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Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254 -
Current Diabetes Reviews Jan 2024Physical exercise is part of the type 1 diabetes mellitus (T1DM) treatment. However, this practice is still neglected due to the wide variety of glycemic responses under...
AIM
Physical exercise is part of the type 1 diabetes mellitus (T1DM) treatment. However, this practice is still neglected due to the wide variety of glycemic responses under the influence of anaerobic exercise. Therefore, this study aimed to investigate the influence of anaerobic exercise on biomarkers of T1DM.
METHODS
The systematic review was conducted on PubMed, Lilacs, and Embase, according to PRISMA. For this purpose, three groups of descriptors were used: adults with T1DM, anaerobic physical exercise, and glycemic control. The search filter was set to human beings older than 18 years of age, longitudinal and cross-sectional studies, with studies published from 2000 to 2023 in English, Spanish, or Portuguese. Titles and abstracts were read independently by two reviewers, and then the articles were selected for this review. The Kappa coefficient was measured to evaluate the selection.
RESULTS
A total of 738 articles were identified, and five were selected to be part of the review after applying the steps of the procedure. Some benefits were observed in fatigue reduction, absence of diabetic ketoacidosis requiring hospitalization, and enhancement of glucose monitoring during exercise. In the anaerobic workouts of the groups with T1DM, glycemic mean values ranged from 124.5-185.0 mg/dl, and glycated hemoglobin records ranged from 6.7-8.1%.
CONCLUSION
Anaerobic exercise improved the biomarkers of T1DM, especially glycemic control, and the reduction of symptomatic hypoglycemic episodes. Anaerobic exercise can be performed by individuals with T1DM, suggesting an individualized training prescription and encouraging its practice associated with aerobic exercise.
PubMed: 38275039
DOI: 10.2174/0115733998274125231126111321 -
The Lancet. Diabetes & Endocrinology Feb 2024The COVID-19 pandemic triggered disruptions to health care and lifestyles that could conceivably impact diabetes management. We set out to identify the impact of... (Review)
Review
The COVID-19 pandemic triggered disruptions to health care and lifestyles that could conceivably impact diabetes management. We set out to identify the impact of disruptions caused by COVID-19 on clinical outcomes in people with diabetes. We performed a systematic review of the available literature in the MEDLINE and OVID databases from Jan 1, 2020, to June 7, 2023, and included 138 studies (n>1 000 000 people). All but five studies were judged to be at some risk of bias. All studies compared prepandemic with pandemic periods. All-cause mortality (six studies) and diabetes-related mortality (13 studies) showed consistent increases, and most studies indicated increases in sight loss (six studies). In adult and mixed samples, data generally suggested no difference in diabetic ketoacidosis frequency or severity, whereas in children and adolescents most studies showed increases with some due to new-onset diabetes (69 studies). Data suggested decreases in hospital admissions in adults but increases in diabetes-related admissions to paediatric intensive care units (35 studies). Data were equivocal on diabetic foot ulcer presentations (nine studies), emergency department admissions (nine studies), and overall amputation rates (20 studies). No studies investigated renal failure. Where reported, the impact was most pronounced for females, younger people, and racial and ethnic minority groups. Further studies are needed to investigate the longer-term impact of the pandemic and the on potential differential impacts, which risk further exacerbating existing inequalities within people with diabetes.
Topics: Adult; Child; Female; Adolescent; Humans; Pandemics; COVID-19; Ethnicity; Minority Groups; Diabetic Foot; Diabetes Mellitus
PubMed: 38272607
DOI: 10.1016/S2213-8587(23)00351-0 -
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 -
Enfermedades Infecciosas Y... 2024The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation,... (Review)
Review
The occurrence of mucormycosis has been observed in individuals with COVID-19. However, there is limited information on the epidemiological factors, presentation, diagnostic certainty, and outcome of this infection in children. PubMed, MEDLINE, Scopus, Embase, Web of Science, LitCovid, and back-references of the identified manuscripts were systematically searched from December 2019 to March 2023. We have identified 14 cases of pediatric mucormycosis in patients with COVID-19. The median age of patients was 10.7 years. Among these cases, 10 were associated with active COVID-19. In 7 cases, the patients had pre-existing diabetes mellitus and concomitant diabetic ketoacidosis. Corticosteroids were administered to treat COVID-19 in 7 of the patients. The most common clinical presentation of the disease was rhino-orbital cerebral mucormycosis. Seven patients died (50%). Given the high mortality rate, clinicians should maintain a high level of clinical suspicion of mucormycosis in pediatric patients with COVID-19.
Topics: Humans; Mucormycosis; COVID-19; Child; Adolescent; Child, Preschool; Female; Male; Diabetic Ketoacidosis
PubMed: 38216422
DOI: 10.1016/j.eimce.2023.11.006 -
Diabetes Research and Clinical Practice Jan 2024This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA). (Review)
Review
AIM
This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA).
