**2. Epidemiology and pathophysiology of diabetes**

Diabetes is a spectrum of diseases characterized by a disorder in glucose metabolism leading to persistent hyperglycemia, with clinical manifestations varying according to disease etiology (**Table 1**).

Type 1 diabetes mellitus (DM) is an autoimmune disorder characterized by the generation of autoantibodies against β cells and the development of a localized inflammatory response with consequent islet destruction. Current models suggest that the disease progresses as a relapsing-remitting disease, with a nonlinear β cell mass loss at each relapse as a result of the imbalance between β cell proliferation and destruction, eventually leading to persistent hyperglycemia. At diagnosis, these patients may present with nearly normal serum concentrations of insulin and C-peptide but with a rapid decrease in the following 8–12 weeks.

Several autoantibodies have been described in patients with type 1 diabetes—antibodies to insulin (IAA), glutamic acid decarboxylase (GAD), Zinc transporter 8 antibodies (ZnT8A), and protein tyrosine phosphatase-like protein IA2 (IA2 or ICA512). The risk for overt diabetes better correlates with the number of autoantibodies present rather than the titter of a single antibody [1].

Type 1 diabetes usually presents at a young age (6 months to 25 years old), and there is a geographical variation, with a tendency toward an increased incidence in developed countries—, as


**Table 1.** Etiology and clinical presentation of diabetes.

recognized by the World Health Organization (WHO), this may be due to differences in registry data, since few data that exist from sub-Saharian Africa, South America, and Asia [2].

A genetic predisposition has been identified with an increased risk for the disease in siblings and offspring of diabetics. There is an increased incidence in patients with human leukocyte antigen–antigen D related (HLA DR)\*03 and DR\*04.

Type 2 diabetes is characterized by peripheral cells insulin resistance with a consequent persistent hyperglycemia. Insulin production and secretion is often maintained with normal or high serum insulin and C-peptide. It usually presents in adulthood and is often associated with obesity and a sedentary lifestyle.

According to the WHO, diabetes incidence and prevalence is increasing [3] at a particularly alarming rate among children. This has led to a shift in the paradigm of age of presentation of type 2 diabetes with an ever-increasing incidence in young adults, and consequent presentation of diabetes complications at younger ages [4].

The first line of treatment for type 2 diabetes is lifestyle modification, followed by oral antidiabetic agents. The mechanism of action of oral agents is diverse, from reduction in glucose absorption, to increase in insulin secretion, stimulation of gluconeogenesis, or reduction of tubular reabsorption with an increase in urinary glucose excretion. Despite these alternatives, several patients still need exogenous insulin to achieve glycemic control. Chronic insulin resistance may lead to β cell exhaustion, and insulin and C-peptide levels may decrease below normal range in patients with long-standing type 2 diabetes.
