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Aims Methods Results Conclusions The present analysis estimated the cost‐effectiveness of treatment with the Tandem t: slim X2 insulin pump with Control IQ technology (CIQ) in children with type 1 diabetes in Sweden.A four‐state Markov model and probabilistic sensitivity analyses (PSA) were used to assess the cost‐effectiveness of CIQ use compared with treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) in conjunction with CGM. Data sources included clinical input data from a recent retrospective, observational study, cost data from local diabetes supply companies and government agencies, and published literature. Outcomes measures were quality adjusted life years (QALYs) at 10, 20 and 30‐year time horizons based on cost per QALY and incremental cost‐effectiveness ratio (ICER).A total of 84 type 1 diabetes children were included (CIQ, n = 37; MDI, n = 19; CSII, n = 28). For all time horizons, the use of CIQ was a dominant strategy (e.g. more effective and less costly) compared with MDI or CSII use: 10‐year ICER, SEK ‐88,010.37 and SEK ‐91,723.92; 20‐year ICER, SEK −72,095.33 and SEK −87,707.79; and 30‐year ICER, SEK −65,573.01 and SEK ‐85,495.68, respectively. PSA confirmed that CIQ use was less costly compared with MDI and CSII.Initiation of CIQ use in children with type 1 diabetes is cost‐saving, besides previously shown improved glycaemic control, and increased quality of life. Further investigations are needed to more fully elucidate the cost‐effectiveness of these technologies in different countries with existing differences in payment models. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) in children and adolescents requires a lifelong commitment to disease control, which involves insulin treatment and constant blood glucose monitoring. Framed by Albert Bandura's self‐efficacy theory, we focused on analysing the impact of domain‐specific self‐efficacy for T1D control in children and adolescents and its relationship with different indicators of glycaemic control over time. The study included 205 participants (56.1% male), including 51.7% children and 48.3% adolescents aged 6–18 (M = 13.27, SD = 3.66) years in four longitudinal phases (6 months between phases). The results revealed that higher self‐efficacy predicted better health outcomes, with more time spent actively monitoring glucose and more time in the target range. The positive effect of self‐efficacy was observed to be maintained over time. This study underscores the importance of taking into account the developmental timing in the onset of T1D. There was a significant relationship between self‐efficacy and glucose indicators in adolescents. Although their glucose indicators were worse, self‐efficacy became more relevant as they moved from parental management to the self‐management of T1D. Implications of the results show the positive effect of self‐efficacy on health per glucose indicators, thus suggesting interventions that promote self‐efficacy in this population. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions There have been several epidemiologic studies on the association between diabetes mellitus and acute pancreatitis. However, there is no solid evidence, and the effect of diabetes mellitus severity on acute pancreatitis incidence is not well known. This study aimed to evaluate the association between diabetic status and the risk of acute pancreatitis in a nationwide population‐based cohort.Among the participants who underwent national health examinations between 2009 and 2012, patients with diabetes mellitus were included. Patients diagnosed with acute pancreatitis before the health examination or diagnosed with pancreatitis within 1 year following the examination were excluded. The association between the number of oral hypoglycemic agents (<3 or ≥3) or insulin use during examination and acute pancreatitis occurrence was analyzed after follow‐up until December 31, 2018.Overall, 2,444,254 patients were included in the final analysis. During the follow‐up period, acute pancreatitis occurred in 10,360 patients with an incidence ratio of 0.585 per 1,000 person‐years, and it was observed that the risk of acute pancreatitis sequentially increased between patients taking oral hypoglycemic agents <3 (incidence ratio = 0.546), those taking ≥3 (incidence ratio = 0.665), and those using insulin (incidence ratio = 0.872). The adjusted hazard ratios of patients taking three or more hypoglycemic agents and those using insulin were 1.196 (95% confidence interval (CI) 1.123–1.273) and 1.493 (95% CI 1.398–1.594), respectively.As diabetes mellitus severity increases, the risk of acute pancreatitis increases. [ABSTRACT FROM AUTHOR]

Background: Medication Treatment Satisfaction (M-TS) from the patients' perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods: Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM). Results: This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions: Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To establish trust in real‐world evidence (RWE) derived from CareLink Personal (CP), Medtronic's data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE.The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP's fitness‐for‐research by the below metrics (using last year's MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results.The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over‐representation of a specific phenotype among users not included. CP includes >50 endpoints, including ‘International Consensus on Time in Range’ based metrics. Data are recorded at 5‐min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety‐nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in‐silico studies was similar to that of real‐world studies from different geographies and with ever growing populations.RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To study the association between femoral neck (FN) bone mineral density (BMD) T‐score and fracture risk in individuals with and without type 2 diabetes (T2D).We performed a single‐centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual‐energy X‐ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T‐score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10‐year absolute fracture risk.In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D).The FN BMD T‐score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24–2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01–2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64–1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73–2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10‐year fracture risk.The FN BMD T‐score was significantly associated with hip, non‐spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T‐score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T‐score to predict fracture risk. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to examine contemporary trends in the use of, time to, and type of first add‐on anti‐hyperglycaemic therapy to metformin in Australia.We used the dispensing records of a 10% random sample of Pharmaceutical Benefits Scheme (PBS) eligible people. We included people aged 40 years and older initiating metformin from 1 January 2018 to 31 December 2020. Our primary outcome was first add‐on anti‐hyperglycaemic medicine within 2 years of metformin initiation. We analysed time to dispensing of first add‐on therapy. All analyses were stratified by metformin initiation year.Overall, 38 747 people aged 40 years and older initiated metformin between 2018 and 2020. Approximately one‐third (n = 12 946) of people received add‐on therapy with the proportion increasing slightly by year of metformin initiation (32.3% in 2018 to 34.8% in 2020). Amongst people with add‐on therapy following metformin initiation, sodium‐glucose cotransporter 2 inhibitor (SGLT2i) use increased from 28.8% (2018) to 35.0% (2020), and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) increased from 3.0% to 9.6%, respectively. Dipeptidyl peptidase‐4 inhibitors and sulfonylureas as first add‐on therapy decreased and insulin remained stable. One‐third of people with add‐on therapy initiated the therapy on the same day metformin was initiated, i.e. initial combination therapy.Amongst people initiating metformin from 2018 to 2020, there was an increasing proportion of SGLT2i and GLP‐1 RA being used as first add‐on therapy. However, the overall prevalence of add‐on therapy was low. Advocacy to promote add‐on therapy with cardiorenal beneficial medicines is critical to reduce type 2 diabetes morbidity and mortality. [ABSTRACT FROM AUTHOR]

