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Physiology (Bethesda, Md.) May 2024The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like... (Review)
Review
The discovery of insulin approximately a century ago greatly improved the management of diabetes, including many of its life-threatening acute complications like ketoacidosis. This breakthrough saved many lives and extended the healthy lifespan of many patients with diabetes. However, there is still a negative perception of ketone bodies stemming from ketoacidosis. Originally, ketone bodies were thought of as a vital source of energy during fasting and exercise. Furthermore, in recent years, research on calorie restriction and its potential impact on extending healthy lifespans, as well as studies on ketone bodies, have gradually led to a reevaluation of the significance of ketone bodies in promoting longevity. Thus, in this review, we discuss the emerging and hidden roles of ketone bodies in various organs, including the heart, kidneys, skeletal muscles, and brain, as well as their potential impact on malignancies and lifespan.
Topics: Humans; Ketone Bodies; Ketosis; Diabetes Mellitus; Longevity; Heart
PubMed: 38260943
DOI: 10.1152/physiol.00031.2023 -
Pediatric Nephrology (Berlin, Germany) Dec 2023Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized...
BACKGROUND
Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs.
METHODS
Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics.
RESULTS
Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4-15.2) years and post-transplant follow-up of 3 (IQR 1-5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03-0.3) and 0.24 mEq/L (95% CI: 0.01-0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72-0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m (95% CI 4.4-12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis.
CONCLUSIONS
Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Adult; Humans; Child; Child, Preschool; Adolescent; Kidney Transplantation; Bicarbonates; Acidosis; Renal Insufficiency, Chronic; Transplant Recipients; Alkalies
PubMed: 37422606
DOI: 10.1007/s00467-023-06072-z -
BJA Education Mar 2024
Review
PubMed: 38375495
DOI: 10.1016/j.bjae.2023.12.005 -
Kidney360 Jun 2024
Randomized Controlled Trial
Topics: Humans; Hyperkalemia; Renal Insufficiency, Chronic; Acidosis; Silicates; Male
PubMed: 38622759
DOI: 10.34067/KID.0000000000000446 -
The American Journal of the Medical... May 2024Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine... (Review)
Review
Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine abnormalities. APS type 2 is the most common subtype of the syndrome, more often observed in adulthood, with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus type 1. Adrenal insufficiency is an essential and necessary clinical manifestation of the syndrome, as it is observed in 100 % of the cases, while it can be accompanied by hyperchloremic metabolic acidosis. Herein, we present a 23 years-old patient with adrenal insufficiency in the context of autoimmune polyglandular syndrome type 2 with coexisting autoimmune thyroiditis and metabolic acidosis with an increased anion gap attributed to prolonged malnutrition. Additionally, we analyze the main clinical features of adrenal insufficiency, which is a central component of autoimmune polyglandular syndrome; highlight characteristics that differentiate the major APS subtypes.
PubMed: 38801948
DOI: 10.1016/j.amjms.2024.05.019 -
Reviews in Endocrine & Metabolic... Aug 2023Interpretation of existing data revealed that chronic metabolic acidosis is a pathognomic feature for type 2 diabetes (T2D), which is described here as "chronic... (Review)
Review
Interpretation of existing data revealed that chronic metabolic acidosis is a pathognomic feature for type 2 diabetes (T2D), which is described here as "chronic metabolic acidosis of T2D (CMAD)" for the first time. The biochemical clues for the CMAD are summarised in the following; low blood bicarbonate (high anionic gap), low pH of interstitial fluid and urine, and response to acid neutralization, while the causes of extra protons are worked out to be; mitochondrial dysfunction, systemic inflammation, gut microbiota (GM), and diabetic lung. Although, the intracellular pH is largely preserved by the buffer system and ion transporters, a persistent systemic mild acidosis leaves molecular signature in cellular metabolism in diabetics. Reciprocally, there are evidences that CMAD contributes to the initiation and progression of T2D by; reducing insulin production, triggering insulin resistance directly or via altered GM, and inclined oxidative stress. The details about the above clues, causes and consequences of CMAD are obtained by searching literature spanning between 1955 and 2022. Finally, the molecular bases of CMAD are discussed in details by interpretation of an up-to-date data and aid of well constructed diagrams, with a conclusion unravelling that CMAD is a major player in T2D pathophysiology. To this end, the CMAD disclosure offers several therapeutic potentials for prevention, delay or attenuation of T2D and its complications.
