Role of Acid-Base Homeostasis in Diabetic Kidney Disease

Khairallah, Pascale; Scialla, Julia J.

doi:10.1007/s11892-017-0855-6

Cited by 14 publications

(12 citation statements)

References 107 publications

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“…While in female patients with type 2 diabetes, the similar negative correlation between HCO 3 − and the risk of diabetes remained signi cant after controlling for C-reactive protein [3]. In addition, multiple studies have pointed that organic anion as one of the sources of endogenous acids, the level of its generation rate was signi cantly rising in patients with diabetes [27]. However, higher level of AG is also a result of the accumulation of endogenous acids.…”

Section: Discussionmentioning

confidence: 84%

“…Moreover, heavier acid loading would promote the rising of blood pressure [27,28], as well as stimulate cortisol [29][30][31] and growth hormone [32] performing insulin anti-regulatory, then further triggered in ammatory response and protein consumption. Insulin resistance added the risks of type 2 diabetes and its complications, as well as poor blood pressure control and in ammation were also important mechanisms of DR [1,33].…”

Section: Discussionmentioning

confidence: 99%

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The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

Wang¹,

Yao

Li³

et al. 2020

Preprint

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Background: Current evidences supported a highly relevant between acid-load and diabetes. The rise of serum anion gap (AG) has performed the significances in metabolic acidosis. Some factors correlated to diabetes might affect its complications such as diabetic retinopathy (DR).Methods: A total of 3,411 Chinese adults with type 2 diabetes were selected form the hospital registry data on DR Sub-study of Liaoning Diabetic Microvascular Complications Study (LD-MCS), included 1,137 DR as the cases and 2,274 non-DR as the matching controls. Fasting venous blood test was applied to ascertain the ion levels, and serum AG (mmol/L) was computed by: AG = (sodium + potassium) – (chlorine + bicarbonate). According to Early Treatment for Diabetic Retinopathy Study standards, DR was diagnosed by two-field fundus photographs and classified as mild non-proliferative DR (NPDR), moderate NPDR, and vision-threatening DR (VTDR). Logistic regression models and linear regression models were used to analyze the relationships.Results: In setting of the non-acidosis, higher AG was significantly associated with DR (P = 0.001), increased with aggravating retinopathy but decreased in VTDR level (P < 0.001). Multivariable-adjusted models showed that AG quartiles were independently linked with higher odds to occurrence (P for trend < 0.001) and severity (P for trend < 0.05) of DR, but with attention to the fluctuation of 75th AG quartiles. Linear logistic regression by stepwise method suggested the growth of age (P = 0.014), glycated hemoglobin (P = 0.018), and the homeostasis model assessment of insulin resistance index (P < 0.001) played an intimate role in the association between AG and DR.Conclusions: Higher AG was independently related to the occurrence and progression of DR. Our findings suggested that serum AG might alter the risk of DR by affecting glucose metabolism and insulin sensitivity in patients with type 2 diabetes.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

Wang¹,

Yao

Li³

et al. 2020

Preprint

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“…Since metabolic acid disposal is regulated by kidneys, renal clearance impacts acid–base balance [ 76 , 77 ], and kidney disturbances can cause significant increases in NEAP values [ 27 ]. Hence, the relationship between dietary acid load and diabetes T2 can be more pronounced in participants with impaired kidney function resulting from altered hemodynamic adaptation to high acid load [ 86 ]. In the case of altered renal clearance, NEAP may impact results by underestimating the actual value of plasmatic acid load.…”

Section: Discussionmentioning

confidence: 99%

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

2018

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Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

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“…There are several clinical scenarios that entangle heart conditions and acidosis. For example, heart failure is usually accompanied by metabolic alkalosis due to drug use and neurohumoral mechanisms; however, metabolic acidosis can develop in end-stage heart failure because of reduced plasma renal flow and renal failure 47 ; during acute myocardial infarction, the drop in cardiac output could cause metabolic acidosis as a result of tissue hypoxia 48,49 ; genetic hypertension could cause hypertrophy and at the same time can be associated with metabolic acidosis 50 ; and diabetes could lead to metabolic acidosis through diabetic nephropathy 51 and diabetic ketoacidosis. 52 Metabolic acidosis was associated with an increased risk for ischemic heart disease and heart failure.…”