Objective This study assesses the impact of a structured clinical pharmacist intervention on glycemic control in diabetic patients maintained on intensive insulin therapy attending the internal medicine clinic in a hospital with limited financial resources. Methods A randomized parallel open-label clinical trial design was employed. Ethical approval was obtained from the Egyptian Ministry of Health (MOH) ethics committee. Adult diabetic patients, on intensive insulin therapy, were recruited from an internal medicine clinic at an MOH hospital. Patients were randomly allocated into two groups; control, on premixed insulin twice daily, and intervention, receiving a structured pharmacist intervention including the addition of regular insulin doses as needed. Patients were followed up for three months. A 1% reduction of HbA1c level at the conclusion was considered the primary outcome. Key findings One hundred and twenty-five patients (62 control and 63 intervention) consented to participate in the study, of whom 98 (46 control and 52 intervention) completed the follow-up period. At three months, the odds ratio for HbA1c reduction by at least by 1% in the intervention group was 3.2 (95% CI 1.45–7.08). Very few cases of hypoglycemia were reported in either group. The HbA1c reduction was not affected by age, weight, or literacy status of the patients. Conclusions Clinical pharmacist interventions, even in environments with scarce resources and socioeconomic challenges, remain effective in achieving better glycemic control. This trial has been registered in the Pan-African Clinical Trial Registry (PACTR201610001812290, https://pactr.samrc.ac.za/). [ABSTRACT FROM AUTHOR]

Microcephaly, epilepsy and diabetes syndrome 1 (MEDS1) is a rare autosomal recessive disorder caused by defects in the immediate early response 3 interacting protein 1 (IER3IP1) gene. Only nine cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who was homozygous for the c.53C>T p.(Ala18Val) variant. This case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain magnetic resonance imaging, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teenagers, and adults living with type 1 diabetes (T1D). Methods: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology, followed by a 13-week period in which URLi insulin was used in the pump. Results: The trial included 179 individuals with T1D (age 6–75 years). With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No diabetic ketoacidosis events occurred. Two participants stopped URLi use because of infusion-site discomfort, and one stopped after developing a rash. Mean time 70–180 mg/dL increased from 65% ± 15% with lispro to 67% ± 13% with URLi (P = 0.004). Mean insulin treatment satisfaction questionnaire score improved from 75 ± 13 at screening to 80 ± 11 after 13 weeks of URLi use (mean difference = 6; 95% confidence interval 4–8; P < 0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment-related impact measure-diabetes score improved from 74 ± 12 to 80 ± 12 (P < 0.001), and mean TRIM-Diabetes Device (score improved from 82 ± 11 to 86 ± 12 (P < 0.001). Conclusions: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with T1D, with quality-of-life benefits of URLi use perceived by the study participants. Clinicaltrials.gov registration: NCT05403502. [ABSTRACT FROM AUTHOR]

Introduction: Sodium glucose cotransporter inhibitors may increase beta-hydroxybutyrate (BHB) in insulin-requiring patients. We determined factors associated with BHB changes from baseline (ΔBHB) and diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) receiving sotagliflozin as an insulin adjunct. Research Design and Methods: This post hoc analysis compared ΔBHB levels in adults with T1D receiving sotagliflozin 400 mg or placebo for 6 months. We evaluated clinical and metabolic factors associated with ΔBHB and used logistic regression models to determine predictors associated with BHB values >0.6 and >1.5 mmol/L (inTandem3 population; N = 1402) or with DKA events in a pooled analysis (inTandem1–3; N = 2453). Results: From baseline (median, 0.13 mmol/L), median fasting BHB increased by 0.04 mmol/L (95% confidence interval, 0.03–0.05; P < 0.001) at 24 weeks with sotagliflozin versus placebo; 67% of patients had no or minimal changes in BHB over time. Factors associated with on-treatment BHB >0.6 or >1.5 mmol/L included baseline BHB and sotagliflozin use. Age, insulin pump use, sotagliflozin use, baseline BHB, and ΔBHB were significantly associated with DKA episodes. Independent of treatment, DKA risk increased by 18% with each 0.1-mmol/L increase in baseline BHB and by 8% with each 0.1-mmol/L increase from baseline. Conclusion: Incremental increases in baseline BHB and ΔBHB were associated with a higher DKA risk independent of treatment. Adding sotagliflozin to insulin increased median BHB over 24 weeks in patients with T1D and was associated with increased DKA events. These results highlight the importance of BHB testing and monitoring and individualizing patient education on DKA risk, mitigation, identification, and treatment. [ABSTRACT FROM AUTHOR]

Objective: Continuous glucose monitoring (CGM) devices are integral in the outpatient care of people with type 1 diabetes, although they lack inpatient labeling. Food and Drug Administration began allowing inpatient use during the coronavirus disease 2019 (COVID-19) pandemic, with some accuracy data now available, primarily from adult hospitals. Pediatric inpatient data remain limited, particularly during diabetic ketoacidosis (DKA) admissions and for patients receiving intravenous (IV) insulin. Design and Methods: This retrospective chart review compared point-of-care glucose values to personal Dexcom G6 sensor data during pediatric hospitalizations. Accuracy was assessed using mean absolute relative difference (MARD), Clarke Error Grids, and the percentage of values within 15/20/30% if glucose value >100 mg/dL and 15/20/30 mg/dL if glucose value ≤100 mg/dL. Results: Matched paired glucose values (N = 612) from 36 patients (median age 14 years, 58.3% non-Hispanic White, 47.2% male) and 42 inpatient encounters were included in this subanalysis of DKA admissions. The MARDs for DKA and non-DKA admissions (N = 503) were 11.8% and 11.7%, with 97.6% and 98.6% of pairs falling within A and B zones of the Clarke Error Grid, respectively. Severe DKA admissions (pH <7.15 and/or bicarbonate <5 mmol/L) had a MARD of 8.9% compared to 14.3% for nonsevere DKA admissions. The MARD during administration of IV insulin (N = 266) was 13.4%. Conclusions: CGM accuracy is similar between DKA and non-DKA admissions and is maintained in severe DKA and during IV insulin administration, suggesting potential usability in pediatric hospitalizations. Further study on the feasibility of implementation of CGM in the hospital is needed. [ABSTRACT FROM AUTHOR]

Aim: To explore the correlation between a singular value of additive OGTT scores and adverse maternal and neonatal outcomes. We postulated that a higher additive OGTT score would predict poorer maternal and neonatal outcomes. Methods: In this retrospective cohort study, data were collected from all women with a documented complete OGTT result and subsequent diagnosis of GDM. The additive OGTT score was calculated by adding each individual hourly glucose measurement. Maternal demographics, pregnancy and labor characteristics, and neonatal outcomes were compared between the lower-sum and higher-sum OGTT groups. A multivariate regression analysis was performed to identify confounders associated with adverse outcomes. Results: In this study, a total of 1497 patients were assessed. The group with higher-sum OGTT scores was characterized by increased rates of GDMA2 (p = 0.008), higher insulin doses (p = 0.009), and higher rates of composite maternal and neonatal adverse outcomes (p = 0.021 and p = 0.030, respectively) compared to the lower-sum OGTT group. Conclusion: The additive OGTT score may aid in predicting the need for insulin treatment, labor course, and neonatal outcomes in GDM patients. [ABSTRACT FROM AUTHOR]

