Type 1 diabetes

Abstract

Over the past decade, knowledge of the pathogenesis and natural history of type 1 diabetes has grown substantially, particularly with regard to disease prediction and heterogeneity, pancreatic pathology, and epidemiology. Technological improvements in insulin pumps and continuous glucose monitors help patients with type 1 diabetes manage the challenge of lifelong insulin administration. Agents that show promise for averting debilitating disease-associated complications have also been identified. However, despite broad organisational, intellectual, and fiscal investments, no means for preventing or curing type 1 diabetes exists, and, globally, the quality of diabetes management remains uneven. This Seminar discusses current progress in epidemiology, pathology, diagnosis, and treatment of type 1 diabetes, and prospects for an improved future for individuals with this disease.

Figure 1. Incidence of type 1 diabetes in children aged 0–14 years, by geographical region and over time

(A) Estimated global incidence of type 1 diabetes, by region, in 2011. (B) Time-based trends for the incidence of type 1 diabetes in children ages 0–14 years in areas with high or high-intermediate rates of disease.^–

Figure 2. Pathological characteristics of the pancreas in type 1 diabetes

(A) Islet infiltrate (ie, insulitis) seen in a patient with recent-onset type 1 diabetes. Immunohistochemistry shows the intra-islet presence of CD3-positive cells (brown) and glucagon-producing alpha cells (pink). Image courtesy of M Campbell Thompson, University of Florida, Gainsville, FL, USA. (B) Histological features of islets and (C) gross pathological characteristics of the pancreas associated with the natural history of type 1 diabetes (ie, preonset, onset, postonset).

Figure 3. Physiological contributions to the pathogenic processes that underlie type 1 diabetes

A series of defects emanating from (A) the bone marrow and thymus, (B) immune system, and (C) β cells collectively lead to loss of insulin production by autoimmune mechanisms. These actions are continuous throughout the natural history of type 1 diabetes. ^,– Teff=effector T cell. Treg=regulatory T cell APC=anaphase-promoting complex.

Figure 4. The natural history of type 1 diabetes—a 25-year-old concept revisited

A re-creation of the model of type 1 diabetes, originally proposed in 1986, is shown in black. Additions and conjures based on recent knowledge gains are shown in purple.

Figure 5. Closed-loop system for type 1 diabetes therapy (artificial pancreas)

(A) Prototype of a closed-loop system. (B) Components of a closed-loop system. Three potential delays in the system include glucose sensing in interstitial fluid, insulin absorption (depends on use of rapid vs regular insulin), and insulin action in peripheral tissues and liver.