Misleading HbA1c Measurement in Diabetic Patients with Hemoglobin Variants.

BACKGROUND AND OBJECTIVES: Hemoglobin A1c (HbA1c) is widely used for the monitoring and management of diabetes mellitus. The aim of this study is to investigate the influence of hemoglobin (Hb) variants on the measurement of HbA1c. MATERIALS AND METHODS: HbA1c levels of 845 blood samples obtained from diabetic patients with various hemoglobin types were measured using a turbidimetric inhibition immunoassay and capillary electrophoresis. RESULTS: Of 845 patients with diabetes, 65.7% (555/845) have the normal hemoglobin type (A2A) and 34.3% (290/845) have various abnormal hemoglobin types, including heterozygous HbE 30.2% (255/845), homozygous HbE 1.9 % (16/845), Hb Constant Spring (CS) trait 1.4% (12/845), CSEA Bart's 0.2% (2/845), and beta-thalassemia trait 0.6% (5/845). In most of the patients with diabetes, HbA1c levels determined by two different methods, inhibition immunoassay and capillary electrophoresis, gave strong positive correlation (R = 0.901, P < 0.001), except for those with homozygous HbE (N = 16) and CSEA Bart's (N = 2). In all 18 patients with homozygous HbE and CSEA Bart's, the HbA1c was undetectable by capillary electrophoresis, meaning that their estimated average glucose was undeterminable, although their HbA1c levels could be measured using an inhibition immunoassay. The discrepancy of HbA1c results obtained from two different methods is noted in patients without HbA. CONCLUSIONS: We have demonstrated the erroneous nature of HbA1c measurement in patients with hemoglobin variants, especially in those without HbA expression. Therefore, in the population with a high prevalence of hemoglobinopathies, hemoglobin typing should be considered as basic information prior to HbA1c measurement.

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BACKGROUND: High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. MATERIALS AND METHODS: T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of ß-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. CONCLUSION: Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Efficacy and Safety of Switching from Low-Dose Statin to High-Intensity Statin for Primary Prevention in Type 2 Diabetes: A Randomized Controlled Trial.

INTRODUCTION: Statin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C <100 mg/dl with low-dose statin treatment. METHODS: T2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level <100 mg/dl while taking simvastatin ≤20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks. RESULTS: One hundred and fifty patients (76 LS, 74 HS, mean age 58.9±8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9±13.6 vs. 68.1±14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p<0.001). Plasma LDL-C <40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p<0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group. CONCLUSION: Switching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.