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Diabetes Care Jun 2023Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor... (Review)
Review
BACKGROUND
Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM are limited.
PURPOSE
To systematically review available evidence to identify presentation characteristics and risk factors for early or severe presentations of adult patients with CIADM.
DATA SOURCES
MEDLINE and PubMed databases were reviewed.
STUDY SELECTION
English full text articles from 2014 to April 2022 were identified with a predefined search strategy. Patients meeting diagnostic criteria for CIADM with evidence of hyperglycemia (blood glucose level >11 mmol/L or HbA1c ≥6.5%) and insulin deficiency (C-peptide <0.4 nmol/L and/or diabetic ketoacidosis [DKA]) were included for analysis.
DATA EXTRACTION
With the search strategy we identified 1,206 articles. From 146 articles, 278 patients were labeled with "CIADM," with 192 patients meeting our diagnostic criteria and included in analysis.
DATA SYNTHESIS
Mean ± SD age was 63.4 ± 12.4 years. All but one patient (99.5%) had prior exposure to either anti-PD1 or anti-PD-L1 therapy. Of the 91 patients tested (47.3%), 59.3% had susceptibility haplotypes for type 1 diabetes (T1D). Median time to CIADM onset was 12 weeks (interquartile range 6-24). DKA occurred in 69.7%, and initial C-peptide was low in 91.6%. T1D autoantibodies were present in 40.4% (73 of 179) and were significantly associated with DKA (P = 0.0009) and earlier time to CIADM onset (P = 0.02).
LIMITATIONS
Reporting of follow-up data, lipase, and HLA haplotyping was limited.
CONCLUSIONS
CIADM commonly presents in DKA. While T1D autoantibodies are only positive in 40.4%, they associate with earlier, more severe presentations.
Topics: Adult; Humans; Middle Aged; Aged; Diabetes Mellitus, Type 1; C-Peptide; Risk Factors; Insulin, Regular, Human; Autoantibodies; Diabetic Ketoacidosis
PubMed: 37220262
DOI: 10.2337/dc22-2202 -
Diabetic Medicine : a Journal of the... Jan 2022To systematically review the literature concerning the psychosocial factors associated with repeat diabetic ketoacidosis for people living with type 1 diabetes.
AIM
To systematically review the literature concerning the psychosocial factors associated with repeat diabetic ketoacidosis for people living with type 1 diabetes.
METHODS
PsycInfo, Web of Science, CINAHL, PubMed and ASSIA were searched according to a registered study protocol (PROSPERO CRD42020167381). Data were extracted into a coding spreadsheet, and findings were synthesised narratively. Included papers were also subject to a quality assessment.
RESULTS
The search yielded 548 unique articles, of which 22 met inclusion criteria for this review. There was considerable variance across studies with regard to design, quality and outcome measured. Nevertheless, there was relatively consistent evidence to suggest that repeat diabetic ketoacidosis in type 1 diabetes is associated with female gender, adolescent to young adult age range, lower socio-economic status and poor mental health. Some evidence was also observed for the role of ethnicity and, for children and young people at least, family, social and behavioural issues. However, this was limited by issues of methodological rigour and scant investigation.
CONCLUSIONS
The review identified four psychosocial factors that appear to play a key role in the cycle of repeat diabetic ketoacidosis. Individuals with these factors present may benefit from targeted support and interventions by specialist healthcare professionals. Knowledge and understanding in this area would be considerably enhanced via increased use of prospective study designs and greater consistency in the operationalisation of variables across studies.
Topics: Cognitive Behavioral Therapy; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Health Personnel; Humans; Mental Health
PubMed: 34324739
DOI: 10.1111/dme.14663 -
BMJ Open Oct 2022To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. (Meta-Analysis)
Meta-Analysis
Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials.
OBJECTIVES
To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes.
METHODS
We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI.
RESULTS
We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion.
CONCLUSIONS
Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD.
PROSPERO REGISTRATION NUMBER
CRD42021239807.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36241355
DOI: 10.1136/bmjopen-2021-060655 -
World Journal of Clinical Cases Aug 2023Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below...
