Total Daily Insulin Research Articles

A Randomized Crossover Trial of Mixed Meal Tolerance Test Response in People with Type1 Diabetes on Insulin Pump Therapy and YG1699 or Dapagliflozin.

YG1699 is a novel inhibitor of sodium-glucose cotransporter 1 (SGLT1) and SGLT2. This double-blind, 3-way crossover trial compared YG1699 to dapagliflozin as an adjunct to insulin in people with type 1 diabetes (T1D) on insulin pump therapy. Treatment periods included four mixed meal tolerance tests (MMTTs) and insulin withdrawal tests per person. Nineteen adults with T1D were randomized to YG1699 10 mg, YG1699 25 mg, and dapagliflozin 10 mg once daily for 1 week in different orders. The primary end point was the difference in area under the curve (AUC) in plasma glucose (AUC0-120min) after an MMTT between treatment groups. Mean change in plasma glucose after an MMTT (AUC0-120min) was lower for YG1699 10 mg vs. dapagliflozin (89.51% of baseline vs. 102.13%, 90% confidence interval (CI) vs. dapagliflozin, -6% to -16%, P = 0.0003) and for YG1699 25 mg (84.83% vs. 102.13%, 90% CI vs. dapagliflozin -13% to -22%, P < 0.0001). At 120 minutes, mean glucose values on no treatment, dapagliflozin, YG1699 10 mg, and YG1699 25 mg were 149 (SE 7.6), 141 (SE 6.1), 128 (SE 6.9), and 115 (SE 7.8) mg/dL, respectively. Insulin dose requirements were lower for YG1699 10 mg and 25 mg vs. dapagliflozin for bolus insulin, and for YG1699 10 mg vs. dapagliflozin for total daily insulin. Safety profiles were similar between treatment groups. YG1699 reduced post-prandial glucose more than dapagliflozin in people with T1D on insulin pump therapy. The results were consistent with dual SGLT1/SGLT2 inhibition by YG1699.

Control-IQ Technology Use in Individuals With High Insulin Requirements: Results From the Multicenter Higher-IQ Trial.

Control-IQ technology version 1.5 allows for a wider range of weight and total daily insulin (TDI) entry, in addition to other changes to enhance performance for users with high basal rates. This study evaluated the safety and performance of the updated Control-IQ system for users with basal rates >3 units/h and high TDI in a multicenter, single arm, prospective study. Adults with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) and at least one basal rate over 3 units/h (N = 34, mean age = 39.9 years, 41.2% female, diabetes duration = 21.8 years) used the t:slim X2 insulin pump with Control-IQ technology version 1.5 for 13 weeks. Primary outcome was safety events (severe hypoglycemia and diabetic ketoacidosis (DKA)). Central laboratory hemoglobin A1c (HbA1c) was measured at system initiation and 13 weeks. Participants continued using glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose transport protein 2 (SGLT-2) inhibitors, or other medications for glycemic control and/or weight loss if on a stable dose. All 34 participants completed the study. Fifteen participants used a basal rate >3 units/h for all 24 hours of the day. Nine participants used >300 units TDI on at least one day during the study. There were no severe hypoglycemia or DKA events. Time in range 70-180 mg/dL was 64.8% over the 13 weeks, with 1.0% time <70 mg/dL. Hemoglobin A1c decreased from 7.69% at baseline to 6.87% at 13 weeks (-0.82%, P < .001). Control-IQ technology version 1.5, with wider range of weight and TDI input and enhancements for users with high insulin requirements, was safe in individuals with T1D in this study.

Efficacy of Semaglutide in Overweight and Obese Patients with Type 1 Diabetes.

Introduction: More than two-thirds of patients with type 1 diabetes (T1D) are overweight (OW) and/or obese (OB) in the USA and Western Europe, resulting in insulin resistance as in type 2 diabetes. None of the currently available glucagon like polypeptide 1 (GLP-1) analogs are approved for patients with T1D. A higher dose of semaglutide has been approved by the Food and Drug Administration (FDA) for subjects with body mass index (BMI) >27 kg/m2. We evaluated the real-world use of semaglutide in patients with T1D. Methods: This was a retrospective chart review study of 50 OW or OB patients with T1D who were initiated on semaglutide and followed for 1 year. The control group comprised of 50 computer-matched patients (for sex, race, weight, BMI, and diabetes duration) during a similar time period and were not on any weight loss medications. Results: Most patients (92%) were non-Hispanic white in both arms. Mean ± standard deviation (SD) age and duration of diabetes were 42 ± 11 and 27 ± 12 years, respectively. The continuous glucose monitors (CGM), insulin pump use, baseline BMI and body weight were also similar in the two groups. Baseline glycosylated hemoglobin (HbA1c) was insignificantly lower in the semaglutide group (7.6% vs. 8.2%, respectively; P = non-significant [NS]). Total daily insulin dose (TDD) and insulin dose per kg body weight were higher in the semaglutide group at baseline with no difference in basal or prandial insulin dose. There were significantly greater declines in mean (±SD), BMI (7.9% ± 2.6%), body weight (15.9 lbs ± 5.4 lbs), HbA1c, CGM glucose SD and coefficient of variation (CV), and increase in CGM time in range (TIR) in the semaglutide group compared to the control group with no difference in insulin dose changes, time above range (TAR), or time below range (TBR). Conclusions: We conclude that use of semaglutide in patients who are OW and/or OB with T1D was effective in lowering body weight and BMI, and improving glycemic metrics in this pilot real-world study. We strongly recommend performing prospective, large-randomized clinical trials with newer GLP-1 analogs like semaglutide and tirzepatide (twin-cretin) for subjects with T1D associated with OW and/or OB.

