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Journal of Family Medicine and Primary... Mar 2022Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) rarely cause euglycemic diabetic ketoacidosis (euDKA) in diabetic patients. The aim was to identify...
BACKGROUND
Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) rarely cause euglycemic diabetic ketoacidosis (euDKA) in diabetic patients. The aim was to identify demographic, clinical, and predisposing factors for euDKA from published case reports.
METHODS
A systematic review of published case reports of euDKA in patients receiving SGLT2 inhibitors and meta-analysis of clinical trials to quantify the risk ratio (RR) of DKA in patients receiving SGLT2 inhibitors. PubMed and EMBASE databases were searched for the case reports of and clinical trials from January 2010 to August 2020. Studies published in English language were included and other languages were excluded. Data related to patients' demography, clinical presentation, drug and dose of SGLT2 inhibitors, and concomitant medication were extracted. Incidence of diabetic ketoacidosis (DKA) extracted from clinical trials. Data related to demographic, clinical, and other parameters presented as ratios and proportions and incidence of DKA in RR using Review Manager 5.3.
RESULTS
Forty-seven of 160 reports with an aggregate of 77 patients were included in the analysis. The majority of the patients were females (67.53%), with T2DM and with gastrointestinal symptoms (58%). Surgery was the most common precipitating factor (/ = 15/77). Canagliflozin (/ = 34/77) was the commonest SGLT2 inhibitor reported along with metformin as the concomitant medication (63.6%). The pooled RR of DKA was 3.70 (95%CI 2.58, 5.29) and I = 0%.
CONCLUSION
euDKA is commonly seen in middle-aged female, T2DM patients taking SGLT2 inhibitors along with metformin. The risk of DKA in patients receiving SGLT2 inhibitors increases by 3.7 times than the other medication.
PubMed: 35495849
DOI: 10.4103/jfmpc.jfmpc_644_21 -
Frontiers in Endocrinology 2022Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous reports suggest that the Coronavirus Disease-2019 (COVID-19) pandemic might have affected incidences of diabetic ketoacidosis (DKA) and new diagnoses of type 1 diabetes. This systematic review and meta-analysis aimed to estimate the risk of DKA, including severe DKA, during the COVID-19 pandemic versus the prior-to-COVID-19 period among pediatric patients with type 1 diabetes.
METHODS
PubMed and EMBASE were searched for observational studies investigating the risk of DKA among pediatric patients with type 1 diabetes during the COVID-19 pandemic and the prior-to-COVID-19 period. A random meta-analysis model was performed to estimate the relative risk of DKA during the COVID-19 pandemic compared to before the pandemic. Subgroup analyses were conducted based on the type 1 diabetes status, established or newly diagnosed. In addition, sensitivity analysis was conducted for studies that reported results from adjusted analysis for potential confounders using fixed effect model.
RESULTS
A total of 20 observational studies reported the risk of DKA, of which 18 reported the risk of severe DKA. The risks of DKA and severe DKA were 35% (RR 1.35, 95%CI 1.2-1.53, = 71%) and 76% (RR 1.76, 95%CI 1.33-2.33, 44%) higher in the during-COVID-19 group compared to the prior-to-COVID-19 group, respectively. Among patients with newly diagnosed type 1 diabetes, the risk of DKA was 44% higher for the during-COVID-19 group compared to the prior-to-COVID-19 group (RR 1.44, 95%CI 1.26-1.65; = 64%). Only two studies reported the risk of DKA among patients with established type 1 diabetes and the cumulative risk was not statistically significant. In the sensitivity analysis, four studies reported an adjusted odds ratio (aOR) of the risk of DKA during COVID-19 compared to the prior-to-COVID-19 period. The fixed estimate from the meta-analysis found an increase in the risk of DKA in the during-COVID-19 group compared to the prior-to-COVID-19 group (aOR 2.04, 95%CI 1.66-2.50).
CONCLUSIONS
This study showed that DKA risk, especially the risk of severe DKA, has increased significantly during the pandemic. Healthcare systems must be aware and prepared for such an increase in DKA cases and take all necessary measures to prevent future spikes during the pandemic.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272775, identifier PROSPERO [CRD42021272775].
Topics: COVID-19; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Incidence; Pandemics; Pediatrics
PubMed: 35355556
DOI: 10.3389/fendo.2022.856958 -
Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
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 -
Journal de Mycologie Medicale Aug 2022Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection... (Review)
Review
Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients. Coexisting mucormycosis, Covid-19 along with diabetes mellitus increase the likelihood of mortality. Despite its occurrence since the beginning of the pandemic, there are still unanswered concerns regarding the origin of this fungal infection and mortality rate and/or relation with diabetic patients. In this review, we describe the detailed view of causative pathogens responsible for mucormycosis, diabetes mellitus and Covid-19 association along with the morbidity cases during the latest Covid-19 crisis. In the case of mucormycosis diagnosis, imaging, histopathological confirmation, fungal culture and molecular identification methods should be considered. Once mucormycosis is diagnosed, a combined treating method consisting of antifungals administration like amphotericin B, surgical intervention is needed for the reversal of the underlying condition. Early detection of this potentially life-threatening infection and timely care is needed in lowering mortality rates.
Topics: Amphotericin B; COVID-19; Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Mucormycosis
PubMed: 35219907
DOI: 10.1016/j.mycmed.2022.101257 -
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 -
Critical Care Explorations Jan 2022This systematic review and meta-analysis compared the use of saline to balanced crystalloid for fluid resuscitation in patients with diabetic ketoacidosis (DKA). (Review)
Review
OBJECTIVES
This systematic review and meta-analysis compared the use of saline to balanced crystalloid for fluid resuscitation in patients with diabetic ketoacidosis (DKA).