BACKGROUND
Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population.
AIM
To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.
METHODS
We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings.
RESULTS
Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments.
CONCLUSION
Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.
PubMed: 37727728
DOI: 10.12998/wjcc.v11.i24.5700 -
Diabetes & Metabolic Syndrome 2021/Aim: Various reports of the occurrence of type 1 diabetes mellitus (T1DM) in patients with COVID-19 have been published, denoting an association between both diseases....
BACKGROUND
/Aim: Various reports of the occurrence of type 1 diabetes mellitus (T1DM) in patients with COVID-19 have been published, denoting an association between both diseases. Therefore, we conducted this systematic review to summarize the prevalence of T1DM in COVID-19 patients and to identify the clinical presentations and outcomes in this patient population.
MATERIALS AND METHODS
Up to 10/27/2020, Medline, Embase, cochrane and google scholar databases were searched for original studies investigating the association between COVID-19 and T1DM. A manual search was conducted to identify missing studies. The quality of included studies was analyzed by the National Institute of Health (NIH) risk of bias tool. Outcomes included length of hospital stay, hospitalization, intensive care unit (ICU) admission, diabetic ketoacidosis (DKA), severe hypoglycemia, and death.
RESULTS
Fifteen studies were included in the qualitative analysis. Included studies reported data of both adult and pediatric patients. The prevalence of T1DM in COVID-19 patients ranged from 0.15% to 28.98%, while the rate of COVID-19 in patients with T1DM ranged from 0% to 16.67%. Dry cough, nausea, vomiting, fever and elevated blood glucose levels were the most commonly reported presentations. The investigated outcomes varied widely among studied populations.
CONCLUSIONS
The prevalence of T1DM in patients with COVID-19 ranged from 0.15% to 28.98%. The most common presentation of COVID-19 in patients with T1DM included fever, dry cough, nausea and vomiting, elevated blood glucose and diabetic ketoacidosis. The outcomes of COVID-19 in terms of length of hospital stay, hospitalization, ICU admission, DKA rate, and severe hypoglycemia were reported variably in included studies. Due to the heterogeneous study populations and the presence of many limitations, more studies are still warranted to reach a definitive conclusion.
Topics: Blood Glucose; COVID-19; Diabetes Mellitus, Type 1; Humans; Length of Stay
PubMed: 33592371
DOI: 10.1016/j.dsx.2021.02.009 -
Glucagon-like peptide-1 receptor agonists as add-on therapy to insulin for type 1 diabetes mellitus.Frontiers in Pharmacology 2023To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes. A...
To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) used as an adjunct to insulin therapy in adults with type 1 diabetes. A search of electronic databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from 1 January 1950 to 23 May 2021 was conducted to find randomized controlled trials. The primary outcome was the change in HbA1c. Eight efficacy and six safety secondary endpoints were evaluated meta-analysis. Weighted mean difference (WMD) and odds ratio (OR), alongside 95% confidence interval (CI), were calculated using the random effects model. Among 1,379 candidate studies, 11 trials comprising 2,856 participants satisfied the inclusion criteria. Overall, GLP-1 RA adjunctive therapy reduced HbA1c by -0.21% (95% CI, -0.33 to -0.10), weight by -4.04 kg (-4.8 to -3.27), systolic pressure by -2.57 mmHg (-4.11 to -1.03), and diastolic blood pressure by -1.02 mmHg (-1.99 to -0.06). In addition, there was a decrease in prandial insulin dose (WMD, -4.23 IU; 95% CI, -5.26 to -3.20), basal insulin dose (-2.40 IU; -3.93 to -0.87), and total insulin dose (-5.73 IU; -10.61 to -0.86). Moreover, GLP-1 RAs did not increase the incidence of severe hypoglycemia, diabetic ketoacidosis, or severe adverse events. However, GLP-1 RAs increased the incidence of gastrointestinal adverse events (OR, 2.96; 95% CI, 2.33-3.77). Our meta-analysis of randomized clinical trials suggests moderate beneficial effects of GLP-1 RAs on the metabolic profile in patients with type 1 diabetes, without an increased risk of serious adverse events. https://www.crd.york.ac.uk/PROSPERO; Identifier: CRD 42020199840.
