Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing.

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPTx) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDAn@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDAn@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPTx hydrogel platform has great potential for treating diabetic wounds.

Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.

BACKGROUND: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. METHOD: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. DISCUSSION: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. TRIAL REGISTRATION: ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Amphipathic KALA fusogenic peptide enhances absorption of insulin and calcitonin by pulmonary membranes of rats.

OBJECTIVE: The aim was to investigate the absorption-enhancing effect (AEE) of lysine-alanine-leucine-alanine (KALA) repeating unit peptide upon pulmonary absorption of peptide and protein medicines among rats. MATERIALS AND METHODS: Absorption of insulin and calcitonin in the lung was evaluated using varying concentrations of KALA peptide from 0.1% to 1.0% (w/v). The study also examined the lung damage caused by the KALA peptide. RESULTS: KALA peptide with various concentrations improved the absorption of insulin and calcitonin in the lungs. It also reduced glucose and calcium levels in the blood compared to the control, with the AEE increasing in a concentration-dependent manner due to the KALA peptide. In toxicity assays, test results for protein and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) did not show a significant increase in the presence of KALA peptide at various concentrations. This implies that the KALA peptide did not cause any membrane damage to lung tissues. In transmembrane electrical resistance (TEER) and permeability detection, a decrease in TEER value and an increase in papp value by the addition of KALA peptide indicated that KALA peptide had the ability to aid the drug delivery through epithelial cells via both paracellular and transcellular pathways. CONCLUSIONS: KALA peptides are suitable as an absorption enhancer at lower concentrations (below 1.0%, w/v) for improving the absorption of insulin and calcitonin from the lung with no observed toxic impact.

Prevalence and associated factors of lipodystrophy in type 1 diabetic children and adolescents at Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia.

INTRODUCTION: Lipodystrophy can cause poor glycemic control in addition to cosmetic problems in children and adolescents with type 1 diabetes mellitus. However, data on its prevalence and associated factors is scarce among children and adolescents who live in developing countries like Ethiopia. OBJECTIVE: To determine the prevalence and identify associated factors of lipodystrophy in children and adolescents with type 1 diabetes mellitus who visited the endocrinology clinic of Ayder Comprehensive Specialized Hospital between May 1 and July 31, 2020. METHOD: This was an institution-based cross-sectional study conducted on 57 children and 65 adolescents with type 1 diabetes mellitus who had been taking insulin injections for a year or more. The dependent variable was lipodystrophy. A pretested, structured questionnaire was used to collect data related to lipodystrophy and other characteristics. The principal investigator oversaw the data collection, which was done by pediatric and child health specialty residents with training. Data was subjected to descriptive statistics, and predictors of lipodystrophy were identified by fitting a multivariable logistic regression model. Statistical significance was declared at p < 0.05. RESULTS: More than half (53.3%) of patients were in the age range of 13 to 17. The male-to-female ratio was almost 1:1. Educational status for 63.1% of patients was primary school. Four-fifths of patients were residing in urban areas. Of the 122 participants, 60 (49.2%) had lipodystrophy (48.3% lipohypertrophy and 0.8% lipoatrophy), with grade II lipohypertrophy being the most common type at 81.7%. The thigh was the most common site of lipodystrophy. In multivariable regression analysis, the long duration of insulin injection (AOR = 3.6, 95% CI, 1.5 to 9.0, p = 0.005) and inappropriate rotation of the injection site (AOR = 9.0, 95% CI, 2.2 to 37.0, p = 0.002) were significantly associated with lipodystrophy. HbA1c testing was conducted for 70 patients, and poor glycemic control (HbA1c ≥ 7%) was found in 43 (61.4%) of them. Patients with lipodystrophy were more likely to have poor glycemic control (75%) than those without lipodystrophy (47.1%) (p = 0.016). CONCLUSION: The prevalence of lipodystrophy was comparable with other studies. Long duration of insulin injection and improper rotation of the injection site are associated with an increased risk of lipodystrophy. Patients with lipodystrophy were more likely to have poor glycemic control, defined by higher HgA1c, than those without lipodystrophy. Proper education of patients and their parents must include correct injection techniques, rotating injection sites, and changing injection sites intermittently to lessen the risk of developing lipodystrophy.

