Should we screen diabetic patients using biguanides for megaloblastic anaemia?

BACKGROUND: Patients taking biguanides on a continuous basis sometimes develop vitamin B12 deficient megaloblastic anaemia. The prevalence of this side effect has not been estimated. METHODS: We screened 600 patients with type 2 diabetes treated with biguanides (phenformin or metformin) for a mean of 11.8 years (SD: 3.6 years) with complete blood counts, red cell indices and red cell morphology. If this showed macrocytosis, we measured total serum vitamin B12 and antiparietal cells antibodies (APCA). Patients with macrocytosis and low serum vitamin B12 levels were treated with cyanocobalamin 1 mg injection daily for seven days. RESULTS: Fifty-four (9%) of the patients had megaloblastic anaemia with low serum total vitamin B12 levels, only three (0.5%) also had abnormally raised APCA. All 54 patients responded to cyanocobalamin with a reticulocyte increase within 10 days. CONCLUSION: Annual screening for megaloblastic anaemia in patients on long term treatment with biguanides may be worthwhile. The anaemia is easily remediable and does not necessitate withdrawal of the drug.

Correlation between increased serum sFas levels and microalbuminuria in type 1 diabetic patients.

OBJECTIVE: The aim of this study was to elucidate if apoptosis dysregulation is present in type 1 diabetic patients with microalbuminuria. SUBJECTS AND METHODS: The following variables were determined in 29 type 1 diabetic patients: the duration of diabetes, soluble Fas (sFas), Bcl-2, hemoglobin A(1c) levels, glomerular filtration rate (GFR) and microalbuminuria, using the urine albumin to urine creatinine ratio (ACR). Age and gender were assessed and patients were categorized into two groups, according to their ACR: the microalbuminuric (MA) group with an ACR > or =30 mg/g, and the normoalbuminuric (NA) group with an ACR <30 mg/g. RESULTS: The differences between the two groups regarding sFas, Bcl-2 and GFR were not statistically significant. However, in the MA group, a significant positive relationship between sFas and ACR was observed (r = 0.736, p = 0.015). Dividing patients into two subgroups--mild versus severe (ACR > or =150 mg/g) microalbuminuric patients--significant differences in sFas (60.4 vs. 87.2 pg/ml; p = 0.047) and GFR (113 vs. 69.5 ml min(-1) 1.73 m(-2); p = 0.021) were observed, whereas in Bcl-2, the difference was not significant (77.96 vs. 71.13 ng/ml). CONCLUSIONS: At the early stages of diabetic nephropathy in type 1 diabetic patients, there seems to be a dysregulation of apoptosis, as expressed by enhanced sFas levels, leading to the speculation that the prevalence of antiapoptotic mechanisms (sFas) may promote mesangial proliferation.