No abstract

O B J E C T I V E -To evaluate the use of GHb as a screening test for undiagnosed diabetes (fasting plasma glucose 7.0 mmol/l) in a re p resentative sample of the U.S. population. RESEARCH DESIGN AND METHODS -The Third National Health and NutritionExamination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged 20 years. Of these subjects, 7,832 participated in a morn i n g examination session, of which 1,273 were excluded because of a previous diagnosis of diabetes, missing data, or fasting time of 8 h before examination. Venous blood was obtained to meas u re fasting plasma glucose and GHb in the remaining 6,559 subjects. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of GHb for detecting diabetes at increasing GHb cutoff levels. R E S U LT S -GHb demonstrated high sensitivity (83.4%) and specificity (84.4%) for detecting undiagnosed diabetes at a GHb cutoff of 1 SD above the normal mean. Moderate sensitivity (63.2%) and very high specificity (97.4%) were evident at a GHb cutoff of 2 SD above the n o rmal mean. Sensitivity at this level ranged from 58.6% in the non-Hispanic white population to 83.6% in the Mexican-American population; specificity ranged from 93.0% in the nonHispanic black population to 98.3% in the non-Hispanic white population.C O N C L U S I O N S -GHb is a highly specific and convenient alternative to fasting plasma glucose for diabetes screening. A GHb value of 2 SD above the normal mean could identify a high pro p o rtion of individuals with undiagnosed diabetes who are at risk for developing diabetes complications.

Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences.

This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget.