Daily Insulin Dose Research Articles

Automated insulin delivery systems in elderly patients with brittle type 2 diabetes

PurposeGeriatric diabetes is complicated by the frailty of this population, and hypoglycemia with insulin is not uncommon in these patients. Automated Insulin Delivery (AID) systems may provide better glycemic control in elderly patients with brittle type 2 diabetes. MethodsThirty-four patients (≥ 60 years) including cancer patients with brittle diabetes were switched to an AID system from multiple-dose insulin (MDI) treatment. HbA1c level, weight, total daily insulin requirement, and C-peptide, creatinine, and lipids were followed for at least six months. ResultsThere were 34 patients (14 male, 41.2 %) with a median age of 67 (IQR 63.0–75.5). Six patients (17.6 %) were on chemotherapy and/or steroids (Ch/S). The patients’ initial median HbA1c % was 9.3 (IQR 7.6–11.0), c-peptide level was 0.9 (IQR 0.5–2.2) ng/mL, and median total daily insulin dose was 41 IU (IQR 32–53).Six months after the patients were switched to an AID system their HbA1c % decreased to 7.1 (IQR 6.5–8.1), p < 0.001 and c-peptide increased to 1.21 (IQR 0.2–1.7) ng/mL, p = 0.878. Total insulin dose decreased with AID systems [32 IU (IQR 23.9–37.8)), p < 0.001].There was a decrease in median HbA1c % in patients on Ch/S [8.7 (IQR 7.0–11.5) to 6.9 (IQR 6.3–9.2)] however it didn’t reach statistical significance p = 0.225. Total insulin dose also decreased without statistical significance [33 IU (IQR 41–28) to 28 (IQR 23–35), p = 0.173].The mean time in range (TIR) percent of the patients with AID systems were as follows; <54 mg/dL was 0.5 %, 56–70 mg/dL was 1.3 %, 70–180 mg/dL was 64.8 %, >180 mg/dL was 26.7 % and > 250 mg/dL was 6.7 %. ConclusionAlthough AID systems are tested mostly in young type 1 patients our results show that elderly patients with brittle type 2 diabetes also benefit from an AID system. Even in very frail patients such as cancer patients, improvement can be seen.

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study.

The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T3mo), 6 months (T6mo) and 12 months (T12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T3mo and T6mo, but not at T12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

8654 Real-World Performance Of The Medtronic Extended Infusion Set In The United States

Abstract Disclosure: T. Kwa: Employee; Self; Medtronic Minimed. G. Zhang: Employee; Self; Medtronic Minimed. J. Kiehl: Employee; Self; Medtronic Minimed. V. Putcha: Employee; Self; Medtronic Minimed. A. Patel: Employee; Self; Medtronic Minimed. S. Chattaraj: Employee; Self; Medtronic Minimed. O. Cohen: Employee; Self; Medtronic Minimed. R.A. Vigersky: Employee; Self; Medtronic Minimed. Real-World Performance of the Medtronic Extended Infusion Set in the United States Objective: The Medtronic extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use and its pivotal trial established clinical safety and efficacy.[1] The purpose of this retrospective analysis was to assess real-world EIS performance and overall glycemic outcomes based on United States (US) data uploaded by MiniMed™ 770G system (MM770G) users at an aggregate level. Methods: Infusion set occlusion alarm events and time in (TIR, 70-180 mg/dL), below (TBR, &amp;lt;70 mg/dL) and above (TAR, &amp;gt;180 mg/dL) range of EIS-MM770G users (N=393) with &amp;gt;30-day device use in the U.S. were analyzed and compared against the data of a cohort of the same median age of 50 years (N=77219) using the MM770G with a standard 2/3-day infusion set (at an aggregate level). Results: EIS users experienced a lower occlusion alarm rate (median 0.011 alerts/patient day) compared to 0.016 alerts/patient day with the standard set (p = 0.005). TIR for EIS users was 69.4%, which was numerically greater than the 69.1% for standard set users (p = 0.258). While TAR was not significantly different (28.9% for EIS and 29.0% for standard set, p = 0.995), TBR was significantly lower (0.5% for EIS and 1.3% for standard set, p = 0.000). The difference in the total daily dose (TDD) of insulin between the two groups (53.0 units for EIS, 49.4 units for standard set) was not statistically significant (p = 0.961). Conclusion: Since the U.S. launch, the EIS has continued to perform similarly to the pivotal trial results and an early real-world analysis of EIS use outside of the US.2 The decreased burden of fewer set changes comes with a lower occlusion alarm rate and does not compromise time spent in target range.

6923 Case Report: Long Standing Type 2 Diabetes with TOFI Phenotype Successfully Weaned Off One Hundred Units of Basal-Bolus Insulin Therapy With Glucagon-Like Peptide 1 Receptor Agonist Therapy

Abstract Disclosure: Y.C. Kon: None. A 60-year-old Indian male was diagnosed with type 2 diabetes in 1997. In July 2017, his fasting blood glucose level (FBGL) was 10.3 mM, paired C-peptide 719 pM, eGFR measured as more than 60 ml/min. Since Sep 2017, he had been compliant on the same stable regimen of sc insulatard 20 units om and 20 units at 10 pm, sc actrapid 20 units t.i.d premeal, PO metformin 850 mg t.i.d and PO dapagliflozin 10 mg om. In the past, he had suffered myocardial infarction, with left ventricular ejection fraction 35%, and had left anterior descending coronary artery stenting. In 2017, he had automatic cardioverter defibrillator implanted for primary arrhythmia prevention. His cardiac medications included bisoprolol fumarate 5 mg om, losartan 25 mg om, spironolactone 25 mg om, aspirin 100 mg om and high intensity statin therapy. Since 2020, his HbA1c had measured 8% to 9% with FBGL at 6 mM to 11 mM. Hence he was referred by his cardiologist in Oct 2022 to optimize glycaemic control. Once every few months, he experienced hypoglycaemic symptoms with corresponding low capillary blood glucose (CBG) of 3 mM, reversed with glucose intake. On physical examination, he weighed 81.6 kg, BMI was 25.4 kg/m2, BP 110/67 mmHg, pulse rate 69/min regular, waist circumference 106 cm. There was no acanthosis nigricans. He did not appear Cushingoid nor acromegalic. As he had “thin outside, fat inside (TOFI)” type 2 diabetes phenotype, he was started on sc liraglutide 1.8 mg om. His actrapid dose was halved to 10 units premeal, and insulatard dose halved to 10 units bid. His dapagliflozin was switched to subsidised empagliflozin 25 mg om. Subsequently, his premeal CBG measured 4 to 7 mM, bedtime CBG 4-6 mM, with occasional minor hypoglycaemic episodes with CBG at 3-4 mM. In July 2023, HbA1c measured 6.3%, FBGL was 5.5 mM and paired C-peptide measured as 554 pM. Basal insulatard was discontinued and he was switched from liraglutide to sc dulaglutide 1.5 mg once weekly. In Oct 2023, his FBGL was 5.2 mM and HbA1c had improved markedly to 5.7%. His weight had reduced from 81.6 kg to 70.0 kg, BMI decreased from 25.4 kg/m2 to 22.9 kg/m2 and waist circumference reduced from 106 cm to 97 cm. As he continued to experience occasional minor hypoglycemic episodes, actrapid insulin was discontinued. On his current therapy of sc dulaglutide 1.5 mg once weekly, PO empagliflozin 25 mg om, PO metformin 850 mg tid, and PO acarbose 50 mg t.i.d, his fasting CBG measured 6.7-7.7 mM, premeal CBG 6.4 to 10.1 mM, off all insulins and without further episodes hypoglycaemia. Conclusion: Patients with long standing “TOFI” type 2 diabetes and robust C-peptide may be trialled on GLP1-receptor agonist therapy to wean off high daily doses of insulin, thus avoiding hypoglycaemia, achieving weight and abdominal fat loss, whilst maintaining glycaemic control. This is especially important in patients with established coronary artery disease. Presentation: 6/3/2024

Effectiveness and safety of glucose-lowering drugs as an adjunct to insulin therapy in Chinese patients with type 1 diabetes: a retrospective, observational study.

