Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus

Abstract

Concept of Diabetes Mellitus: Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long-term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis. Diabetes mellitus is associated with a broad range of clinical presentations, from being asymptomatic to ketoacidosis or coma, depending on the degree of metabolic disorder. Classification (Tables 1 and 2, and Figure 1): Table 1. Etiological classification of diabetes mellitus and glucose metabolism disorders I. Type 1 (destruction of pancreatic β-cells, usually leading to absolute insulin deficiency) A. Autoimmune B. Idiopathic II. Type 2 (ranging from predominantly insulin secretory defect, to predominantly insulin resistance with varying degrees of insulin secretory defect) III. Due to other specific mechanisms or diseases (see Table 2 for details) A. Those in which specific mutations have been identified as a cause of genetic susceptibility (1) Genetic abnormalities of pancreatic β-cell function (2) Genetic abnormalities of insulin action B. Those associated with other diseases or conditions (1) Diseases of exocrine pancreas (2) Endocrine diseases (3) Liver disease (4) Drug- or chemical-induced (5) Infections (6) Rare forms of immune-mediated diabetes (7) Various genetic syndromes often associated with diabetes IV. Gestational diabetes mellitus Note: Those that cannot at present be classified as any of the above are called unclassifiable. The occurrence of diabetes-specific complications has not been confirmed in some of these conditions. Table 2. Diabetes mellitus and glucose metabolism disorders due to other specific mechanisms and diseases A. Those in which specific mutations have been identified as a cause of genetic susceptibility B. Those associated with other diseases or conditions (1) Genetic abnormalities of pancreatic β-cell functionInsulin gene (abnormal insulinemia, abnormal proinsulinemia, neonatal diabetes mellitus) HNF 4α gene (MODY1) Glucokinase gene (MODY2) HNF 1α gene (MODY3) IPF-1 gene (MODY4) HNF 1β gene (MODY5) Mitochondria DNA (MIDD) NeuroD1 gene (MODY6) Kir6.2 gene (neonatal diabetes mellitus) SUR1 gene (neonatal diabetes mellitus) AmylinOthers(2) Genetic abnormalities of insulin actionInsulin receptor gene (type A insulin resistance, leprechaunism, Rabson–Mendenhall syndrome etc.) Others (1) Diseases of exocrine pancreasPancreatitisTrauma/pancreatectomyNeoplasmHemochromatosisOthers(2) Endocrine diseasesCushing’s syndromeAcromegalyPheochromocytomaGlucagonomaAldosteronismHyperthyroidismSomatostatinomaOthers(3) Liver diseaseChronic hepatitisLiver cirrhosis Others(4) Drug- or chemical-inducedGlucocorticoidsInterferonOthers(5) InfectionsCongenital rubellaCytomegalovirusOthers(6) Rare forms of immune-mediated diabetesAnti-insulin receptor antibodiesStiffman syndromeInsulin autoimmune syndromeOthers(7) Various genetic syndromes often associated with diabetesDown syndromePrader-Willi syndromeTurner syndromeKlinefelter syndromeWerner syndromeWolfram syndromeCeruloplasmin deficiencyLipoatrophic diabetes mellitusMyotonic dystrophyFriedreich ataxiaLaurence-Moon-Biedl syndromeOthers The occurrence of diabetes-specific complications has not been confirmed in some of these conditions. Figure 1Open in figure viewerPowerPoint A scheme of the relationship between etiology (mechanism) and patho-physiological stages (states) of diabetes mellitus. Arrows pointing right represent worsening of glucose metabolism disorders (including onset of diabetes mellitus). Among the arrow lines, indicates the condition classified as ‘diabetes mellitus’. Arrows pointing left represent improvement in the glucose metabolism disorder. The broken lines indicate events of low frequency. For example, in type 2 diabetes mellitus, infection can lead to ketoacidosis and require temporary insulin treatment for survival. Also, once diabetes mellitus has developed, it is treated as diabetes mellitus regardless of improvement in glucose metabolism, therefore, the arrow lines pointing left are filled in black. In such cases, a broken line is used, because complete normalization of glucose metabolism is rare. The classification of glucose metabolism disorders is principally derived from etiology, and includes staging of pathophysiology based on the degree of deficiency of insulin action. These disorders are classified into four groups: (i) type 1 diabetes mellitus; (ii) type 2 diabetes mellitus; (iii) diabetes mellitus due to other specific mechanisms or diseases; and (iv) gestational diabetes mellitus. Type 1 diabetes is characterized by destruction of pancreatic β-cells. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Glucose metabolism disorders