Topics: Humans; Chronic Disease; Diabetes Mellitus, Type 2; Acidosis; Hydrogen-Ion Concentration; Extracellular Space; Ion Transport; Gastrointestinal Microbiome
PubMed: 37380824
DOI: 10.1007/s11154-023-09816-2 -
Postgraduate Medical Journal Aug 2023Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in... (Review)
Review
Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.
Topics: Humans; Thiamine Deficiency; Thiamine; Acidosis, Lactic; Alcoholism; Food
PubMed: 37125640
DOI: 10.1136/pmj-2022-141972 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2023
Topics: Humans; Acidosis; Ketosis; Gastric Inhibitory Polypeptide; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-2 Receptor
PubMed: 37938168
DOI: 10.1080/15563650.2023.2277337 -
The American Journal of Emergency... Oct 2023Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality. (Review)
Review
INTRODUCTION
Metformin toxicity is a rare but serious condition that carries with it a high rate of morbidity and mortality.
OBJECTIVE
This review highlights the pearls and pitfalls of metformin toxicity, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence.
DISCUSSION
Metformin is a common medication used for treatment of diabetes mellitus. Metformin toxicity is a spectrum of conditions that may be differentiated into three subgroups: metformin-associated lactic acidosis (MALA), metformin-induced lactic acidosis (MILA), and metformin-unrelated lactic acidosis (MULA). MILA is a condition found predominantly in patients chronically taking metformin or those with large acute overdoses. Conversely, MULA occurs in patients on metformin but with a critical illness stemming from a separate cause. MALA is rare but the most severe form, with mortality rates that reach 50%. Differentiating these entities is difficult in the ED setting without obtaining metformin levels. Patients with metformin toxicity present with nonspecific gastrointestinal symptoms and vital sign abnormalities. Laboratory analysis will reveal a high lactate with anion gap metabolic acidosis. Patients presenting with elevated lactate levels in the setting of metformin use should be considered at risk for the most severe form, MALA. Patients with MALA require aggressive treatment with intravenous fluids, treatment of any concomitant condition, and early consideration of hemodialysis, along with specialist consultation such as nephrology and toxicology.
CONCLUSIONS
An understanding of metformin toxicity can assist emergency clinicians in diagnosing and managing this potentially deadly disease.
Topics: Humans; Metformin; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Acidosis, Lactic; Prevalence; Lactic Acid
PubMed: 37517113
DOI: 10.1016/j.ajem.2023.07.020 -
Maedica Dec 2023ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic...
ST waveform analysis (STAN) was introduced to improve the interpretation of cardiotocography (CTG) resulting in reduction of unnecessary interventions and metabolic acidosis. A systematic review was conducted with the aim to evaluate the effect of STAN method compared with isolated CTG on perinatal and neonatal outcomes. A search of electronic databases (PubMed, Cochrane, Scopus) was conducted to identify randomized controlled trials (RCTs) in English language. Outcomes considered operative deliveries, fetal blood sampling (FBS), metabolic acidosis, perinatal and neonatal death, neonatal seizures, neonatal encephalopathy, transfer to the neonatal intensive care unit (NICU) and Apgar score. Seven RCTs were included in the present review. The first two RCTs showed that the combination of STAN and CTG was a better option than using CTG alone, because there was a documented reduction in the rate of operative deliveries due to fetal distress and metabolic acidosis. The following studies showed no statistically significant changes with the combination of methods, except from a reduction in FBS. The findings from the RCTs were inconclusive. Most studies did not demonstrate a superiority of the combination regarding operative deliveries and neonatal outcomes but there were many methodological differences between the trials.
PubMed: 38348066
DOI: 10.26574/maedica.2023.18.4.684