To assess the real-world impact of glucose-lowering drugs (GLDs) as an adjunct to insulin in Chinese patients with type 1 diabetes (T1DM). This dual-center, observational, retrospective study included 121 T1DM patients receiving GLDs as adjuncts and 56 participants with insulin-only drugs as comparators. Glycated hemoglobin A1c (HbA1c), daily insulin dosage, fasting blood glucose (FBG), postprandial blood glucose (PBG), nocturnal blood glucose (NBG) and the difference in trough and peak blood glucose levels on the same day (Δ TP) were assessed at baseline and at the end of the study. In total, HbA1c decreased by 1.14% in the GLD+insulin group (p < 0.0001) and 0.36% in the insulin-only group (p = 0.0423, mean adjusted difference, -0.09% [95% CI, -0.55 to 0.37]). The total daily insulin concentration was reduced by 7.34 U per day in the GLD+insulin group vs. 5.55 U per day in the insulin-only group (mean adjusted difference, -2.32 U [95% CI, -4.97 to 0.33]). In particular, among patients with fasting C-peptide levels < 17 pmol/L, the total daily insulin concentration was significantly reduced by 9.22 U vs. 5.09 U per day (mean adjusted difference, -3.84 [95% CI, -6.85-0.84]; p = 0.0129). There were no notable differences in the other glycemic indices between the two groups. A gradual downward trend in changes in glycemic outcomes was observed among patients treated with various combinations of metformin, acarbose, and dipeptidyl peptidase 4 inhibitor (DPP-4i). Similar reductions in the daily insulin dose were also detected in most of the GLD+insulin group in addition to the DPP-4i-only group. No severe hypoglycemia was induced by additional GLDs. The use of additional GLDs tends to improve glycemic outcomes and reduce insulin requirements in patients with T1DM. These results indicate that the use of GLDs as an adjunctive therapy may have been an effective treatment strategy among adults with T1DM in China.

Glucagon-like-peptide-1 agonist therapy in adults with cystic fibrosis

Glucagon-like-peptide-1 (GLP-1) agonists are commonly used to improve glycemic control and promote weight loss in individuals with type 2 diabetes mellitus (T2DM) and/or obesity. However, there is a paucity of evidence regarding GLP-1 agonist use in people with cystic fibrosis (pwCF). We present 11 people with CF (males: 3, females: 7; age range 24–47; BMI range 25.7–43.7) treated with GLP-1 agonists (semaglutide: 9,tirzepatide: 2) for variable duration (1–50 months). All experienced weight loss on GLP- 1 agonist therapy (median change in weight = -7.2 kg; change in BMI [kg/m2] = -0.9 to -8.1). Eight pwCF showed improvement in percent predicted forced expiratory volume in 1 second (ppFEV1) [change = -5 to + 18] and nine pwCF showed improvement in percent predicted forced vital capacity (ppFVC) [change= +1 to + 26]. Of the 7 pwCF with CFRD, all reduced their insulin quantity (mean, 31.5 % decrease in total daily insulin dose), and glucose time in range improved for most (mean, +11 % increase from baseline). Four pwCF stopped using GLP-1 agonists: 2 due to severe nausea/vomiting, 1 due to lack of perceived benefit, and 1 due to change in insurance coverage. This report is the largest published series to date of pwCF treated with GLP-1 agonist therapy. With the addition of GLP-1 agonists, all individuals experienced weight loss and a reduction in daily insulin dose, and most had improvement in pulmonary function. Future multi-center studies are needed to corroborate the efficacy and safety of these agents in the CF population.

Impact of triple transmembrane regulator therapy on glucose metabolism in cystic fibrosis related diabetes during clinical practice

AimsTo evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Cystic Fibrosis Related Diabetes (CFRD) glycemic control and insulin treatment in patients with CFRD during clinical practice. MethodsWe carried out a retrospective observational study of 23 adult patients with CFRD who started treatment with ETI. They had, at least, one F508del mutation. Data were collected before ETI initiation and 3, 6, and 12 months after. ResultsGlycemic control measured by HbA1c significantly improved by 0.3 % (0.1–0.5) after 3 months of ETI therapy (p = 0.004) and kept this improvement during follow-up (p < 0.001). The proportion of patients needing multiple daily injections of insulin was reduced by 16 % (p = 0.023). Total daily insulin dose dropped by 0.12 (0.05–0.18) UI/kg/day (p < 0.001). Data derived from Flash Continuous Glucose Monitoring (CGM) for patients treated with insulin stayed unchanged after insulin reduction, except for a significant 8 % (0.3–15.6) increase in the Time In Tight Range (TITR) between 70 and 140 mg/dL (p = 0.043). ConclusionETI therapy impacted CFRD in clinical practice reducing insulin needs and improving glycemic control measured by HbA1c and CGM. The improvements can be observed from the first 3 months of treatment.

