Metformin-Induced Hemolytic Anemia in a Patient With Glucose-6- Phosphate Dehydrogenase Deficiency

Abstract

It is well known that hyperglycemia is associated with increased mortality from cardiovascular disease (CVD) and all-cause mortality. It has recently been reported that subjects with low fasting plasma glucose (FPG) levels also had a high risk of CVD and all-cause mortality (1). However, there is a paucity of information about the etiologic basis underlying the association between low FPG and increased CVD and all-cause mortality. Thus, in the present study, we investigated the association of FPG levels with white blood cell (WBC) counts, which indicate a state of low-grade systemic inflammation.We investigated the cross-sectional association of WBC counts with FPG levels among 3,256 Japanese men aged 34 -69 years. The subjects were divided into six categories according to FPG level: Ͻ80 mg/dl, 80 to Ͻ90 mg/dl, 90 to Ͻ100 mg/dl, 100 to Ͻ110 mg/dl, 110 to Ͻ126 mg/dl, and diabetes.The crude mean WBC counts were 6, 409, 6,308, 6,111, 6,111, 6,109, and 6,610 cells/mm 3 in the subjects with FPG levels of Ͻ80 mg/dl, 80 to Ͻ90 mg/dl, 90 to Ͻ100 mg/dl, 100 to Ͻ110 mg/dl, 110 to Ͻ126 mg/dl, and diabetes, respectively. The crude mean WBC counts differed significantly by FPG category and showed a U-shaped association with FPG levels (P value for quadratic trend Ͻ0.001). Even after adjusting for age, BMI, smoking, alcohol, health status, and other factors associated with elevated WBC count or glycometabolism, the respective adjusted-mean WBC counts were 6,273, 6,255, 6,175, 6,165, 6,075, and 6,429 cells/mm 3 . The WBC count maintained a U-shaped association with FPG level (P value for quadratic trend ϭ 0.041).Although it is well known that hyperglycemia is the cause of microvascular complications in several organs, there are few studies on the adverse effect of hypoglycemia. Early studies of hypoglycemia focused on brain damage and heart dysfunction. An acute decrease in FPG is recognized as the cause of them, whereas the long-term effect of low FPG remains unclear.Infection and inflammation may contribute to vascular injury and atherogenesis. Inflammation may also promote atherosclerotic plaque ruptures and thrombosis (2,3). WBC serves as an important biomarker for these disease processes.This study shows that the U-shaped association between WBC counts and FPG levels (especially low FPG levels) involves higher WBC counts that could not be linked to inflammatory disease or other factors or to any disease known to increase WBC counts. These findings suggest that a state of low-grade systemic inflammation may be present not only in diabetic subjects but also in people with low FPG, possibly explaining in part the high risk of CVD and all-cause mortality of such people. • (1) to clinical practice continues to be a major challenge (2,3). Physicians in training present a unique opportunity for shaping practice behavior. We tested the effect of an intramural contest on the outcome of diabetes management by 155 medical residents at a major U.S. teaching hospital. The contest was approved by the house staff leadership and w...

Glucose‐6‐phosphate dehydrogenase deficiency induced haemolysis in a woman with newly diagnosed diabetes after normalisation of hyperglycaemia

“…People with G6PD deficiency can develop severe haemolytic anaemia in conjunction with new‐onset diabetes, particularly within the setting of ketoacidosis. This phenomenon has been reported previously, but is uncommon .…”

“…Evidence of haemolysis in people with diabetes and G6PD deficiency was first reported in 1972 [2]. Since that time, sporadic cases have appeared in the literature, highlighting the rare precipitating factors of acute haemolytic anaemia in G6PD-deficient individuals [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Seventeen papers have been published, involving 23 individuals from around 12 countries; most of these individuals had hyperglycaemia with or without diabetic ketoacidosis.…”

Glucose 6 Phosphate Dehydrogenase Deficiency Unmasked by Diabetic Ketoacidosis: An Underrated Phenomenon

“…In a G6PD-deficient subject, hemolysis may occur as a result of ingestion of various drugs, ingestion of specific food substances and commonly, infection. None of the above-mentioned history could be detailed causes of G6PD deficiency in diabetic subjects could be because of hypoglycaemia [1], ketoacidosis in the African [3,4], but not Mediterranean variant of G6PD [5], and following administration of metformin [6] or glibenclamide [7]. In the present case, the patient was not on any oral hypoglycemic medication.…”

Metformin poisoning: A complex presentation

“…The cause of haemolytic anaemia can be immune mediated[2] or due to G6PD deficiency caused by metformin. [3] The possible explanation for haemolysis in our case could be hepatitis A, which was excluded by history but not investigated in our case, or immune aetiology as the predictive value of a positive Coomb’s test for a patient with haemolytic anaemia is 83%. [4]…”