Background: Intranasal insulin (INI) is being explored as a treatment for Alzheimer's disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes. Objective: To show reliable delivery of insulin to the brain using the Aptar Cartridge Pump System (CPS) intranasal delivery system. Methods: To visualize INI biodistribution, we developed a novel PET radiotracer, Gallium 68-radiolabeled (NOTA-conjugated) insulin, [68Ga]Ga-NOTA-insulin. We used the Aptar CPS to administer [68Ga]Ga-NOTA-insulin to anesthetized healthy adult vervet monkeys and measured brain regional activity and whole-body dosimetry following PET/CT scans. Results: We observed brain penetration of [68Ga]Ga-NOTA-insulin following intranasal administration with the Aptar CPS. Radioactive uptake was seen in multiple regions, including the amygdala, putamen, hypothalamus, hippocampus, and choroid plexus. A safety profile and whole-body dosimetry were also established in a second cohort of vervets. Safety was confirmed: vitals remained stable, blood glucose levels were unchanged, and no organ was exposed to more than 2.5 mSv of radioactivity. Extrapolations from vervet organ distribution allowed for estimation of the [68Ga]Ga-NOTA-insulin absorbed dose in humans, and the maximum dose of [68Ga]Ga-NOTA-insulin that can be safely administered to humans was determined to be 185 MBq. Conclusions: The use of [68Ga]Ga-NOTA-insulin as a PET radiotracer is safe and effective for observing brain uptake in vervet monkeys. Further, the Aptar CPS successfully targets [68Ga]Ga-NOTA-insulin to the brain. The data will be essential in guiding future studies of intranasal [68Ga]Ga-NOTA-insulin administration in humans. [ABSTRACT FROM AUTHOR]

Aim: To assess the long‐term glycaemic outcomes, with additional metrics, in adults with type 1 diabetes (T1D) using the Tandem t:slim X2 with Control‐IQ technology advanced hybrid closed‐loop (AHCL) system. Methods: This was a single‐centre, retrospective study involving 56 T1D patients who transitioned to the Tandem t:slim X2 with Control‐IQ system. The primary and secondary endpoints consisted of variations in time in tight range (TiTR; 70‐140 mg/dL) and the glycaemia risk index (GRI), respectively. Additional standardized continuous glucose monitoring (CGM) metrics, mean sensor glucose, coefficient of variation, the glucose management indicator (GMI), HbA1c and insulin daily dose, were also evaluated. Variables were measured at baseline and at 15 days, 3 months, 6 months and 1 year after Tandem t:slim X2 Control‐IQ initiation. Glucose outcomes are expressed as mean (standard deviation). Results: Use of Tandem t:slim X2 with Control‐IQ over 1 year was associated with an increase in mean TiTR, from 38.11% (17.05%) to 43.10% (13.20%) (P =.059), and with a decline in the GRI, from 41.03 (25.48) to 28.55 (16.27) (P =.008). CGM metrics, including time in range and time above range, showed consistent improvements. Mean sensor glucose, the GMI and HbA1c decreased significantly over time. After an initial increase, insulin daily dose remained stable throughout the 12 months. Conclusions: The results highlight the sustained effectiveness of Tandem t:slim X2 with Control‐IQ in improving glycaemic outcomes over 1 year and support the use of this technology for the management of T1D. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the real‐world effectiveness of automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D). Materials and Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for studies published up until 2 March 2024. We included pragmatic randomized controlled trials (RCTs), cohort studies, and before–after studies that compared AID systems with conventional insulin therapy in real‐world settings and reported continuous glucose monitoring outcomes. Percent time in range (TIR; 3.9–10 mmol/L), time below range (TBR; <3.9 mmol/L), time above range (TAR; >10 mmol/L), and glycated haemoglobin (HbA1c) level were extracted. Data were summarized as mean differences (MDs) with 95% confidence interval. Results: A total of 23 before–after studies (101 704 participants) were included in the meta‐analysis. AID systems were associated with an increased percentage of TIR (11.61%, 10.47 to 12.76; p < 0.001). The favourable effect of AID systems was consistently observed when used continuously for 6 (11.76%) or 12 months (11.33%), and in both children (12.16%) and adults (11.04%). AID systems also showed favourable effects on TBR (−0.53%, −0.63 to −0.42), TAR (−9.65%, −10.63 to −8.67) and HbA1c level (−0.42%, −0.47 to −0.37) when compared with previous treatments. Conclusions: Similar improvements in glycaemic parameters were observed in real‐world settings in RCTs using AID systems in T1D. AID systems benefit both children and adults by increasing TIR for both short‐ and long‐term interventions. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Germany that examines the relationship between regional socioeconomic factors and the use of certain medications for adults with type 2 diabetes. The study finds that individuals in socioeconomically disadvantaged areas have lower access to newer glucose-lowering medications, such as SGLT2 inhibitors and GLP-1RAs. This disparity in access may contribute to socioeconomic disparities in cardiovascular health outcomes. The study suggests that further investigation into structural factors is needed to address these disparities. The study also highlights the importance of raising awareness among healthcare providers and overcoming barriers to access for newer treatment options in order to reduce inequalities. [Extracted from the article]

This article discusses a study comparing the effectiveness of advanced hybrid closed-loop (AHCL) pump therapy and multiple daily injection therapy (MDI) in children with newly diagnosed type 1 diabetes. The study found that AHCL systems had positive effects on glucose control and psychological outcomes, achieving recommended glycemic outcomes and reducing the frequency of hypoglycemia. The research was conducted in a real-world setting and included data on glucose metrics, glycated hemoglobin (HbA1c), and quality of life. The results suggest that AHCL systems may be a beneficial treatment option for pediatric type 1 diabetes. Another study mentioned in the text examined glucose management in individuals with type 1 diabetes. The study showed improvements in glucose management over time, with participants experiencing lower average glucose levels and spending more time in the target range. However, there were also increases in time above range and time below range at certain time intervals. The study concludes that AHCL therapy is a better option for pediatric patients with newly diagnosed type 1 diabetes, leading to better glucose control and improved quality of life. [Extracted from the article]

Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life‐long insulin replacement. Exogenous multiple‐daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real‐time changing life‐log variables, such as activity, diet and stress, which results in recurrent hypo‐ and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose‐stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one‐to‐one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods: The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results: Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions: Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option. [ABSTRACT FROM AUTHOR]

• Ability to delivery insulin via skin with accurate dosing using multi-layer detachable microneedles. • Ability to target drugs only in the dermis using multi-layer detachable microneedles. • Ability to sustain the release of insulin into blood circulation through the use of detachable microneedles. • Ability to stabilize insulin at room temperature. • Explaination at the mechanistic level of insulin stabilization. The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration. [Display omitted] [ABSTRACT FROM AUTHOR]