Closed-Loop Insulin Therapy for People With Type 2 Diabetes Treated With an Insulin Pump: A 12-Week Multicenter, Open-Label Randomized, Controlled, Crossover Trial.

Continuous glucose monitoring (CGM) combined with continuous subcutaneous insulin infusion (CSII) achieves better glycemic control than multi-injection therapy in people with type 2 diabetes. The effectiveness of closed-loop therapy needs to be further evaluated in this population. The study objective was to measure the impact of a hybrid closed-loop device (DBLG1) compared with CSII + CGM on glycemic control in people with type 2 diabetes previously treated with CSII. The randomized, controlled, crossover, two-period, open-label, and multicenter study was conducted from August 2022 to July 2023 in 17 individuals (9 to receive 6 weeks of CSII + CGM first and 8 to receive 6 weeks of closed-loop therapy first). The primary end point was the percentage time in range (TIR: 70-180 mg/dL). Secondary outcomes were other CGM-glucose metrics, physical activity, and sleep objectively measured using 1-week actimetry. Data were analyzed using a modified intention-to-treat approach. Mean age was 63 (SD 9) years and 35% were women. Mean HbA1c at inclusion was 7.9% (SD 0.9). TIR increased to 76.0% (interquartile range 69.0-84.0) during the closed-loop condition vs. 61.0% (interquartile range 55.0-70.0) during the CSII + CGM condition; mean difference was 15.0 percentage points (interquartile range 8.0-22.0; P < 0.001). Analyses of secondary end points showed a decrease in time above range, in glucose management indicator, in glucose variability, and an increase in daily insulin dose. Actimetric sleep analysis showed an improvement in sleep fragmentation during closed-loop treatment. Closed-loop therapy improved glycemic control more than did CSII + CGM in people with type 2 diabetes.

Assessment of insulin dose changes in pediatric patients with type 1 diabetes mellitus starting on continuous subcutaneous insulin infusion

ObjectiveTo assess change in total daily dose (TDD) of insulin following a switch from subcutaneous (SC) injections to continuous subcutaneous insulin infusion (CSII) in pediatric patients with type 1 diabetes (T1D). Secondary objectives were to determine the change in %basal insulin, insulin to carbohydrate (I:C) ratios, insulin sensitivity factor (ISF), and HbA1c/IDAA1c. MethodsA retrospective chart review of patients < 18 years of age who transitioned from SC to CSII at the Alberta Children’s Hospital (Calgary, Alberta, Canada) between January 2019 and March 2022. ResultsThere was an increase of 0.04 units/kg/day in TDD from baseline vs 1–3 months later (p = 0.04, 95 % confidence interval (CI) [0.002, 0.072]). When stratified by age, a similar increase in TDD was observed in age 5–12 years only (p = 0.05, 95 % CI [0.0006, 0.8236]). There was a decrease in overall %basal insulin by 3 (44 % of TDD at baseline vs 41 % of TDD on CSII). (p = 0.02, 95 % CI [−5.5, −0.4]). No strengthening was seen in I:C ratios from baseline vs 1–3 months later. There was a significant strengthening of I:C ratios at all meals in the basal bolus group from 1–3 weeks to 1–3 months post-CSII; overall strengthening of ISF at both time points; and an overall HbA1c decrease −0.30 (p < 0.0001, CI [−0.45, −0.15]). Each extra year with diabetes was associated with a decrease in HbA1c by 0.07 % (p = 0.006). ConclusionsTDD of insulin was not found to be decreased post CSII initiation and patient characteristics should be considered when changing from SC to CSII. HbA1c was significantly improved post CSII.

Association of physical activity patterns with nocturnal hypoglycemia events in youth with type 1 diabetes.