PubMed: 38249345
DOI: 10.3389/fphar.2023.975880 -
Cureus Jan 2022Traditionally, normal saline solution (NSS) has been the fluid of choice in diabetic ketoacidosis (DKA) patients, but the NSS is an acidic fluid and may lead to the... (Review)
Review
Traditionally, normal saline solution (NSS) has been the fluid of choice in diabetic ketoacidosis (DKA) patients, but the NSS is an acidic fluid and may lead to the delayed resolution of DKA. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry to compare the efficacy of low chloride solutions with normal saline solution in DKA resolution. Randomized clinical trials with normal saline as a control arm and low chloride solutions as an intervention arm were included. Four studies were included in the analysis. The investigated outcomes, including time to resolution for DKA and duration of insulin infusion, varied depending on the endpoint were reported in the studies. Overall, balanced solutions were generally associated with faster correction of pH. The time to reach overall DKA endpoints was comparable in both groups. We concluded that crystalloid solutions may be used as an initial resuscitation fluid in the DKA population and may lead to earlier resolution of acidosis. More clinical trial data is required to reach statistical significance for the hypothesis.
PubMed: 35186583
DOI: 10.7759/cureus.21324 -
Diabetes, Obesity & Metabolism Jan 2022To assess the efficacy and safety of sotagliflozin in patients with type 2 diabetes. (Meta-Analysis)
Meta-Analysis
AIM
To assess the efficacy and safety of sotagliflozin in patients with type 2 diabetes.
METHODS
We searched Medline, Embase, the Cochrane Library, and grey literature sources up to August 2021 for randomized controlled trials (RCTs) that compared sotagliflozin with placebo or other antidiabetic agents in patients with type 2 diabetes. Our primary outcome was change in HbA1c from baseline. We additionally assessed three secondary efficacy and 15 safety outcomes. We synthesized data using weighted mean differences (WMDs) and odds ratios (ORs), along with 95% confidence intervals (CIs).
RESULTS
We included 11 RCTs comprising 16 411 subjects in the meta-analysis. Compared with placebo, sotagliflozin reduced HbA1c (WMD -0.42%, 95% CI -0.56 to -0.29), body weight (WMD -1.33 kg, 95% CI -1.57 to -1.09), and systolic blood pressure (WMD -2.44 mmHg, 95% CI -2.81 to -2.07). No difference was evident against other active comparators. Sotagliflozin reduced myocardial infarction (OR 0.72, 95% CI 0.54 to 0.97) and heart failure (OR 0.68, 95% CI 0.58 to 0.79) compared with placebo, and had a neutral effect on all-cause mortality, cardiovascular mortality, and stroke. Treatment with sotagliflozin was safe regarding the incidence of serious adverse events, hypoglycaemia, and diabetic ketoacidosis. Nevertheless, it was associated with an increased incidence of diarrhoea, genital infections, and volume depletion events.
CONCLUSIONS
Sotagliflozin reduces blood glucose, body weight, and systolic blood pressure, and demonstrates a beneficial effect on heart failure and myocardial infarction. Its overall safety profile is comparable with other sodium-glucose co-transporter-2 inhibitors.
Topics: Diabetes Mellitus, Type 2; Glycosides; Humans; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 34545668
DOI: 10.1111/dom.14555 -
Journal of Diabetes Research 2022Ramadan is the sacred month of the Islamic Hijri (lunar) calendar, and during this entire month, healthy adult Muslims abstain from eating and drinking from dawn to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ramadan is the sacred month of the Islamic Hijri (lunar) calendar, and during this entire month, healthy adult Muslims abstain from eating and drinking from dawn to sunset. Muslims with Type 2 Diabetes Mellitus (T2DM) who choose to fast during Ramadan encounter major risks such as hypoglycemia, hyperglycemia, diabetic ketoacidosis, dehydration, and thrombosis. Although patients with poor glycemic control and on multiple insulin injections are at high risk and exempt from fasting, many still insist on it. Thus, healthcare professionals play a pivotal role in managing diabetes-related complications in patients who fast during Ramadan. However, there is a lack of standard guidelines to be followed in association with structured education and administration of drugs and dosage. Therefore, we performed a systematic review and meta-analysis of the literature to determine the safety and efficacy of different classes of drugs and the importance of structured education during Ramadan.
