Correction of metabolic acidosis improves insulin resistance in chronic kidney disease

Antonio Bellasi, Lucia Di Micco, Domenico Santoro, Stefania Marzocco, Emanuele De Simone, Mario Cozzolino, Luca Di Lullo, Pasquale Guastaferro, Biagio Di Iorio, UBI study investigators, Simona Adesso, Annamaria Bruzzese, Giuseppe Conte, Adamasco Cupisti, Antonella De Blasio, Alfonso Frallicciardi, Rachele Grifa, Rosa Martino, Matteo Piemontese, Maria Luisa Sirico, Giuseppe Struzziero, Raffaele Tortoriello, Fabio Vitale, Antonio Bellasi, Lucia Di Micco, Domenico Santoro, Stefania Marzocco, Emanuele De Simone, Mario Cozzolino, Luca Di Lullo, Pasquale Guastaferro, Biagio Di Iorio, UBI study investigators, Simona Adesso, Annamaria Bruzzese, Giuseppe Conte, Adamasco Cupisti, Antonella De Blasio, Alfonso Frallicciardi, Rachele Grifa, Rosa Martino, Matteo Piemontese, Maria Luisa Sirico, Giuseppe Struzziero, Raffaele Tortoriello, Fabio Vitale

Abstract

Background: Correction of metabolic acidosis (MA) with nutritional therapy or bicarbonate administration is widely used in chronic kidney disease (CKD) patients. However, it is unknown whether these interventions reduce insulin resistance (IR) in diabetic patients with CKD. We sought to evaluate the effect of MA correction on endogenous insulin action in diabetic type 2 (DM2) CKD patients.

Methods: A total of 145 CKD subjects (83 men e 62 women) with DM2 treated with oral antidiabetic drugs were included in the study and followed up to 1 year. All patients were randomly assigned 1:1 to either open-label (A) oral bicarbonate to achieve serum bicarbonate levels of 24-28 mmol/L (treatment group) or (B) no treatment (control group). The Homeostatic model assessment (HOMA) index was used to evaluate IR at study inception and conclusion. Parametric and non-parametric tests as well as linear regression were used.

Results: At baseline no differences in demographic and clinical characteristics between the two groups was observed. Average dose of bicarbonate in the treatment group was 0.7 ± 0.2 mmol/kg. Treated patients showed a better metabolic control as confirmed by lower insulin levels (13.4 ± 5.2 vs 19.9 ± 6.3; for treated and control subjects respectively; p < 0.001), Homa-IR (5.9[5.0-7.0] vs 6.3[5.3-8.2]; p = 0.01) and need for oral antidiabetic drugs. The serum bicarbonate and HOMA-IR relationship was non-linear and the largest HOMA-IR reduction was noted for serum bicarbonate levels between 24 and 28 mmol/l. Adjustment for confounders, suggests that serum bicarbonate rather than treatment drives the effect on HOMA-IR.

Conclusions: Serum bicarbonate is related to IR and the largest HOMA-IR reduction is noted for serum bicarbonate between 24 and 28 mmol/l. Treatment with bicarbonate influences IR. However, changes in serum bicarbonate explains the effect of treatment on HOMA index. Future efforts are required to validate these results in diabetic and non-diabetic CKD patients.

Trial registration: The trial was registered at www.clinicaltrial.gov (Use of Bicarbonate in Chronic Renal Insufficiency (UBI) study - NCT01640119 ).

Keywords: CKD; Diabetes; Homa-test; Metabolic acidosis; Sodium bicarbonate.

Figures

Fig. 1
Fig. 1
The bagplots describe the association between serum bicarbonate and HOMA test in subjects randomized to oral sodium bicarbonate (Treated) or conventional therapy (controls) at study inception and conclusion. Legend: The inner polygon (called bag) contains 50 % of all points. Observations outside the outermost polygon (called fence) are outliers. The observations between the bag and fence are marked by line segments. The asterisk symbol (*) near the center of the graph represents the bivariate median
Fig. 2
Fig. 2
The scatterplots represent the relationship between serum bicarbonate (a) and changes in serum bicarbonate (b) and HOMA index at study completion. Legend: solid green line represents the linear regression line; solid red line represents the smoothed linear regression line

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