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Diabetes, Metabolic Syndrome and... 2023Poorer glycemic control and higher diabetic ketoacidosis (DKA) rates are seen in racial/ethnic minorities with type 1 diabetes (T1D). Use of diabetes technologies such...
AIM
Poorer glycemic control and higher diabetic ketoacidosis (DKA) rates are seen in racial/ethnic minorities with type 1 diabetes (T1D). Use of diabetes technologies such as continuous glucose monitors (CGM), continuous subcutaneous insulin infusion (CSII) and automated insulin delivery (AID) systems has been shown to improve glycemic control and reduce DKA risk. We examined race/ethnicity differences in diabetes technology use and their relationship with HbA1c and DKA.
METHODS
Data from patients aged ≥12 years with T1D for ≥1 year, receiving care from a single diabetes center, were examined. Patients were classified as Non-Hispanic White (n=3945), Non-Hispanic Black (Black, n=161), Hispanic (n=719), and Multiracial/Other (n=714). General linear models and logistic regression were used.
RESULTS
Black (OR=0.22, 0.15-0.32) and Hispanic (OR=0.37, 0.30-0.45) patients were less likely to use diabetes technology. This disparity was greater in the pediatric population (p-interaction=0.06). Technology use associated with lower HbA1c in each race/ethnic group. Among technology users, AID use associated with lower HbA1c compared to CGM and/or CSII (HbA1c of 8.4% vs 9.2%, respectively), with the greatest difference observed for Black adult AID users. CSII use associated with a lower odds of DKA in the past year (OR=0.73, 0.54-0.99), a relationship that did not vary by race (p-interaction =0.69); this inverse association with DKA was not observed for CGM or AID.
CONCLUSION
Disparities in diabetes technology use, DKA, and glycemic control were apparent among Black and Hispanic patients with T1D. Differences in technology use ameliorated but did not fully account for disparities in HbA1c or DKA.
PubMed: 37551339
DOI: 10.2147/DMSO.S416192 -
International Journal of Molecular... Feb 2024The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated... (Review)
Review
The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of ≥27 kg/m treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol.
Topics: Humans; Diabetes Mellitus, Type 1; Dipeptidyl-Peptidase IV Inhibitors; Glucose; Hypoglycemic Agents; Insulin; Multicenter Studies as Topic; Risk Assessment; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38396657
DOI: 10.3390/ijms25041972 -
Kidney360 Feb 2024Ketone bodies have a negative image because of ketoacidosis, one of the acute and serious complications in diabetes. The negative image persists despite the fact that... (Review)
Review
Ketone bodies have a negative image because of ketoacidosis, one of the acute and serious complications in diabetes. The negative image persists despite the fact that ketone bodies are physiologically produced in the liver and serve as an indispensable energy source in extrahepatic organs, particularly during long-term fasting. However, accumulating experimental evidence suggests that ketone bodies exert various health benefits. Particularly in the field of aging research, there is growing interest in the potential organoprotective effects of ketone bodies. In addition, ketone bodies have a potential role in preventing kidney diseases, including diabetic kidney disease (DKD), a diabetic complication caused by prolonged hyperglycemia that leads to a decline in kidney function. Ketone bodies may help alleviate the renal burden from hyperglycemia by being used as an alternative energy source in patients with diabetes. Furthermore, ketone body production may reduce inflammation and delay the progression of several kidney diseases in addition to DKD. Although there is still insufficient research on the use of ketone bodies as a treatment and their effects, their renoprotective effects are being gradually proven. This review outlines the ketone body-mediated renoprotective effects in DKD and other kidney diseases.
Topics: Humans; Diabetic Nephropathies; Ketone Bodies; Ketosis; Diabetes Complications; Hyperglycemia; Diabetes Mellitus
PubMed: 38227425
DOI: 10.34067/KID.0000000000000359 -
Frontiers in Clinical Diabetes and... 2023Diabetic ketoacidosis is one of the major life-threatening conditions associated with acute metabolic complications. It remains a major public health problem in...
Incidence and predictors of mortality in children with diabetic ketoacidosis in the comprehensive specialized referral hospitals of West Amhara Region, Northwest Ethiopia: a retrospective follow-up study.
BACKGROUND
Diabetic ketoacidosis is one of the major life-threatening conditions associated with acute metabolic complications. It remains a major public health problem in developing countries such as Ethiopia.
OBJECTIVE
To assess the incidence and prediction of mortality in children with diabetic ketoacidosis in West Amhara Region Comprehensive Specialized Referral Hospitals, Northwest Ethiopia, in 2022.
