New Classifications

The ADA classification and the proposed WHO classification encompass both clinical stages, etiological types of diabetes mellitus and other categories of hyperglycemia (Table 3.3). Diabetes may progress through several clinical stages during its natural history regardless of its etiology. The clinical staging reflects this specific aspect. Moreover, individual subjects may move from stage to stage in either direction (Figure 3.2). Even in the

DIABETES MELLITUS: DIAGNOSIS AND CLASSIFICATION Table 3.3 Etiological classification of diabetes mellitus

I. Type 1 diabetes * (^-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 ^-cell function

1. Chromosome 20, HNF-4a (MODY1)

2. Chromosome 7, glucokinase (MODY2)

3. Chromosome 12, HNF-1a (MODY3)

4. Chromosome 13, IPF-1 (MODY4)

5. Mitochondrial DNA 3243 mutation

6. Others

B. Genetic defects in insulin action

1. Type A insulin resistance

2. Leprechaunism

3. Rabson-Mendenhall syndrome

4. Lipoatrophic diabetes

5. Others

C. Diseases of the exocrine pancreas

1. Fibrocalculous pancreatopathy

2. Pancreatitis

3. Trauma/pancreatectomy

4. Neoplasia

5. Cystic fibrosis

6. Hemochromatosis

7. Others

D. Endocrinopathies

1. Cushing's syndrome

2. Acromegaly

3. Pheochromocytoma

4. Glucagonoma

5. Hyperthyroidism

6. Somatostinoma

7. Aldosteronoma

8. Others

E. Drug- or chemical-induced

1. Nicotinic acid

2. Glucocorticoids

3. Thyroid hormone

4. a-adrenergic agonists

5. ^-adrenergic agonists

6. Thiazides

7. Dilantin

8. Pentamidine

9. Vacor

10. a-interferon therapy

11. Diazoxide

12. Others

F. Infections

1. Congenital rubella

2. Cytomegalovirus

3. Others

G. Uncommon forms of immune-mediated diabetes

1. Insulin autoimmune syndrome (antibodies to insulin)

2. Anti-insulin receptor antibodies

3. 'Stiff-man' syndrome

4. Others

H. Other genetic syndromes sometimes associated with diabetes

1. Down's syndrome

2. Klinefelter's syndrome

3. Turner's syndrome

4. Wolfram's syndrome

5. Friedreich's ataxia

6. Huntington's chorea

7. Laurence-Moon-Biedl syndrome

8. Myotonic dystrophy

9. Porphyria

10. Prader-Willi syndrome

11. Others

IV. Gestational diabetes mellitus (GDM)

*Patients with any form of diabetes may require insulin treatment at some stage of their disease. Such use of insulin does not, of itself, classify the patient.

absence of information concerning the underlying etiology, persons with diabetes or those who are developing the disease can be categorized by stage according to clinical characteristics. The classification by etiological type results from improved understanding of the cases of diabetes.

The new classification takes into account the various degrees of hyperglycemia in individual subjects with any of the disease processes which may lead to diabetes. These are glycemic stages ranging from normoglycemia (normal glucose tolerance) to hyperglycemia (established diabetes where insulin is requested for survival). All individuals with the disease can be categorized according to clinical stage and this is achievable in all circumstances (2). The stage of glycemia may change over time depending on the extent of the underlying disease processes (Figure 3.2). As shown in Figure 3.2 a disease process may be present but may not have progressed far enough to cause hyperglycemia. The etiological classification reflects the fact that the defect or process which may lead to a manifest disease, diabetes, may be identifiable at any stage in the development of diabetes even at the stage of normoglycemia. For instance, the presence of islet cell antibodies in a normoglycemic individual makes it likely that individual has the Type 1 autoimmune process.

For Type 2 diabetes, there are not many good highly specific indicators. Future research will probably reveal some of them.

The same disease process can cause various degrees of 'dysglycemia' such as impaired fasting glycemia (IFG) and/or impaired glucose tolerance (IGT) without fulfilling the criteria for the diagnosis of diabetes (2). Weight reduction, exercise and/or oral agents treatment can result in adequate glycemic control in some persons with diabetes. These persons, therefore, do not require insulin. Other persons require insulin for adequate glycemic control but can survive without it. By definition these persons have some residual insulin secretion. Patients with extensive beta-cell destruction (no residual insulin secretion) do require insulin for survival. The severity of the metabolic abnormality can either regress (e.g., with weight reduction), progress (e.g., with weight gain) or stay the same.

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