Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

Metformin is the first line drug of choice for the treatment of type II diabetes. Lactic acidosis can develop as a side effect, especially when renal failure leads to drug accumulation. Lactic acidosis is usually attributed to an abnormal inhibition of hepatic lactate clearance.

Growing evidence suggest that metformin can dose-dependently inhibit hepatocyte mitochondrial function. Whether a similar effect occurs in extra-hepatic human tissues remains unknown.

The investigators hypothesize that mitochondrial dysfunction occurs during metformin intoxication even in tissues other than the liver, thus contributing to the development of lactic acidosis. The aim of this study is to investigate mitochondrial integrity in circulating platelets of patients with lactic acidosis due to metformin intoxication.

Inclusion Criteria:

1. Lactic acidosis (pH < 7.35 or base deficit > 5 mmol/L and lactate > 5 mmol/L)
2. Metformin intoxication (serum drug level > 4 mcg/mL)
3. Absence of evidence of any other condition that could primarily explain the lactic acidosis

Exclusion Criteria:

1. Less than 18 years of age
2. Hemoglobin < 8 g/dL (10 g/dL if ischemic cardiac disease)