METHODS
An institution-based retrospective follow-up study was conducted among 423 study participants with a confirmed diagnosis of diabetic ketoacidosis from 01/01/2017 to 31/12/2021. Data were entered, coded, cleaned, and checked using Epi-Data version 4.6 and exported to Stata version 14 for data analysis.
RESULTS
A total of 401 child records were included in the final analysis and were followed for 3781 days during the study period. The overall mortality of children with diabetic ketoacidosis was 10.6 per 1000 person-days observed (95% CI: 7.8-14.4) during the entire follow-up period. Hypoglycemia (AHR=4.6; 95% CI: 2.13-10.1), rural residence (AHR=2.9; 95% CI=1.01-8.11), age younger than five (AHR=4.4; 95% CI=1.4-13.7) or between five and 10 (AHR=3.1; 95% CI=1.1-8.8), and female gender (AHR=2.6; 95% CI=1.1-5.8) were significant predictors of mortality.
CONCLUSIONS
The incidence rate of mortality in children with diabetic ketoacidosis was relatively high. Age, rural residence, female gender, and hypoglycemia were significantly predictive of mortality. Community education or mass campaigns about the signs and symptoms of diabetic ketoacidosis may reduce the mortality rate in children.
PubMed: 37719988
DOI: 10.3389/fcdhc.2023.1204133 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events...
OBJECTIVE
Immune checkpoint inhibitors(ICIs) have improved survival and are increasingly used for cancer. However, ICIs use may be limited by immune-related adverse events (irAEs), such as ICI-induced diabetes mellitus(ICI-DM). The objective of the present study was to characterize ICI-DM patients and real-world adherence to guidelines.
RESEARCH DESIGN AND METHODS
The present study was a retrospective review of electronic records of ICI-DM patients at the First Affiliated Hospital of Nanjing Medical University between July 2018 and October 2022.
RESULTS
34.8% (8/23)patients monitored blood glucose in every treatment cycle. The proportion of patients with severe diabetic ketoacidosis(DKA) was lower in the tight glycemic monitoring group than the non-tight glycemic monitoring group (16.7% vs. 55.6%, = 0.049). 78.3%(18/23) patients with hyperglycemia visited a non-endocrinologist first, but 95.7% of patients were then referred to an endocrinologist. Twenty patients were tested for distinguishing the etiology of hyperglycemia and 20% patients with positive glutamic acid decarboxylase antibody(GADA), 55% with C-peptide <3.33pmol/L. High screening rates for other ICI-induced endocrinopathies were observed and half of the patients with ICI-DM developed other endocrine gland irAEs, with the most common being thyroiditis. Moreover, five patients developed non-endocrine serious adverse events(SAEs). Twelve (52.2%) patients were withdrawn from ICI due to ICI-DM. The time to progression of tumor in ICI-DM patients in the continue and interruption group was longer than in the withdrawal group (333.5 ± 82.5 days vs. 183.1 ± 62.4 days, = 0.161). Only 17.4% of ICI-DM patients were completely managed according to guidelines. Thus, the present study proposed a screening, diagnosis, and management algorithm for ICI-DM in real-world practice.
CONCLUSION
The present study reported the largest number of ICI-DM cases described in a single institute, providing insight into real-world ICI-DM management guideline adherence and highlighting the clinical challenges in ICI-DM management.
Topics: Humans; Algorithms; Antibodies; Diabetes Mellitus; Diabetic Ketoacidosis; Hyperglycemia; Immune Checkpoint Inhibitors; Guideline Adherence
PubMed: 37554766
DOI: 10.3389/fendo.2023.1213225 -
Cureus Sep 2023Hypertriglyceridemia (HTG)-induced pancreatitis is a known complication of uncontrolled diabetes mellitus (DM). However, the coexistence of diabetic ketoacidosis (DKA)...
Hypertriglyceridemia (HTG)-induced pancreatitis is a known complication of uncontrolled diabetes mellitus (DM). However, the coexistence of diabetic ketoacidosis (DKA) and acute pancreatitis in the presence of HTG is rare and presents diagnostic and therapeutic challenges. We present the case of a 42-year-old female with poorly controlled type 2 DM who developed severe HTG-induced pancreatitis complicated by DKA. She initially presented with abdominal pain, metabolic acidosis, and marked hyperglycemia. Subsequent investigations revealed significantly elevated serum triglyceride and lipase levels and characteristic findings of acute pancreatitis on imaging. This case report highlights the complex interplay of metabolic disturbances in diabetes and the importance of timely recognition and tailored management to achieve a successful outcome.
PubMed: 37868435
DOI: 10.7759/cureus.45631 -
Diabetes Technology & Therapeutics Oct 2023Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote...
Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.
