Diabetes Mellitus

Diabetes mellitus (DM) is a syndrome of disturbed energy metabolism, conveniently defined by the degree of hyperglycemia, resulting from an absolute or relative deficiency of insulin action. These concepts are the basis of the current classification as type 1 DM (T1DM), type 2 DM (T2DM), and other predominantly genetic forms. T1DM is a disease of insulin deficiency associated with autoimmune destruction of functional beta cells, a process begun by environmental insults in genetically determined susceptible hosts; it is the most common form of DM in childhood. In this chapter, we discuss the advances in understanding the genetics, pathophysiology, evolution, and treatment of all forms of DM, increasingly driven by technologic advances in glucose sensing, continuous glucose monitoring, and algorithmically regulated pumps that constitute an “artificial pancreas,” together with newer insulin preparations that facilitate simulating normal basal and bolus patterns in normal persons. T2DM is increasing in adolescents, particularly with obesity and prevalence in minority populations; obesity with insulin resistance has unmasked genetic defects in the regulation of insulin synthesis and secretion. For these individuals, lifestyle modification and weight loss remain the cornerstone of prevention and treatment. However, if this approach fails, newer modalities of treatment, such as a variety of incretin hormones, inhibitors of its destruction, agents that promote glucose excretion, and rarely bariatric surgery are revolutionizing treatment. Several of the genes involved in T2DM cause specific syndromes of monogenic diabetes at birth (neonatal DM) and during adolescence (maturity onset-diabetes of youth [MODY]), often misdiagnosed as T1- or T2DM and for which oral treatments rather than insulin injections are available and effective. Together, these advances are associated with better quality of life, less complications, and the promise of potential prevention of diabetes in childhood.