Reality of Metformin associated lactic acidosis: A case report and literature search

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 758-785-Diabetes Case Reports: Type 1, Type 2, MODY & Complications
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-785
Sri Harsha Tella*1, Avani Reddy Alla2, Alejandro Trepp3, Valentina D. Tarasova1 and J Christopher Gallagher4
1Creighton University, Omaha, NE, 2NRI Medical College and General Hospital, 3Creighton University, 4Creighton University Medical Cen, Omaha, NE
Introduction:Lactic acidosis was well recognised as a side effect of phenormin treatment but uncommon in Diabetic patients treated with metformin except in patients with morbidities and less common in diabetes without mobidity.

Clinical Case:We describe a case of a 73-year-old African American female with a 3-year history of Diabetes who presented to the clinic for an annual physical exam. Routine laboratoty work showed an anion gap (AG) of 24 (normal 10-12) and normal electrolytes.She was admitted to the hospital:serum lactic acid was 4.1 mmol/L in the setting of acidosis. Physical exam was normal, HbA1C: 6.8, BMI: 23.4 kg/m2, serum creatinine 1.0mg/dl, eGFR:86 ml/min and normal liver tests. Echo revealed an ejection fraction of 55-60% with grade 1 diastolic dysfunction. There was no evidence or signs of intercurrent illness. The patient was on Metformin 1000 mg twice daily for 3 years with no previous history of lactic acidosis or renal impairment. Treatment was initiated with IV fluids and metformin was discontinued. The next day serum lactic acid was reduced to 1.5mmol/L and the anion gap was 12. Four days later, the patient was rechallenged with Metformin and serum lactate increased to 3.8 mmol/L and anion gap increased to 21.

Discussion:Genetic polymorphisms of OCT1 protein, which increases hepatic uptake of metformin, may be a causative factor for lactic acidosis in patients without risk factors. When metformin levels are high, oxidative phosphorylation is reduced and aerobic metabolism switches to anaerobic. Metformin can decrease intestinal glucose absorption, hepatic gluconeogenesis-by decreasing pyruvate carboxylase activity, limiting enzyme in formation of glucose from lactate, thereby increasing intestinal lactate production. High levels of metformin activate AMP kinase in mitochondrion which in turn increases NADH and inhibits oxidative metabolism. Metformin promotes the conversion of glucose to lactate in the splanchnic bed of small intestine causing the intracellular redox potential to shift from aerobic to anaerobic metabolism.

Conclusion:Lactic acidosis in metformin use is not just a problem in patients with pre-existing risk factors. In fact, by definition, metformin-induced lactic acidosis is diagnostic of lactic acidosis in the absence of other evident causes of lactic acidosis. Periodic monitoring of the anion gap in patients on metformin might detect more cases and avoid more severe outcome when the patient has an intercurrent illness.

Nothing to Disclose: SHT, ARA, AT, VDT, JCG

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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