Intensive Insulin Therapy Research Articles

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial

ObjectiveTo evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with...

Type 1 diabetes mellitus; ovarian reserve; anti-Müllerian hormone; ovarian function

BACKGROUND: Prolonged course of diabetes mellitus often leads to the development of vascular complications, insufficiency of ovarian function. The occurrence of diabetes mellitus in women before pregnancy (pregestational diabetes mellitus) it can have various adverse consequences for the mother, fetus, child and the course of pregnancy. Pregnancy planning in women with pregestational diabetes significantly improves the outcomes of pregnancy and childbirth. AIM: The aim of this study was to analyze gonadotropic and ovarian function parameters in patients with type 1 diabetes mellitus depending on the age of onset, duration and compensation level of the disease. MATERIALS AND METHODS: The patients included into this clinical prospective study were divided into two groups. The main group consisted of 216 patients with type 1 diabetes mellitus aged 18 to 39 years (mean age: 27.1 ± 3.1 years). The control group consisted of 30 healthy women of reproductive age. Chemiluminescent immunoassay was used to determine blood serum levels of anti-Müllerian hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, free testosterone, and sex hormone-binding globulin from day 2 to day 5 of the menstrual cycle. Serum progesterone levels were measured on days 20–23 of the menstrual cycle for three consecutive cycles. Glycated hemoglobin levels were also studied in the blood serum of patients with type 1 diabetes mellitus. All the patients underwent pelvic ultrasound examination to assess the cohort of antral follicles and ovarian volume. RESULTS: The average age of menarche in patients with type 1 diabetes mellitus who developed the disease at the age of under 10 years was 14.2 ± 1.2 years. This was higher than in the group of girls with the onset of the disease over the age of 10 years (13.5 ± 1.2 years) and in women of the control group (11.9 ± 1.1 years). When assessing the ovarian reserve in patients with type 1 diabetes mellitus, we found a decrease in anti-Müllerian hormone level and antral follicle count in the group of women with disease onset at the age of under 10 years. We did not find differences in the ovarian reserve parameters in patients depending on disease duration. Normogonadotropic normoprolactinemic ovarian insufficiency was detected in 154 (71.3%) of 216 patients, while the rest 62 (28.7%) women had an ovulatory menstrual cycle. In patients with anovulation, luteal phase deficiency and ovulatory menstrual cycle, we found no differences between the age of development of type 1 diabetes mellitus, its duration, glycated hemoglobin levels, total daily insulin dose and insulin dose per kilogram of body mass. In patients receiving intensive insulin therapy with continuous subcutaneous insulin infusion, glycated hemoglobin level was lower than in those receiving multiple dose insulin injection therapy. CONCLUSIONS: The average age of menarche in patients with type 1 diabetes mellitus is higher than in healthy women. The ovarian reserve parameters in patients with early onset of the disease, before 10 years of age, are lower than in patients who developed type 1 diabetes mellitus after 10 years of age. Duration of pregnancy planning period depends on compensation level of the disease and lasts from six to 12 months. This requires the doctor and patient to prepare for the implementation of reproductive tasks as early as possible, especially in patients whose disease onset occurred in pre-pubertal period.

