Glycated hemoglobin, diabetes mellitus and cardiovascular disease risk

Patients with diabetes mellitus are at increased risk of developing numerous serious health problems, especially cardiovascular disease (CVD). In this regard, it has been studied that high levels of glycated hemoglobin A1c (HbA1c) are an independent risk factor for CVD in diabetic and non-diabetic individuals. The relationship between HbA1c and CVD is somewhat complex, and the predictive value of HbA1c is uncertain. HbA1c shows the mean blood plasma glucose concentration over the previous three months and is relatively insensitive to short-term lifestyle changes. Research has evidenced a strong correlation between HbA1c and microvascular complications, such as diabetic retinopathy, thus HbA1c is widely used as a tool to monitor glycemic control and quality of care in patients with diabetes. Because of this common use, as well as the standardization methods for measuring HbA1c following the National Glycohemoglobin Standardization Program (NGSP) recommendations, the World Health Organization (WHO) recently recommended that HbA1c as a diagnostic test for diabetes mellitus. Accordingly, the guidelines of the American Diabetes Association 2009 (ADA) indicates that a HbA1c level above 6.5% is one of four diagnostic criteria for diabetes mellitus. Accuracy in the diagnosis of diabetes mellitus is an important issue for public health, since a correct diagnosis implies a better management and control of disease and its complications by the patient, but it also implies a better management of the resources used to improve the quality of life of these patients. Furthermore, in non-diabetic subjects the implementation of periodic measurements in blood tests of HbA1c is an important resource to control vascular indicators, such as arterial stiffness, and prevent complications micro- and macrovascular that they may appear before diabetes mellitus. Cardiovascular disease is one of the main diseases and one of the leading causes of death worldwide and, therefore, a problem for public health. Controlling HbA1c levels may help prevent and control CVD, in addition to diabetes mellitus, but also prevent cardiovascular mortality or even other causes. Therefore, an optimal level of HbA1c should be defined to be used by clinicians as a reference point for decision-making in the treatment of their patients, both diabetes mellitus and CVD. Moreover, as HbA1c is associated with several complications during pregnancy, especially in diabetic women, it would be useful to include this biomarker more frequently than usual monitoring in pregnancies and especially since the first antenatal visit. Finally, physical activity may be a useful mechanism to control HbA1c levels in the non-diabetic population and, in view of their association, prevent the onset of diabetes mellitus or CVD. It is necessary to define what type of exercise and what physical activity characteristics are the best to control these levels. Thus, several questions remain unclear regarding these important issues: i) which of the main glycemic measures is more accurate to identify diabetes-specific retinopathy, and in consequence diabetes mellitus; ii) which glycemic measures are more related to vascular complications; iii) which is the optimal HbA1c levels range to diminish CVD, cardiovascular mortality and all-cause mortality; iv) which is the relationship between HbA1c and complications of diabetes mellitus in vulnerable populations such as pregnant women; and v) which is the better type of physical activity to control HbA1c levels. The aim of this doctoral dissertation is to provide scientific evidence aimed to clarify these important questions, due to in view of the increasing incidence of diabetes mellitus in industrialized countries and the problems that cause its complications for patients and public health. With this aim, this doctoral dissertation is based on data from several systematics reviews and meta-analysis as well as data from the EVIDENT II project. This dissertation is part of the health and quality of life research line of the Health and Social Research Center of the University of Castilla-La Mancha in Cuenca, Spain, with the objective of studying the relationship between cardio-metabolic markers and body adiposity, vascular dysfunction and lifestyle (diet and physical activity). After this research work, this doctoral dissertation allows as to conclude that: - HbA1c test might be the most appropriate method for the diagnosis of type 2 diabetes in nonpregnant adults. - Arterial stiffness is associated with increased glycaemic levels in non-diabetic subjects, but better when they are measured using HbA1c levels. - HbA1c is a reliable risk factor for all-cause mortality and cardiovascular mortality in both non-diabetic and diabetic populations. - The increase of HbA1c is a predictor of preeclampsia in pregnant women with type 1 diabetes mellitus. - Physical activity interventions, specially resistance and alternative exercises, are effective for reducing HbA1c levels in non-diabetic populations