Type 1 Diabetes/IDDM
The incidence of IDDM varies considerably with geography and ethnicity. In Japan, China, and in African Americans the incidence (number of new cases per 100 000 person-years) in the age group of 0-14 years is below 5. In most European regions it is about 1020 per 100 000 person-years, and in Finland and Sardinia it is above 30 [2,9,10,11].
The highest incidence of IDDM is found in children below the age of 15, but IDDM or type 1 diabetes may become manifest at any age. The estimated incidence in adults is about half that observed in children of the respective population. However, the figure may be much higher if cases of LADA are included, which may comprise about 10% of all patients initially diagnosed as having type 2 diabetes mellitus [12]. Worldwide a trend to increasing incidence in children and adolescents has been observed [13–15]. According to a Finnish study the incidence is increasing more in younger than older age groups [16]. Firstborn children are at highest risk. The risk increases with the age of the mother [17].
Table 1.2 Shortened version of the classification of diabetes according to the Expert Committee on the Diagnosis and Classification of Diabetes mellitus [3]
| I. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency) A. Immune-mediated B. Idiopathic II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance) III. Other specific types A. Genetic defects of β-cell function B. Genetic defects in insulin action C. Disease of the exogenic pancreas D. Endocrinopathies E. Drug- or chemical-induced F. Infections G. Uncommon forms of immune-mediated diabetes H. Other genetic syndromes sometimes associated with diabetes IV. Gestational diabetes (GDM) |
Reliable data about the prevalence of IDDM/type 1 diabetes mellitus are not available. Type 1 diabetes is associated with genetic as well as environmental factors. The rising incidence can hardly be explained by a change in the gene pool, so environmental factors must be playing a major role. However, it is impossible at present to decide what these environmental factors are.
The life expectancy of IDDM subjects is reduced. The number of lost years of life depends on the age at diagnosis (it is highest in early-onset IDDM) and on the quality of care as well as on chronic complications [18–20]. In the USA, mortality “among males was 5.4 times higher and in females it was 11.5 times higher than in the total US population.” “Among people with age at diagnosis < 30 years, IDDM reduces life expectancy by at least 15 years.” In 70-90% the cause of death is related to diabetes [21]. In long-term type 1 diabetes vascular complications are the most important predictors and causes of death[22–24] (Table 1.3). In the USA, ketosis has been the cause of death in about 10% of people with IDDM who died at 0-44 years of age. Hypoglycemia may be the undiagnosed cause of sudden death. It was noted as an underlying cause of death in about 1 of 300 deaths due to diabetes [25]. Others have estimated that 2-4% of all deaths in IDDM subjects are due to hypoglycemia [26].
Type 2 Diabetes/NIDDM
Type 2 diabetes mellitus is by far the most common type of diabetes. By extrapolation from the incidence of diabetic retinopathy in recently diagnosed subjects it may be concluded that the disease will manifest a couple of years before it is diagnosed. Most cases are diagnosed in individuals under the age of 60 years. The highest prevalence is found in the age group of 65-75 years.
Since type 2 diabetes develops insidiously, it is difficult to determine its incidence. Most reliable are prevalence data of clinical NIDDM/type 2 diabetes and of impaired glucose tolerance (IGT), which is assumed to precede clinical NIDDM/type 2 diabetes. Considerable regional differences exist in the prevalence of NIDDM/type 2 diabetes depending on relative body weight, life style, ethnic origin, nutritional habits, social status, education, and the age structure of the population [27,28]. Type 2 diabetes/NIDDM used to be the disease of affluent societies in highly developed industrialized regions. This is no longer true. The highest prevalence is now found in Fiji, Micronesia, and among the Pima Indians. There is a worldwide trend towards both increasing prevalence and incidence and a lowering of the age at manifestation. It has been predicted that the number of diabetic subjects worldwide will double during the next two decades. This will be due not only to a rising incidence but also to increasing life expectancies in the growing world population.
Type 2 diabetes is associated with an increased mortality. In western countries the loss of life years is about 30% of normal life expectancy (Table 1.4). Because the NIDDM/type 2 diabetes population is older as a whole, the average absolute number of lost years is smaller than in type 1 diabetes and becomes insignificant in the very old. The main cause of death is cardiovascular disease [22,29] (Table 1.3).The association between blood glucose control and the risk of dying is rather weak [30].
Other types of diabetes mellitus, such as gestational diabetes mellitus (GDM), maturity-onset diabetes in the young (MODY), malnutrition-related diabetes mellitus (MRDM), and endocrine syndromes associated with diabetes mellitus will not be discussed in this chapter.
Type 1 Diabetes
More than 20 different regions of the human genome show some linkage with type 1 diabetes mellitus [31]. Many of these genes carry a risk, others protect.
The strongest linkage is seen for the major histo-compatibility complex, which is located on chromosome 6 (IDDM1 locus). The importance of some HLA class II genes (e.g., DR7, DR9, DQA1 0301, DQB1 0201) differs among ethnic groups [9], as may be true for HLA class I genes. The physiological role of HLA molecules is to present foreign and self antigens to T