This study sought to elucidate the interactions among physical activity (PA) patterns, mean glucose concentrations, and the incidence of nocturnal hypoglycemia events in children and adolescents with type 1 diabetes, examining the moderating influence of daily dosage on these associations. Eighty-two participants aged 6 to 18 years (43.9% girls) from the Diactive-1 Cohort Study, diagnosed with type 1 diabetes, were included. Data collection involved continuous glucose monitoring, accelerometry to assess real-world PA, as well as documentation of daily insulin doses and carbohydrate counting over the same seven days. A total of 19 participants experienced at least one nocturnal hypoglycemia event over a span of 574 measurement days (106 days with and 451 days without nocturnal hypoglycemia). Higher levels of vigorous PA (VPA) were associated with lower same-day mean glucose levels (p = 0.014). Additionally, higher levels of moderate PA (p = 0.023), VPA (p = 0.011), and moderate-to-vigorous PA (p = 0.010) were associated with a greater number of nocturnal hypoglycemia events. Specifically, a significant association was identified between VPA and nocturnal hypoglycemia events when the daily insulin dose were at or above 1.04 units per kilogram of body weight per day (p = 0.016). Daily VPA is associated with glucose reductions, potentially leading to more hypoglycemic episodes, particularly when there's an excess of daily insulin. This highlights the need for careful insulin management in children and adolescents with type 1 diabetes engaging in VPA.

Ensuring patient safety when managing concentrated insulin glargine and insulin degludec at hospital admission

AbstractThe development and use of concentrated insulins have increased in recent years. This can pose unique challenges when transitioning to a non‐concentrated insulin during an inpatient admission. There is no clear consensus on the recommended interchange of the various concentrated insulins in the inpatient setting, with suggestions ranging from implementing a 1:1 unit dose conversion, a minimum 20% dose reduction or selecting an approach based on the total daily dose of the concentrated insulin. In a retrospective cohort analysis at a single health system, a greater number of hypoglycemic events occurred when implementing a 1:1 unit conversion of insulin glargine 300 units/mL (iGlar300) to insulin detemir 100 units/mL (iDet100) compared to the same conversion from insulin glargine 100 units/mL (iGlar100) to iDet100. This prompted identification of a standardized approach that would improve patient safety while also being operationally feasible at a multi‐hospital network. The solution of implementing a minimum 20% dose reduction successfully improved hypoglycemia rates upon transitioning from iGlar300 to iDet100, though many logistical challenges were faced. Although iDet100 is being phased off the market, adhering to this minimum 20% dose reduction is the recommended approach when transitioning from iGlar300 to iGlar100, and this challenge persists as a relevant issue. Ensuring health systems are equipped to implement dose reductions when transitioning from concentrated basal insulins to non‐concentrated basal insulin counterparts is paramount for maintaining patient safety. This paper will discuss the limited evidence available supporting optimal dosing when transitioning iGlar300 and insulin degludec 200 units/mL (iDeg200) to non‐concentrated basal insulins and serve as a “how to” implementation guide for other health systems, based on one health system's approach in navigating this emerging patient safety issue.

Changes in Basal and Bolus Insulin Requirements with Tirzepatide as an Adjunctive Therapy in Adults with Type 1 Diabetes Using Tandem Control-IQ.

This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8months of tirzepatide treatment. In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64% female and mean body mass index of 39.6kg/m2). Data were compared from baseline and over 8months. Within 2months of tirzepatide treatment, there were significant reductions in total daily insulin [median (IQR) 73.9 (47.6-95.8) to 51.7 (46.7-66.8) units/day, p < 0.001], basal insulin [47 (28.2-51.8) to 32.4 (25.5-46.3) units/day, p < 0.001], and bolus insulin [31.4 (19.9-38.3) to 17.9 (14.9-22.2) units/day, p < 0.001] requirements. Insulin dose reduction from 2 to 8months was modest. The frequency of user-initiated boluses did not differ throughout the study. Despite reductions in total insulin requirement, time in range (70-180mg/dl) increased by 7%, A1c reduced by 0.5%, weight reduced by 9%, without increase in time below 70mg/dl. This pilot study provides clinical guidance on insulin titration for adults with T1D who may initiate tirzepatide therapy. Based on the findings of this study, we recommend reducing 25% of total daily insulin dose at tirzepatide initiation in adults with T1D using AID with baseline A1c of less than 7.5%. Higher doses of tirzepatide were associated with greater weight loss, however, the reduction in insulin requirement was minimal.