DATA SOURCES
We searched databases including Medline, Embase, and the Cochrane registry.
STUDY SELECTION
We included randomized controlled trials (RCTs) that compared saline to balanced crystalloid in patients with DKA.
DATA EXTRACTION
We pooled estimates of effect using relative risk for dichotomous outcomes and mean differences (MDs) for continuous outcomes, both with 95% CIs. We assessed risk of bias for included RCTs using the modified Cochrane tool and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation methodology.
DATA SYNTHESIS
We included eight RCTs ( = 482 patients). Both time to DKA resolution (MD, 3.51 hr longer; 95% CI, 0.90 longer to 6.12 longer; moderate certainty) and length of hospital stay (MD, 0.89 d longer in saline group; 95% CI, 0.34 longer to 1.43 d longer; moderate certainty) are probably longer in the saline group compared with the balanced crystalloid group, although for the latter, the absolute difference (under 1 d) is small. Post-resuscitation serum chloride level may be higher (MD, 1.62 mmol/L higher; 95% CI, 0.40 lower to 3.64 higher; low certainty), and post-resuscitation serum bicarbonate is probably lower (MD, 1.50 mmol/L; 95% CI, 2.33 lower to 0.67 lower; moderate certainty) in those receiving saline.
CONCLUSIONS
In patients with DKA, the use of saline may be associated with longer time to DKA resolution, higher post-resuscitation serum chloride levels, lower post-resuscitation serum bicarbonate levels, and longer hospital stay compared with balanced crystalloids. Pending further data, low to moderate certainty data support using balanced crystalloid over saline for fluid resuscitation in patients with DKA.
PubMed: 35018349
DOI: 10.1097/CCE.0000000000000613 -
Diabetology & Metabolic Syndrome Oct 2021One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA).
BACKGROUND
One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA).
OBJECTIVES
To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA.
DESIGN
A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed.
METHODS
Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient's final treatment outcome (survival or death).
RESULTS
Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from < 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399-638 mg/dl], 11.4% [IQR 9.9-13.5%], 7.16 [IQR 7.00-7.22], 10 mmol/l [IQR 6.9-13 mmol/l], and 24.5 mEq/l [18-29.2 mEq/l]; respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27%; p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07-15.19; p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38-7.91; p = 0.007], and male gender [OR 2.61, 95% CI 1.37-5.17; p = 0.004] compared to those who survived.
CONCLUSION
DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are individuals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level > 1000 mg/dl, and anion gap ≥ 30 mEq/l.
PubMed: 34702335
DOI: 10.1186/s13098-021-00740-6 -
Cureus Sep 2021Diabetes mellitus (DM) is associated with dreadful changes in the cardiovascular and renal systems, causing increased morbidity and mortality. Sodium-glucose... (Review)
Review
Diabetes mellitus (DM) is associated with dreadful changes in the cardiovascular and renal systems, causing increased morbidity and mortality. Sodium-glucose cotransport-2 (SGLT2) inhibitors belong to the oral hypoglycemic group of drugs believed to reduce these events by various mechanisms in DM. We performed a systematic review to determine the effectiveness of SGLT2 inhibitors in reducing cardiovascular and renal complications and address safety concerns in participants with type 2 diabetes mellitus (T2DM). We explored PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane library, and ResearchGate for randomized controlled trials and observational studies done on the advantages of SGLT2 inhibitors in the prevention or reduction of worsening cardiovascular and renal changes in T2DM. Studies were screened for the quality assessment using the Cochrane risk-of-bias assessment tool and Newcastle-Ottawa scale. We screened 5615 articles, out of which 22 articles with 7,02,977 diabetes mellitus patients treated with SGLT2 inhibitors were used for the systematic review after meticulously filtering articles based on inclusion and exclusion criteria. The trials included one of the following drugs - empagliflozin, dapagliflozin, canagliflozin, and luseogliflozin. SGLT2 inhibitors significantly reduced the risk of heart failure (HF), frequency of hospitalizations due to HF, all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction. Renal outcomes showed a significant lowering of risk of acute kidney failure, progression of chronic kidney disease, renal mortality, and improvement in urinary albumin creatinine ratio. We noticed an initial worsening of the estimated glomerular filtration rate followed by stabilizing and reaching the baseline on long-term treatment, especially in end-stage renal failure patients. The review showed that SGLT2 inhibitors have adverse reactions similar to that of a placebo, with a slight increase in treatable genital mycotic and urinary tract infections but no evidence of diabetic ketoacidosis, fractures, and amputations. According to the available data, SGLT2 inhibitors can significantly prevent or reduce cardiovascular diseases and kidney abnormalities in patients with type 2 diabetes mellitus with tolerable safety outcomes.
PubMed: 34650848
DOI: 10.7759/cureus.17668 -
BJOG : An International Journal of... Oct 2021To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with...
OBJECTIVE
To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM).
DESIGN
A consensus developmental study.
SETTING
International.
POPULATION
Two hundred and five stakeholders completed the first round.
METHODS
The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS.
MAIN OUTCOME MEASURES
All outcomes were extracted from the literature.
RESULTS
We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death.
CONCLUSIONS
This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM.
TWEETABLE ABSTRACT
165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.
Topics: Consensus; Delphi Technique; Diabetes, Gestational; Female; Humans; International Cooperation; Outcome Assessment, Health Care; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Stakeholder Participation; Treatment Outcome
PubMed: 34218508
DOI: 10.1111/1471-0528.16825