Report of the Committee on the classification and diagnostic criteria of diabetes mellitus

Abstract

In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan.
Concept of diabetes mellitus: Diabetes mellitus represents a group of diseases of heterogeneous etiology, characterized by chronic hyperglycemia and other metabolic abnormalities, which are due to deficiency of insulin effect. After a long duration of metabolic derangement, specific complications of diabetes (retinopathy, nephropathy, and neuropathy) may occur. Arteriosclerosis is also accelerated. Depending on the severity of the metabolic abnormality, diabetes may be asymptomatic, or may be associated with symptoms (thirst, polyuria, and weight loss), or may progress to ketoacidosis and coma.
Classification (cf. Tables 1 and 2 and Fig. 1): Both etiological classification and staging of pathophysiology by the degree of deficiency of insulin effect need to be considered. The etiological classification of diabetes and related disorders of glycemia includes, (1) type 1; (2) type 2; (3) those due to specific mechanisms and diseases; and (4) gestational diabetes mellitus. Type 1 is characterized by destructive lesions of pancreatic β cells either by an autoimmune mechanism or of unknown cause. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Category (3) includes two subgroups; subgroup A is diabetes in which specific mutations have been identified as a cause of genetic susceptibility, while subgroup B is diabetes associated with other pathologic conditions or diseases. The staging of glucose metabolism includes normal, borderline and diabetic stages. The diabetic stage is further classified into three substages; non-insulin requiring, insulin-requiring for glycemic control, and insulin-dependent (ID) for survival. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment.
Diagnosis (cf. Tables 3 and 4): The confirmation of chronic hyperglycemia is a prerequisite for the diagnosis of diabetes mellitus. The state of glycemia may be classified within three categories, diabetic type; borderline type; and normal type. Diabetic type is defined when fasting plasma glucose (FPG) is 7.0 mmol/l (126 mg/dl) or higher, and/or plasma glucose 2 h after 75 g glucose load (2hPG) is 11.1 mmol/l (200 mg/dl) or higher. A casual plasma glucose (PG) ≥11.1 mmol/l (200 mg/dl) also indicates diabetic type. Normal type is defined when FPG is below 6.1 mmol/l (110 mg/dl) and 2hPG below 7.8 mmol/l (140 mg/dl). Borderline type includes those who are neither diabetic nor normal types. These cutoff values are for venous PG measurements. The persistence of ‘diabetic type’ in a subject indicates that he or she has diabetes. For children, a dose of 1.75 g/kg (maximum, 75 g) is used for oral glucose tolerance test (OGTT). The procedure for clinical diagnosis is as follows.

• Diabetes mellitus is diagnosed when hyperglycemia meeting the criteria for ‘diabetic type’ is shown on two or more occasions examined on separate days.

• Diabetes can be diagnosed by a single PG test of ‘diabetic type’ if one of the following three conditions co-exists, (1) typical symptoms of diabetes mellitus; (2) HbA_1c ≥6.5% by a standardized method; or (3) unequivocal diabetic retinopathy.

• If the above conditions ((1) or (2)) have been present in the past and well documented, the subject is diagnosed either to have diabetes or to be suspected of diabetes, even if the present level of glycemia does not reach that of ‘diabetic type’.

• If the diagnosis of diabetes cannot be established by these procedures, re-testing of PG is recommended after an appropriate interval.

• The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions.

Epidemiological aspects and screening: In order to determine the prevalence of diabetes in a population, ‘diabetic type’ may be regarded as ‘diabetes’. The use of 2hPG cutoff level of ≥11.1 mmol/l (200 mg/dl) is recommended. If this is difficult, the FPG cutoff level of ≥7.0 mmol/l (126 mg/dl) can be used, but is likely to lead to under-ascertainment. For screening, the most important point is not to overlook ‘diabetes’. In addition to parameters of hyperglycemia, clinical information such as family history, obesity etc., should be regarded as indications for further testing.
Normal type and borderline type: Only FPG and 2hPG are adopted as cutoff values, but in clinical situations, it is recommended to measure PG also at 30 and 60 min during 75 g OGTT. Among people with normal type, those with 1hPG higher than 10.0 mmol/l (180 mg/dl) are at higher risk to develop diabetes than those with lower 1hPG. When OGTT is performed, the borderline type corresponds to the sum of impaired fasting glycemia (IFG) plus impaired glucose tolerance (IGT) according to the new WHO report. Subjects in this category are at higher risk of developing diabetes than those with ‘normal type’. Those with low insulinogenic index (the ratio of increment of plasma insulin to that of PG at 30 min during OGTT) are at particularly high risk to develop diabetes. Microvascular complications are rare but arteriosclerotic complications are fairly frequent in this category.
Gestational diabetes mellitus (GDM): The current definition of GDM is ‘ any glucose intolerance developed or detected during pregnancy’. We adopt the proposal of the Japan Society of Gynecology and Obstetrics for the diagnosis of GDM (1984). GDM is defined when two or more values during a 75 g OGTT are higher than the following cutoff levels; FPG ≥5.5 mmol/l (100 mg/dl), 1hPG ≥10.0 mmol/l (180 mg/dl) and 2hPG ≥8.3 mmol/l (150 mg/dl). As a screening test, subjects with casual PG ≥5.5 mmol/l (100 mg/dl) are recommended for further testing. Patients who have had documented glucose intolerance before pregnancy, and who present as ‘diabetic type’ should be under closer supervision than those who develop GDM during pregnancy for the first time.
HbA_1c: There is a large overlap in the distribution of HbA_1c between groups with ‘normal type’ and ‘borderline type’ and mild ‘diabetic type’. Therefore, HbA_1c is not a suitable parameter to detect mild glucose intolerance. HbA_1c higher than 6.5% suggests diabetes, but HbA_1c below 6.5% alone should not be taken as evidence against the diagnosis of diabetes.
Comparison with reports of American Diabetes Association (ADA) in 1997 and WHO in 1999: The present report is unique in the following points when compared with those of the ADA ‘Diabetes Care 20 (1997) 1183’ and WHO ‘Report of a WHO Consultation (1999)’. (1) Diabetes due to specific mechanisms and diseases is divided into two subgroups; diabetes in which genetic susceptibility is clarified at the DNA level and diabetes associated with other diseases or conditions. (2) Cutoff PG levels are the same as those of ADA and WHO, but a term ‘type’ is added to each glycemic category, because a single coding of ‘diabetic type’ hyperglycemia does not define diabetes. Diabetes is diagnosed when ‘diabetic type’ hyperglycemia is shown on two or more occasions. (3) A single ‘diabetic type’ hyperglycemia is considered sufficient for the diagnosis of diabetes, if the patient has typical symptoms, HbA_1c ≥6.5%, or diabetic retinopathy. (4) OGTT is recommended for those with mild hyperglycemia, because FPG criteria alone would overlook many subjects with ‘diabetic type’ in Japan. High 1hPG without elevation of FPG and 2hPG is also considered to be a risk factor for future diabetes. (5) Borderline type in the present report corresponds to the sum of IFG and IGT by WHO when OGTT is performed. (6) New criteria for GDM by OGTT are proposed.