6849 Insulin Edema in newly diagnosed T1DM Pediatric Patient

Abstract Disclosure: A. Ansar: None. K. McNerney: None. Background: Insulin edema is a rare complication of insulin therapy, especially in the pediatric populations. The pathogenesis is not fully understood but has been linked to Insulin’s role in renal sodium handling and vascular permeability. It has been seen with the initiation of insulin in newly diagnosed patients or the intensification of insulin therapy in those with poor glycemic control.Clinical Case: A previously healthy 12 year old girl presented to the ED with polyuria, polydipsia and fatigue. She was alert and oriented but had kussmaul breathing. She was tachycardic but all other vitals were appropriate. Lab work up showed that she was in DKA with pH 7.07 and bicarbonate 7 mmol/L. Her corrected sodium and electrolytes were normal. Her HbA1C was elevated at 11.7% (4.0-5.6%). Initial fluid resuscitation was performed with 20 mL/kg NS fluids. She was transferred to our Pediatric ICU and was started on the DKA protocol consisting of intravenous insulin infusion at 0.1 unit/kg per hour and 2-bags of dextrose and non-dextrose containing intravenous fluids. She was given a new diagnosis of Type 1 Diabetes. She was transitioned to subcutaneous insulin 22 hours later with multiple daily injections with insulin lispro and glargine, with total dose of insulin at 0.7 unit/kg per day. She was transferred to the general care floor and received diabetes education while in the hospital. On the fifth day after discharge, patient started complaining of leg tightness, puffiness around her eyes and generalized swelling of both feet. She returned to the ED, where she was found to be hemodynamically stable and normotensive with a blood pressure of 113/54 mmHg. Her weight had increased 8.8 kg from the weight at discharge. Her physical exam was notable facial and bilateral periorbital edema, abdominal distension, and 2+ bilateral non-pitting non-tender edema of both legs extending to her medial malleolus. Neurologic exam was performed which was unremarkable. Work up was performed to rule out other causes of edema, including a complete blood count, electrolytes, kidney and liver function tests, all of which were normal. She received 20 mg of furosemide and was instructed to perform fluid restriction to 1 L/m2/day and sodium restriction to <2 grams per day at home. She followed up in clinic 3 days after her ED visit where her weight had decreased by 4.2 kg and her edema had mostly resolved with only 1+ bilateral non-pitting edema. Her total dose of insulin remained at 0.7 unit/kg per day, with acceptable blood glucose levels at home. Her fluid restriction was discontinued and patient was instructed to follow up as usual, and she had no further edema in follow-up. Conclusion: This was a rare case of a newly diagnosed pediatric patient presenting with Insulin edema, which is essential for clinicians to recognize, so they can identify patients presenting with this uncommon side effect to rule out conditions that may present in a similar manner. Presentation: 6/2/2024

7555 Gender-Related Differences in Outcomes of Patients With Diabetic Ketoacidosis: An Analysis of the National Readmission Database

Abstract Disclosure: E. Ahsan: None. C. Lesniak: None. M. Akula: None. K. Hu: None. K. Chalasani: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. J. Heaton: None. Introduction: Diabetic ketoacidosis (DKA), one of the most serious complications of diabetes, is a significant cause of morbidity and mortality. Hospitalizations for DKA have increased significantly over the past two decades. Despite this, there is a notable absence of data on gender-related variations in the clinical characteristics and outcomes of individuals hospitalized with DKA. Understanding these distinctions is crucial for optimizing disease prevention and care. Thus, the primary aim of this study was to explore whether gender influences the outcomes of DKA. Methodology: We analyzed the National Readmissions Database (NRD) from 2016 to 2020 by evaluating patients admitted with a primary diagnosis of DKA without coma. Patients were included if they were at least 18 years old and admitted between January and November. Patients meeting inclusion criteria were stratified by sex. The groups were assessed for 30-day readmissions, all causes of mortality, length of stay, and total cost. Descriptive statistics, Cox proportional hazards, and adjusted Wald tests were used to compare the groups. Results: Between 2016 and 2020, 642,431 patients met the inclusion criteria with a median age of 44, of which 46.5% were female and 53.5% were male. Early readmission occurred in 33,639.20 females and 31,101.92 males. Cox regression analysis showed a significant difference in readmission risk for female patients than males (HR 1.20, 95% CI 1.17-1.22, P = <0.001). The length of stay was higher in male patients than in female patients (adjusted Wald test, P =<0.001). Inpatient mortality was higher in females than in males (Cox regression analysis, P = 0.009). Total cost was higher in males compared to females (adjusted Wald test, P = <0.001). Conclusion: Regrettably, the majority of studies on diabetic ketoacidosis (DKA) have not given due attention to gender differences. Our study, however, reveals statistically significant variations in in-hospital mortality and 30-day readmission rates between men and women hospitalized with DKA, with women exhibiting higher rates than men. Additionally, the length of stay and total cost were found to be higher for men. To comprehend the underlying reasons for these distinctions, further investigations are warranted. Early introduction and intensification of insulin therapy may prove beneficial for this patient group in mitigating the risk of DKA and other complications associated with diabetes mellitus. Presentation: 6/2/2024