The standard of care for burned patients experiencing hyperglycemia associated with the hypermetabolic response is insulin therapy. Insulin treatment predisposes burn patients to hypoglycemia, which increases morbidity and mortality. Metformin has been suggested as an alternative to insulin therapy for glycemic control in burn patients given its safety profile, but further research is warranted. This study investigated whether metformin use in burn patients is associated with improved glycemic control and morbidity/mortality outcomes compared to insulin use alone. Using the TriNetX database, we conducted a retrospective study of burned patients who were administered insulin, metformin, or both within one week of injury. Demographic, comorbidity, and burn severity information were collected. Patients were categorized by treatment type, propensity score-matched, and compared for the following outcomes within 3 months: hyperglycemia, hypoglycemia, sepsis, lactic acidosis, and death. Statistical significance was set a priori at p ≤ 0.05. The insulin cohort was at increased risk for all outcomes (all p < 0.0001) compared to the metformin cohort, and an increased risk for sepsis, lactic acidosis, and death (all p ≤ 0.0002) compared to the insulin/metformin combination cohort. When compared to the metformin cohort, the combination cohort was at increased risk for all outcomes (all p ≤ 0.0107) except death. Treatment with metformin after burn is associated with a reduced risk of morbidity and mortality compared to insulin. The combination of insulin and metformin is no more effective in reducing the risk of hyperglycemia and hypoglycemia than insulin alone but is less effective than metformin alone. • Uncontrolled hyperglycemia in burned patients increases morbidity and mortality. • Insulin predisposes to hypoglycemia, which increases mortality in burned patients. • Morbidity and mortality are reduced in patients treated with metformin vs. insulin. • Metformin may serve as a viable alternative to insulin in these patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to compare glycemic variability (GV) parameters using both a flash glucose monitoring (FGM) system and cardiometabolic risk parameters in hospitalized patients with type 2 diabetes mellitus (T2DM) between cohorts receiving short-term intensive insulin infusion (STII) plus empagliflozin (EMPA) combination therapy vs. STII therapy alone. Methods: In a 2-week, open-label, randomized, parallel-group clinical trial, newly diagnosed patients with T2DM [fasting plasma glucose (FPG) > 11.1 mmol/L or hemoglobin A1c (HbA1c) > 9.0%] or patients with poor glycemic control (HbA1c > 7.0%) on oral antidiabetic drugs (OAD) received either STII+EMPA therapy (n = 30) or STII therapy alone (n = 30). FGM was carried over 14 days, and the data were used to calculate time in range (TIR [3.9–10 mmol/L]) and compare GV parameters. 1,5-Anhydroglucitol (1,5-AG) and cardiometabolic indicators of oxidative stress, inflammation, and vascular endothelial function were also compared. Results: After treatment, the TIR percentage was significantly higher (p < 0.05), and the time below range (TBR; < 3.9 mmol/L) was significantly lower (p < 0.05) in the STII+EMPA group than that in the STII group. The various measured glycemic parameters were significantly lower, and the average daily dose of insulin was also significantly lower in patients with STII+EMPA treatment (all p < 0.05). Plasma 1,5-AG levels were significantly higher (p < 0.05) in the STII+EMPA group than that in the control group. Conclusions: Newly diagnosed patients with T2DM or with poor glycemic control on OAD attained greater benefit and lower GV from STII+EMPA treatment than that for STII treatment alone. The 1,5-AG marker is a good indicator of the effects of short-term glycemic control. [ABSTRACT FROM AUTHOR]

Objective: Acute worsening of glycemic control in diabetic patients and new–onset type I diabetes were reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Latent autoimmune diabetes in adults (LADA) is defined as a slowly evolving immune–mediated diabetes. A few cases of LADA diagnosed after SARS-CoV-2 vaccination have been reported in the literature. This study aims to report LADA after mRNA-based SARS-CoV-2 vaccinations in subjects with a history of well-controlled type 2 diabetes. Methods: We report four cases with LADA diagnosed after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, all subjects had well-controlled type 2 diabetes with oral anti-diabetic medication. One case had autoimmune thyroid disease. One subject was presented with diabetic ketoacidosis. Results: Glycemic control of the presented cases had deteriorated 6–10 weeks after BNT162b2 vaccination. All patients were male and had high levels of glutamic acid decarboxylase 65 antibody (GAD65ab). An intensive insulin regimen was initiated at the time of diagnosis. The need for insulin therapy in two patients disappeared during follow-up. Two subjects were managed with basal insulin and oral antidiabetics. GAD65ab disappeared just 1 year after the diagnosis of LADA in a subject. Conclusion: In case of impaired glycemic control after SARS-CoV-2 vaccination in a well-controlled diabetic patient, LADA should be considered. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to identify metabolites associated with loss of glycemic control in youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured 480 metabolites in fasting plasma samples from the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study. Participants (N = 393; age 10–17 years) were randomly assigned to metformin, metformin plus rosiglitazone, or metformin plus lifestyle intervention. Additional metabolomic measurements after 36 months were obtained in 304 participants. Cox models were used to assess baseline metabolites, interaction of metabolites and treatment group, and change in metabolites (0–36 months), with loss of glycemic control adjusted for age, sex, race, treatment group, and BMI. Metabolite prediction models of glycemic failure were generated using elastic net regression and compared with clinical risk factors. RESULTS: Loss of glycemic control (HbA1c ≥8% or insulin therapy) occurred in 179 of 393 participants (mean 12.4 months). Baseline levels of 33 metabolites were associated with loss of glycemic control (q < 0.05). Associations of hexose and xanthurenic acid with treatment failure differed by treatment randomization; youths with higher baseline levels of these two compounds had a lower risk of treatment failure with metformin alone. For three metabolites, changes from 0 to 36 months were associated with loss of glycemic control (q < 0.05). Changes in d-gluconic acid and 1,5-AG/1-deoxyglucose, but not baseline levels of measured metabolites, predicted treatment failure better than changes in HbA1c or measures of β-cell function. CONCLUSIONS: Metabolomics provides insight into circulating small molecules associated with loss of glycemic control and may highlight metabolic pathways contributing to treatment failure in youth-onset diabetes. [ABSTRACT FROM AUTHOR]

Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application. By integrating GRI with glucose-sensitive elements, GRI is capable of releasing or activating insulin in response to plasma or interstitial glucose levels without external monitoring, thereby improving glycemic control and reducing hypoglycemic risk. In this Perspective, we first introduce the history of GRI development and then review major glucose-responsive components that can be leveraged to control insulin delivery. Subsequently, we highlight the recent advances in GRI delivery carriers and insulin analogs. Finally, we provide a look to the future and the challenges of clinical application of GRI. Article Highlights: This Perspective introduces the characteristics and mechanisms of three key glucose-sensing components and discusses strategies for developing glucose-responsive insulin. This Perspective introduces the preparation, property, and therapeutic efficacy of leading glucose-responsive formulations and devices. This Perspective summarizes clinical outcomes of clinically evaluated formulations and discusses the requirements for clinical translation of glucose-responsive insulin. [ABSTRACT FROM AUTHOR]