Introduction

In the past, the Japan Diabetes Society (JDS) has presented two reports on the diagnostic criteria for diabetes mellitus, in 1970 and 1982 [1], [2]. Before 1970, the methods for glucose tolerance testing and the diagnostic criteria for diabetes were not standardized. Various criteria were used, using different glucose load, and mutual comparison of results was almost impossible.

The first Committee of JDS presented cutoff levels of blood glucose for 50 g and 100 g glucose tolerance tests (OGTT). In this 1970 report, a subtitle ‘A recommendation on the criteria of OGTT to be used for the diagnosis of diabetes mellitus’ was added [1]. The Committee took the standpoint that OGTT is an important test to help diagnosis but not to define diabetes.

In 1979, the National Diabetes Data Group (NDDG) in USA proposed a classification of diabetes and diagnostic criteria using a 75 g OGTT [3]. In 1980, the WHO Expert Committee presented a report similar to that of NDDG [4]. These two reports adopted diagnostic criteria using a 75 g OGTT, and classified diabetes into IDDM (type 1), non-insulin-dependent diabetes (NIDDM) (type 2), and other types. They also created the concept of impaired glucose tolerance (IGT).

After publication of these reports, JDS organized the second Committee to examine the diagnosis of diabetes mellitus and to revise the 1970 JDS recommendation. This Committee regarded the WHO report as a basis for international standardization. In addition, the Committee continued the principle of the first JDS Committee, namely that diabetes mellitus is not defined simply by glycemic cutoff values but is a disease (or diseases) which possesses other clinical characteristics [2]. The report of the second JDS Committee in 1982 adopted the terms, ‘diabetic type’, ‘borderline type’, and ‘normal type’ to describe the OGTT results. The cutoff plasma glucose (PG) values for diabetic type were set as the same as those for ‘diabetes’ by WHO criteria, whereas the cutoff values for ‘normal type’ were set lower than the lower limits of IGT. The normal type was defined as a group which would not progress to diabetes after follow-up of several years. The borderline type was defined as those being neither normal nor of diabetic type.

The borderline type of the 1982 JDS Committee included not only IGT but also milder degrees of glucose intolerance than IGT, thus creating two different categories of mild glucose intolerance (i.e. borderline type and IGT). Some researchers complained of the inconvenience of having two such categories. The Committee adopted the WHO classification of diabetes without modification. In 1985, WHO made a small revision to the 1980 report [5].

Since that time, many discoveries have been made regarding the etiology of diabetes, and epidemiological data have accumulated. Moves, to seek a new classification and to revise the diagnostic criteria for diabetes mellitus, have emerged in Japan as well as internationally. In 1995, JDS assigned a new Committee to reconsider the classification and diagnostic criteria of diabetes. Meanwhile in 1997, the American Diabetes Association (ADA) proposed a new classification based on etiology, and revised criteria for the diagnosis of diabetes mellitus [6]. WHO also presented a provisional report in 1998 and a final report in 1999 [7].

The new Committee of JDS sent inquiries to Council members of the JDS, asking about problems in the old 1982 JDS report [8]. The Committee evaluated the 1997 ADA and 1998 WHO reports carefully after their publication, and proceeded to hold an ad-hoc symposium on the diagnosis and classification of diabetes mellitus in Tokyo in 28 June 1998 (Proceedings, J. Jpn. Diabetes Soc. 41 (Suppl. 2), 1999). The Committee met 16 times, held intensive discussions on published and unpublished data obtained in Japan and produced the following final report.