Case Study: Potential Pitfalls of Using Hemoglobin A1c as the Sole Measure of Glycemic Control

Abstract

### Case 1 A 55-year-old man of Southeast Asian descent presented with abnormal renal function for investigation. He had a 6-month history of gradual but progressive lethargy, tiredness, and poor concentration. There was no history of inherited or acquired kidney disease, and he had been fit and healthy before recent onset of symptoms. He had a strong family history of type 2 diabetes with an affected father, aunt, and brother. He was a nonsmoker and consumed ∼ 0.35 oz of alcohol daily. Clinically, he appeared well, with a blood pressure of 160/105 mmHg and regular pulse of 88 bpm. His weight was 222 lb (110 kg) and height 5′8″ (1.72 m) (BMI ∼37 kg/m2). Fundoscopy showed evidence of early nonproliferative retinal disease with macula sparing. His general examination was otherwise normal, with no evidence of nephromegaly, renal bruit, or microvascular disease. Urinalysis revealed the presence of proteinuria, confirmed to be 1.8 g/day with no hematuria. He had a blood urea nitrogen (BUN) level of 99.7 mg/dl and creatinine of 6.1 mg/dl with sodium of 136 mmol/l and potassium of 5.4 mmol/l. His fasting glucose level was 122.5 mg/dl. A follow-up oral glucose tolerance test (OGTT) confirmed the presence of impaired fasting glycemia and impaired glucose tolerance, with a fasting glucose level of 117.1 mg/dl (6.5 mmol/l) and a 2-hour post-OGTT glucose level of 160.4 mg/dl (8.9 mmol/l). His hemoglobin A1c (A1C) levels (performed by high-performance liquid chromatography) were 4.5 and 4.2% on two separate occasions with abnormal chromatograms (Figure 1). Follow-up electrophoresis revealed the presence of hemoglobin E. Further investigation of his renal abnormality, including biopsy, confirmed the presence of diabetic nephropathy, with no other causes for chronic renal failure being apparent. On follow-up, his diabetes control was excellent with dietary and lifestyle management. Figure 1. E pattern hemoglobinopathy interfering with the analysis …