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European Journal of Pharmacology Mar 2019The prevalence of type 2 diabetes mellitus (T2D) has risen in the United States and worldwide, with an increase in global prevalence from 4.7% to 8.5% between 1980 and... (Review)
Review
The prevalence of type 2 diabetes mellitus (T2D) has risen in the United States and worldwide, with an increase in global prevalence from 4.7% to 8.5% between 1980 and 2014. A variety of antidiabetic drugs are available with different mechanisms of action, and multiple drugs are often used concomitantly to improve glycemic control. One of the newest classes of oral antihyperglycemic agents is the sodium glucose cotransporter-2 (SGLT2) inhibitors or "flozins". Recent clinical guidelines have suggested the use of SGLT2 inhibitors as add-on therapy in patients for whom metformin alone does not achieve glycemic targets, or as initial dual therapy with metformin in patients who present with higher glycated hemoglobin (HbA1c) levels. The FDA has approved fixed-dose combination (FDC) tablets with each of the three available SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) and metformin. Both drug classes are associated with the rare but serious life-threatening complications that result from metabolic acidosis, including lactic acidosis (with metformin) and euglycemic diabetic ketoacidosis (with SGLT2 inhibitors). This review summarizes the current literature on the pharmacokinetics and the molecular targets of metformin and SGLT2 inhibitors. It also addresses the common adverse effects and highlights the molecular mechanisms by which this dual antihyperglycemic therapy contributes to high anion gap metabolic acidosis. In conclusion, while the combination of metformin and SGLT2 inhibitors would be a better option in improving glycemic control with a low risk of hypoglycemia, an increase in the risk of metabolic acidosis during combination therapy may be borne in mind.
Topics: Acidosis, Lactic; Benzhydryl Compounds; Canagliflozin; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Drug Therapy, Combination; Glucosides; Humans; Metformin; Risk; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 30639796
DOI: 10.1016/j.ejphar.2019.01.002 -
Jornal Brasileiro de Nefrologia 2015Metabolic acidosis is a common problem in dialysis patients and plays an important role in the pathogenesis of protein-energy malnutrition in these patients.
INTRODUCTION
Metabolic acidosis is a common problem in dialysis patients and plays an important role in the pathogenesis of protein-energy malnutrition in these patients.
OBJECTIVES
To assess the prevalence of metabolic acidosis in hemodialysis and search their association with nutritional status.
METHODS
A cross-sectional study was performed in hemodialysis patients at a single center. Nutritional status was assessed by anthropometric, biochemical and multifrequency bioelectrical impedance analysis. Metabolic acidosis was defined as serum bicarbonate (BIC) < 22 mEq/L and patients were divided into 3 groups according to BIC (< 15.15 to 21.9 and ≥ 22). The association between BIC and continuous variables was investigated using the Kruskal Wallis test. The linear correlation between BIC and the variables of the study was also tested.
RESULTS
We studied 95 patients, 59% male, mean age 52.3 years. The prevalence of metabolic acidosis was 94.7%. BMI, interdialytic weight gain and PTH were significantly different among the 3 groups of BIC. The BIC was negatively correlated with urea, phosphorus and interdialytic weight gain. There was no significant correlation with albumin, phase angle and lean body mass index.
CONCLUSION
The prevalence of metabolic acidosis was high in this population, and a lower BIC correlated with higher levels of urea, PTH, phosphorus, interdialytic weight gain and lower BMI. The evaluation of acid-basic status should be routinely implemented in dialysis patients by considering the negative effects of acidosis on the nutritional status, inflammation and bone disease.
Topics: Acidosis; Adult; Aged; Body Mass Index; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Nutritional Status; Renal Dialysis
PubMed: 26648495
DOI: 10.5935/0101-2800.20150073 -
BMJ Case Reports Dec 2021Starvation ketoacidosis (SKA) is a rarer cause of ketoacidosis. Most patients will only have a mild acidosis, but if exacerbated by stress can result in a severe...
Starvation ketoacidosis (SKA) is a rarer cause of ketoacidosis. Most patients will only have a mild acidosis, but if exacerbated by stress can result in a severe acidosis. We describe a 66-year-old man admitted with reduced consciousness and found to have a severe metabolic acidosis with raised anion gap. His body mass index (BMI) was noted to be within the healthy range at 23 kg/m; however, it was last documented 1 year previously at 28 kg/m with no clear timeframe of weight loss. While his acidosis improved with intravenous fluids, he subsequently developed severe electrolyte imbalance consistent with refeeding during his admission. Awareness of SKA as a cause for high anion gap metabolic acidosis is important and knowledge of management including intravenous fluids, thiamine, dietetic input and electrolyte replacement is vital.