Transitioning to Insulin Analogs in Tunisian Children with Type 1 Diabetes: Efficacy and Safety.

INTRODUCTION: there is a lack of research evaluating the impact of therapeutic switching from human insulin to analogues, particularly in paediatric populations from low- and middle-income countries. AIM: The study aimed to retrospectively assess the effectiveness and safety of transitioning from human insulin to insulin analogs in Tunisian children with diabetes. METHODS: This retrospective descriptive study included children with type 1 diabetes who changed their insulin therapy protocol after at least one year of treatment with human insulin. Clinical, therapeutic, and glycaemic homeostasis parameters were assessed following the transition from human insulin (NPH + rapid-acting insulin) to the Basal-Bolus insulin analog- protocol. RESULTS: The study included 60 patients. Following the switch, all patients showed a significant reduction in mean fasting blood glucose levels (11.11 mmol/l vs. 8.62 mmol/l; p=0.024). Glycated haemoglobin A1C levels decreased notably in children who adhered to their diet (from 9.93% to 8.38%; p=0.06) and/or engaged in regular physical activity (from 10.40% to 8.61%; p=0.043). The average number of hypoglycemic events per year decreased from 4.03 events/year to 2.36 events/year (p=0.006), along with a decrease in the rate of patients hospitalized for acid-ketotic decompensation (from 27% to 10%; p=0.001). Financial constraints led to 82% of patients reusing microfine needles ≥2 times per day, and 12% were compelled to revert to the initial insulin therapy protocol due to a lack of access to self-financed microfine needles or discontinued social coverage. CONCLUSIONS: Although insulin analogues offer clear benefits, their use poses challenges as a therapeutic choice for children with diabetes in low- to middle-income countries. These challenges hinder the achievement of optimal glycemic control goals.

Personalized insulin dosing using reinforcement learning for high-fat meals and aerobic exercises in type 1 diabetes: a proof-of-concept trial.

In type 1 diabetes, high-fat meals require more insulin to prevent hyperglycemia while meals followed by aerobic exercises require less insulin to prevent hypoglycemia, but the adjustments needed vary between individuals. We propose a decision support system with reinforcement learning to personalize insulin doses for high-fat meals and postprandial aerobic exercises. We test this system in a single-arm 16-week study in 15 adults on multiple daily injections therapy (NCT05041621). The primary objective of this study is to assess the feasibility of the novel learning algorithm. This study looks at glucose outcomes and patient reported outcomes. The postprandial incremental area under the glucose curve is improved from the baseline to the evaluation period for high-fat meals (378 ± 222 vs 38 ± 223 mmol/L/min, p = 0.03) and meals followed by exercises (-395 ± 192 vs 132 ± 181 mmol/L/min, p = 0.007). The postprandial time spent below 3.9 mmol/L is reduced after high-fat meals (5.3 ± 1.6 vs 1.8 ± 1.5%, p = 0.003) and meals followed by exercises (5.3 ± 1.2 vs 1.4 ± 1.1%, p = 0.003). Our study shows the feasibility of automatically personalizing insulin doses for high-fat meals and postprandial exercises. Randomized controlled trials are warranted.

Modern insulin treatment for type 2 diabetes.

This review summarises the current and possible future insulin treatment of type 2 diabetes. The type 2 diabetes treatment guidelines prioritise a person-centred approach with various options before insulin addressing cardiorenal protection. Long-acting daily insulin injections are warranted in severe hyperglycaemia or when glycaemic targets are not met. Insulin, when possible, should be combined with other agents to lower insulin dosage, weight gain and hypoglycaemia. Once-weekly insulin offers a promising treatment, reducing injection burden, enhancing treatment satisfaction, and lowering the risk of severe hypoglycaemia, potentially improving type 2 diabetes management.

Single-arm, first-in-human feasibility study results for an ultra-low-cost insulin pump.