METHODOLOGY
This is a systematic review of randomized controlled trials and analytical studies. We selected studies based on eligibility criteria. The databases Medline, Cochrane library and Embase were searched from their inception till November 2, 2022, using search strategy. We used the term such as "diabetes mellitus", "treatment", "hypoglycaemia", "diabetic ketoacidosis", "low blood sugar", "high blood sugar" and Mesh terms like "disease management", "hypoglycaemia", "diabetic ketoacidosis", and "diabetes mellitus" to form search strategy.
RESULTS
Hypoglycemia: Both 10 % dextrose (D10) and 50 % dextrose (D50) are effective options with similar hospital mortality D10 (4.7 %) and D50 (6.2 %). DKA: Low dose insulin is non-inferior to standard dose with time till resolution of DKA 16.5 (7.2) hours and 17.2 (7.7) hours (p value = 0.73) respectively. In children, subcutaneous insulin was associated with reduced ICU admissions and hospital readmissions (67.8 % to 27.9 %). Plasmalyte (PL) is noninferior to sodium chloride (SC), with ICU length of stay 49 h (IQR 23-72) and 55 h (IQR 41-80) respectively, hyperchloremia was associated with longer in-hospital length of stay and longer time to resolution of DKA. And potassium replacement at < 10 mmol/L was associated with higher mortality (n = 72).
CONCLUSION
We conclude either of the 10 % or 50 % dextrose is effective for management of hypoglycaemia. For DKA subcutaneous insulin and intravenous insulin, chloride levels ≤ 109 mEq/L, potassium above 10 mmol/l, IV fluids like Plasmalyte and normal saline are effective.
Topics: Child; Humans; Diabetic Ketoacidosis; Blood Glucose; Hypoglycemia; Insulin; Emergency Medical Services; Insulin, Regular, Human; Potassium; Diabetes Mellitus
PubMed: 38154537
DOI: 10.1016/j.diabres.2023.111078 -
Frontiers in Public Health 2023Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered...
OBJECTIVE
Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered diabetes is insulin, but a detailed therapeutic method has not yet been established. To prevent severe symptoms and mortality of diabetic ketoacidosis in advanced-stage cancer patients, the establishment of effective treatment of CPI-triggered diabetes, other than insulin therapy, is required.
METHODS
We present a case of a 76-year-old man with CPI-triggered diabetes who was treated with nivolumab and ipilimumab for lung cancer. We also conducted a systematic review of 48 case reports of type 1 diabetes associated with nivolumab and ipilimumab therapy before June 2023.
RESULTS
The patient's hyperglycemia was not sufficiently controlled by insulin therapy, and after the remission of ketoacidosis, the addition of a sodium-glucose transporter (SGLT) 2 inhibitor, dapagliflozin, improved glycemic control. Most of the reported nivolumab/ipilimumab-induced type 1 diabetes was treatable with insulin, but very few cases required additional oral anti-diabetic agents to obtain good glucose control.
CONCLUSION
Although SGLT2 inhibitors have been reported to have adverse effects on ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPI-triggered diabetes, SGLT2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient's ketoacidosis.
Topics: Male; Humans; Aged; Nivolumab; Sodium-Glucose Transporter 2 Inhibitors; Ipilimumab; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Insulin; Lung Neoplasms
PubMed: 38106883
DOI: 10.3389/fpubh.2023.1264056 -
Frontiers in Pharmacology 2023As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients...
Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis.
As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis. Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis. Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)]. Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.
PubMed: 38044937
DOI: 10.3389/fphar.2023.1303694 -
Diabetes Therapy : Research, Treatment... Feb 2024The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of... (Review)
Review
The MiniMed™ 780G is a second-generation automated insulin delivery system that implements a modified proportional-integral-derivative algorithm with some features of an MD-Logic artificial pancreas algorithm. The system may deliver automatic correction boluses up to every 5 min, and it allows the user to choose between three glucose target setpoints (100, 110 and 120 mg/dL). We aimed to review the current evidence on this device in children, adolescents, and young adults living with type 1 diabetes. We screened 783 papers, but only 31 manuscripts were included in this review. Data on metabolic outcomes show that this system is safe as regards severe hypoglycaemia and diabetic ketoacidosis. The glycated haemoglobin may drop to levels about 7%, with CGM reports showing a time in range of 75-80%. The time above range and the time below range are within the recommended target in most of the subjects. Few studies evaluated the psychological outcomes. This system seems to be more effective than the first-generation automated insulin delivery systems. The MiniMed™ 780G has been associated with an improvement in sleep quality in subjects living with diabetes and their caregivers, along with an improvement in treatment satisfaction. Psychological distress is as reduced as the glucose control is improved. We also discuss some case reports describing particular situations in clinical practice. Finally, we think that data show that this system is a further step towards the improvement of the treatment of diabetes as concerns both metabolic and psychological outcomes.
PubMed: 38038896
DOI: 10.1007/s13300-023-01501-6 -
Frontiers in Endocrinology 2023The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain... (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.
OBJECTIVE
The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.
RESULTS
Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.
CONCLUSION
Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Topics: Female; Humans; Male; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Nasopharyngitis; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38027214
DOI: 10.3389/fendo.2023.1256548