Aims: In tackling rising diabetes‐related emergencies, the need to understand and address emergency service usage by people with type 1 diabetes is vital. This review aimed to quantify current trends in presentations for type 1 diabetes‐related emergencies and identify public health strategies that reduce the frequency of diabetes‐related emergencies and improve glycaemic management. Methods: Medline (OVID), Cochrane and CINAHL were searched for studies published between 2000 and 2023, focusing on people with type 1 diabetes, severe hypoglycaemia and/or diabetic ketoacidosis, and ambulance and/or emergency department usage. There were 1313 papers identified, with 37 publications meeting review criteria. Results: The incidence of type 1 diabetes‐related emergencies varied from 2.4 to 14.6% over one year for hypoglycaemic episodes, and between 0.07 and 11.8 events per 100 person‐years for hyperglycaemic episodes. Notably, our findings revealed that ongoing diabetes education and the integration of diabetes technology, such as continuous glucose monitoring and insulin pump therapy, significantly reduced the incidence of these emergencies. However, socio‐economic disparities posed barriers to accessing these technologies, subsequently shifting the cost to emergency healthcare and highlighting the need for governments to consider subsidising these technologies as part of preventative measures. Conclusions: Improving access to continuous glucose monitoring and insulin pump therapy, in combination with ongoing diabetes education focusing on symptom recognition and early management, will reduce the incidence of diabetes‐related emergencies. Concurrent research assessing emergency healthcare usage patterns during the implementation of such measures is essential to ensure these are cost‐effective. [ABSTRACT FROM AUTHOR]

Introduction: This review presents a critical appraisal of differences in the methodologies and quality of model-based and empirical data-based cost-utility studies on continuous glucose monitoring (CGM) in type 1 diabetes (T1D) populations. It identifies key limitations and challenges in health economic evaluations on CGM and opportunities for their improvement. Methods: The review and its documentation adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. Searches for articles published between January 2000 and January 2023 were conducted using the MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit databases. Published studies using models and empirical data to evaluate the cost utility of all CGM devices used by T1D patients were included in the search. Two authors independently extracted data on interventions, populations, model settings (e.g., perspectives and time horizons), model types and structures, clinical outcomes used to populate the model, validation, and uncertainty analyses. They subsequently met to confirm consensus. Quality was assessed using the Philips checklist for model-based studies and the Consensus Health Economic Criteria (CHEC) checklist for empirical studies. Model validation was assessed using the Assessment of the Validation Status of Health-Economic decision models (AdViSHE) checklist. The extracted data were used to generate summary tables and figures. The study protocol is registered with PROSPERO (CRD42023391284). Results: In total, 34 studies satisfied the selection criteria, two of which only used empirical data. The remaining 32 studies applied 10 different models, with a substantial majority adopting the CORE Diabetes Model. Model-based studies often lacked transparency, as their assumptions regarding the extrapolation of treatment effects beyond available evidence from clinical studies and the selection and processing of the input data were not explicitly stated. Initial scores for disagreements concerning checklists were relatively high, especially for the Philips checklist. Following their resolution, overall quality scores were moderate at 56%, whereas model validation scores were mixed. Strikingly, costing approaches differed widely across studies, resulting in little consistency in the elements included in intervention costs. Discussion and Conclusion: The overall quality of studies evaluating CGM was moderate. Potential areas of improvement include developing systematic approaches for data selection, improving uncertainty analyses, clearer reporting, and explaining choices for particular modeling approaches. Few studies provided the assurance that all relevant and feasible options had been compared, which is required by decision makers, especially for rapidly evolving technologies such as CGM and insulin administration. High scores for disagreements indicated that several checklists contained questions that were difficult to interpret consistently for quality assessment. Therefore, simpler but comprehensive quality checklists may be needed for model-based health economic evaluation studies. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing body of evidence demonstrating the benefit of flash glucose monitoring in people living with type 2 diabetes mellitus (T2DM). This real-world study aimed to evaluate the effect of initiating flash glucose monitoring on change in HbA1c after 3–6 months in adults living with T2DM treated with multiple daily injections of insulin. Methods: A retrospective observational study using data from ten clinical centres in the UK for adults with T2DM treated with multiple daily injections of insulin for at least 1 year was conducted. Patients who had been using the FreeStyle Libre/Libre 2 Flash Glucose Monitoring System for at least 3 months with baseline HbA1c 64–108 mmol/mol (8.0–12.0%) recorded up to 3 months prior to system use were included. Pregnant patients and those on dialysis were excluded. Patients with an HbA1c value measured 3–6 months after commencing flash glucose monitoring were included in the final analysis for evaluation of change. Results: In total, 87 patients were included in the final analysis (mean age, 60.0 ± 11.8 years, 60.9% male, mean body mass index (BMI), 31.6 ± 5.4 [mean ± SD]). From a mean baseline HbA1c of 80 ± 11 mmol/mol (9.5% ± 1.0%), HbA1c lowered by 11 ± 14 mmol/mol (1.0% ± 1.3%) at 3–6 months (p < 0.0001). A decrease was observed independent of age, baseline HbA1c, sex, duration of insulin use and BMI subgroups. Conclusions: Initiation of flash glucose monitoring was associated with a clinically and statistically significant improvement in HbA1c in a real-world setting at 3–6 months. [ABSTRACT FROM AUTHOR]