Safety and efficacy of glucagon-like peptide-1 receptor agonists among kidney transplant recipients: a systematic review and meta-analysis.

Evidence supporting glucagon-like peptide-1 receptor agonists (GLP-1RAs) in kidney transplant recipients (KTRs) remains scarce. This systematic review and meta-analysis aims to evaluate the safety and efficacy of GLP-1RAs in this population. A comprehensive literature search was conducted in the MEDLINE, Embase and Cochrane databases from inception through May 2023. Clinical trials and observational studies that reported on the safety or efficacy outcomes of GLP-1RAs in adult KTRs were included. Kidney graft function, glycaemic and metabolic parameters, weight, cardiovascular outcomes and adverse events were evaluated. Outcome measures used for analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes and standardized mean difference (SMD) or mean difference (MD) with 95% CI for continuous outcomes. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD 42023426190). Nine cohort studies with a total of 338 KTRs were included. The median follow-up was 12months (interquartile range 6-23). While treatment with GLP-1RAs did not yield a significant change in estimated glomerular filtration rate [SMD -0.07ml/min/1.73m2 (95% CI -0.64-0.50)] or creatinine [SMD -0.08mg/dl (95% CI -0.44-0.28)], they were associated with a significant decrease in urine protein:creatinine ratio [SMD -0.47 (95% CI -0.77 to -0.18)] and haemoglobin A1c levels [MD -0.85% (95% CI -1.41 to -0.28)]. Total daily insulin dose, weight and body mass index also decreased significantly. Tacrolimus levels remained stable [MD -0.43ng/ml (95% CI -0.99 to 0.13)]. Side effects were primarily nausea and vomiting (17.6%), diarrhoea (7.6%) and injection site pain (5.4%). GLP-1RAs are effective in reducing proteinuria, improving glycaemic control and supporting weight loss in KTRs, without altering tacrolimus levels. Gastrointestinal symptoms are the main side effects.

Increased Insulin Requirements in Severe Cases of Covid-19 are Higher Than in Moderate Cases.

Despite the low overall death rate of coronavirus disease 2019 (COVID-19), no study has examined the association between COVID-19 severity and the total daily insulin dose required for glycemic control. The aim of this study was to determine the maximum total daily insulin dose required according to COVID-19 severity, and the number of days required to reach the maximum insulin dose in patients with COVID-19 who used insulin during hospitalization. This retrospective cohort study included participants aged 20-90 years with a confirmed diagnosis of COVID-19 who used insulin during hospitalization at Kyoto Prefectural University of Medicine Hospital between March 4, 2020, and May 31, 2021. Factors associated with maximum insulin dose during hospitalization were evaluated using linear regression analyses. The maximum insulin doses were 31.8, 76.8, and 230.7 U/day, and the numbers of days between COVID-19 diagnosis and the need for maximum insulin were 15.6, 17.1, and 13.7 days in patients without ventilator management, with ventilator management, and with ventilator and extracorporeal membrane oxygenation management, respectively. Multivariate linear regression analyses revealed that hemoglobin A1c level (β = 15.87, P = 0.001), use of a ventilator (β = 50.53, P < 0.001), and use of extracorporeal membrane oxygenation (β = 150.36, P < 0.001) were independent determinants of maximum insulin dose. Patients with severe COVID-19 required a significantly higher maximum insulin dose than did those with moderate COVID-19. The maximum insulin dose was reached approximately 2weeks after onset. Furthermore, the hemoglobin A1c level on admission and the use of a ventilator or extracorporeal membrane oxygenation during hospitalization were associated with the need for maximum insulin dose.

