Diagnosis and Classification of Diabetes Mellitus
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Uncommon forms of immune-mediated diabetes
In this category, there are two known conditions, and others are likely to occur. The stiff-man syndrome is an autoimmune disorder of the central nervous system characterized by stiffness of the axial muscles with painful spasms. Patients usually have high titers of the GAD autoantibodies, and approximately one-third will develop diabetes.
Anti–insulin receptor antibodies can cause diabetes by binding to the insulin receptor, thereby blocking the binding of insulin to its receptor in target tissues. However, in some cases, these antibodies can act as an insulin agonist after binding to the receptor and can thereby cause hypoglycemia. Anti–insulin receptor antibodies are occasionally found in patients with systemic lupus erythematosus and other autoimmune diseases. As in other states of extreme insulin resistance, patients with anti–insulin receptor antibodies often have acanthosis nigricans. In the past, this syndrome was termed type B insulin resistance.
Other genetic syndromes sometimes associated with diabetes
Many genetic syndromes are accompanied by an increased incidence of diabetes mellitus. These include the chromosomal abnormalities of Down’s syndrome, Klinefelter’s syndrome, and Turner’s syndrome. Wolfram’s syndrome is an autosomal recessive disorder characterized by insulin-deficient diabetes and the absence of ß-cells at autopsy. Additional manifestations include diabetes insipidus, hypogonadism, optic atrophy, and neural deafness. Other syndromes are listed in Table 1.
Gestational diabetes mellitus (GDM)
GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. The definition applies regardless of whether insulin or only diet modification is used for treatment or whether the condition persists after pregnancy. It does not exclude the possibility that unrecognized glucose intolerance may have antedated or begun concomitantly with the pregnancy. GDM complicates 4% of all pregnancies in the U.S., resulting in 135,000 cases annually. The prevalence may range from 1 to 14% of pregnancies, depending on the population studied. GDM represents nearly 90% of all pregnancies complicated by diabetes.
Deterioration of glucose tolerance occurs normally during pregnancy, particularly in the 3rd trimester.
Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)
The Expert Committee recognized an intermediate group of subjects whose glucose levels, although not meeting criteria for diabetes, are nevertheless too high to be considered normal. This group is defined as having fasting plasma glucose (FPG) levels 100 mg/dl (5.6 mmol/l) but <126 mg/dl (7.0 mmol/l) or 2-h values in the oral glucose tolerance test (OGTT) of 140 mg/dl (7.8 mmol/l) but <200 mg/dl (11.1 mmol/l). Thus, the categories of FPG values are as follows:
* FPG <100 mg/dl (5.6 mmol/l) = normal fasting glucose;
* FPG 100–125 mg/dl (5.6–6.9 mmol/l) = IFG (impaired fasting glucose);
* FPG 126 mg/dl (7.0 mmol/l) = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described below).
The corresponding categories when the OGTT is used are the following:
* 2-h postload glucose <140 mg/dl (7.8 mmol/l) = normal glucose tolerance;
* 2-h postload glucose 140–199 mg/dl (7.8–11.1 mmol/l) = IGT (impaired glucose tolerance);
* 2-h postload glucose 200 mg/dl (11.1 mmol/l) = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described below).
Patients with IFG and/or IGT are now referred to as having "pre-diabetes" indicating the relatively high risk for development of diabetes in these patients. In the absence of pregnancy, IFG and IGT are not clinical entities in their own right but rather risk factors for future diabetes as well as cardiovascular disease. They can be observed as intermediate stages in any of the disease processes listed in Table 1. IFG and IGT are associated with the metabolic syndrome, which includes obesity (especially abdominal or visceral obesity), dyslipidemia of the high-triglyceride and/or low-HDL type, and hypertension. It is worth mentioning that medical nutrition therapy aimed at producing 5–10% loss of body weight, exercise, and certain pharmacological agents have been variably demonstrated to prevent or delay the development of diabetes in people with IGT; the potential impact of such interventions to reduce cardiovascular risk has not been examined to date.
Note that many individuals with IGT are euglycemic in their daily lives. Individuals with IFG or IGT may have normal or near normal glycated hemoglobin levels. Individuals with IGT often manifest hyperglycemia only when challenged with the oral glucose load used in the standardized OGTT.
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Martha M. Funnell, MS, RN, CDE
Michigan Diabetes Research and Training Center
University of Michigan Medical School
Ann Arbor, Michigan
Robert M. Anderson, EdD
Michigan Diabetes Research and Training Center
University of Michigan Medical School
Ann Arbor, Michigan
Shereen Arent, JD
National Director of Legal Advocacy
American Diabetes Association
American Diabetes Association Complete Guide to Diabetes
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