Subcutaneous Insulin Research Articles

Performance of a Continuous Subcutaneous Insulin Infusion (CSII) Pump With Acoustic Volume and Flow Sensing in Simulated High-Consequence Situations.

Goal: An insulin pump's failure to deliver insulin in the right amount at the right time is a preventable cause of hospitalization. We evaluated key performance metrics of a novel insulin pump that prevents "silent insulin non-delivery" caused by blockage, delivery of air and site leakage. This is accomplished via an acoustic sensor that measures the volume of insulin delivered with each pulse in real-time. Methods: We tested long and short-term flow accuracy, occlusion-detection time and pressure, and air management of the new device (ND) versus 3 U.S. commercial insulin pumps (CIPs) using standardized methods. Results: The ND outperformed CIPs on long-term basal flow rate error. Occlusion detection was 5 to 22.5 times faster depending on the basal rate and resulted in significantly lower (2 to 5x) pressures at time of occlusion. With air included in the drug reservoir, the tested CIPs can infuse air without detection, while the ND prevented air delivery without interruption. Conclusions: Bench tests of the ND versus 3 commercially available pumps showed improved occlusion detection and air management without flow performance tradeoffs. Additionally, the lower delivery pressure measured at time of occlusion suggests a substantially lower potential for site leakage at both basal and bolus rates. These enhancements combine to decrease the likelihood of silent insulin non-delivery.

Judicious use of modern technology with antihyperglycemic agents: The changing landscape of type 2 diabetes management

Abstract Background: Continuous subcutaneous insulin infusion (CSII) pump has shown good outcomes in patients with both type 1 and type 2 diabetes mellitus. Here, we present an individual with type 2 diabetes and obesity who was on a high dosage of insulin and oral hypoglycemic agents (OHA) were able to get diabetes under good control with weight reduction after using a hybrid artificial closed-loop insulin pump system along with glucagon-like peptide 1 receptor agonist (GLP-1RA) and sodium-glucose co-transporter-2 (SGLT-2) inhibitor. Case Presentation: A 60-year-old lady with type 2 diabetes presented with uncontrolled blood sugars despite high doses of insulin and a combination of OHAs. She was also depressed and frustrated due to uncontrolled blood sugars despite repeated changes made in her treatment plan using an insulin pump along with GLP-1RA (dulaglutide) and SGLT-2 inhibitor (empagliflozin). Results: After changing the treatment plan, her HbA1c levels decreased from 10.1% to 7.3% after 3 months. The microalbuminuria reverted to normoalbuminuria (59.9–12.2 µg/mg of creatinine). Improvement has been observed in the fasting C-peptide levels from 0.50 to 0.86 pmol/L and stimulated C–C-peptide levels from 1.2 to 2.05 pmol/L. As she lost nearly 7 kg of weight, she felt satisfied with a better quality of life. Even her depression settled down. Conclusion: Use of CSII pump along with dulaglutide and empagliflozin helped in controlling blood sugars, bringing down weight with an overall improvement in mental health and renal function; in this, difficult to treat the patient.

Hemorrhagic Shock Associated with a Subcutaneous Insulin Pump Catheter: First Time Reported Side Effect.

Continuous subcutaneous insulin infusion (CSII) systems, used to treat diabetes for over 40 years may improve glycemic control but also have rare major complications. We report the first hemorrhagic shock on the infusion site of an insulin pump, due to a rectus abdominis hematoma. An eighty-one years old woman with history of cardiovascular events and type 1 diabetes, presented with hemorrhagic shock due to a rectus abdominis hematoma rapidly constituted at the insulin injection site. The situation improved after conservative treatment (blood transfusions, IV fluids, replacement of the CSII with insulin injections). Contributive factors to this complication were overdose of anticoagulant, oversized insulin canula and cough. We recommend increased monitoring of patients using insulin pump with hemorrhagic risk factors. Specific education for the prevention and detection of signs of hemorrhage should lead patients to report this situation promptly, in order to avoid this life-threatening complication.