GLYCAEMIC CONTROL AND HYPOGLYCAEMIA AMONG PATIENTS WITH DIABETES IN A PHARMACIST-MANAGED INSULIN TITRATION PROGRAMME

The impact of a pharmacist-managed insulin titration has never been systematically assessed among patients with diabetes. This study aimed to evaluate the impact of pharmacist-managed insulin titration on glycaemic control, total daily insulin dose, hypoglycaemia, hunger and body weight. Data was collected retrospectively from patients treated with insulin under the care of a pharmacist-managed insulin titration programme at the Diabetes and Endocrine Clinic, Hospital Pulau Pinang, Pulau Pinang, Malaysia. Patients who followed-up with pharmacists at one month to two months intervals and completed at least eight visits were included. Ninety-one patients (59.3% male) aged 50.82 ± 17.63 years old with 13.38 ± 8.88 years of diabetes were evaluated. Glycaemic control improved significantly from baseline to 4th month (–1.19%, p &lt; 0.001) and 8th month (–1.37%, p &lt; 0.001). Majority of patients were on twice daily premixed insulin (44.0%) followed by basal insulin (28.5%), basal bolus (18.7%) and thrice daily premixed insulin (8.8%). Total daily insulin dose increased significantly from baseline to 8th month among patients on basal insulin (0.24 ± 0.15 versus 0.29 ± 0.18 units/kg/day, p = 0.008) whereas the opposite was seen in patients treated fully on insulin (1.06 ± 0.48 units/kg/day versus 0.96 ± 0.37 units/kg/day, p = 0.005). Total hypoglycaemia and hunger episodes reduced significantly from 160 episodes/month to 30 episodes/month, p = 0.001 and 39 cases/month to 5 cases/ month, p &lt; 0.001, respectively, across all groups. Mean weight increased by 0.66 kg from baseline to 8th month, p = 0.045. Insulin dose had a positive correlation to hypoglycaemia, r = 0.338, p = 0.001. Pharmacist-managed insulin titration programme significantly improved glycaemic control and reduced hypoglycaemia occurrences.

Therapy Settings Associated with Optimal Outcomes for t:slim X2 with Control-IQ Technology in Real-World Clinical Care.

Objective: To determine insulin dosing parameters that are associated with and predict optimal outcomes for people using t:slim X2 with Control-IQ technology (CIQ). Methods: Retrospective deidentified data from CIQ users were analyzed to determine the effect of Correction Factor, Carbohydrate-to-Insulin (C:I) Ratio, and basal rate settings (standardized by total daily insulin [TDI]) on glycemic control. We performed an associative analysis followed by linear regressions to determine the relative importance of the settings and confounding variables (e.g., age or number of user-initiated boluses) in predicting consensus glycemic outcomes. Results: Data from 20,764 individuals were analyzed (median age 39 years [interquartile range 19, 59], 55% female, TDI 46.4 U [33-65.2]). More aggressive Correction Factor settings, C:I ratio settings, and basal programs were all strongly associated with higher time in range (TIR, 70-180 mg/dL) and to a lesser degree to higher time <70 mg/dL. In linear regression, more aggressive Correction Factor predicted higher TIR, lower coefficient of variation, and importantly had only negligible impact on time below range. Higher basal rate settings and lower C:I ratio predicted increased TIR as well as increased hypoglycemia. The most important predictor in all glycemic outcomes was the average number of user-given boluses per day. Conclusion: Basal rates, C:I ratios, and Correction Factor settings all impact glycemic outcomes in CIQ users in usual clinical care. The correction Factor setting may be the most impactful "lever to pull" for clinicians and CIQ users to optimize TIR while not increasing hypoglycemia.

FRI631 Insulin Antibody Mediated Extremely Insulin Resistant In Pregnancy

Abstract Disclosure: Z. Liu: None. D. James: None. S. Dagogo-Jack: None. Background: Insulin antibodies can rarely complicate diabetes management during pregnancy. Here, we report a patient with extreme insulin resistance during pregnancy associated with positive insulin antibodies. Clinical Case: A 40-year-old primigravida with Type 2 Diabetes (T2DM) was admitted at week 32 for uncontrolled Hypertension (HTN) and extremely high insulin requirement. T2DM was diagnosed 8 years ago and treated with basal insulin 50 units/d, dulaglutide, metformin, and glimepiride. Her HbA1c was 14% one month prior to pregnancy. During pregnancy, patient’s regimen was changed to basal bolus insulin, and oral agents were discontinued. Total daily insulin dose average 740 units (5.6 units/kg/day) at week 32. Patient’s weight was 112 kg at the beginning of pregnancy, increasing to 131 kg in the third trimester. On the high insulin regimen, her HbA1c was 5.6% at week 32. Due to the extreme insulin requirement (indicative of severe insulin resistance), we ordered insulin antibody (IAA), which came back positive at 15 µU/ml (NR &amp;lt;5 µU/ml). Diabetes control remained suboptimal, with frequent post-prandial hyperglycemia followed by hypoglycemia during hospitalization. Insulin regimen was optimized using U-500 in divided doses, starting with 112 units tid. At 34 weeks (hospital day 14), patient underwent cesarean section with delivery of a viable infant (weight 1450 grams, Apgar score 5 and 9 at 1 and 5 minutes). Shortly after delivery, the patient’s insulin requirement plummeted to 62 units daily and she was successfully discharged home. Diabetes control has been stable, with HbA1c ranging between 5.7% and 7% one year after delivery on total insulin dose of 60 units or less per day. Attempts to schedule patient for repeat antibody testing were unsuccessful. Conclusion: Despite the lack of data on repeat antibody testing, this is a compelling case of pregnancy associated extreme insulin resistance likely induced by insulin antibodies. Our conclusion is supported by the dramatic decrease in insulin requirement following postpartum. Presentation: Friday, June 16, 2023