BACKGROUND: Use of Continuous Subcutaneous Insulin Infusion (CSII) has been shown to improve glycemic outcomes in Type 1 Diabetes (T1D), but high costs limit accessibility. To address this issue, an inter-operable, open-source Ultra-Low-Cost Insulin Pump (ULCIP) was developed and previously shown to demonstrate comparable delivery accuracy to commercial models in standardised laboratory tests. This study aims to evaluate the updated ULCIP in-vivo, assessing its viability as an affordable alternative for those who cannot afford commercially available devices. METHODS: This first-in-human feasibility study recruited six participants with T1D. During a nine-hour inpatient stay, participants used the ULCIP under clinical supervision. Venous glucose, insulin, and ß-Hydroxybutyrate were monitored to assess device performance. RESULTS: Participants displayed expected blood glucose and blood insulin levels in response to programmed basal and bolus insulin dosing. One participant developed mild ketosis, which was treated and did not recur when a new pump reservoir was placed. All other participants maintained ß-Hydroxybutyrate < 0.6 mmol/L throughout. CONCLUSION: The ULCIP safely delivered insulin therapy to users in a supervised inpatient environment. Future work should focus on correcting a pump hardware issue identified in this trial and extending device capabilities for use in closed loop control. Longer-term outpatient studies are warranted. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623001288617) on the 11 December 2023.

A systematic review and meta-analysis comparing outcomes between using subcutaneous insulin and continuous insulin infusion in managing adult patients with diabetic ketoacidosis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to synthesize the current literature to determine the safety and efficacy of using subcutaneous insulin compared to an intravenous (IV) insulin infusion in managing diabetic ketoacidosis (DKA). METHODS: We searched Ovid-Medline, EMBASE, SCOPUS, BIOSIS and CENTRAL from inception to April 26, 2024. Randomized controlled trials (RCTs) and observational studies that assessed the use of subcutaneous compared to intravenous insulin for the treatment of mild to moderate DKA were included. Data extraction and quality assessment were performed by two independent reviewers and disagreements were resolved through further discussion or by a third reviewer. The Cochrane Risk of Bias tool version 2.0 was used to evaluate the RCTs and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS)-I tool was used to evaluate the observational studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Meta-analyses were conducted using random-effects models. We followed the PRISMA guidelines for reporting our findings. RESULTS: Six RCTs (245 participants) and four observational studies (8444 patients) met our inclusion criteria. Some studies showed a decreased length of stay (Mean Difference [MD] in days: -0.39; 95% CI: -2.83 to 2.08; I2: 0%) among individuals treated with subcutaneous insulin compared to intravenous insulin. There was no difference in the risk of all-cause mortality, time to resolution of DKA (MD in hours: 0.17; 95% confidence interval [CI]: -3.45 to 3.79; I2: 0%) and hypoglycemia (Risk Ratio [RR]: 1.02; 95% CI: 0.88 to 1.19; I2: 0%) between the two groups. CONCLUSION: Treatment of DKA with subcutaneous insulin may be a safe and effective alternative to IV insulin in selected patients. The limited available evidence underscores the need for further studies to explore optimal dosing, patient selection criteria and long-term outcomes.

Type 1 Diabetes Mellitus in the First Years of Life - Onset, Initial Treatment, and Early Disease Course.

OBJECTIVE: This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D). METHODS: The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 - June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6-<12 months, G2: 1519 patients 12-<24 months, G3: 4001 patients 24-48 months). RESULTS: In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83-2.63/100 patient-years (PY) for DKA and 9.37-24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM. CONCLUSIONS: Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months.

Three months use of Hybrid Closed Loop Systems improves glycated hemoglobin levels in adolescents and children with type 1 diabetes: A meta-analysis.