Topics: Acid-Base Equilibrium; Acidosis; Aged; Humans; Ketosis; Male; Refeeding Syndrome; Starvation; Water-Electrolyte Imbalance
PubMed: 34880037
DOI: 10.1136/bcr-2021-245065 -
Frontiers in Endocrinology 2022Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of...
INTRODUCTION
Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors.
METHODS
Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated.
RESULTS
Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors.
CONCLUSIONS
Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting.
Topics: Adult; Humans; Male; Female; Hypoaldosteronism; Hyperkalemia; Aldosterone; Hyponatremia; Mineralocorticoids; Addison Disease; Retrospective Studies; Sodium; Acidosis
PubMed: 36303866
DOI: 10.3389/fendo.2022.990148 -
British Journal of Hospital Medicine... Aug 2022Metabolic acidosis is a common complication among acutely unwell hospitalised patients. Untreated, it can result in undesirable cardiovascular, respiratory and...
Metabolic acidosis is a common complication among acutely unwell hospitalised patients. Untreated, it can result in undesirable cardiovascular, respiratory and neurological consequences. Metabolic acidosis can occur as an isolated entity or coexist with other acid-base disorders, making diagnosing the aetiology difficult. Accurate identification of the underlying cause is imperative for proper and timely management. A systematic approach can help simplify the assessment of patients and can aid in establishing the correct diagnosis, even in more complex cases. This article provides a practical, step-by-step guide for the assessment of adult patients with metabolic acidosis.
Topics: Acid-Base Equilibrium; Acidosis; Adult; Humans
PubMed: 36066292
DOI: 10.12968/hmed.2021.0582 -
The Journal of International Medical... Dec 2016Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy....
Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy. Methods Eighty patients (18 - 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate. Results Blood gas analysis showed that 71% ( n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% ( n = 45), while that of mild metabolic acidosis was 15% ( n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients. Conclusions In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.
Topics: Acidosis; Adolescent; Adult; Aged; Anticonvulsants; Blood Gas Analysis; Cross-Sectional Studies; Female; Fructose; Humans; Male; Middle Aged; Respiratory Rate; Seizures; Severity of Illness Index; Topiramate
PubMed: 27789806
DOI: 10.1177/0300060516669897 -
Clinical Medicine (London, England) Mar 2024This review concerns the rare, acquired, usually iatrogenic, high-anion-gap metabolic acidosis, pyroglutamic acidosis. Pyroglutamate is a derivative of the amino acid... (Review)
Review
This review concerns the rare, acquired, usually iatrogenic, high-anion-gap metabolic acidosis, pyroglutamic acidosis. Pyroglutamate is a derivative of the amino acid glutamate, and is an intermediate in the 'glutathione cycle', by which glutathione is continuously synthesized and broken down. The vast majority of pyroglutamic acidosis cases occur in patients on regular, therapeutic doses of paracetamol. In about a third of cases, flucloxacillin is co-prescribed. In addition, the patients are almost always seriously unwell in other ways, typically with under-nourishment of some form. Paracetamol, with underlying disorders, conspires to divert the glutathione cycle, leading to the overproduction of pyroglutamate. Hypokalaemia is seen in about a third of cases. Once the diagnosis is suspected, it is simple to stop the paracetamol and change the antibiotic (if flucloxacillin is present), pending biochemistry. N-acetyl-cysteine can be given, but while the biochemical justification is compelling, the clinical evidence base is anecdotal.
Topics: Humans; Pyrrolidonecarboxylic Acid; Acetaminophen; Acidosis; Floxacillin; Anti-Bacterial Agents
PubMed: 38431210
DOI: 10.1016/j.clinme.2024.100030 -
Journal of Ayub Medical College,... 2020Blood gases can provide information about the perinatal, natal and postnatal condition of newborn. Severity of metabolic acidosis has deleterious effect on the outcome...
BACKGROUND
Blood gases can provide information about the perinatal, natal and postnatal condition of newborn. Severity of metabolic acidosis has deleterious effect on the outcome of babies. When the cord blood gases are not available the arterial blood gases are used for interpreting the status of newborn. The purpose of study was to determine the relationship between severity of metabolic acidosis at admission with the stage of hypoxic ischemic encephalopathy, and its outcome in asphyxiated neonates.
