Elsevier

Autoimmunity Reviews

Volume 9, Issue 5, March 2010, Pages A355-A365
Autoimmunity Reviews

The geoepidemiology of type 1 diabetes

https://doi.org/10.1016/j.autrev.2009.12.003Get rights and content

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absolute insulin deficiency resulting from the progressive immune-mediated destruction of pancreatic islet β cells. It is thought to be triggered by as yet unidentified environmental factors in genetically susceptible individuals, the major genetic contribution coming from loci within the HLA complex, in particular HLA class II. The worldwide incidence of T1D varies by at least 100-fold, being highest in Finland and Sardinia (Italy) and lowest in Venezuela and China. The incidence has been increasing worldwide at an annual rate of approximately 3%. While genetic factors are thought to explain some of the geographic variability in T1D occurrence, they cannot account for its rapidly increasing frequency. Instead, the declining proportion of newly diagnosed children with high-risk genotypes suggests that environmental pressures are now able to trigger T1D in genotypes that previously would not have developed the disease during childhood. Although comparisons between countries and regions with low and high-incidence rates have suggested that higher socioeconomic status and degree of urbanization are among the environmental factors that play a role in the rising incidence of T1D, the findings are too inconsistent to allow firm conclusions. Morbidity and mortality as well as causes of death also show considerable geographic variation. While glycemic control has been identified as a major predictor of the micro- and macrovascular complications of T1D and shows considerable geographical variability, it does not appear to be the only factor involved in the regional differences in complication rates. The role of genetics in susceptibility to nephropathy, retinopathy and other diabetic complications largely remains to be explored.

Introduction

Type 1 diabetes (T1D) is subdivided into type 1A (autoimmune) and type 1B (idiopathic). Here we use the term T1D to refer to the autoimmune type, which is characterized by immune-mediated destruction of pancreatic β cells resulting in absolute insulin deficiency. The development of T1D is thought to be triggered by environmental factors in genetically susceptible subjects. Although T1D is frequently called a disease of childhood, the majority of T1D cases present in adult life. Yet, data on incidence, genetics, the effectiveness of new therapeutic approaches and, to a lesser extent, acute and long-term morbidity and mortality are largely confined to childhood-onset T1D. This is regrettable since T1D patients with adult-onset differ from those with childhood-onset in terms of genetic, immunological, and clinical features. Yet little is known about how this affects the course of the disease, particularly the development of chronic complications and the risk of mortality associated with them.

The major chronic complications of T1D can be subdivided into microvascular (diabetic nephropathy, retinopathy, and neuropathy) and macrovascular complications, manifesting as cardiovascular disease, in particular ischemic heart disease, but also cerebrovascular disease, and peripheral vascular disease. The Diabetes Control and Prevention Trial (DCCT) and also the Epidemiology of Diabetes Interventions and Complications study along with other clinical trials showed that more intensive insulin therapy resulted in better glycemic control. This, in turn, was associated with a marked reduction in the long-term complications of T1D, in particular proliferative retinopathy (PDR), but also nephropathy, and cardiovascular disease. As a result, the trend in diabetes centers worldwide has been to intensify insulin treatment by using basal–bolus multiple daily injection regimens or continuous subcutaneous insulin infusion. New insulin analogues with fast, intermediate, or long action also are intended to provide more physiological metabolic control. In addition, self-monitoring of blood glucose (SMBG) or continuous glucose monitoring have become firmly established tools in improving glycemic control — at least in economically developed countries. Another advance in the care of T1D patients is the more aggressive treatment of comorbidities such as hypertension and dyslipidemia.

Section snippets

Epidemiology

The incidence of childhood-onset T1D in the age group 0–14 years varies more than 100-fold worldwide, with Finland and Sardinia (Italy) having the highest rates (> 40 and 37.8/105, respectively), whereas the lowest rates have been reported from Venezuela (0.1/105) and China (0.1–4.5/105), with other Asian countries also displaying a low frequency [1] (see also Table 1). Like Finland, the Scandinavian countries and Scotland have very high-incidence rates, while the occurrence is high in the UK and

Genetics

Several lines of evidence indicate that the risk of developing T1D is at least partially determined by genetics. These include the concordance between monozygotic twins, the familial clustering of T1D cases, and observations from migrant studies. The proband-wise concordance rates reported from population-based twin studies were 53% and 43% for Danish and Finnish monozygotic twins, respectively. Heritability was estimated at 72% and 88%, respectively. Familial aggregation of T1D, which may

Acute complications

There is large geographical variation of the incidence of diabetic ketoacidosis (DKA) at presentation. Relatively low frequencies of DKA at diagnosis have been reported for various ethnic groups in the 0–19-year age range in the USA: varying between 15.8% in the oldest age group to 28.9% in children aged 0–4 years in non-Hispanic whites; ranging from 16.7 (for ≥ 15 year-olds) to 30.8 (for 0–9-years-olds) in African-Americans; ∼ 25% overall in Hispanics; and between 26.1 and 33.3% for Asian and

Mortality

Reports from numerous countries indicate that the mortality risk in T1D has decreased over recent decades. Nonetheless, both absolute and relative mortality in T1D patients remain at least two-fold higher than in the respective control population, but the standardized mortality rates (SMRs) differ greatly between countries. This becomes most obvious in direct comparisons of patients diagnosed and followed during the same time periods. For example, in a WHO study that followed various cohorts

Take-home messages

  • The worldwide incidence of T1D varies at least 100-fold.

  • Some of this variation appears to be attributable to differential distribution of genetic risk determinants.

  • T1D incidence has been increasing at an annual rate of ∼ 3% throughout much of the world.

  • This rise in T1D incidence is best explained by increasing environmental pressures.

  • The environmental triggers or promoters of T1D have not been conclusively identified.

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