Investigation of The Effect of Combined Exercises on Glycemic Control in Individuals with Type 1 Diabetes

The aim of the present study was to investigate the effect of the combined physical exercise protocols on the blood glucose (BG) of children with T1D. The study was conducted over four weeks using self-controlled clinical trials. The first two weeks were control period and the last two weeks were the experimental period. A total of 6 exercise sessions were performed 3 days a week during the experimental period. The exercise program consisted of aerobic, stretching, and resistance exercises. Each exercise session was performed for 40 minutes. A total of 15 children with T1D, whose mean age was 13.3±SD, were included in the study. The blood glucose and insulin dose data of the participants were recorded in both periods through the continuous glucose measurement system and the registry. It was determined that aerobic exercises provided a significant decrease in blood glucose (p &lt; .05). There was no statistically significant difference between the mean BG values in the control (211.7±37.3) and experimental (208.7±40.4) periods (p &gt;0.05). On the other hand, a statistically significant decrease was found in the total daily insulin doses used by participants during the experimental (31.6±20.8 Unit) period (p &lt; 0.001). Physical exercises had an acute positive effect on blood glucose in children with T1D. However, the effect of exercise alone is not sufficient for chronic glycemic control in T1D. For chronic glycemic control, first of all, the injected insulin doses should be carefully regulated according to carbohydrates and exercise.

Assessing Time in Range with Postprandial Glucose-Focused Titration of Ultra Rapid Lispro (URLi) in People with Type1 Diabetes.

To assess time in range (TIR) (70-180mg/dL) with postprandial glucose (PPG)-focused titration of ultra rapid lispro (URLi; Lyumjev®) in combination with insulin degludec in people with type1 diabetes (T1D). This phase2, single-group, open-label, exploratory study was conducted in 31 participants with T1D on multiple daily injection therapy. Participants were treated with insulin degludec and Lispro for an 11-day lead-in and then URLi for a 46-day treatment period consisting of 35-day titration and 11-day endpoint maintenance period. Glucose targets for the titration period were PPG < 140mg/dL or < 20% increase from premeal, fasting glucose 80-110mg/dL, and overnight excursion ± 30mg/dL or less. Participants used the InPen™ bolus calculator and Dexcom G6 continuous glucose monitoring (CGM). Primary endpoint mean TIR (70-180mg/dL) with URLi during the maintenance period was 70.2%. TIR (70-180mg/dL) and times below/above range were not significantly different with URLi (maintenance) versus lispro (lead-in). HbA1c decreased from 7.1% at screening to 6.8% at endpoint (least squares mean [LSM] change from baseline, - 0.36%; P < 0.001). Fructosamine and 1,5-anhydroglucitol improved (P < 0.001). Mean hourly glucose using CGM was reduced from 8:00AM to 4:00PM with URLi. Overall highest PPG excursion across meals was significantly reduced at URLi endpoint compared with lispro lead-in (mean 56.5 vs 72.4mg/dL; P < 0.001). Insulin-to-carbohydrate ratio (U/Xg) was reduced (more insulin given) at breakfast at URLi endpoint vs lead-in (LSM 9.0 vs 9.7g; P = 0.002) and numerically decreased at other meals. Total daily insulin dose (TDD) was higher at URLi endpoint compared with lispro lead-in (mean 50.2 vs 47.0U; P = 0.046) with similar prandial/TDD ratio (mean 52.1% vs 51.2%). There were no severe hypoglycemia events during the study. URLi in a basal-bolus regimen focusing on PPG targets demonstrated improved overall glycemic control and reduced PPG excursions without increased hypoglycemia in participants with T1D. ClinicalTrial.gov, NCT04585776.

Safety Event Outcomes and Glycemic Control with a Hybrid Closed-Loop System Used by Chinese Adolescents and Adults with Type 1 Diabetes Mellitus.

