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Frontiers in Endocrinology 2022Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs-... (Review)
Review
Combined diabetic ketoacidosis and hyperosmolar hyperglycemic state in type 1 diabetes mellitus induced by immune checkpoint inhibitors: Underrecognized and underreported emergency in ICIs-DM.
BACKGROUND
Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs- diabetes mellitus (DM) cases and is always ignored by physicians. This study aimed to conduct a systematic review to recognize better the rare adverse event of combined DKA-HHS associated with immune checkpoints.
METHODS
A electronic search in Pubmed/Cochrane/Web of Science, complemented by manual searches in article references, was conducted to identify clinical features of ICIs-combined DKA-HHS.
RESULTS
we identified 106 patients with ICIs- type 1 diabetes mellitus (T1DM) from 82 publications: 9 patients presented a coexistence of metabolic acidosis, severe hyperglycemia, and/or DKA; All patients were not diagnosed as combined DKA-HHS. Compared with ICIs-DKA patients, combined DKA-HHS cases were prone to higher hyperglycemia (1020 ± 102.5 vs 686.7 ± 252.6mg/dL). Moreover, acute kidney injury (87.5% vs 28.6%) and prior chemotherapy (66.7% vs 31.6%) showed higher occurrences with the onset of ICIs-HHS or combined DKA-HHS.B.
CONCLUSIONS
Combined DKA-HHS portends a poor diagnosis in patients with coexistence features of DKA and HHS, which healthcare professionals and patients should be aware of due to differences in treatment. Our observational retrospective case series shows that patients with more risk factors were more likely to develop combined DKA-HHS. We are the first to report this group of patients' clinical characteristics and outcomes.
Topics: Humans; Diabetic Ketoacidosis; Hyperglycemic Hyperosmolar Nonketotic Coma; Diabetes Mellitus, Type 1; Immune Checkpoint Inhibitors; Retrospective Studies; Hyperglycemia
PubMed: 36686495
DOI: 10.3389/fendo.2022.1084441 -
Cureus Dec 2022Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has... (Review)
Review
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disease that lacks a definitive treatment. Lately, there has been an increased interest in the scientific community about the role of arginine in the short and long-term settings of the disease. We aim to conduct a systematic review of the clinical use of arginine in the management of MELAS and explore the role of arginine in the pathophysiology of the disease. We used PubMed advanced-strategy searches and only included full-text clinical trials on humans written in the English language. After applying the inclusion/exclusion criteria, four clinical trials were reviewed. We used the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for this systematic review. We used the Cochrane Collaboration risk-of-bias tool to assess the bias encountered in each study. Overall, IV arginine seems to be effective in improving symptoms during acute attacks of MELAS, while oral arginine supplementation increases endothelial function, preventing further stroke-like episodes.
PubMed: 36686069
DOI: 10.7759/cureus.32709 -
Pharmacology 2023Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are...
INTRODUCTION
Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are high. Here, we investigate the impact of renal dysfunction and renal replacement therapy (RRT) on the outcomes of critically ill patients with metformin-associated LA (MALA). Furthermore, we assessed associations between mortality and metformin dose, metformin plasma/serum concentrations, lactate level, and arterial pH. Finally, we investigated whether the recommended classification in MALA, metformin-unrelated LA, metformin-induced LA, and LA in metformin therapy appears useful in this regard.
METHODS
We performed a retrospective analysis based on a systematic PubMed search for publications on hyperlactatemia/LA in metformin-treated ICU patients from January 1995 to February 2020. Case-level data including demographics and clinical conditions were extracted, and logistic regression analyses were performed.
RESULTS
A total of 92 ICU patients were reported. Two of these patients had no comorbidities interfering with lactate metabolism. In the overall group, arterial pH, lactate levels, and metformin plasma/serum concentrations were similar in survivors versus non-survivors. Ingested daily metformin doses and plasma/serum creatinine levels were significantly higher in survivors versus non-survivors (p = 0.007 vs. p = 0.024, respectively). Higher plasma/serum creatinine levels, higher lactate levels, and lower arterial pH were all associated with patients receiving RRT (all p < 0.05). Overall mortality was 22% (20 out of 92 patients) and did not differ between the RRT and non-RRT groups.
CONCLUSION
Mortality is high in ICU patients with metformin-associated hyperlactatemia/LA. Unexpectedly, higher ingested metformin dose and plasma/serum creatinine were associated with a better outcome. Survival was similar in patients with or without need for RRT.
Topics: Humans; Hyperlactatemia; Acidosis, Lactic; Retrospective Studies; Creatinine; Metformin; Intensive Care Units; Lactates; Hypoglycemic Agents
PubMed: 36652938
DOI: 10.1159/000528252 -
Pediatric Nephrology (Berlin, Germany) Jun 2023Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular... (Review)
Review
BACKGROUND
Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury.
METHODS
We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered.
RESULTS
For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted.
CONCLUSIONS
Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Humans; Valproic Acid; Kidney Tubules, Proximal; Kidney; Proteinuria; Epilepsy
PubMed: 36645492
DOI: 10.1007/s00467-022-05869-8 -
Cureus Dec 2022Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against... (Review)
Review
Metformin and sulphonylureas are the most commonly used first-line anti-diabetic agents. However, medical practice guidelines and clinical experience caution against using these drugs in severe diabetic kidney disease. Consequently, the choice of anti-diabetic medicine in various stages of diabetic nephropathy should balance the benefits and risks to the patient. We aim to synthesize available evidence on the effectiveness and safety of metformin concerning sulfonylureas in patients with diabetic renal disease. The COSMOS-E (Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology) and MOOSE (Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology) guidelines were followed when designing the systematic review. The present study assessed the effectiveness of metformin and sulphonylurea monotherapy regarding renal function. Studies published from 2001 to 2022 were included. We have identified 570 records from PubMed, BioMed Central, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde), ScienceDirect, and PLoS (The Public Library of Science) Medicine databases. Eight cohort studies met the inclusion criteria. All studies reported adjusted hazard ratios with confidence limits. Metformin was found to be more effective in the following events: all-cause mortality, GFR (glomerular filtration rate), ESRD (end-stage renal disease) or death events, one-year risk of death or end-stage renal disease, cardiovascular events, heart failure hospitalization, and hypoglycemic episodes. However, metformin was less effective in acute renal replacement therapy, end-stage renal disease, and/or death, with a one-year risk of acute dialysis. Lactic acidosis was not significant with metformin. The present study recommends that metformin therapy is safe compared to sulfonylurea therapy in diabetic nephropathy patients, provided that the contraindications given in the guidelines are strictly adhered to.