Success of Insulin Infusion Transitions in Moderate to Severe Diabetic Ketoacidosis With Transition Anion Gap of Less Than or Equal to 12 mEq/L Versus Greater Than 12 mEq/L.

Background: Patients with diabetic ketoacidosis (DKA) are transitioned from intravenous (IV) to subcutaneous (SQ) insulin upon DKA resolution. Although an anion gap (AG) ≤12 mEq/L is recommended before transition to SQ insulin, there are limited data to support this threshold. Objective: To compare the rates of successful transitions to SQ insulin in patients with DKA with an AG ≤ 12 mEq/L versus > 12 mEq/L. Methods: Retrospective cohort study of adult critically ill patients with moderate to severe DKA between September 2019 and December 2022. The primary outcome was the success of insulin transition between patients transitioned with an AG ≤ 12 mEq/L and those transitioned with an AG > 12 mEq/L. Transition was considered successful if the AG did not increase above the value at transition at 24 hours and insulin infusion was not restarted. Secondary outcomes include the individual components of the primary outcome and ICU length of stay (LOS); safety outcomes included hypoglycemia and electrolyte derangements. Results: In total, 92 patients were included, with 43 patients transitioned at AG ≤ 12 mEq/L and 49 patients transitioned at AG > 12 mEq/L. Transition was unsuccessful in 3 patients (7%) with AG ≤ 12 mEq/L and 2 patients (4%) with AG > 12 mEq/L (P = .66). There was no difference in the incidence of the individual components of this outcome between groups or in safety outcomes. Conclusion: This retrospective study showed no difference in success of insulin transition between the groups. Larger studies are needed to evaluate the impact of treatment characteristics on transition success and patient outcomes.

Hypoglycemic Effect of Orally Delivered Insulin Nanoparticles Compared to Subcutaneous Recombinant Human Soluble Insulin in Hyperglycemic Male Rats

Background: Insulin is available as an injectable drug and remains the mainstay of therapy. Researchers have attempted to develop an oral formulation of insulin, particularly utilizing nanoparticles (NPs). Objective: To assess the efficacy and safety of insulin-loaded D-α-Tocopherol polyethylene glycol succinate (TPGS)-emulsified PEG-capped PLGA NP in comparison to insulin-loaded PLGA NP and subcutaneous (SC) insulin in an in vitro and in vivo diabetic rat model. Methods: Two biocompatible and biodegradable NPs were used, in which 20 IU/kg of recombinant human soluble insulin was incorporated. NP1 was PLGA-loaded with human insulin, while NP2 was PLGA-PEG-TPGS-loaded with human insulin. The physical characteristics of the NPs were examined in an in vitro and in vivo study on a hyperglycemic rat model for a 24-hour duration. Results: For the first 3 hours, SC insulin showed a better reduction in serum glucose levels (SG) compared to both NP1 and NP2. A smooth, sustained reduction in SG was observed and maintained till the end of 24 hours with both NPs. NP1 maintained SG reduction for 6 hours before experiencing an increase, while NP2 demonstrated superior sustained reduction in SG beyond the 12-hour evaluation period. Conclusions: PLGA-PEG-TPGS NP can act as a potential carrier for oral insulin delivery and maintain good glycemic control for up to 24 hours.

Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial

BackgroundWeight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. ObjectivesTo examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. MethodsIn a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. ResultsIn the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. ConclusionMild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. Trial registration numberThis trial was registered at the clinicaltrials.gov as NCT05259475.

