cardiovascular risk in diabetic women, stimulate new research, and contribute to better awareness and care.
Alexandra Kautzky-Willer
Alexandra Kautzky-Willer
Giovannella Baggio
Giovannella Baggio
Maria Chiara Rossi
Maria Chiara Rossi
Annunziata Lapolla
Annunziata Lapolla
Giuseppina T. Russo
Giuseppina T. Russo
References
- 1.GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016;388(10053):1459–1544. doi: 10.1016/S0140-6736(16)31012-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kautzky-Willer A., Harreiter J., Pacini G. Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocrine Reviews. 2016;37(3):278–316. doi: 10.1210/er.2015-1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.International Diabetes Federation. IDF Diabetes Atlas. 7th edn. Brussels: International Diabetes Federation; 2015. [PubMed] [Google Scholar]
- 4.The EUGenMed, Cardiovascular Clinical Study Group, Regitz-Zagrosek V., Oertelt-Prigione S., et al. Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes. European Heart Journal. 2016;37(1):24–34. doi: 10.1093/eurheartj/ehv598. [DOI] [PubMed] [Google Scholar]
- 5.Sattar N. Gender aspects in type 2 diabetes mellitus and cardiometabolic risk. Best Practice & Research. Clinical Endocrinology & Metabolism. 2013;27(4):501–507. doi: 10.1016/j.beem.2013.05.006. [DOI] [PubMed] [Google Scholar]
- 6.Peters S. A., Huxley R. R., Sattar N., Woodward M. Sex differences in the excess risk of cardiovascular diseases associated with type 2 diabetes: potential explanations and clinical implications. Current Cardiovascular Risk Reports. 2015;9(7):p. 36. doi: 10.1007/s12170-015-0462-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bushnell C., McCullough L. Stroke prevention in women: synopsis of the 2014 American Heart Association/American Stroke Association guideline. Annals of Internal Medicine. 2014;160(12):853–857. doi: 10.7326/M14-0762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Regensteiner J. G., Golden S., Huebschmann A. G., et al. Sex differences in the cardiovascular consequences of diabetes mellitus: a scientific statement from the American Heart Association. Circulation. 2015;132(25):2424–2447. doi: 10.1161/CIR.0000000000000343. [DOI] [PubMed] [Google Scholar]