METHODS
This was descriptive cross-sectional study of 384 neonates born at ≥35 weeks to <42 weeks from June to December 2018, admitted in Neonatology department of the Children's hospital & the Institute of Child Health, Lahore within first 6 hours of birth. The neonates with history of delayed cry at birth and arterial pH ≤7.30 and base deficit ≥10 were included in the study. The pH and base deficit of babies was analyzed in relation to the stage of HIE, duration of stay and death or discharge of the babies using SPSS-20. The p-value was calculated using chi-square test.
RESULTS
Total of 470 neonates were eligible. Eighty-four neonates were excluded. Finally, 384 neonates were included and analyzed for the outcome variables. With severe metabolic acidosis pH <7.01, all the babies developed HIEII/III. Majority (82.1%) of the babies expired and 27.9% had prolonged hospital stay.
CONCLUSIONS
Increasing severity of metabolic acidosis at admission increases the likelihood of adverse outcome in asphyxiated neonates.
Topics: Acidosis; Asphyxia Neonatorum; Cross-Sectional Studies; Humans; Infant, Newborn; Patient Admission; Treatment Outcome
PubMed: 32583992
DOI: No ID Found -
Endocrine Journal Jul 2023Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have... (Review)
Review
Pseudohypoaldosteronism (PHA) type II (PHA2) is a genetic disorder that leads to volume overload and hyperkalemic metabolic acidosis. PHA2 and PHA type I (PHA1) have been considered to be genetic and pediatric counterparts to type IV renal tubular acidosis (RTA). Type IV RTA is frequently found in adults with chronic kidney disease and is characterized by hyperchloremic hyperkalemic acidosis with normal anion gap (AG). However, we recently observed that PHA1 was not always identical to type IV RTA. In this study, we focused on the acid-base balance in PHA2. Through a literature search published between 2008-2020, 46 molecularly diagnosed cases with PHA2 were identified (median age of 14 years). They comprised 11 sets of familial and 16 sporadic cases and the pathology was associated with mutations in WNK 4 (n = 1), KLHL3 (n = 17), and CUL3 (n = 9). The mean potassium (K) level was 6.2 ± 0.9 mEq/L (n = 46, range 4.0-8.6 mEq/L), whereas that of chloride (Cl) was 110 ± 3.5 mEq/L (n = 41, 100-119 mEq/L), with 28 of 41 cases identified as hyperchloremic. More than half of the cases (18/35) presented with metabolic acidosis. Although AG data was obtained only in 16 cases, all but one cases were within normal AG range. Both Cl and HCO3 levels showed significant correlations with K levels, which suggested that the degree of hyperchloremia and acidosis reflect the clinical severity, and is closely related to the fundamental pathophysiology of PHA2. In conclusion, our study confirmed that PHA2 is compatible with type IV RTA based on laboratory findings.
Topics: Adult; Humans; Child; Adolescent; Pseudohypoaldosteronism; Hypoaldosteronism; Acidosis; Mutation; Hyperkalemia
PubMed: 37081692
DOI: 10.1507/endocrj.EJ22-0607 -
Iranian Journal of Kidney Diseases Jul 2018Chronic kidney disease is defined as a glomerular filtration rate lower than 60 mL/min/1.73 m2, which is regarded as a public health priority and part of the growing... (Review)
Review
Chronic kidney disease is defined as a glomerular filtration rate lower than 60 mL/min/1.73 m2, which is regarded as a public health priority and part of the growing burden of noncommunicable diseases. Reduced kidney function is concomitant with high levels of inflammatory factors, abnormal lipid profile, and anemia, as well as bone abnormalities, calcium deposition outside the bones, endothelial dysfunction, and cardiomyopathy. Furthermore, metabolic acidosis is a common complication in chronic kidney disease that is associated with secondary hyperparathyroidism and faster kidney disease progression. Effective preventive approaches may slow progression of chronic kidney disease and reduce the risk of subsequent morbidity and mortality. It seems that correction of metabolic acidosis slows down the decline in glomerular filtration rate and is one of the noble approaches. A diet rich in fruits and vegetables instead of bicarbonate therapy is feasible and economical and appears to have a positive effect on kidney hemodynamic function.
Topics: Acid-Base Equilibrium; Acidosis; Animals; Diet, Healthy; Disease Progression; Fruit; Glomerular Filtration Rate; Humans; Hydrogen-Ion Concentration; Kidney; Renal Insufficiency, Chronic; Treatment Outcome; Vegetables
PubMed: 30087214
DOI: No ID Found