Insulin infusion sets associated with adverse events: strategies for improved diabetes education

IntroductionInsulin Infusion Sets (IIS) play a crucial role in ensuring the safe delivery of insulin through a Continuous Subcutaneous Insulin Infusion (CSII) for individuals with Type 1 Diabetes (T1D). Recent advancements in therapy have highlighted the need to address issues such as unexplained hyperglycemia and IIS occlusion.ObjectiveTo investigate the adverse events (AEs) associated with IIS that impact the treatment of T1D, with a specific focus on promoting effective educational practices.MethodsOne hundred and eighteen patients under treatment at the Diabetes Center Insulin Pump Ambulatory, Federal University of São Paulo responded to a semi-structured questionnaire. Over 6 months, a nurse researcher interviewed them via video calls.ResultsCatheter-related adverse events (AEs) included catheter knots, folding, and accidental traction. AEs associated with cannula use were mainly related to cannula fixation adhesive, insulin leakage, bleeding episodes, and skin problems. The cannula patch tends to detach easily in hot conditions or when used for more than 3 days, leading to local itching. Adhesive glue can cause redness and pain. Insulin leakage typically occurs after the catheter disconnects from the cannula, accidental cannula traction, or beneath the cannula patch. Bleeding has been reported inside the cannula or at the insertion site, resulting in local pain and, in some cases, obstruction of insulin flow. When accidental cannula traction occurs, it is recommended to replace the entire IIS system. In situations involving bleeding, leakage, insulin odor, or unsuccessful attempts to correct hyperglycemic episodes with a “bolus” of insulin, it is advisable to change the IIS system and evaluate appropriate techniques for handling and infusing the device. Moreover, regular inspections of the device and reservoir/cartridge are essential.ConclusionSerious AEs can occur even in cases where the occlusion alarm is not activated, leading to interruptions in insulin flow. Conversely, in less severe situations, alarm activation can occur even in the absence of insulin flow interruption. Accidental catheter traction and catheter bending are commonly encountered in everyday situations, while issues related to the cannula directly affect blood glucose levels. AEs related to the IIS cannula often involve insulin leakage into the skin, bleeding, and skin events attributed to adhesive issues with the cannula.

Factors associated with maternal hyperglycaemia and neonatal hypoglycaemia after antenatal betamethasone administration in women with diabetes in pregnancy.

Bespoke glycaemic control strategies following antenatal corticosteroids for women with diabetes in pregnancy (DIP) may mitigate hyperglycaemia. This study aims to identify predictive factors for the glycaemic response to betamethasone in a large cohort of women with DIP. Evaluation of a prospective cohort study of 347 consecutive DIP pregnancies receiving two doses of 11.4 mg betamethasone 24 h apart between 2017 and 2021 and treated with the Pregnancy-IVI intravenous insulin protocol. Regression modelling identified factors associated with maternal glycaemic time-in-range (TIR) and maternal insulin requirements following betamethasone. Factors associated with neonatal hypoglycaemia (glucose <2.6 mmol/L) in infants born within 48 h of betamethasone administration (n = 144) were investigated. The mean maternal age was 31.9 ± 5.8 years, with gestational age at betamethasone of 33.5 ± 3.4 weeks. Gestational diabetes was present in 81% (12% type 1; 7% type 2). Pre-admission subcutaneous insulin was prescribed for 63%. On-infusion maternal glucose TIR (4.0-7.8 mmol/L) was 83% [IQR 77%-90%] and mean on-IVI glucose was 6.6 ± 0.5 mmol/L. Maternal hypoglycaemia (<3.8 mmol/L) was uncommon (0.47 h/100 on-IVI woman hours). Maternal glucose TIR was negatively associated with indicators of insulin resistance (type 2 diabetes, polycystic ovary syndrome), late-pregnancy complications (pre-eclampsia, chorioamnionitis) and the 1-h OGTT result. Intravenous insulin requirements were associated with type of diabetes, pre-eclampsia and intrauterine infection, the 1-h OGTT result and the timing of betamethasone administration. Neonatal hypoglycaemia was associated with pre-existing diabetes but not with measures of glycaemic control. An intravenous infusion protocol effectively controls maternal glucose after betamethasone. A risk-factor-based approach may allow individualisation of therapy.

Diabetes technology and sexual health: which role?