BACKGROUND: Longer outpatient studies have demonstrated that hybrid closed loop (HCL) use has led to a concomitant reduction in glycated hemoglobin(HbA1c) by 0.3%-0.7%. However, reports have also indicated that HbA1c levels are not declined in the long-term use of HCL. Therefore, we wonder that 3 months use of HCL could improve glycated hemoglobin levels in adolescents and children with T1D. METHODS: Relevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Pediatrics or Child or Adolescent", "Insulin Infusion Systems" and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of HCL on HbA1c in adolescents, and children with T1D. RESULTS: Nine studies involving 927 patients were identified. Three months use of HCL show a beneficial effect on HbA1c management (p <0.001) as compared to standard of care in adolescents and children with T1D, without evidence of heterogeneity between articles (I2 = 40%, p = 0.10). HCL did significantly increase the overall average percentage of hypoglycemic time between 70 and 180 mg/dL (TIR) (p <0.001; I2 = 51%). HCL did not show a beneficial effect on hypoglycemic time <70 mg/dL and <54 mg/dL (p >0.05). The overall percentage of hyperglycemic time was significantly decreased in HCL group compared to the control group when it was defined as >180 mg/dL (p <0.001; I2 = 83%), >250 mg/dL (p = 0.007, I2 = 86%) and >300 mg/dL (p = 0.005; I2 = 76%). The mean glucose level was significantly decreased by HCL (p <0.001; I2 = 58%), however, no significant difference was found in coefficient of variation of sensor glucose (p = 0.82; I2 = 71%) and daily insulin dose (p = 0.94; I2 <0.001) between the HCL group and the control group. CONCLUSIONS: HCL had a beneficial effect on HbA1c management and TIR without increased hypoglycemic time as compared to standard of care in adolescents and children with T1D when therapy duration of HCL was not less than three months. TRIAL NUMBER AND REGISTRY URL: CRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

Association of continuous subcutaneous insulin therapy and diabetic retinopathy in type 1 diabetes: A national cohort study.

AIM: This study aimed to investigate the short-and long-term effect on diabetic retinopathy (DR) in individuals with type 1 diabetes treated with continuous subcutaneous insulin injections (CSII) compared to those using multiple daily injections (MDI). METHODS: We conducted a register-based matched cohort study utilizing data from the Danish Registry of Diabetic Retinopathy as well as several other national Danish health registers. Our cohort consisted of all individuals with type 1 diabetes who attended the Danish screening program for DR from 2013 to 2022. We included individuals registered with CSII treatment, and compared them to individuals using MDI, matched by age, sex, and DR level. Cox regression analysis was performed to evaluate the outcomes. RESULTS: The study included 674 individuals treated with CSII and 2006 matched MDI users. In our cohort 53.4 % were female and median age was 36 (IQR 27-47). Average follow-up risk-time was 4.8 years. There was no difference in the risk of DR worsening between the CSII group and MDI group (HR 1.05 [95%CI 0.91; 1.22], p = 0.49). However, an increased risk of focal photocoagulation was observed in the CSII group (HR 2.40 [95%CI 1.11; 5.19], p = 0.03). CONCLUSIONS: Our findings indicate that CSII treatment does not confer a significant difference in the overall short- and long-term risk of DR worsening or ocular intervention compared to MDI treatment. These results provide insights into the DR outcomes of CSII treatment in individuals with type 1 diabetes.

Equivalent Electrical Circuit Approach to Enhance a Transducer for Insulin Bioavailability Assessment.

The equivalent electrical circuit approach is explored to improve a bioimpedance-based transducer for measuring the bioavailability of synthetic insulin already presented in previous studies. In particular, the electrical parameter most sensitive to the variation of insulin amount injected was identified. Eggplants were used to emulate human electrical behavior under a quasi-static assumption guaranteed by a very low measurement time compared to the estimated insulin absorption time. Measurements were conducted with the EVAL-AD5940BIOZ by applying a sinusoidal voltage signal with an amplitude of 100 mV and acquiring impedance spectra in the range [1-100] kHz. 14 units of insulin were gradually administered using a Lilly's Insulin Pen having a 0.4 cm long needle. Modified Hayden's model was adopted as a reference circuit and the electrical component modeling the extracellular fluids was found to be the most insulin-sensitive parameter. The trnasducer achieves a state-of-the-art sensitivity of 225.90 ml1. An improvement of 223 % in sensitivity, 44 % in deterministic error, 7 % in nonlinearity, and 42 % in reproducibility was achieved compared to previous experimental studies. The clinical impact of the transducer was evaluated by projecting its impact on a Smart Insulin Pen for real-time measurement of insulin bioavailability. The wide gain in sensitivity of the bioimpedance-based transducer results in a significant reduction of the uncertainty of the Smart Insulin Pen. Considering the same improvement in in-vivo applications, the uncertainty of the Smart Insulin Pen is decreased from [Formula: see text]l to [Formula: see text]l.Clinical and Translational Impact Statement: A Smart Insulin Pen based on impedance spectroscopy and equivalent electrical circuit approach could be an effective solution for the non-invasive and real-time measurement of synthetic insulin uptake after subcutaneous administration.

Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of ß-cell function.

OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.

Continuous glucose monitoring for self-management of diabetes in people living with type 2 diabetes mellitus on basal insulin therapy: A microsimulation model and cost-effectiveness analysis from a US perspective with relevance to Medicaid.

BACKGROUND: Reducing the risks of complications is a primary goal of diabetes management, with effective glycemic control a key factor. Glucose monitoring using continuous glucose monitoring (CGM) technology is an important part of diabetes self-management, helping patients reach and maintain targeted glucose and glycated hemoglobin (HbA1c) levels. Although clinical guidelines recommended CGM use, coverage by Medicaid is limited, likely because of cost concerns. OBJECTIVE: To assess the cost-effectiveness of FreeStyle Libre CGM systems, compared with capillary-based self-monitoring of blood glucose (SMBG), in US individuals with type 2 diabetes mellitus using basal insulin. METHODS: A patient-level microsimulation model was used to compare CGM with SMBG for a population of 10,000 patients. A 10-year horizon was used, with an annual discount rate of 3.0% for costs and utilities. Model population characteristics were based on US national epidemiology data. Patient outcomes were based on published clinical trials and real-world studies. Annual costs, reflective of 2023 values, included CGM and SMBG acquisition costs and the costs of treating diabetic ketoacidosis, severe hypoglycemia, and diabetes complications. The effect of CGM was modeled as a persistent 1.1% reduction in HbA1c relative to SMBG based on US real-world evidence. Disutilities were based on published clinical trials and other relevant literature. The primary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to test the validity of the model results when accounting for a plausible variation of inputs. RESULTS: In the base case analysis, CGM was dominant to SMBG, providing more QALYs (6.18 vs 5.97) at a lower cost ($70,137 vs $71,809) over the 10-year time horizon. A $10,456 increase in glucose monitoring costs was offset by a $12,127 reduction in treatment costs. Cost savings reflected avoidance of acute diabetic events (savings owing to reductions in severe hypoglycemia and diabetic ketoacidosis were $271 and $2,159, respectively) and a reduced cumulative incidence of diabetes complications, particularly renal failure (saving $5,292), myocardial infarction (saving $1,996), and congestive heart failure (saving $1,061). Scenario analyses were consistent with the base case results, and the incremental cost-effectiveness ratio for CGM vs SMBG ranged from dominant to cost-effective. In probabilistic analysis, CGM was 100% likely to be cost-effective at a willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: CGM is cost-effective compared with SMBG for US patients with type 2 diabetes mellitus receiving basal insulin therapy. This suggests that state Medicaid programs could benefit from broader coverage of CGM.

A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment.

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127-functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.

Development of a Basal Insulin Titration System to Support Healthcare Providers in Treatment of People with Type 2 Diabetes: Preliminary Results.

The study aims to develop a system for insulin titration in type 2 diabetes to assist primary healthcare providers. Usability testing with end-users is ongoing.

Detailed Insights into Basal Insulin Adherence in People with Type 2 Diabetes Using a Data-Driven Assessment Method.

INTRODUCTION: Basal insulin non-adherence is a challenge in people with type 2 diabetes (T2D). METHODS: Using injection data recorded by a connected insulin pen, we employed a novel three-step methodology to assess three aspects of adherence (overall adherence, adherence distribution, and dose deviation) in individuals with insulin-treated T2D undergoing telemonitoring. RESULTS: Among participants, 52% were considered overall adherent. However, deviations from the recommended dose were observed in all participants, with increased and reduced doses being the predominant forms of non-adherence. CONCLUSIONS: Our study underscores the prevalence of basal insulin dosing irregularities in individuals with insulin-treated T2D undergoing telemonitoring.