7.1.1 Autoimmune Diabetes Mellitus
This form of diabetes, previously encompassed by the terms insulin-dependent diabetes, Type 1 diabetes, or juvenile-onset diabetes, results from autoimmune mediated destruction of the beta cells of the pancreas. The rate of destruction is quite variable, being rapid in some individuals and slow in others (24). The rapidly progressive form is commonly observed in children, but also may occur in adults (25). The slowly progressive form generally occurs in adults and is sometimes referred to as latent autoimmune diabetes in adults (LADA). Some patients, particularly children and adolescents, may present with ketoacidosis as the first manifestation of the disease (26). Others have modest fasting hyperglycaemia that can rapidly change to severe hyperglycaemia and/or ketoacidosis in the presence of infection or other stress. Still others, particularly adults, may retain residual beta-cell function, sufficient to prevent ketoacidosis, for many years (27). Individuals with this form of Type 1 diabetes often become dependent on insulin for survival eventually and are at risk for ketoacidosis (28). At this stage of the disease, there is little or no insulin secretion as manifested by low or undetectable levels of plasma C-peptide (29).
Markers of immune destruction, including islet cell autoantibodies, and/or autoantibodies to insulin, and autoantibodies to glutamic acid decarboxylase (GAD) are present in 85-90 % of individuals with Type 1 diabetes mellitus when fasting diabetic hyperglycaemia is initially detected (30). The peak incidence of this form of Type 1 diabetes occurs in childhood and adolescence, but the onset may occur at any age, ranging from childhood to the ninth decade of life (31). There is a genetic predisposition to autoimmune destruction of beta cells, and it is also related to environmental factors that are still poorly defined. Although patients are usually not obese when they present with this type of diabetes, the presence of obesity is not incompatible with the diagnosis. These patients may also have other autoimmune disorders such as Graves' disease, Hashimoto's thyroiditis, and Addison's disease (32).
7.1.2 Idiopathic
There are some forms of Type 1 diabetes which have no known aetiology. Some of these patients have permanent insulinopenia and are prone to ketoacidosis, but have no evidence of autoimmunity (33). This form of diabetes is more common among individuals of African and Asian origin. In another form found in Africans an absolute requirement for insulin replacement therapy in affected patients may come and go, and patients periodically develop ketoacidosis (34).
Type 2 (predominantly insulin resistance with relative insulin deficiency
or predominantly an insulin secretory defect with/without insulin resistance)
Diabetes mellitus of this type previously encompassed non-insulin-dependent diabetes, or adult-onset diabetes. It is a term used for individuals who have relative (rather than absolute) insulin deficiency. People with this type of diabetes frequently are resistant to the action of insulin (35,36). At least initially, and often throughout their lifetime, these individuals do not need insulin treatment to survive. This form of diabetes is frequently undiagnosed for many years because the hyperglycaemia is often not severe enough to provoke noticeable symptoms of diabetes (37,38). Nevertheless, such patients are at increased risk of developing macrovascular and microvascular complications (37,38).
There are probably several different mechanisms which result in this form of diabetes, and it is likely that the number of people in this category will decrease in the future as identification of specific pathogenetic processes and genetic defects permits better differentiation and a more definitive classification with movement into "Other types". Although the specific aetiologies of this form of diabetes are not known, by definition autoimmune destruction of the pancreas does not occur and patients do not have other known specific causes of diabetes listed in Tables 3-5.
The majority of patients with this form of diabetes are obese, and obesity itself causes or aggravates insulin resistance (39,40). Many of those who are not obese by traditional weight criteria may have an increased percentage of body fat distributed predominantly in the abdominal region (41). Ketoacidosis is infrequent in this type of diabetes; when seen it usually arises in association with the stress of another illness such as infection (42,43). Whereas patients with this form of diabetes may have insulin levels that appear normal or elevated, the high blood glucose levels in these diabetic patients would be expected to result in even higher insulin values had their beta-cell function been normal (44). Thus, insulin secretion is defective and insufficient to compensate for the insulin resistance.
On the other hand, some individuals have essentially normal insulin action, but markedly impaired insulin secretion. Insulin sensitivity may be increased by weight reduction, increased physical activity, and/or pharmacological treatment of hyperglycaemia but is not restored to normal (45,46). The risk of developing Type 2 diabetes increases with age, obesity, and lack of physical activity (47,48). It occurs more frequently in women with prior GDM and in individuals with hypertension or dyslipidaemia. Its frequency varies in different racial/ethnic subgroups (47-50). It is often associated with strong familial, likely genetic, predisposition (49-51). However, the genetics of this form of diabetes are complex and not clearly defined.
Some patients who present with a clinical picture consistent with Type 2 diabetes have autoantibodies similar to those found in Type 1 diabetes, and may masquerade as Type 2 diabetes if antibody determinations are not made. Patients who are non-obese or who have relatives with Type 1 diabetes and who are of Northern European origin may be suspected of having late onset Type 1 diabetes
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