The aim of this review is to evaluate the effects of new technology used in the management of diabetes mellitus (DM), including the use of continuous glucose monitoring (CGM) and the administration of insulin through continuous subcutaneous insulin infusion (CSII), on male and female sexual function. This narrative review was performed for all available prospective, retrospective and review articles, published up to June 2023 in PubMed. Data were extracted from the text and from the tables of the manuscript. Sexual dysfunctions are an underestimated comorbidity of DM in both male and female. Although erectile dysfunction (ED) is recognized by the guidelines as a complication of DM, female sexual dysfunction (FSD) is poorly investigated in clinical setting. In addition to the complications of DM, the different types of therapies can also influence male and female sexual response. Furthermore, insulin therapy can be administered through multiple-daily injections (MDI) or a CSII. The new technologies in the field of DM allow better glycemic control which results in a reduction in the occurrence or aggravation of complications of DM. Despite this evidence, few data are available on the impact of new technologies on sexual dysfunctions. The use of DM technology might affect sexual function due to the risk of a worse body image, as well as discomfort related to CSII disconnection during sexual activity. However, the use is related to an improved metabolic control, which, in the long-term associates to a reduction in all diabetes complications, including sexual function.

Characteristics of Children with Newly Diagnosed Type 1 Diabetes Mellitus in Brunei Darussalam.

This study aims to characterize the presentation, biochemical status of children with T1DM at diagnosis, the type of subcutaneous insulin regimens initiated, and to determine the incidence of T1DM in Bruneian children aged 18 years and younger. A retrospective electronic and paper medical chart review was performed on patients aged 18 years and younger diagnosed with T1DM from 2013 to 2018 in Brunei Darussalam. A total of 31 children with a mean age of 10.2 ± 3.6 years old were diagnosed with T1DM, of which 66.7% presented with diabetic ketoacidosis (DKA), a majority in severe DKA with an intercurrent illness (p = 0.021). The mean HbA1c was 13.6 ± 2.7% with a mean serum glucose of 37.0 ± 14.9 mmol/L at diagnosis. In the majority of the children (67.7%), multiple daily injections of subcutaneous insulin were initiated. The incidence of T1DM in children aged 18 years and younger was 4.9 per 100,000 for the year 2018. The majority of the patients in this study presented with severe DKA with an intercurrent illness. This highlights the importance of childhood T1DM awareness among the public and healthcare providers. The incidence of childhood T1DM in Brunei Darussalam is similar to other countries in the Asian region, being relatively low, compared to the rest of the world.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled type 2 diabetes mellitus: a comparison of cardiovascular effects

Abstract Background Both hyper- and hypo-glycaemia, as well as large glycaemic variability (GV) are associated with increased cardiovascular events in patients with type 2 diabetes mellitus (T2DM); possible contributing mechanisms of the increased cardiovascular risk include endothelial dysfunction and cardiac sympatho-vagal imbalance. Recent studies suggest that continuous subcutaneous insulin infusion (CSII) improves glycaemic control compared to multiple daily insulin injections (MDI). Purpose In this study, we assessed whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. Methods We enrolled in a small randomized pilot study consecutive T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to CSII (Group 1) or to continue MDI (Group 2); insulin dose was adjusted to achieve optimal glycaemic target ranges. Patients were studied at baseline and after 6 months by: 1) assessment of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring; 3) a 7-day continuous glucose monitoring (CGM) was performed at baseline and follow-up in 8 and 7 patients of Group 1 and 2, respectively. Results Overall, 21 patients were enrolled, 12 randomized to CSII and 9 to MDI. Daily insulin dose, glycated hemoglobin levels and CGM parameters did not differ significantly between the 2 groups, both at baseline and at follow-up. Both FMD (6.7±2.5 vs 4.6±2.0 %, p=0.51) and NMD (8.9±3.1 vs 7.0±3.0 %, p=0.18), as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. No relation between GV and both peripheral dilator function and cardiac autonomic function was also detected. Conclusions In this small, randomized pilot study we show that, in T2DM patients, CSII achieves similar medium-term glycaemic control compared to MDI, without any significant adverse effect on the cardiovascular system.

