At the beginning of this book the results of the so called “The Predatorr Survey”, a Romanian epidemiological study, are commented. This survey indicates a high prevalence of metabolically healthy obese phenotype and a better overall metabolic profile in metabolically healthy obese individuals than that observed in lean and obese subjects with metabolic syndrome. The metabolically healthy phenotype may be the key to understanding the mechanisms that link obesity to cardiovascular and metabolic risk. Thus, it seems to be important to stratify obesity based on the metabolic phenotype in order to identify the subjects which need to be prioritized for early pharmacological therapy besides lifestyle optimisation (Chap. 1).
The enhanced generation and accumulation of advanced glycation endproducts (AGEs) have been linked to increased risk for vascular complications in diabetes. AGEs result from the nonenzymatic reaction of reducing sugars with proteins, lipids and nucleic acids potentially altering their function by disrupting molecular conformation, promoting crosslinking, altering enzyme activity, reducing their clearance and impairing receptor recognition. AGEs may also activate specific receptors, like the receptor for AGEs (RAGE), which is present on the surface of all cells relevant to vascular disease and diabetes complications, triggering oxidative stress, inflammation and apoptosis. Understanding the pathogenic mechanisms of AGEs is paramount for the development of therapeutic strategies (Chap. 2).
The most interesting connections between HbA1c and chronic complications of diabetes are evaluated. Several studies concluded that risk of vascular complications in diabetes begins to increase at an HbA1c level of 6.5%. In the Framingham Heart Study, one percentage point elevation in HbA1c was correlated with a 1.39 - fold increased risk of cardiovascular disease. Elevated HbA1c is independently related to cardiovascular disease even in subjects without a diabetes diagnosis (Chap. 3).
Individual deprivation, although not frequently explored in daily practice or epidemiological studies, can be an important risk factor for diabetic incidence, micro- and macrovascular complications. Nevertheless, concerns remain as to whether the management of diabetic patients of low socioeconomic status is different from that of a privileged patient, and how we can close this gap (Chap. 4).
