The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

Type 1 diabetes is a chronic metabolic disease whose aetiology and pathogenesis remain not completely understood. Most diabetic cases are complex diseases resulting from interactions between genetic and environmental determinants in genetically predisposed individuals. Genome-wide association studies allowed understanding a genetic architecture of many genetic loci with many variants of small effect. Hence, genetic risk modelling to derive prediction of individual risk and risk to relatives are difficult to reconcile. Testing for multiple antibodies can individuate individuals at very high risk for autoimmune type 1 diabetes with good sensitivity. However, currently no intervention can effectively prevent or delay diabetes, and awareness of risk is useless or even stressful. Moreover, both genetic risk and serum autoantibody profiling are uneconomical when applied in the general population. Over the years, our research efforts have sought primarily to gain a comprehensive understanding of the common phenotypic elements that characterise families with a sporadic case of type 1 diabetes. The chapter provides a research-based overview of these familial peculiarities that include multifaceted, easily detectable, clinical perturbations: physical (BMI), cardiovascular (blood pressure response to exercise and circadian blood pressure pattern), biochemical (fasting plasma glucose, HbA1c, lipids, homeostasis model assessment of insulin sensitivity, plasma markers of oxidative damage), cellular (cellular markers of oxidative damage, transplasma membrane electron transport systems, mirochondrial membrane potential), and immunological (lymphocyte subsets). First question: may insulin-resistance be their common denominator? Therefore, second question: could an early correction of one/some of these common clinical abnormalities modify the natural history of the disease and thence its epidemiology? A proper (more realistic) public health intervention (by general and family practitioners) should be designed beyond the conventional boundaries that have for so long limited the visual field