Interventional Radiology Approaches for Managing Postpancreatic Transplant Complications and Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-secreting beta cells in the pancreas, resulting in metabolic disturbances and long-term complications. While subcutaneous insulin remains the primary approach for achieving normoglycemia, pancreatic transplantation has emerged as an effective intervention for long-standing T1DM, providing insulin independence and normalized glycosylated hemoglobin levels. However, complications associated with pancreatic transplantation are frequent, necessitating thorough evaluation using diverse imaging modalities. This manuscript presents an overview of vascular complications encountered with pancreatic transplantation, including vascular complications such as arterial and venous graft thrombosis, vessel stenosis, pseudoaneurysm, arterio-enteric fistula, and arteriovenous malformations (AVM). Additionally, the manuscript discusses other associated complications such as pancreatitis, pseudocyst formation, fistulas, pseudo-thrombosis of the iliac vein, post-transplantation lymphoproliferative disorder, and fluid collections. The integration of various imaging modalities plays a crucial role in diagnosing and managing these complications, with interventional radiologists assuming a vital role in employing image-guided procedures. Moreover, the manuscript explores pancreatic islet cell transplantation as a promising cellular-based therapy for T1DM, offering stable long-term glycemic control and decreased reliance on exogenous insulin in a significant proportion of recipients. This minimally invasive procedure involves the image-guided transcatheter infusion of islet cells obtained from deceased donors into the recipient's liver. The importance of interventional radiologists in managing complications related to pancreatic transplantation is underscored, with endovascular or image-guided approaches being utilized to address the diverse spectrum of encountered complications. Furthermore, the potential of islet cell transplantation as a minimally invasive alternative to traditional pancreatic transplantation is emphasized, as it offers the prospect of alleviating many associated complications.

Unexpected evolution of a monster case of insulin-induced skin lipohypertrophy

In this journal, in 2020, we published the case of a 74-year-old female outpatient with type-2 diabetes mellitus who self-injected insulin four times a day according to the basal-bolus regimen, with an high glycemic variability and an high rate of severe hypoglycemic episodes. Three years before, we had found two extraordinarily large skin lipohypertrophies, with large underlying fluid collections with high insulin concentration. A long educational and intensive training completely repaired the skin lesions with the disappearance of the subcutaneous insulin reservoirs. Glycemic variability has been reduced dramatically, severe hypoglycemia has almost completely disappeared and the daily dose of insulin has been reduced by 38%. However, this extraordinary, albeit unexpected, result was achieved in five years.

Using stories to explore the lived experience of alcohol consumption in people with diabetes mellitus

Abstract Background: Evidence supports the risks of dangerous episodes of hypoglycaemia, hyperglycaemia, or extreme glucose variability in type 1 diabetes during and after alcohol consumption. Minimal evidence regarding preventative self‐care strategies exists, and people with type 1 diabetes can develop personal tactics to overcome risks. Combining the lived experience of managing alcohol consumption while living with diabetes will enrich new patient and health care professional education.Methods: Participants were recruited from social media, and attended between one and three online storytelling workshops. Demographic data were collected by questionnaire, and qualitative data were collected by note‐taking during the online sessions and evaluated by thematic analysis.Results: Nine participants aged 18–36 years (type 1 diabetes = seven [three female], and type 2 diabetes = two [both male]) were recruited. Insulin administration was by multiple daily injection therapy (n=5 including one type 2 diabetes), continuous subcutaneous insulin infusion (n=3) without hybrid closed loop, and sulphonylurea plus morning long‐acting analogue insulin (n=1 type 2 diabetes). From the nine participant stories three diabetic ketoacidosis, three hypoglycaemia, and one extreme glucose variability episodes occurred. Four clustered themes were found: living with diabetes, managing alcohol, app development suggestions, and future development suggestions.Discussion: New insights discovered were: distressing glucose risks including diabetic ketoacidosis episodes, misinterpretation of glucose and intoxication symptoms, trial and error approaches, and non‐disclosure to health care professionals regarding severe glucose situations. Copyright © 2023 John Wiley &amp; Sons.

