This chapter gives an overview of nontraditional associations of insulin and diabetes with physiological conditions. It has been reported that, abnormal glucose metabolism leads to hypothyroidism or hyperthyroidism. Insulin resistance is the central metabolic abnormality of polycystic ovary syndrome, which is also a known risk factor for cardiovascular diseases. Osteocalcin, secreted from osteoblasts plays an important role in insulin secretion and insulin sensitivity. The decrease in average duration of sleep influences in obesity and type 2 diabetes mellitus. Sleep lose also affect glucose metabolism through increased sympathetic activity, increased secretion of cortisol and reduces glucose uptake by muscle. Recent clinical and biochemical studies have shown that physical exercise helps in postponing the onset of type 2 diabetes and also prevents cancer. Incretins secreted by the gastrointestinal tract assist in glucose metabolism and it has extra-glycemic actions. Insulin is not only important for glucose metabolism but also perform a role in central nervous system.