Impact of metabolic and bariatric surgery on weight loss and insulin requirements in type 1 and insulin-treated type 2 diabetes.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

Glycemia control after total pancreatoduodenectomy

Aim. To study the features of correction of carbohydrate metabolism disorders and nutritional deficiency in patients after total pancreatoduodenectomy; to develop a unified protocol for managing patients after total pancreatoduodenectomy. Materials and methods. From 2007 to 2022, 62 patients underwent total pancreatoduodenectomy in the Hepatopancreatic Surgery Unit of the Botkin Hospital. The patients were divided into two groups, comparable in terms of basic parameters. The first group included patients (n = 32) who underwent “classical” total pancreatoduodenectomy with gastric resection and splenectomy. The second group consisted of patients (n = 30) who underwent total pancreatoduodenectomy in the modification of Botkin Hospital. In the perioperative period, patients of both groups were examined for carbohydrate metabolism with the selection and assessment of the average daily dose of short-acting and long-acting insulin, assessment of enzyme and protein deficiency with the selection of enzyme replacement therapy and nutritional support. For a more accurate assessment of carbohydrate metabolism disorders, all patients underwent continuous monitoring of the level of glycemia intraoperatively and in the early postoperative period (FreeStyle Libre flash monitoring system, Abbott). The glycated hemoglobin level was assessed on day 90 and body mass index – on days 30, 60 and 90 after surgery. Results. The mean level of glycemia in patients after total pancreatoduodenectomy in the modification of the Botkin Hospital accounted for 8.0 mmol/l and the variability (daily fluctuations in glycemia) comprised 39 %, which was significantly lower compared to the group of “classical” total pancreatoduodenectomy with 7.6 mmol/l and 48 %, respectively. Seven patients (21.9 %) after total pancreatoduodenectomy in the modification of the Botkin Hospital experienced a severe hypoglycemic episode, while a similar severe hypoglycemic episode was noted in 25 patients (80.6 %) after pancreatectomy in its “classical” variant, of which 18 patients (60 %) required hospitalization in the endocrinology unit in order to correct the sugar-lowering therapy. In turn, only three patients (9.4 %) after total pancreatoduodenectomy modified by the Botkin Hospital required hospitalization due to severe hypoglycemia. The mean level of glycated hemoglobin in patients of the first and second groups on day 90 accounted for 7.2 % and 7.7 %, respectively (p = 0.789). The average body mass index on day 90 after surgery was higher in the group of organ-preserving total pancreatoduodenectomy: 24 kg/m2, compared to the “classical” pancreatectomy with 21.2 kg/m2 (p = 0.001). The daily dose of both short-acting and long-acting insulin was higher in the organ-preserving total pancreatoduodenectomy group of 17.4 ± 5.6 U/day and 12 ± 4.6 U/day, respectively, compared to the group of “classical” total pancreatoduodenectomy of 13.8 ± 4.6 U/day and 10.8 ± 2.7 U/day, respectively. This can be attributed to the faster normalization of the patient's body weight and the preserved function of physiological digestion due to the pylorus-preserving variant of total pancreatoduodenectomy. Conclusion. Management of patients after total pancreatoduodenectomy is claimed to be an extremely complex task that requires a multidisciplinary approach involving surgeons, intensivists, endocrinologists and gastroenterologists at all stages of patient management. Organ-preserving modification of total pancreatoduodenectomy with preservation of the stomach, spleen and splenic vessels in the modification of the Botkin Hospital improves treatment results and simplifies the selection of insulin therapy for this group of patients.

Evaluation of type 1 diabetes’ partial clinical remission after three years of heterologous adipose tissue derived stromal/stem cells transplantation associated with vitamin D supplementation

BackgroundMesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. Methods: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. Results: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. Conclusion: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control.Trial Registration37001514.0.0000.5257.

Impact of the State of Emergency Declaration for Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic Suppression on Individuals with Type 1 Diabetes Mellitus.

Objective To examine the impact of lifestyle changes caused by the first emergency declaration issued in 2020 on glycemic control and body weight changes in Japanese individuals with type 1 diabetes mellitus. Methods This study included Japanese individuals with type 1 diabetes mellitus who visited Tokyo Women's Medical University Hospital between January 2019 and September 2020 (n=278). Seasonal changes in glycated hemoglobin (HbA1c) levels and the body mass index (BMI) were compared. A self-administered questionnaire regarding changes in treatment, diet, exercise, sleep, and telecommuting was used to assess lifestyle changes. Results Although HbA1c levels decreased from winter to summer in 2019 and 2020, the annual change was slightly but significantly greater in 2020 than in 2019. Seasonal changes in the BMI between 2019 and 2020 were also significantly different. An increase in the daily insulin dose, overall blood glucose level, diurnal change in blood glucose level, and food intake were significantly associated with increased HbA1c levels. Furthermore, HbA1c levels decreased with increasing moderate physical activity and sleep duration. The change in the BMI increased with increasing insulin dose, overall high blood glucose levels, and food intake. However, an increase in moderate physical activity was associated with a decrease in the BMI. HbA1c levels were significantly lower after the first emergency declaration in individuals with type 1 diabetes mellitus than that before the emergency declaration, even after accounting for seasonal variations. Conclusion Decreased HbA1c levels were associated with a decreased food intake, increased moderate exercise, and increased sleep duration during the state of emergency. The BMI remained relatively unchanged.