Giant Subcutaneous Hematoma Associated with Subcutaneous Insulin Injection in a Patient with Diabetes: a Case Report

The complications of insulin self-injection include subcutaneous bleeding, nerve damage, and subcutaneous induration due to repeated injection at the same site. However, considering the short length and thinness of the needle, it is unlikely that these complications will ever become serious. Here, we report a case of a 50-year-old man with abdominal giant hematoma due to insulin self-injection, which requires surgical treatment. The patient had obesity and took anticoagulants and steroids for 12 years. These drugs seemed to have affected the vessel wall and led to its compromise or destruction and subsequent hemorrhagic events.

An injectable and biodegradable zwitterionic gel for extending the longevity and performance of insulin infusion catheters.

Continuous subcutaneous insulin infusion (CSII) is an essential insulin replacement therapy in the management of diabetes. However, the longevity of clinical CSII is limited by skin complications, by impaired insulin absorption and by occlusions associated with the subcutaneous insertion of CSII catheters, which require replacement and rotation of the insertion site every few days. Here we show that a biodegradable zwitterionic gel covering the tip end of commercial off-the-shelf CSII catheters fully resolves early skin irritations, extends the longevity of catheters and improves the rate of insulin absorption (also with respect to conventional syringe-based subcutaneous injection) for longer than 6 months in diabetic mice, and by 11 days in diabetic minipigs (from 2 to 13 days, under standard CSII-wearing conditions of insulin pump therapy and in a continuous basal-plus-bolus-infusion setting). The implanted gel displayed anti-inflammatory and anti-foreign-body-reaction properties and promoted the local formation of new blood vessels. The gel is subcutaneously injected before the tip of catheter is inserted into it, and should be generally applicable to CSII catheters and other implantable devices.

Advances in diabetes management: have pregnancy outcomes in women with type 1 diabetes changed in the last decades?

AimsOver the recent years multiple therapeutic and management opportunities have been made available to treat pregnant women with Type 1 diabetes (T1DM). However, analyses assessing whether these different approaches may have any specific advantage/disadvantage in metabolic control and neonatal outcomes is still limited. The aim of this study was to compare metabolic control and neonatal outcomes in pregnant women with T1DM among different basal insulins (NPH vs. analogue), insulin administration ways [Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusion (CSII)] and glucose monitoring systems [Self-Monitoring of Blood Glucose (SMBG) vs. real-time/intermittently scanned Continuous Glucose Monitoring (rtCGM/isCGM)]. MethodsA retrospective analysis on metabolic data and neonatal outcomes of 136 T1DM pregnant women (76% on MDI, based on NPH (51%) or analogue (49%); 24% on CSII; 24% using rtCGM/isCGM), managed between 2008 and 2020, was performed, comparing different therapeutic approaches. ResultsMetabolic data and neonatal outcomes were comparable among women treated with different basal insulins. Women on CSII planned their pregnancy more frequently (82 vs. 60%; p = 0.043) and had better pregestational HbA1c (52 ± 5 vs. 60 ± 13 mmol/mol; p = 0.044) and first trimester HbA1c (48 ± 4 vs. 51 ± 8 mmol/mol; p = 0.047). Pregestational and first trimester HbA1c were also lower in women using rtCGM/isCGM (53 ± 8 vs. 58 ± 13 mmol/mol; p = 0.027 and 46 ± 5 vs. 51 ± 7 mmol/mol; p = 0.034, respectively). In the whole cohort, LGA risk was directly correlated to HbA1c at third trimester (correlation coefficient: 0.335, p = 0.001) and inversely correlated to the achievement of HbA1c target (≤6% [<42 mmol/mol]) at third trimester (correlation coefficient: − 0.367, p < 0.001). ConclusionTreatment with insulin analogs didn’t significantly change metabolic control and neonatal outcomes in T1DM women, while CSII and rtCGM/isCGM can optimize preconception and first trimester pregnancy glycemic control. Irrespective of the therapeutic management, third trimester HbA1c remains the strongest risk factor for LGA.

