Key Point

• Fasting serum glucose values of 100 to 125 mg/dL are considered to be prediabetes to indicate that these values have an increased risk of progressing to diabetes by various pathophysiologic processes.

Diabetes mellitus has been subdivided into four groups: type 1, type 2, other specific types, and gestational diabetes mellitus (GDM). The diagnosis of DM is made by finding any one of the following criteria subsequently confirmed on another day by any of the criteria:

1. Typical symptoms of hyperglycemia, such as weight loss, polyuria, and polydipsia, associated with a casually found serum glucose value greater than 200 mg/dL.

2. Fasting serum (blood) glucose (FSG, FBG) value of 126 mg/dL or greater.

3. An FSG value of 200 mg/dL or greater obtained 2 hours after a 75-g glucose challenge (after 72 hours of eating 300 g of carbohydrate daily).

The diagnosis of GDM is made during pregnancy using specific criteria discussed later.

Glucose circulating in the blood enters red blood cells (RBCs) and reacts with the amino acid sequence of hemoglobin (Hb), resulting in a glycosylated product called hemoglobin A1c. The HbA1c value reflects the average FSG value of the prior 3 months that hemoglobin circulated in RBCs (given that RBCs have a mean half-life of 90 days). The HbA1c value has become extraordinarily useful in gauging the level of gly-cemic control, and values of 6.5% or greater are now being considered a level diagnostic of DM. However, the test has limitations as the result can be lowered by anemia, renal disease, and other disorders that shorten RBC survival (e.g., chronic disease, hemoglobinopathy). Some forms of hemoglobinopathy can also increase the HbA1c test despite near-normal glycemic control. The fructosamine test measures the glyco-sylation of albumin, which has a shorter circulating half life than hemoglobin, and may be used to resolve inconsistencies between average glucose values and HbA1c level, although this is related to the albumin concentration. Insulin and C-peptide levels are readily affected by the toxic effects of glucose and fatty acids on beta cells, making low levels difficult to interpret.

Fasting glucose values of 100 to 125 mg/dL are consistent with prediabetes and increase the risk of progressing to diabetes through various pathophysiologic processes. Finding these values allows the family physician to initiate prospective and preventive interventions. Participants in the Diabetes Prevention Program had impaired glucose tolerance, and those randomized to metformin or intensive lifestyle modification had reduced incidence of diabetes compared to those randomized to placebo (Knowler et al., 2002). Predictors of prediabetes changing to normal glucose regulation over 3-year follow-up included lower baseline fasting and 2-hour glucose levels, younger age, intensive lifestyle modification, and greater weight loss (Perreault et al., 2009).

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