Section: Clinical Relevancementioning

confidence: 99%

Real‐time influence of intracellular acidification and Na⁺/H⁺ exchanger inhibition on in‐cell pyruvate metabolism in the perfused mouse heart: A ³¹P‐NMR and hyperpolarized ¹³C‐NMR study

et al. 2023

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Disruption of acid–base balance is linked to various diseases and conditions. In the heart, intracellular acidification is associated with heart failure, maladaptive cardiac hypertrophy, and myocardial ischemia. Previously, we have reported that the ratio of the in‐cell lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) activities is correlated with cardiac pH. To further characterize the basis for this correlation, these in‐cell activities were investigated under induced intracellular acidification without and with Na+/H+ exchanger (NHE1) inhibition by zoniporide. Male mouse hearts (n = 30) were isolated and perfused retrogradely. Intracellular acidification was performed in two ways: (1) with the NH4Cl prepulse methodology; and (2) by combining the NH4Cl prepulse with zoniporide. 31P NMR spectroscopy was used to determine the intracellular cardiac pH and to quantify the adenosine triphosphate and phosphocreatine content. Hyperpolarized [1‐13C]pyruvate was obtained using dissolution dynamic nuclear polarization. 13C NMR spectroscopy was used to monitor hyperpolarized [1‐13C]pyruvate metabolism and determine enzyme activities in real time at a temporal resolution of a few seconds using the product‐selective saturating excitation approach. The intracellular acidification induced by the NH4Cl prepulse led to reduced LDH and PDH activities (−16% and −39%, respectively). This finding is in line with previous evidence of reduced myocardial contraction and therefore reduced metabolic activity upon intracellular acidification. Concomitantly, the LDH/PDH activity ratio increased with the reduction in pH, as previously reported. Combining the NH4Cl prepulse with zoniporide led to a greater reduction in LDH activity (−29%) and to increased PDH activity (+40%). These changes resulted in a surprising decrease in the LDH/PDH ratio, as opposed to previous predictions. Zoniporide alone (without intracellular acidification) did not change these enzyme activities. A possible explanation for the enzymatic changes observed during the combination of the NH4Cl prepulse and NHE1 inhibition may be related to mitochondrial NHE1 inhibition, which likely negates the mitochondrial matrix acidification. This effect, combined with the increased acidity in the cytosol, would result in an enhanced H+ gradient across the mitochondrial membrane and a temporarily higher pyruvate transport into the mitochondria, thereby increasing the PDH activity at the expense of the cytosolic LDH activity. These findings demonstrate the complexity of in‐cell cardiac metabolism and its dependence on intracellular acidification. This study demonstrates the capabilities and limitations of hyperpolarized [1‐13C]pyruvate in the characterization of intracellular acidification as regards cardiac pathologies.

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Role of Acid-Base Homeostasis in Diabetic Kidney Disease

Cited by 14 publications

References 107 publications

The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Real‐time influence of intracellular acidification and Na⁺/H⁺ exchanger inhibition on in‐cell pyruvate metabolism in the perfused mouse heart: A ³¹P‐NMR and hyperpolarized ¹³C‐NMR study

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Role of Acid-Base Homeostasis in Diabetic Kidney Disease

Cited by 14 publications

References 107 publications

The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

The Association Between Anion Gap and Diabetic Retinopathy: Based on Hospital Registry Data in Liaoning Diabetic Microvascular Complications Study

Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

Real‐time influence of intracellular acidification and Na+/H+ exchanger inhibition on in‐cell pyruvate metabolism in the perfused mouse heart: A 31P‐NMR and hyperpolarized 13C‐NMR study

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Real‐time influence of intracellular acidification and Na⁺/H⁺ exchanger inhibition on in‐cell pyruvate metabolism in the perfused mouse heart: A ³¹P‐NMR and hyperpolarized ¹³C‐NMR study