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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #2: Classification of Diabetes Mellitus and Other Categories of Glucose Intolerance Part 2 of 6

Dec 15, 2015


Type 1 process

Type 1 indicates the processes of β-cell destruction that may ultimately lead to diabetes in which insulin is required for survival in order to prevent the development of ketoacidosis, coma, and death.This category comprises:

  • Immune-mediated diabetes mellitus: This is the classical form of type 1 diabetes, which can occur at any age, and results from a cell-mediated autoimmune destruction of the pancreatic β cells. The type 1 process is characterized by the presence ofICA, anti-GAD, islet antigen 2 (IA2) or insulin autoantibodies which identify the autoimmune process associated with β-cell destruction [9]. Other autoimmune disorders such as Grave’s disease, Hashimoto’s thyroiditis and Addison’s disease may be associated with type 1 diabetes mellitus [9].

The rate of β-cell destruction is quite variable, typically being rapid in children and slower in adults. Typically, type 1 diabetes requires insulin therapy from the time of presentation in both adults and children, but a slowly progressive form, latent autoimmune diabetes in adults (LADA), is well described [8]. Blood glucose in LADA can initially be controlled by lifestyle change and oral hypoglycemic agents, and may therefore masquerade as type 2 diabetes. However, in comparison to the typical patient with type 2 diabetes, LADA patients are leaner and progress much more rapidly to requiring insulin. Importantly, markers of autoimmunity (most commonly anti-GAD antibodies) are present, and therefore LADA falls within type 1 autoimmune diabetes.

  • Idiopathic:There are some forms of type 1 diabetes which have no known etiology, and no evidence of autoimmunity. Some of these patients have permanent insulinopenia and are prone to ketoacidosis [10].This form is more common among individuals of African and Asian origin [11].

Type 2 process

Type 2 diabetes is the commonest form of diabetes and is characterized by disorders of insulin resistance and insulin secretion, either of which may be the predominant feature. Both are usually present at the time when diabetes is clinically manifest. Insulin levels may be normal or even elevated at the time when diabetes is diagnosed. However, in the setting of insulin resistance, these levels are inadequate to maintain normoglycemia. This relative insulin deficiency is what differentiates diabetic insulin-resistant individuals from normoglycemic insulin-resistant individuals. Indeed, it is noteworthy that, to date, the majority of the genes that have been associated with type 2 diabetes are related to insulin secretion, and not to insulin resistance [12].

At least initially, and often throughout their lifetime, these individuals do not need insulin treatment to survive [13]. Type 2 diabetes is frequently asymptomatic and undiagnosed for many years because the hyperglycemia is often not severe enough to provoke noticeable symptoms [14]. Nevertheless, such patients are at increased risk of developing macrovascular and microvascular complications. Type 2 diabetes is a very heterogeneous disorder and there are certainly many different causes of this form of diabetes. However, it is likely that the number of patients placed in this category will decrease in the future as identification of specific pathogenic processes and genetic defects permit better differentiation and a more definitive classification. Although the specific etiologies of type 2 diabetes are not known, autoimmune destruction of the pancreas does not occur and patients do not have any of the other specific causes of diabetes listed in Table 1.2.


Most patients with the type 2 process of diabetes are overweight or obese, and obesity itself causes insulin resistance. Many of those not obese by traditional criteria, for example body mass index, may have an increased percentage of body fat distributed predominantly in the abdominal region [13]. Ketoacidosis seldom occurs in type 2 diabetes and when seen, it usually arises in association with the stress of another illness such as infection. Ketosis-prone atypical diabetes, also referred to as ketosis-prone type 2 diabetes is characterized by presentation with severe hyperglycemia and ketoacidosis requiring immediate insulin therapy [15]. More than 50% of these individuals will revert to an insulin-free near-normoglycemia within weeks or months with multiorgan insulin resistance not dissimilar to type 2 diabetes [16]. This condition is commonly found in sub-Saharan Africa and African migrants and is referred to as “Flatbush diabetes”[17].

The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity. It occurs more frequently in women with prior GDM, in those with hypertension or dyslipidemia, and its frequency varies between different ethnic subgroups [7]. Type 2 diabetes is often associated with strong familial, likely genetic, predisposition but the genetics of type 2 diabetes are quite complex and not clearly defined [18]. Some patients who present a clinical picture consistent with type 2 diabetes have been shown to have antibodies similar to those found in type 1 diabetes.

Although diagnosis in most patients with type 2 diabetes is made in adult years, the disease is now increasingly seen in adolescents and even children, especially in a background of high obesity prevalence. At presentation, ketosis or even ketoacidosis, may occur in this younger age group and insulin is often required in the initial management. However, once the acute metabolic disturbance is rectified, insulin can often be withdrawn, and glycemic control achieved with lifestyle measures and oral pharmacotherapy.


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