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OBJECTIVE: To assess the inherent potential of glycated hemoglobin as a screening test for type 2 diabetes by determining the biological variation in nondiabetic subjects. RESEARCH DESIGN AND METHODS: HbA1c values were measured by high-performance liquid chromatography (HPLC) in 12 nondiabetic subjects (7 men and 5 women; median age, 40 years [range, 21-55 years]) on 10 fortnightly occasions. The nondiabetic index of individuality (IOI) for HbA1c (i.e., the square root of the ratio of intra- to interindividual variance) was determined. Any test with an IOI of 1.4 has the most potential in disease screening, while one of 0.6 will be of little value. RESULTS: The analytical variance contributed to 9% of the total test variance, intraindividual variance, 6%; and interindividual variance, 85%. The IOI was, therefore, only 0.27. Thus, nondiabetic HbA1c values vary markedly between subjects, while values in the same individual change little with time. As such, to lie outside the assay reference range, the HbA1c values of some nondiabetic subjects must exceed 12 SD from their usual mean value, while in others a change of only 2 SD would be sufficient. CONCLUSIONS: This fundamental characteristic of HbA1c means that even if analytical methods improve, glycated hemoglobin measurements will always be of limited value when screening for type 2 diabetes. If similar interindividual differences also exist in diabetic subjects, then patients with the same glycemic control may vary by at least 1-2%, which has implications in setting glycated hemoglobin targets.

Insulin resistance is increased in women with polycystic ovary syndrome (PCOS), and it may increase the risk of type 2 diabetes. In addition, hyperinsulinemia may contribute to androgen excess and could be a factor in the infertility associated with PCOS. This prospective, randomized, open-label study compared metformin therapy with orlistat in 21 women with PCOS. Orlistat reportedly produces significant, sustained weight loss and improves carbohydrate metabolism. After an 8-week period of dietary change, the women were randomized to receive either 500 mg metformin 3 times daily (n 11) or 120 mg orlistat 3 times daily (n 10) for 3 months.