Technology use and clinical outcomes in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes.

Technology use has been shown to improve diabetes control, but minority youths tend to have low rates of technology use and exhibit suboptimal glycemic control. We examined the impact of continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII) on glycemic control in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes (T1D). A cross-sectional study was conducted among 140 pediatric T1D patients seen at a multidisciplinary clinic. From January to November 2022, data on demographics and glycated hemoglobin (HbA1c) levels were collected. Patients were categorized as technology (CGM, CSII, or both) or non-technology users (finger stick meter (FS) and multiple daily injections (MDI)). The majority identified as Hispanic (79 %) and had public health insurance (71 %). Sixty-nine percent used technology. Compared with non-technology users, technology users had significantly lower mean HbA1c levels (9.60 vs. 8.40 %, respectively) (p=0.0024), though no group (CGM+CSII, CGM+MDI, FS+CSII, and FS+MDI) achieved a mean HbA1c level of <7.0 %. Regarding minority status, no significant differences in mean HbA1c levels existed between Hispanics and Blacks in the CGM+MDI and FS+CSII groups (p=0.2232 and p=0.9224, respectively). However, there was a significant difference in mean HbA1c levels between Hispanic and Black non-technology users (9.19 vs. 11.26 %, respectively) (p=0.0385). Technology users demonstrated better glycemic control than non-technology users. Further research is needed to investigate factors affecting glycemic control in minority youths with T1D.

Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial

ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA1c] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete. Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA1c were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product. In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52. Novo Nordisk.

Ultra rapid lispro (Lyumjev®) shortens time to recovery from hyperglycaemia compared to Humalog® in individuals with type 1 diabetes on continuous subcutaneous insulin infusion.

To compare the time tohyperglycaemia recovery after ultra rapid lispro (URLi; Lyumjev®) versus Humalog in a randomized, double-blind crossover study. Thirty-two adults with type 1 diabetes on continuous subcutaneous insulin infusion participated in two periods: each period included hyperglycaemia induced by a missed mealtime bolus (day 1) and by suspension of basal insulin delivery (day 2). When hyperglycaemia [plasma glucose (PG) >240 mg/dl] occurred, a correction bolus of URLi or Humalog was given and time to hyperglycaemia recovery (PG = 140 mg/dl), pharmacokinetics and glucodynamics were compared. Following a missed mealtime bolus, URLi significantly reduced maximum PG (-13 mg/dl; p = .02), and produced numerically more rapid decline in PG (23 mg/dl/h; p = .07), and faster recovery from hyperglycaemia (-23 min; p = .1) versus Humalog, although differences were not significant. Following basal suspension, URLi significantly reduced maximum PG (-6 mg/dl; p = .02), and produced faster PG decline (24 mg/dl/h; p < .001) and faster recovery from hyperglycaemia (-16 min; p < .01) vs. Humalog. Following a correction bolus of URLi, accelerated insulin lispro absorption was observed versus Humalog: early 50% tmax was reduced by 6 or 12 min, and AUC0-15min was increased 2.5- or 4.3-fold after correction boluses by subcutaneous infusion (day 1) or injection (day 2), respectively (all p < .001). During episodes of hyperglycaemia commonly experienced in people with type 1 diabetes, URLi provided a faster recovery versus Humalog from a missed mealtime bolus or during basal insulin suspension. URLi shows significant acceleration of insulin absorption versus Humalog when boluses are administered by subcutaneous infusion or injection.