Introduction: Patients with type 2 diabetes (T2D) who require intensification of basal insulin therapy need treatment options that can improve their health-related quality of life (HRQoL) and translate into better outcomes. These analyses compared patient-reported outcomes (PROs) in patients with T2D receiving tirzepatide or insulin lispro. Methods: The randomised, open-label, multinational, phase 3b SURPASS-6 trial (NCT04537923) was conducted at 135 medical research centres and hospitals in 15 countries and compared two recommended treatment intensification strategies in people with T2D and inadequate glycaemic control on basal insulin: addition of once-weekly tirzepatide versus addition of prandial insulin lispro. Randomisation was stratified by country, baseline glycated haemoglobin level and metformin use. PROs were measured using the Short Form-36 Health Survey version 2 (SF-36v2) acute form (secondary outcome), EQ-5D-5L, Ability to Perform Physical Activities of Daily Living (APPADL) questionnaire and Impact of Weight on Self-Perceptions (IW-SP) questionnaire (tertiary/exploratory outcomes). PROs were compared for the tirzepatide-pooled dose group (5, 10 and 15 mg) and each tirzepatide dose group versus insulin lispro at 52 weeks using the modified intention-to-treat efficacy analysis set. Results: Between 19 October 2020 and 01 November 2022, 2267 people were assessed and 1428 participants with T2D were randomised. At 52 weeks, participants in the tirzepatide-pooled group had statistically significant improved scores across all SF-36v2 domains and both component summary scores compared with insulin lispro-treated participants (p < 0.05), with the largest differences observed in the general health, vitality and mental health domains. Statistically significant improved APPADL and IW-SP total scores, as well as EQ visual analogue scale and EQ-5D-5L index scores (after adjustment for baseline scores), were observed in tirzepatide-pooled participants compared with insulin lispro-treated participants. Conclusions: In adult patients with T2D and inadequate glycaemic control with basal insulin, tirzepatide treatment was associated with greater improvements in HRQoL than prandial insulin therapy in addition to clinically significant improvements in glycaemic and body weight-related parameters. Plain Language Summary: Basal insulin, which controls blood sugar at times when not eating but when the body still needs energy, may not provide sufficient glycaemic control for some people with type 2 diabetes (T2D). These people require additional therapy to improve their health-related quality of life (HRQoL) and achieve better outcomes. This phase 3 study (SURPASS-6) compared patient-reported outcomes, including HRQoL, between people with T2D on basal insulin receiving additional therapy with tirzepatide or insulin lispro (a fast-acting insulin analogue mealtime injection). Patient-reported outcomes were assessed using several validated measures – the Short Form-36 Health Survey version 2 (SF-36v2) acute form (a measure of HRQoL), the EQ-5D-5L (a measure of overall health status), the Ability to Perform Physical Activities of Daily Living (APPADL) questionnaire and the Impact of Weight on Self-Perceptions (IW-SP) questionnaire. The results in the two treatment groups were compared at the end of the treatment period (52 weeks). At 52 weeks, participants in the tirzepatide group had statistically significant improved scores across all HRQoL aspects measured by the SF-36v2 compared with participants in the insulin lispro group, with the largest differences observed in general health, vitality and bodily pain. Statistically significant improved EQ-5D-5L, APPADL and IW-SP scores were also observed in participants in the tirzepatide group compared with the insulin lispro group. In adults with T2D who require therapy in addition to basal insulin, tirzepatide treatment was associated with greater improvements in HRQoL than mealtime insulin therapy, as well as clinically significant improvements in blood sugar and body weight control. [ABSTRACT FROM AUTHOR]

Introduction: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and continuous glucose monitoring (CGM) improve glycemia in patients with type 2 diabetes (T2D). However, it is unknown whether adding CGM to GLP-1 RA therapy further improves A1c. We evaluated changes in A1c levels 6 months after initiation of FreeStyle Libre (FSL) in adults with sub-optimally controlled T2D already on GLP-1 RA therapy. Methods: This retrospective, observational study used Optum's de-identified Market Clarity Data, a linked electronic health record-claims database to assess changes in A1c after FSL acquisition. Inclusion criteria were T2D diagnosis, ≥ 18 years, baseline A1c ≥ 8%, with the first FSL acquisition between 2018 and 2022. Patients were required to be on GLP-1 RA prior to FSL with at least one GLP-1 RA prescription within 90 days of FSL acquisition. GLP-1 RA initiation was defined as the earliest GLP-1 RA prescription from 2017 onwards. Paired changes in A1c were assessed at 6 months after initial FSL acquisition. Results: The study cohort included 1454 adults with T2D (age 55 ± 10 years, 52% male, 38% with intensive insulin therapy, median 471 days from GLP-1 RA initiation to FSL, and baseline A1c 9.8 ± 1.5%). After FSL acquisition, patients experienced an A1c decrease of 1.5 ± 1.9% (p < 0.001). Patients with a baseline A1c > 10% had the largest reduction (n = 497, − 2.7 ± 2.2%, p < 0.001). Significant improvements were observed in subgroups based on insulin therapy and GLP-1 RA formulation. Those initiating GLP-1 RA therapy > 24 months before FSL acquisition also showed improvements in A1c (n = 478; − 1.3 ± 1.7%, p < 0.001). Conclusions : In a large, real-world study of adults with T2D, those on prior GLP-1 RA therapy experienced significant A1c improvements after acquiring FSL, irrespective of GLP-1 RA duration, GLP-1 RA formulation, or insulin therapy type. These findings support the use of FSL in adults with T2D treated with GLP-1 RA. [ABSTRACT FROM AUTHOR]

Aim: Pancreatic reconstruction after pancreaticoduodenectomy (PD) that leaves a small remnant pancreas is often difficult. Pancreatic fistula is a major complication after PD, and fistulas are rare in patients with hard pancreas. However, the clinical impact of non‐reconstructed small remnant after PD with hard pancreas is unknown. Methods: We included all patients who underwent PD for pancreatic tumor without pancreatic reconstruction in two institutions supervised by one surgeon between January 2004 and March 2021. Their short‐ or long‐term outcome after surgery was retrospectively analyzed. Results: PD was performed in 774 patients, of whom 16 patients were without reconstruction (2.1%) with negative margins at the pancreatic stump. Pancreatic transection was performed above or to the left of the superior mesenteric artery, with a median remnant pancreas length of 3.7 cm (range, 1.3–10.0). A major complication (≥ Clavien–Dindo Grade IIIa) occurred in one patient (6%). Fistula of grade B occurred in one patient (6%). After a median follow‐up of 44 months (95%CI, 10.6–77.3), insulin administration was unnecessary in 11 patients. Conclusion: The preservation of a small pancreatic remnant without reconstruction after PD can be performed safely and may enable the keeping of pancreatic endocrine function for some selected patients with hard pancreas. [ABSTRACT FROM AUTHOR]

In recent years, diabetes technologies have revolutionized the care of people with type 1 diabetes (T1D). Emerging evidence suggests that people with type 2 diabetes (T2D) can experience similar benefits from these advances in technology. While glycaemic outcomes are often a primary focus, the lived experience of the person with diabetes is equally important. In this review, we describe the impact of diabetes technologies on patient‐reported outcome measures (PROMs). We highlight that most of the published studies investigated PROMs as secondary outcomes. Continuous glucose monitoring systems may have an important role in improving PROMs in individuals with T1D, which may be driven by the prevention or proactive management of hypoglycaemia. In people with T2D, continuous glucose monitoring may also have an important role in improving PROMs, particularly in those treated with insulin therapy. The impact of insulin pumps on PROMs seems positive in T1D, while there is limited evidence in T2D. Studies of hybrid closed‐loop therapies suggest increased treatment satisfaction, improved quality of life and decreased diabetes‐related distress in T1D, but it is unclear whether these benefits are because of a ‘class‐effect’ or individual systems. We conclude that PROMs deserve a more central role in trials and clinical practice, and we discuss directions for future research. [ABSTRACT FROM AUTHOR]