Background: While evidence supports glycemic control benefits for individuals with type 1 diabetes mellitus (T1DM) using hybrid closed-loop (HCL) systems, HCL automated insulin delivery therapy in China has not been assessed. This study evaluated safety events and effectiveness during HCL system use by Chinese adolescents and adults with T1DM. Methods: Sixty-two participants (n = 12 adolescents with a mean ± standard deviation [SD] of 15.5 ± 1.1 years and n = 50 adults [mean ± SD of 37.6 ± 11.1 years]) with T1DM and baseline A1C of 7.1% ± 1.0% underwent a run-in period (∼2 weeks) using open-loop Manual Mode (sensor-augmented pump) insulin delivery with the MiniMed™ 770G system with the Guardian™ Sensor (3) glucose sensor, followed by a study period (4 weeks) with HCL Auto Mode enabled. Analyses compared continuous glucose monitoring data and insulin delivered during the run-in versus study period (Wilcoxon signed-rank test or t-test). Safety events included rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Compared to baseline run-in, overall Auto Mode use increased time in range (TIR, 70-180 mg/dL) from 75.3% to 80.9% (P < 0.001) and reduced time below range (TBR, <70 mg/dL) from 4.7% to 2.2% (P < 0.001). Subgroup analysis demonstrated that participants (n = 29) with baseline A1C <7.0% had TBR that reduced from 5.6% to 2.0%, while participants (n = 21) with baseline A1C ≥7.5% had time above range (TAR, >180 mg/dL) that reduced from 31.6% to 20.8%. Auto Mode use also increased the percentage achieving combined recommendations for time at sensor glucose ranges (i.e., TIR of >70%, TBR of <4% and TAR of <25%) from 24.2% at baseline to 77.4% at study end. Total daily insulin dose reduced from 42.8 ± 19.8 to 40.7 ± 18.9 U (P = 0.013). There were no severe hypoglycemic, DKA, or serious adverse events. Conclusions: Chinese adolescents and adults, some of whom met target A1C at baseline, safely achieved significantly improved glycemia with 1 month of MiniMed 770G system use when compared to open-loop insulin delivery. ClinicalTrials.gov ID: NCT04663295.

The Impact of COVID 19 on Glycemic Control in Children with Type 1 Diabetes on Insulin Pump Therapy: A Single Centre Study

Background Children with type 1 diabetes (T1DM) are at risk of glycemic deterioration during the COVID-19 pandemic due to several factors. However, some studies reported glycemic improvement in these children. Aim To assess the impact of COVID-19 on children with T1DM on insulin pump in terms of glycemic control and insulin therapy adjustments. Methodology Forty-two children with T1DM on insulin pump (Medtronic) for at least 3 months were recruited from the Pediatric and Adolescent Diabetes Unit (PADU), Ain-Shams University, Cairo, Egypt. They were assessed for insulin requirements, frequency of diabetic ketoacidosis and clinically significant hypoglycemia. Auxological parameters, HbA1c and lipid profile were assessed. Continuous glucose monitoring was performed using Medtronic i-pro device for 5 days for each patient. Data were compared to previous patients’ data obtained from their medical records. Study period was performed between 29/6/2020 until 29/12/2020. Results This study was carried out on 42 children with T1DM on insulin pump (15 males and 27 females with a male to female ratio of 1: 1.8) with a mean age of 11.31± 3.28 years, mean BMI of 18.80± 3.35 and mean disease duration of 4.40± 2.93 years. The mean insulin requirements of the studied children before the COVID- 19 pandemic was 0.83 ± 0.28 U/kg/d, range 0.5- 1.8 U/Kg/d with a mean basal percentage of 51.19 ± 3.46 %, range 45-60 % .As regards the laboratory data of the studied children with a mean HbA1c of 9.0±1.2%, range: 7-11.8%, mean fasting cholesterol of 184.88 ± 27.03 mg/dl, range: 142-233 mg/dl, mean fasting triglycerides of 89.81 ± 32.69 mg/dl, range: 43-148 mg/dl, mean LDL of 87.77±9.97 mg/dl, range: 68-98 mg/dl, mean HDL of 58.33± 12.28, range: 32-83 and median UACR was 13(10-21.9) mg/g, range: 7.0-94. There was a statistically significant increase in the total daily insulin units(P = 0.001), basal percentage (P = 0.011) and time in range (p = 0.009) with a significant decrease in the frequency of DKA (P = 0.001), hypoglycemia (P = 0.004), HbA1c (p = 0.001) and glycemic variability (p = 0.001) after the COVID-19 pandemic. Conclusion Glycemic control improved during the COVID-19 pandemic among children with T1DM on insulin pump therapy reflected by improvement in TIR and decrease in glycemic variability. Declarations Conflicts of interest disclosure The authors declare that they have no conflict of interest. Funding sources No funding sources

The effects of large-scale social restriction during the covid-19 pandemic on glycemic control and occurrence of complications in children with type-1 diabetes mellitus

Background The global pandemic of severe acute respiratory syndrome caused by the coronavirus-2 (SARS-CoV-2) infection has resulted in a national large-scale social restriction (LSSR) to limit the spread of the virus.&#x0D; Objective To determine the impacts of LSSR on glycemic controls and the occurrence of complications in type-1 diabetes mellitus (T1DM) children. &#x0D; Methods A retrospective longitudinal study was carried out in Dr. Sardjito Hospital, Yogyakarta. Subjects were 0-18 years old T1DM patients diagnosed before the LSSR with at least six months of disease. Data on demographics, T1DM status, HbA1c level, and complications pre-LSSR, and during LSSR were taken from medical records. Paired T-tests were used to assess the difference in HbA1c level between the two-time points&#x0D; Results: We included information on 21 children based on the inclusion and exclusion criteria. Their median (range) age was 13.9 (1.42-17.3) years, with a median (range) diabetes duration of 2.6 (0.0-10.92) years. Glycemic control improved in 76% of the children. The mean HbA1c before and during LSSR was 10.9 (SD 2.7) and. 9.7 (SD 2.3), respectively; P&lt;0.05. The glycemic control was not associated with sex, age, duration of diabetes, travel time to the clinic, or a total daily insulin dose. There was also no significant difference in the occurrence of complications.&#x0D; Conclusion Despite limitations during LSSR, glycemic control improved in most patients with T1DM. This might be related to improved health awareness during the pandemic, more regular meals, and better parental control.

Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis.

Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM. PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool. A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (-0.09%/mg), weight (-2.2 kg/mg), and TDI (-4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (-0.51% vs -0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse. Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.

Hand grip strength is inversely associated with total daily insulin dose requirement in patients with type 2 diabetes mellitus: a cross-sectional study.

Short-term (2 weeks to 3 months) insulin intensive therapy using continuous subcutaneous insulin infusion (CSII) can improve islet beta cell function and prolong glycemic remission in patients with newly diagnosed type 2 diabetes mellitus (T2DM). However, the total daily insulin dose (TDD, IU/kg/d) required to achieve near-normoglycemic control with CSII still needs to be frequently adjusted based on blood glucose monitoring. Although real-time continuous glucose monitoring (rtCGM), which measures the interstitial fluid glucose concentration continuously without much difficulty, facilitates the adjustment of insulin dosage, its adoption in the T2DM population is strictly limited by insurance coverage and lack of awareness of rtCGM among clinicians. Thus, it is of clinical significance to identify easy-to-use parameters that may allow a more rapid and accurate prediction of TDD requirement. This study aimed to explore the association between hand grip strength (HGS) and TDD requirement in patients with T2DM receiving CSII therapy. A total of 180 eligible patients with T2DM were enrolled in the study and divided into three groups based on their HGS: low (L), medium (M), and high (H). The TDD requirement was calculated on day 7 or 8 of CSII treatment. Anthropometric parameters, including HGS, skeletal muscle mass, skeletal muscle index (SMI) and 6-m gait speed, and laboratory data, were collected on the morning of the second day after admission, within the first 24 h of CSII therapy. These parameters were used to identify significant predictors of TDD requirement using Pearson or Spearman correlation test, and stepwise multiple regression analysis. There were no significant differences in age, duration of T2DM, waist-to-hip ratio (WHR), body mass index (BMI), blood pressure, liver function, estimated glomerular filtration rate, triglyceride, total cholesterol, glycosylated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta cell function (HOMA-β) among the groups. The H group had higher body muscle mass-to-fat ratio (BMFR), skeletal muscle mass-to-fat ratio (SMFR), SMI, 6-m gait speed, and lower TDD requirement than the M and L groups. The HGS negatively correlated with TDD requirement (r = -0.33, p < 0.001) after adjusting for sex, age, BMI, WHR, HbA1c, Ln (HOMA-β), Ln (HOMA-IR), Ln (BMFR), Ln (SMFR), SMI, and 6-m gait speed. Multivariate stepwise regression analysis indicated that HGS was an independent predictor of TDD requirement in patients with T2DM (β = -0.45, p < 0 001). Lower HGS is associated with an increased TDD requirement in T2DM patients. HGS may facilitate the prediction of TDD requirement in T2DM patients receiving CSII therapy.

Managing type 1 diabetes mellitus with a ketogenic diet.

Traditional guidelines for type 1 diabetics do not restrict carbohydrates to improve clinical outcomes for patients. This paper highlights the favorable blood glucose control outcomes when a type 1 diabetic focuses on caloric intake from protein and healthy fats instead of the traditional carbohydrate-focused meals. We followed a male type 1 diabetic in his 20s adopting a ketogenic diet through a process of slowly lowering total daily carbohydrate intake. Diabetes-related biomarkers were measured throughout the process. Diabetes-related biomarkers saw massive improvements and ended up in the official non-diabetic range. Total daily insulin requirements dropped by 70%. The patient also experienced great improvements in his quality of life. This study demonstrates the possibility of improving diabetes-related biomarkers through dietary changes, which have positive effects on health outcomes in patients living with this disease. The adaptation of a ketogenic diet improved diabetes-related biomarkers in this patient. Diabetes-related biomarkers, such as HbA1c, are the main risk factors for developing complications in diabetics. The ketogenic diet is a feasible approach to minimizing the risk of developing complications in diabetics. Total daily insulin requirements dropped by 67% adapting a ketogenic diet. The patient experienced enormous changes in the quality of life after adapting to the new diet. The safe and physiological state of ketosis might be associated with additional benefits for the patient.

Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes

AimsCombined CFTR modulator therapies have dramatically altered pulmonary outcomes in patients with cystic fibrosis (CF). Their impact on glucose metabolism requires further investigations. This study aims to evaluate insulin requirements after initiation of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes. MethodsWe retrospectively analyzed: 1) the effects of tezacaftor + ivacaftor and elexacaftor + tezacaftor + ivacaftor on FEV1, weight, BMI, HbA1c, and daily insulin dose, in 17 CFRD patients and 2) the impact of tezacaftor + ivacaftor on HOMA indices in 15 CF patients without diabetes. ResultsAge was 37±12y in the CFRD group (70% men), 88% of whom were homozygous for F508del mutation. Diabetes duration was 15±10y. Median duration of combined CFTR modulator therapy was 16 months (IQR: 4) Thirteen patients received tezacaftor + ivacaftor, of whom 9 were switched to elexacaftor + tezacaftor + ivacaftor. Four patients received elexacaftor + tezacaftor + ivacaftor up front. A decrease in insulin needs was noticed in 88% of patients (0.85±0.3 vs 0.71±0.3U/kg/day; p = 0001). Total daily insulin dose decreased from 50±16 to 44±20U/day (p = 0.017). BMI improved (20.9 (IQR: 1.90) vs 22.1 kg/m2 (IQR: 3.70); p = 0.014). HbA1c went from 7.3±1.1 to 7.7±1.6% (p = 0.072). Median age was 22y (IQR: 11) in the CF group without diabetes (67% men), 93% of whom were homozygous for F508del mutation. Duration of combined CFTR modulator therapy was 10±5 months. HOMA-B changes were not significant (129.2 (IQR: 84.8) vs 103.5% (IQR: 66.3) nor were HOMA-S changes (from 94±64 to 95±49%). HOMA-BxS decreased from 112±45 to 104±29% (NS). BMI rose from 21.9±3 to 23.1±3.5 kg/m2 (p = 0.047). HbA1c was unchanged (5.0±0.5%). FEV1 improved in both groups (+11% and + 7% of predicted value; p < 0.001; p = 0.013). ConclusionCombined CFTR modulator therapies are correlated with a decrease in insulin doses and positive effects on BMI and FEV1. HOMA indices did not change on tezacaftor + ivacaftor among CF patients without diabetes.

1851-PUB: Intractable Diabetic Ketoacidosis with Enfortumab Vedotin

Enfortumab Vedotin (EV) is an antibody-drug conjugate for metastatic urothelial carcinoma. Hyperglycemia and diabetic ketoacidosis (DKA) have been reported in patients using EV. The incidence increases with higher BMI. The one case report available on the association between EV and DKA resulted in development of multiorgan failure and death. This case, however, describes a positive outcome with recovery from DKA. We present a case of a 59 year-old Caucasian woman with morbid obesity, prediabetes and recurrent metastatic urothelial cell carcinoma who presented with hyperglycemia after 2 doses of EV. Labs were indicative of DKA without an infectious etiology. She was admitted to the ICU for intravenous insulin drip treatment. Hyperglycemia and ketosis persisted despite using a maximum insulin drip rate of 60 units/hour. Starvation ketosis was a factor, so a diet was started. On day 2, NPH insulin and prandial lispro were added along with the insulin drip, resulting in a total daily insulin dose of 1660 units. Nevertheless, hyperglycemia persisted. U-500 regular insulin was initiated and by day 4, the patient received a total of 2940 units of insulin in one day with normalized serum ketones. Insulin drip requirements decreased with blood glucose controlled solely on subcutaneous insulin. She remained euglycemic, so U-500 insulin was switched to daily glargine. Eventually, she was off all insulin and maintained blood glucose below 130 mg/dL. Work up for insulin resistance included a C-peptide of 42.6 ng/mL (normal 1.1-4.4) with glucose of 230 mg/dL, negative glutamic acid decarboxylase 65 and insulin antibodies, and a glucagon level of 213 pg/mL (normal ≤80) with glucose of 220 mg/dL. Although the mechanism by which EV causes hyperglycemia is not known, this case illustrates that hyperglycemia was due to severe insulin resistance associated with EV. Understanding this, along with glycemic effects of targeted therapies with Vedotin are necessary to investigate the causal mechanism and treatment for EV related hyperglycemia/DKA. Disclosure A.Elahi: None. J.Duron: None. T.Porter: None.