METHODS
In this review, an extensive PubMed search was performed to obtain literature on T2DM patients who fast during the month of Ramadan until the year 2020. Preference was given to fully downloadable articles. The articles were extracted based on the eligibility criteria. The extracted data were analyzed using Review Manager software version 5.3.
RESULTS
A total of 32 articles were included for the review and 7 studies for meta-analysis. Majority of the studies demonstrated the importance of structured education either as a group session or as a one-on-one session with the healthcare professionals in preventing diabetes-related risks during Ramadan. As far as glucose-lowering drugs are concerned, DPP-4 inhibitor combined with metformin remains the drug of choice for T2DM patients who fast during Ramadan. The newer class of glucose-lowering agents appear to lower the risk of hypoglycemia in comparison with sulphonylureas, while among sulphonylureas gliclazide is relatively safe. The meta-analysis indicates that DPP-4 inhibitors would significantly reduce the risk of hypoglycemia as compared to sulphonylurea (odds ratio = 0.38, 95% CI: 0.26 to 0.55, < 0.00001).
CONCLUSION
The results of our systematic review show that structured education and counselling by healthcare professionals can be an effective tool in preventing complications associated with fasting during Ramadan in people with T2DM. Additionally, the safest class of oral glucose-lowering drugs preferred during Ramadan fasting in T2DM patients is DPP-4 inhibitors.
Topics: Adult; Diabetes Mellitus, Type 2; Holidays; Humans; Hypoglycemic Agents; Islam; Medication Adherence; Patient Education as Topic
PubMed: 35242880
DOI: 10.1155/2022/3846253 -
International Immunopharmacology Jun 2022Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological... (Review)
Review
Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological disorders, astrocyte disintegration leads to the release of glial fibrillary acidic protein (GFAP) from tissue into the bloodstream. Elevated serum levels of GFAP can serve as blood biomarkers, and a useful prognostic tool to facilitate the early diagnosis of several neurological diseases ranging from stroke to neurodegenerative disorders. This systematic review synthesizes studies published between January 2012 and September 2021 that used GFAP as a potential blood biomarker to detect neurological disorders. The following electronic databases were accessed: MEDLINE, Scopus, and Web of Science. In all the databases, the following search strategy was used: ¨GFAP¨ OR ¨glial fibrillary acidic protein¨ AND ¨neurological¨ OR ¨neurodegenerative¨ AND ¨plasma¨ OR ¨serum¨. The initial search identified 1152 articles. After the exclusion criteria were applied, 48 publications that reported GFAP levels in neurological disorders were identified. A total of16 different neurological disorders that have plasmatic GFAP levels as a possible biomarker for the disease were described in the articles, being: multiple sclerosis, frontotemporal lobar degeneration, Alzheimer's disease, Parkinson disease, COVID-19, epileptic seizures, Wilson Disease, diabetic ketoacidosis, schizophrenia, autism spectrum disorders, major depressive disorder, glioblastoma, spinal cord injury, asthma, neuromyelitis optica spectrum disorder and Friedreich's ataxia. Our review shows an association between GFAP levels and the disease being studied, suggesting that elevated GFAP levels are a potentially valuable diagnostic biomarker in the evaluation of different neurological diseases.
Topics: Biomarkers; Body Fluids; COVID-19; Depressive Disorder, Major; Glial Fibrillary Acidic Protein; Humans; Nervous System Diseases; Prognosis
PubMed: 35255304
DOI: 10.1016/j.intimp.2022.108624