Background: Multiple clinician adjustable parameters impact upon glycemia in people with type 1 diabetes (T1D) using Medtronic Mini Med 780G (MM780G) AHCL. These include glucose targets, carbohydrate ratios (CR), and active insulin time (AIT). Algorithm-based decision support advising upon potential settings adjustments may enhance clinical decision-making. Methods: Single-arm, two-phase exploratory study developing decision support to commence and sustain AHCL. Participants commenced investigational MM780G, then 8 weeks Phase 1-initial optimization tool evaluation, involving algorithm-based decision support with weekly AIT and CR recommendations. Clinicians approved or rejected CR and AIT recommendations based on perceived safety per protocol. Co-design resulted in a refined algorithm evaluated in a further identically configured Phase 2. Phase 2 participants also transitioned to commercial MM780G following "Quick Start" (algorithm-derived tool determining initial AHCL settings using daily insulin dose and weight). We assessed efficacy, safety, and acceptability of decision support using glycemic metrics, and the proportion of accepted CR and AIT settings per phase. Results: Fifty three participants commenced Phase 1 (mean age 24.4; Hba1c 61.5mmol/7.7%). The proportion of CR and AIT accepted by clinicians increased between Phases 1 and 2 respectively: CR 89.2% vs. 98.6%, p < 0.01; AIT 95.2% vs. 99.3%, p < 0.01. Between Phases, mean glucose percentage time < 3.9mmol (< 70mg/dl) reduced (2.1% vs. 1.4%, p = 0.04); change in mean TIR 3.9-10mmol/L (70-180mg/dl) was not statistically significant: 72.9% ± 7.8 and 73.5% ± 8.6. Quick start resulted in stable TIR, and glycemic metrics compared to international guidelines. Conclusion: The co-designed decision support tools were able to deliver safe and effective therapy. They can potentially reduce the burden of diabetes management related decision making for both health care practitioners and patients. Trial registration: Prospectively registered with Australia/New Zealand Clinical Trials Registry(ANZCTR) on 30th March 2021 as study ACTRN12621000360819. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To test the effect of the glucagon‐like peptide‐1 receptor agonist, liraglutide, on residual beta‐cell function in adults with newly diagnosed type 1 diabetes.In a multicentre, double‐blind, parallel‐group trial, adults with newly diagnosed type 1 diabetes and stimulated C‐peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8‐mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow‐up with only insulin treatment. The primary endpoint was the between‐group difference in C‐peptide area under the curve (AUC) following a liquid mixed‐meal test after 52 weeks of treatment.Sixty‐eight individuals were randomized. After 52 weeks, the 4‐hour AUC C‐peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end‐of‐treatment, C‐peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo‐treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient.Treatment with liraglutide improves residual beta‐cell function and reduces the dose of insulin during the first year after diagnosis. Beta‐cell function was similar at 6 weeks postliraglutide treatment. [ABSTRACT FROM AUTHOR]

Background: The prevalence of type 2 diabetes (DM) has been increasing globally, particularly among older adults who are more susceptible to DM-related complications. Elderly individuals with diabetes are at higher risk of developing hypoglycemia compared with younger diabetes patients. Hypoglycemia in elderly patients can result in serious consequences such as cognitive changes, increased risk of falls, heart and other vascular problems, and even high mortality rate. Objective: To assess prevalence, and factors associated with hypoglycemia events among geriatric outpatients with type 2 diabetes mellitus. Methods: The study was conducted at King Abdullah University Hospital (KAUH) at the outpatient diabetes clinic from October 1st, 2022 to August 1st, 2023. Variables such as socio-demographics, medication history, and comorbidities were obtained using electronic medical records. The prevalence of hypoglycemia was determined through patient interviews during their clinic visit. Patients were prospectively monitored for hospital admissions, emergency department visits, and mortality using electronic medical records over a three-month follow-up period. Logistic regression models were conducted to identify factors associated with hypoglycemia and hospital admissions/ emergency visits. Ethical Approval (Reference # 53/151/2022) was obtained on 19/9/2022. Results: Electronic medical charts of 640 patients who have type 2 diabetes mellitus and age ≥ 60 years were evaluated. The mean age ± SD was 67.19 (± 5.69) years. Hypoglycemia incidents with different severity levels were prevalent in 21.7% (n = 139) of the patients. Insulin administration was significantly associated with more hypoglycemic events compared to other antidiabetic medication. Patients with liver diseases had a significantly higher risk of hypoglycemia, with odds 7.43 times higher than patients without liver diseases. Patients with dyslipidemia also had a higher risk of hypoglycemia (odd ratio = 1.87). Regression analysis revealed that hypoglycemia and educational level were significant predictors for hospital admission and emergency department (ER) visits. Hypoglycemia was a positive predictor, meaning it increased the odds of these outcomes, while having a college degree or higher was associated with reduced odds of hospital admission and ER visits. Conclusion: Current study identified a considerable prevalence of hypoglycemia among older patients with type 2 diabetes, particularly, among those with concurrent liver diseases and dyslipidemia. Furthermore, hypoglycemia was associated with an increased rate of emergency department visits and hospital admissions by 2 folds in this population. [ABSTRACT FROM AUTHOR]

Background: Many studies have explored the risk factors associated with cognitive impairment in patients with Type 2 diabetes mellitus (T2DM). However, research on determining the optimal threshold for these risk factors and comparative studies on the therapeutic effects of insulin and metformin is limited. This study aims to establish the optimal threshold for cognitive impairment risk factors in T2DM patients and compare the efficacy of insulin and metformin in treating mild cognitive impairment (MCI). Methods: A total of 308 patients with T2DM were included. The optimal threshold for cognitive impairment risk factors was determined using receiver operating characteristic curve and binary logistic regression models. MCI patients were divided into three groups: insulin, metformin, and insulin with metformin. The treatment effect was evaluated after a 6-month follow-up. Results: The study identified several factors that influenced cognitive function in T2DM patients, including female gender, duration of diabetes >13.50  years, years of education >7.50  years, and serum sodium level  >  141.90  mmol/L. Metformin and insulin with metformin showed superior therapeutic effects compared to insulin alone, but no difference was observed between metformin and combination therapy. Conclusion: Special attention should be given to female and those with diabetes duration >13.50  years, as well as to individuals with educational level ≤  7.50  years and serum sodium concentration ≤  141.90  mmol/L. Metformin and insulin with metformin effectively improve MCI in patients with T2DM and outperform insulin monotherapy. The efficacy of metformin and combination therapy was found to be comparable [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes (GD) can threaten the health of both the mother and the foetus if it is not effectively managed. While there exists a growing body of research on self-management interventions for GD, there is a lack of reviewed studies regarding the various self-management interventions in Africa. The purpose of this review is to map the evidence of self-management interventions for GD in Africa. Methods: Searches for records were conducted in four major databases, including PubMed, PubMed Central, Science Direct and Journal Storage. Additional documents from Google and Google Scholar were also added. The guidelines for conducting scoping reviews by Arksey and O'Malley were followed. Results: The results revealed that intermittent fasting, education on diet, insulin injection, blood glucose monitoring, physical activities, lifestyle modification and foot care were the available self-management interventions for GD in Africa. Most of the reviewed studies reported intermittent fasting and patient education as effective self-management interventions for GD in Africa. The barriers identified in the reviewed studies were either patient-related or facility-related. Patient-related barriers included lack of awareness, and negative attitude, while facility-related barriers included lack of access to education on GD, especially, face-to-face educational interventions. Conclusion: It is crucial to consider the cultural and personal needs, as well as the educational level of women with gestational diabetes when creating an effective self-management intervention. Optimal results can be achieved for self-management of gestational diabetes by integrating multidisciplinary approaches. [ABSTRACT FROM AUTHOR]

