Overview of Atypical Diabetes

Abstract

Although type 1 diabetes mellitus and, to a lesser extent, type 2 diabetes mellitus, are the prevailing forms of diabetes in youth, atypical forms of diabetes are not uncommon and may require etiology-specific therapies. By some estimates, up to 6.5% of children with diabetes have monogenic forms. Mitochondrial diabetes and cystic fibrosis related diabetes are less common but often noted in the underlying disease. Atypical diabetes should be considered in patients with a known disorder associated with diabetes, aged less than 25 years with nonautoimmune diabetes and without typical characteristics of type 2 diabetes mellitus, and/or with comorbidities associated with atypical diabetes.

Keywords: Atypical diabetes; Cystic fibrosis–related diabetes (CFRD); Maturity-onset diabetes of the young (MODY); Mitochondrial diabetes; Monogenic diabetes; Neonatal diabetes.

Fig. 1.

Diagnostic algorithm for atypical diabetes. GU, genitourinary; Hx, History.

Fig. 2.

Mechanisms of monogenic diabetes. In this schematic of a pancreatic β cell, the genes known to cause monogenic diabetes are shown in red. Some mitochondrial disorders also are known to cause diabetes, as reviewed in mitochondrial diabetes section.

Fig. 3.

Plasma glucose (A) and insulin secretory rates (B) in response to the mixed-meal tolerance test in subjects with pancreatic insufficient (PI) CF. Individuals were categorized based on a preceding OGTT (EGI, early glucose intolerance [plasma glucose at 1 hour greater than or equal to 155 mg/dL and plasma glucose at 2 hours less than or equal to140 mg/dL]; NGT, normal glucose tolerance). Significant decline in β-cell secretory capacity is evident in PI-EGI. (From Nyirjesy SC, Sheikh S, Hadjiliadis D, et al. β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL. Pediatr Diabetes. 2018;19(7):1173–1182; with permission.)