RESUMO
BACKGROUND: Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. OBJECTIVE: This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. SETTING: This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. METHODS: 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. MAIN OUTCOME MEASURE: Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. RESULTS: There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. CONCLUSIONS: Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.
RESUMO
OBJECTIVE: Even though diabetes patients exhibit an increased oxidative stress, its correlation with diabetic nephropathy is not fully understood. The purpose of this study was to determine whether lipid peroxidation marker correlates well with eGFR and UACR in type 2 diabetes mellitus patients. METHODS: We collected urine and serum samples of Indonesian type 2 diabetes mellitus outpatients with normo- and microalbuminuria at a Local Government Clinic (from ages: 39-74 years). Urinary 8-iso-PGF2α was measured by ELISA, the serum malondialdehyde by TBARS assay, and urinary albumin by BCG albumin assay. eGFR was calculated using the corrected-Cockcroft-Gault (CG), MDRD, and CKD-EPI equation. Other necessary data were obtained through questionnaires. RESULTS: The results showed that the increasing level of malondialdehyde was mildly correlated with the decline in eGFR (MDRD). In contrary, there was a significant positive correlation between 8-iso-PGF2α concentration and eGFR based on the corrected-CG, MDRD study, and CKD-EPI equation (r=0.457, p<0.001; r=0.424, p<0.001; r=0.443, p<0.001). This relationship still persisted in the normoalbuminuric subjects (n=43) (r=0.491, p=0.001; r=0.461, p=0.002; r=0.455, p=0.002). The multivariate analysis showed that 8-iso-PGF2α together with fasting plasma glucose was the most predictive factor for the high 2-quantile eGFR (adjusted OR 1.001, (95% CI, 1.000-1.001)). However, there was no significant correlation between UACR with malondialdehyde (r=0.268, p=0.050) and 8-iso-PGF2α(r=-0.030, p=0.808). UACR itself was inversely correlated with eGFR based on the corrected-CG, the MDRD, and CKD-EPI (r=-0.232, p<0.05; r=-0.228, p<0.05; r=-0.232, p<0.05). CONCLUSIONS: Increased 8-iso-PGF2α and malondialdehyde in type 2 diabetes mellitus patients may play a role in the pathophysiologic significance of diabetic nephropathy, even while considering the effect of potential confounders.