A sensor-augmented pump with a predictive low-glucose suspend system could lead to an optimal time in target range during pregnancy in Japanese women with type 1 diabetes.

It is challenging for pregnant women with type 1 diabetes to maintain optimum glucose level to attain good neonatal outcomes. This study evaluated the efficacy of sensor-augmented insulin pump (SAP) with a predictive low-glucose suspend (PLGS) system in pregnant Japanese women with type 1 diabetes. SAP with PLGS was used in 11 of the 22 women with type 1 diabetes who delivered between 2011 and 2021 at the two medical institutions in Japan. Glucose management, insulin delivery suspension time (IST) and neonatal outcomes were retrospectively studied. In SAP with PLGS cases (n = 11), average glycated hemoglobin levels were < 6.5% throughout the pregnancy, and the time in range (TIR, 63-140mg/dl) was > 70% in the second and third trimesters. PLGS was safely used without inducing ketoacidosis. Positive correlation was observed between IST and TIR (r = 0.62, p < 0.01). Negative correlation was observed between IST and time below range (TBR) (r = - 0.40, p = 0.02), and IST and time above range (TAR) (r = - 0.45, p = 0.01). Total daily insulin dose was adequately increased without increasing hypoglycemia. There was only one heavy-for-date HFD) infant among the 11 newborns in SAP with PLGS cases. In cases without SAP (n = 11), target glycemic levels were difficult to achieve and there were 5 HFD infants among the 11 newborns. SAP with PLGS was safely and effectively used in pregnant women with type 1 diabetes to achieve target glucose levels without increasing the risk of hypoglycemia, which may have led to good neonatal outcomes. The online version contains supplementary material available at 10.1007/s13340-024-00716-7.

Impact of early-morning administration of rapid-acting insulin on the increase in blood glucose levels related to the dawn phenomenon in individuals with type 1 diabetes.

An early-morning elevation of blood glucose levels known as the dawn phenomenon and consequent postbreakfast hyperglycemia occur in some individuals with type 1 diabetes (T1D). Whereas insulin pump therapy can mitigate this phenomenon, some individuals prefer or are limited to alternative treatments. We have now assessed the effectiveness of early-morning administration of rapid-acting insulin for amelioration of the dawn phenomenon in individuals with T1D. Thirteen individuals with T1D who experienced the dawn phenomenon as determined by continuous glucose monitoring (CGM) and who received a small dose of rapid-acting insulin on waking were included in this retrospective study. We evaluated the change in sensor glucose levels during a 2-h period from before to after breakfast consumed at 0700h. The change in blood glucose levels during additional time intervals, average daily sensor glucose values, CGM indices, and insulin dose were also evaluated. The early-morning administration of 0.5-1 unit of rapid-acting insulin was associated with a significant reduction in 2-h glucose variability between before (0700h) and after breakfast from a median of 90.7-51.0mg/dL. The glucose variability from 0300 to 0700 or 0900h was also significantly decreased, from 67.7 to 29.0mg/dL and from 172.5 to 78.3mg/dL, respectively. Average sensor glucose levels throughout the day were significantly reduced (from 192.7 to 156.7mg/dL), as was the daily total insulin dose. Early-morning administration of rapid-acting insulin effectively managed the dawn phenomenon and subsequent postbreakfast hyperglycemia in individuals with T1D. The online version contains supplementary material available at 10.1007/s13340-024-00709-6.

The opportunities and challenges of the disease-modifying immunotherapy for type 1 diabetes: A systematic review and meta-analysis

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00–0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04–0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, −0.07units/kg/day, 95% CI, −0.11 to −0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, −0.11units/kg/day, 95% CI, −0.23 to −0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.