Evidence for consistency of the glycation gap in diabetes.

OBJECTIVE: Discordance between HbA(1c) and fructosamine estimations in the assessment of glycemia is often encountered. A number of mechanisms might explain such discordance, but whether it is consistent is uncertain. This study aims to coanalyze paired glycosylated hemoglobin (HbA(1c))-fructosamine estimations by using fructosamine to determine a predicted HbA(1c), to calculate a glycation gap (G-gap) and to determine whether the G-gap is consistent over time. RESEARCH DESIGN AND METHODS: We included 2,263 individuals with diabetes who had at least two paired HbA(1c)-fructosamine estimations that were separated by 10 ± 8 months. Of these, 1,217 individuals had a third pair. The G-gap was calculated as G-gap = HbA(1c) minus the standardized fructosamine-derived HbA(1c) equivalent (FHbA(1c)). The hypothesis that the G-gap would remain consistent in individuals over time was tested. RESULTS: The G-gaps were similar in the first, second, and third paired samples (0.0 ± 1.2, 0.0 ± 1.3, and 0.0 ± 1.3, respectively). Despite significant changes in the HbA(1c) and fructosamine, the G-gap did not differ in absolute or relative terms and showed no significant within-subject variability. The direction of the G-gap remained consistent. CONCLUSIONS: The G-gap appears consistent over time; thus, by inference any key underlying mechanisms are likely to be consistent. G-gap calculation may be a method of exploring and evaluating any such underlying mechanisms.

Clinical impact of variability in HbA1c as assessed by simultaneously measuring fructosamine and use of error grid analysis.

BACKGROUND: Haemoglobin A1c (HbA1c) is the only measure of glycaemic control used for many patients with diabetes, but it has limitations and might sometimes be misleading. HbA(1c) concentrations are influenced by conditions that alter red-cell life and there is evidence that biochemical variation in intracellular glycation rates also influence HbA1c concentrations. This paper is the first to propose a method of using simultaneously measured HbA1c and fructosamine, and error grid analysis, in the clinical setting, to gain a better understanding of glycaemic control. METHODS: Cross-sectional analytical study using HbA1c and fructosamine measures on the same blood sample from 1744 patients having blood taken for hospital diabetes clinic appointments. No other selection or exclusion criteria were applied. RESULTS: The fructosamine results were converted to a HbA1c equivalent which was then compared with the HbA1c. In an Altman-Bland plot, the paired result differences ranged between -6.9% and +5.5% HbA1c with 1139 (65%), 438 (25%), 130 (8%) and 37 (2%) being < or =1%, 1-2%, 2-3% or >3% of HbA1c difference, respectively. In clinical error grid analysis, 864 (50%) results had tight concordance for clinical interpretation, 761 (43%) had one block disunity of probably little clinical significance, but 105 (6%) were two blocks and 14 (1%) were three blocks discordant. CONCLUSION: HbA1c may not accurately reflect glucose control. Our method, utilizing co-assessment with serum fructosamine, evaluates the possible clinical impact of this. We suggest the analysis used in this paper should be used routinely in diabetes practice.

The sweat test: effect of elution time on chloride and sodium concentrations.

BACKGROUND: The National Committee for Clinical Laboratory Standards guidelines and Guidelines for the Performance of the Sweat Test for the Diagnosis of Cystic Fibrosis in the United Kingdom recommend that sweat be eluted from filter paper for a minimum of 40 min. In the absence of published data, this recommendation is based on expert opinion. We therefore investigated the effect of elution time on chloride and sodium concentrations. METHODS: The effect of elution time (up to three hours) on chloride and sodium concentrations was studied as recommended for measurement of quality control samples using external quality assessment solutions. RESULTS: There were no significant differences in eluted chloride and sodium concentrations with time of elution up to 3 h. CONCLUSION: Elution time within 3 h had no effect on chloride and sodium concentrations when eluted from filter paper.

Calcium and vitamin D supplementation failed to improve bone mineral density in Indo-Asians suffering from hypovitaminosis D and secondary hyperparathyroidism.

BACKGROUND: The association of low bone mineral density (BMD) in Asians with hypovitaminosis D (HD) and when complicated with secondary hyperparathyroidism (HD-SHPT) has been shown previously. OBJECTIVE: Our aim was to study the effectiveness of calcium and vitamin D therapy in Indo-Asians with HD and HD-SHPT. METHODS: One hundred forty-three patients attending our rheumatology clinic, including 97 (68%) with HD aged 48.9+/-11.6 years (86% female) and 46 (32%) with HD-SHPT aged 55.9+/-12.6 years (85% female), were recruited. Baseline investigations included routine biochemistry and 25-hydroxy vitamin D [25(OH)D], and parathyroid hormone (PTH) assays. Bone mineral densities (BMDs) of femoral neck, lumbar spine (LS), and distal radius (DR) were measured by dual energy X-ray absorptiometry. Patients were commenced on 1.0-1.25 g of calcium plus 400 IU of vitamin D. Blood tests were repeated at 6 and 12 months. Thirty-six patients with t scores of <-1 had their BMDs remeasured at 2 years. Unpaired t- and Mann-Whitney U tests were used in statistics. Results were considered significant at P< or =0.05. RESULTS: Femur t and z scores failed to improve in either group. The reduction in LS t scores but not z scores was significant in both groups. Significant reductions in DR t and z scores occurred in the HD group only. Calcium and 25(OH)D increased significantly in both groups. Alkaline phosphatase and PTH were suppressed significantly only in HD-SHPT. CONCLUSION: The failure of BMD to improve could be due to lack of compliance with medication between years 1 and 2, when most patients were under the supervision of primary care. To overcome this, we recommend continuance of blood monitoring at least once a year.