Topics: Humans; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Feasibility Studies; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Insulin, Regular, Human; Pilot Projects
PubMed: 37578778
DOI: 10.1089/dia.2023.0304 -
Diabetes Technology & Therapeutics Aug 2023The use of continuous glucose monitoring (CGM) in pediatric patients with diabetic ketoacidosis (DKA) remains investigational, and data on its accuracy in pediatric...
The use of continuous glucose monitoring (CGM) in pediatric patients with diabetic ketoacidosis (DKA) remains investigational, and data on its accuracy in pediatric intensive care units (PICU) are limited. This study evaluated the accuracy of three CGM devices in pediatric patients with DKA in the PICU. We compared 399 matched pairs of CGM and point-of-care capillary glucose (POC) values and grouped patients based on whether they changed their CGM sensor during their PICU stay. Eighteen patients with a mean age of 10.98 ± 4.20 years were included, with three patients in the sensor change group. The overall mean absolute relative difference (MARD) was 13.02%. The Medtronic Guardian Sensor 3 ( = 331), Dexcom G6 ( = 41), and Abbott FreeStyle Libre 1 ( = 27) showed MARD values of 13.40%, 11.12%, and 11.33%, respectively. The surveillance error grid (SEG), Bland-Altman plot, and Pearson's correlation coefficient demonstrated satisfactory clinical accuracy of the CGM devices (SEG zones A and B, 98.5%; mean difference, 15.5 mg/dL; Pearson's correlation coefficient [], 0.76, < 0.0001). MARD was significantly lower in subjects who did not experience a sensor change (11.74% vs. 17.31%, = 0.048). Also, a statistically significant negative correlation was found between serum bicarbonate levels and POC-CGM values ( = -0.34, < 0.001). The severity of DKA has a major effect on reducing the accuracy of the CGM, especially during the first several days in the intensive care unit. The reduced accuracy appears to be related to acidosis, as reflected in the serum bicarbonate levels.
Topics: Humans; Child; Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; Diabetic Ketoacidosis; Critical Illness; Bicarbonates; Intensive Care Units, Pediatric; Reproducibility of Results; Diabetes Mellitus
PubMed: 37155338
DOI: 10.1089/dia.2023.0012 -
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 -
Journal of Clinical Medicine Mar 2024Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns... (Review)
Review
Sodium glucose cotransporter-2 inhibitors (SGLT2is) represent an emerging class of drugs with diverse indications. Despite their therapeutic potential, concerns regarding safety, particularly diabetic ketoacidosis (DKA), remain contentious, with uncertainty regarding differences among various SGLT2is. This study aimed to conduct a network meta-analysis and meta-regression to evaluate the risk of SGLT2i-induced DKA and associated factors. We systematically searched electronic databases for randomized clinical trials assessing SGLT2is across indications, reporting incidences of DKA. Mixed treatment comparison pooled estimates (MTCPEs) were calculated, and odds ratios (OR) with 95% confidence intervals (95% CI) served as effect estimates. We analyzed differences across dose categories (low, medium, and high) and conducted a meta-regression analysis to identify risk factors. The strength of evidence for key comparisons was determined. Our analysis included 73 articles encompassing 85,997 participants assessing the risk of DKA. SGLT2is were associated with a heightened risk of DKA compared to placebo/control interventions (OR: 1.83; 95% CI: 1.35, 2.46), a finding confirmed by bootstrap analysis. Among SGLT2is, dapagliflozin (OR: 1.9; 95% CI: 1.17, 3.08), sotagliflozin (OR: 1.93; 95% CI: 1.14, 3.25), canagliflozin (OR: 1.11; 95% CI: 1.11, 12.45), and ertugliflozin (OR: 3.92; 95% CI: 1.04, 14.77) exhibited increased DKA risk. No significant differences were observed among specific SGLT2is. Sub-group analyses revealed a high risk of DKA with low (OR: 1.98; 95% CI: 1.3, 2.95) and high doses (OR: 2.4; 95% CI: 1.7, 3.3), type 1 diabetes (OR: 3.6; 95% CI: 1.6, 8.1), type 2 diabetes (OR: 1.6; 95% CI: 1.3, 2.4), as well as a diabetes duration exceeding 10 years (OR: 3.4; 95% CI: 1.1, 10.8). The evidence of certainty for most comparisons was moderate. SGLT2 inhibitors (SGLT2is) have been found to elevate the risk of DKA. The key factors that significantly predict the likelihood of DKA include the presence of diabetes (whether T1D or T2D) and the duration of diabetes. Based on these findings, standard treatment guidelines should advise taking specific precautions against DKA in patients identified as high-risk.
PubMed: 38541972
DOI: 10.3390/jcm13061748