1261-P: Prevalence of Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Type 1 Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a common comorbid condition in patients with type 2 diabetes. However, little is known about its prevalence among patients with type 1 diabetes (T1D). We used transient elastography to measure controlled attenuation parameter (CAP) as steatosis indicator and liver stiffness measurement (LSM) as fibrosis indicator. We evaluated 537 patients with T1D: age 49±16 years; 55% females; 81% non-Hispanic whites; BMI 27.6±5.5 kg/m2; diabetes duration 29±15.6 years; A1C 7.1±1.0%; total daily insulin (TDI) 49±28 U/day; ALT 19±10 IU/L; AST 22±8 IU/L. The prevalence of NAFLD (CAP≥274 dB/m) was 28.5% (95% CI 24.6-32.6) and fibrosis (LSM≥7 kPa) 8.4% (95% CI 6-11). Moreover, 4.1% (95%CI 2.6-6.2) of NAFLD had ≥F2 fibrosis (LSM ≥ 8.2 kPa) suggesting nonalcoholic steatohepatitis (NASH). Higher CAP positively correlated with higher BMI (p&amp;lt;0.001); diabetes duration (p&amp;lt;0.01); and TDI (p&amp;lt;0.001). It was common in males (OR 2.1, 95%CI 1.3-3.5, p&amp;lt;0.01). Among those with NAFLD, mean ALT was 21±11 IU/L (p=0.02), AST 22±7 IU/L, BMI 32.7±5.8 kg/m2, and waist circumference (WC) 103±15 cm. Among those with fibrosis, mean ALT was 23±10 IU/L (p=0.01), AST 24±7 IU/L (p=0.03), BMI 31.7±6.4 kg/m2 and WC 104±15 cm. Obesity (BMI &amp;gt;30 kg/m2) and larger WC (&amp;gt;102 cm in men, &amp;gt;88 cm in women) were associated with increased risk for hepatic steatosis (OR 3.1, 95% CI 1.6-6.0, p=0.001; OR 4.0, 95% CI 2.2-7.5, p&amp;lt;0.001, respectively). In conclusion, prevalence of NAFLD and liver fibrosis is considerable among patients with T1D, while liver enzymes are within normal range. Obesity and large waist circumference are associated with increased risk of hepatic steatosis. Independent predictors of NAFLD include: higher BMI, longer diabetes duration, higher TDI and male gender. Screening for NAFLD and liver fibrosis is advisable for patients with T1D irrespective of their liver enzymes, particularly in patients with higher BMI, longer diabetes duration or among those treated with larger insulin dose. Disclosure T.Salah: None. R.Mccarragher: None. L.Demattos: None. M.Tran: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation. S.Tomah: Employee; Altimmune. M.Al-badri: None. K.Kibaa: None. S.E.Dhaver: None. M.P.Curry: Advisory Panel; Mallinckrodt PLC, Alexion Pharmaceuticals, Inc., Albireo. M.Lai: None. Z.Jiang: Advisory Panel; Olix Pharmaceutical, Research Support; Pfizer Inc., Gilead Sciences, Inc. A.Khater: None.

1371-P: Factors Influencing the Development of Polycystic Ovary Syndrome in Premenopausal Women with Type 1 Diabetes

Objective: Polycystic ovary syndrome (PCOS) is common in women with type 1 diabetes (T1D). Reported prevalence rates vary according to diagnostic criteria used for PCOS. However, not all women with T1D develop hyperandrogenic traits and factors that influence the occurrence of PCOS have not been well stablished yet. We aim to assess the factors associated to the occurrence of PCOS in premenopausal women with T1D. Methods: Cross-sectional study. For this analysis, we included 110 patients with T1D, 24 diagnosed with PCOS by ESHRE/ASRM-Rotterdam criteria (prevalence: 22%, 95%CI: 15-30%). Women aged 18 to 45 years were consecutively recruited from a Diabetes Clinic at a tertiary hospital in Madrid, Spain. All participants were under intensive insulin treatment, had been diagnosed with T1D at least 1 year ago, and had a gynecological age of at least 2 years. A comparison between both groups T1D-PCOS and T1D-without PCOS was performed. We used Stata software v23 (StataCorp LLC) for statistical analysis. Results: Mean age was 30.3 ± 8.7 yrs and mean HbA1c was 7.31 ± 1.4%. Three-quarters (75%) of these patients were on multiple insulin doses. Women with T1D and PCOS were younger than those without PCOS (26.3 ± 7.4 in DM1-PCOS vs 31.2 ± 8.7, P &amp;lt; 0.05). Total daily insulin dose (TDI) was higher in T1D-PCOS group compared to T1D-without PCOS (0.71 ± 0.35 vs 0.58 ± 0.19, P = 0.025). There was a trend towards a more common premenarcheal diagnosis of T1D in T1D-PCOS (62.5% vs 46.5%, P = 0.116). Age (OR: 0.93, P = 0.016) and TDI (OR: 7.84; P = 0.043) were significant predictors of PCOS in the univariate logistic regression analysis. After introducing these variables in a multivariate regression analysis, only age was retained as a significant predictor factor of PCOS in women with T1D (OR: 0.93; P = 0.040). Conclusions: In this study, premenopausal women with T1D and PCOS were younger, used higher daily insulin doses and tend to have a more common premenarcheal diagnosis of T1D as compared to T1D women without PCOS. Disclosure A.Bayona: None. L.Nattero-chávez: None. M.De la calle de la villa: None. E.F.Durán: None. B.Dorado avendaño: None. M.Luque-ramírez: None. H.F.Escobar-morreale: None.