PubMed: 36628027
DOI: 10.7759/cureus.32286 -
World Journal of Clinical Pediatrics Nov 2022Insulin pump therapy is a real breakthrough in managing diabetes Mellitus, particularly in children. It can deliver a tiny amount of insulin and decreases the need for...
BACKGROUND
Insulin pump therapy is a real breakthrough in managing diabetes Mellitus, particularly in children. It can deliver a tiny amount of insulin and decreases the need for frequent needle injections. It also helps to maintain adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues. Children are suitable candidates for pump therapy as they need a more freestyle and proper metabolic control to ensure adequate growth and development. Therefore, children and their caregivers should have proper education and training and understand the proper use of insulin pumps to achieve successful pump therapy. The pump therapy continuously improves to enhance its performance and increase its simulation of the human pancreas. Nonetheless, there is yet a long way to reach the desired goal.
AIM
To review discusses the history of pump development, its indications, types, proper use, special conditions that may enface the children and their families while using the pump, its general care, and its advantages and disadvantages.
METHODS
We conducted comprehensive literature searches of electronic databases until June 30, 2022, related to pump therapy in children and published in the English language.
RESULTS
We included 118 articles concerned with insulin pumps, 61 were reviews, systemic reviews, and meta-analyses, 47 were primary research studies with strong design, and ten were guidelines.
CONCLUSION
The insulin pump provides fewer needles and can provide very tiny insulin doses, a convenient and more flexible way to modify the needed insulin physiologically, like the human pancreas, and can offer adequate and optimal glycemic control to reduce the risk of metabolic derangements in different tissues.
PubMed: 36439904
DOI: 10.5409/wjcp.v11.i6.463 -
Cureus Oct 2022The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30... (Review)
Review
The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30 and under. In this meta-analysis, the Overall use of IV insulin in patients with mild/moderate vs. severe diabetic ketoacidosis was compared in randomized controlled trial articles from January 2011 to December 2021 using EMBASE, Medline, and CENTRAL. Only 8 of 3258 studies met the inclusion criteria. This review shows that intravenous insulin can significantly decrease plasma glucose and potassium levels in mild/moderate cases and severe cases. However, it can decrease the resolution time of acidosis more quickly in mild/moderate cases than in severe cases. In the current meta-analysis, the use of IV insulin is secure and efficient. There was no discernible difference in the effectiveness of IV insulin between mild/moderate and severe DKA.
PubMed: 36439560
DOI: 10.7759/cureus.30721 -
Lancet (London, England) Nov 2022Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.
METHODS
We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.
FINDINGS
We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.
INTERPRETATION
In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.
FUNDING
UK Medical Research Council and Kidney Research UK.
Topics: Humans; Adult; Adolescent; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic; Heart Failure; Ketosis; Disease Progression; Glucose; Sodium; Randomized Controlled Trials as Topic
PubMed: 36351458
DOI: 10.1016/S0140-6736(22)02074-8 -
Journal of Medical Virology Jan 2023
Meta-Analysis
Comments on Rahmati et al., The global impact of COVID-19 pandemic on the incidence of pediatric new-onset type 1 diabetes and ketoacidosis: A systematic review and meta-analysis. J Med Virol. 2022; 1-16 (doi: 10.1002/jmv.27996).
Topics: Humans; Child; COVID-19; Diabetes Mellitus, Type 1; Incidence; Pandemics; Ketosis
PubMed: 36324006
DOI: 10.1002/jmv.28272 -
BMC Geriatrics Oct 2022Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT)...
BACKGROUND
Ketosis has been exploited for its neuroprotective impact and treatment of neurological conditions via ketone production. Exogenous medium-chain triglyceride (MCT) supplementation may induce nutritional ketosis. The aim of this systematic review is to explore the effects of MCTs on memory function in older adults without cognitive impairment.
METHODS
A systematic literature search of PubMed, Cochrane Library, Scopus, and Web of Science was employed from inception until April 2022 for randomized controlled trials (RCTs) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, investigating the impact of MCT oils on components of memory. Risk of bias (RoB2) tool was utilized for quality assessment.
RESULTS
Six trials were included for qualitative synthesis, in which two studies examined the effect of MCTs through a ketogenic meal. MCT supplementation compared to controls was associated with improved indices of memory function in 4 out of 6 studies, particularly working memory. A meta-analysis was not employed due to the low number of studies, therefore, a true effect measure of MCT supplementation was not explored.
CONCLUSIONS
MCT supplementation may enhance working memory in non-demented older adults. These effects may be more prominent in individuals with lower baseline scores, from short and long-term supplementation. Further studies are warranted to confirm these findings in terms of optimal dose and MCTs composition, which may protect from memory decline during aging.
Topics: Humans; Aged; Randomized Controlled Trials as Topic; Triglycerides; Ketone Bodies; Ketosis; Oils
PubMed: 36273115
DOI: 10.1186/s12877-022-03521-6