This article presents the findings of a pilot study that investigated the use of real-time continuous glucose monitoring (RT-CGM) in non-critical care insulin-treated inpatients under non-diabetes specialty teams in a hospital setting. The study compared the use of RT-CGM with conventional blood glucose monitoring (CBG) and found that there was no significant difference in glycemic control between the two methods. The study suggests that future research should focus on incorporating structured education for general ward staff and specialist input from inpatient diabetes teams to enhance the effectiveness of RT-CGM in hospital settings. However, the study acknowledges its limitations, including a small sample size and short study duration. [Extracted from the article]

Key points The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague–Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25 mg/kg, i.p.) in combination with a 14–23‐week high‐fat diet or saline injections and a low‐fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2 h post) intracerebroventricular (i.c.v.) insulin microinjections (500 mU, 50 nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36 ± 14 mmHg) vs. 1 h (21 ± 14 mmHg) vs. 2 h (11 ± 6 mmHg), P < 0.05) and RSNA (ΔRSNA Pre (107.5 ± 40%), vs. 1 h (75.4 ± 46%) vs. 2 h (51 ± 35%), P < 0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41 ± 0.19 vs. 0.11 ± 0.05 ng/ml, control (n = 14) vs. T2DM (n = 4), P < 0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3‐kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function. [ABSTRACT FROM AUTHOR]

Background: Several studies were performed on transdermal (TD) insulin delivery in vitro and in vivo, and recently, the study groups included a clinical trial in humans. Therefore, this systematic review was conducted to get summary information about the effectiveness, safety, and preferability of TD insulin in comparison with subcutaneous insulin delivery. Methods: We conducted a thorough search to find studies in the databases Cochrane Library, MEDLINE via PubMed, Web of Science Core Collection, EMBASE, Scopus, Hinari, Medlib, and Magiran until January 2024. We included 18 randomized clinical trials. Results: Although there are various types of TD delivery methods, the TD insulin delivery methods that have undergone clinical trials are the TD patch, micro needle TD insulin delivery, and TD insulin jet injector. Eighteen studies were conducted on TD insulin delivery, which showed either superior or comparable effectiveness, safety, and preferability of TD insulin in comparison with SC insulin. About eleven out of eighteen studies (61.1%) showed more effective blood glucose control than SC delivery, and the remaining seven studies showed comparable effectiveness with SC delivery. Eleven studies (61.1%) showed equal tolerability of TD insulin versus SC insulin, and seven studies (38.9%) showed more tolerability of TD insulin over SC insulin. In most studies, eleven out of eighteen (61.1%) showed a higher preference for TD insulin delivery over traditional SC delivery; sixth out of eighteen (33.3%) showed equal preferability for TD insulin versus SC insulin; and only one study (5.6%) showed that TD insulin delivery was less preferable than SC insulin. Conclusion: The review revealed that clinical trials have demonstrated the effectiveness of TD insulin delivery methods such as TD patches, MN-based insulin delivery, and insulin jet injectors compared to traditional SC routes of administration. The studies showed the superior or comparable effectiveness of TD insulin in controlling blood glucose levels. Additionally, TD insulin delivery was found to be equally or more tolerable than SC insulin delivery in all studies. Overall, the majority of studies favored TD insulin delivery over traditional SC delivery methods, highlighting its potential as a preferred option for insulin administration. [ABSTRACT FROM AUTHOR]

There are genetic and environmental risk factors that contribute to the development of cognitive decline in Alzheimer's disease (AD). Some of these include the genetic predisposition of the apolipoprotein E4 genotype, consuming a high-fat diet (HFD), and the female sex. Brain insulin receptor resistance and deficiency have also been shown to be associated with AD and cognitive impairment. Intranasal (INL) insulin enhances cognition in AD, but the response varies due to genotype, diet, and sex. We investigated here the combination of these risk factors in a humanized mouse model, expressing E3 or E4, following a HFD in males and females on cognitive performance and the brain distribution of insulin following INL delivery. The HFD had a negative effect on survival in male mice only, requiring sex to be collapsed. We found many genotype, diet, and genotype x diet effects in anxiety-related tasks. We further found beneficial effects of INL insulin in our memory tests, with the most important findings showing a beneficial effect of INL insulin in mice on a HFD. We found insulin distribution throughout the brain after INL delivery was largely unaffected by diet and genotype, indicating these susceptible groups can still receive adequate levels of insulin following INL delivery. Our findings support the involvement of brain insulin signaling in cognition and highlight continuing efforts investigating mechanisms resulting from treatment with INL insulin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause. Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient’s intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit. Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV. [ABSTRACT FROM AUTHOR]

Aim Materials and Methods Results Conclusions To study safety, efficacy and weight loss with ADO09, a co‐formulation of insulin A21G and pramlintide, in type 1 diabetes.A randomized, two‐arm ambulatory 16‐week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment.A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed.These results extend previous observations on the efficacy and safety of this insulin/pramlintide co‐formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic disorder of glucose metabolism that threatens several organs, including the submandibular (SMG) salivary glands. Antox (ANX) is a strong multivitamin with significant antioxidant benefits. The goal of this study was to demonstrate the beneficial roles of ANX supplementation in combination with insulin in alleviating diabetic SMG changes. For four weeks, 30 rats were divided into equal five groups (n = 6): (1) control group; (2) diabetic group (DM), with DM induced by streptozotocin (STZ) injection (50 mg/kg i.p.); (3) DM + ANX group: ANX was administrated (10 mg/kg/day/once daily/orally); (4) DM + insulin group: insulin was administrated 1U once/day/s.c.; and (5) DM + insulin + ANX group: co-administrated insulin. The addition of ANX to insulin in diabetic rats alleviated hyposalivation and histopathological alterations associated with diabetic rats. Remarkably, combined ANX and insulin exerted significant antioxidant effects, suppressing inflammatory and apoptotic pathways associated with increased salivary advanced glycation end-product (AGE) production and receptor for advanced glycation end-product expression (RAGE) activation in diabetic SMG tissues. Combined ANX and insulin administration in diabetic rats was more effective in alleviating SMG changes (functions and structures) than administration of insulin alone, exerting suppressive effects on AGE production and frustrating RAGE downstream pathways. [ABSTRACT FROM AUTHOR]