8010 Potent MSB-61 as Type 1 Diabetes (T1D) therapy: mechanism of action in insulin secretion

Abstract Disclosure: N. Ajmal: None. M. Bogart: None. K. Corbin: None. P. Khan: None. M. Shafqat: None. S. Bergmeier: None. G. Gu: None. X. Tong: None. C.S. Nunemaker: None. Type 1 diabetes (T1D) is a chronic autoimmune disorder caused by proinflammatory cytokines (Interleukin 1-beta; IL1-β, Tumor Necrosis Factor-alpha; TNF-α, and Interferon-gamma; IFN-ϒ) from immune cells that destroy insulin-producing beta cells in pancreatic islets and lead to hyperglycemia. The development of possible treatments to cure T1D is needed besides intensive insulin therapy that does not halt disease progression. We have identified a small molecule called MSB-61 that can protect islet cells from endoplasmic reticulum stressors (66% protection) and cytokines (33% protection) as measured by propidium iodide in islets isolated from mice using 50uM MSB-61. Importantly, we observed large increases in insulin secretion during overnight exposure to 50uM MSB-61. Insulin secretion began to increase in response to MSB-61 at ∼4h, reaching a plateau at ∼8h of greater than 4-fold insulin release compared to controls. The Kegg pathway analysis of RNA-seq data on MSB-61 suggested that multiple genes upregulated by MSB-61 are involved in insulin secretion through an amplifying pathway that includes cAMP/PKA and Pi3k/Akt signaling cascades. Based on RNA sequencing data, this study aimed to test MSB-61 for identifying pathway by which it potentiates insulin secretion. Islets from CD-1 mice and mouse insulinoma Min-6 cell lines were used to test amplifying pathways by using cAMP/PKA and Pi3k/Akt analogs and antagonists with and without MSB-61, and overnight insulin secretion and insulin content will be measured by enzyme-linked immunosorbent assay (ELISA). MSB-61 showed no potential effects on insulin secretion when tested for Pi3k/Akt pathway in the presence of analogs and antagonists such as 740-Y-P and wortmannin. It further suggests MSB-61 might potentiate insulin secretion through the cAMP/PKA pathway, which is still under investigation. RNA sequencing analysis of mouse islets showed several genes that belong to Ras family member-2 and have GTPase activity. Genes with GTPase activity will be further investigated to help identify if MSB-61 stimulates insulin secretion through an amplifying pathway involving the cAMP/PKA downstream signaling cascade. Identifying the mechanism of action and signaling pathway by which MSB-61 potentiates insulin secretion will open new ways of identifying T1D therapeutic interventions that would help replace standard insulin therapy. Presentation: 6/3/2024

Best practices and rationale for expanding Medicaid access to continuous glucose monitoring.

Numerous studies have demonstrated that use of continuous glucose monitoring (CGM) significantly improves overall glycemic control and reduces the frequency and severity of hypoglycemic events in individuals treated with intensive insulin, nonintensive insulin, and noninsulin therapies, with reductions in both all-cause and diabetes-related health care resource utilization and lower costs. However, implementation of CGM including prescribing and assessment of the ambulatory glucose profile to make clinical decisions in primary care settings is low. A recent pilot program was initiated at MetroHealth System (Cleveland, Ohio) to implement a CGM integration program for primary care offices throughout the system. Based on the experience and successes from this health system as well as current literature, rationale will be discussed to support the expansion of CGM to individuals enrolled in all Medicaid programs.

Objetivos del tratamiento de la diabetes mellitus tipo 1

There are three ways to assess blood glucose control in type 1 diabetes (DM1): glycated hemoglobin (HbA1c, general target less than or equal to 7%), time in the 70–180mg/dl range (general target 70% or higher), and capillary blood glucose. Diabetes education is a fundamental element in achieving self-management of the disease. It is based on three fundamental pillars: nutrition, insulin therapy, and management of diabetes technology (sensors, insulin pumps, smart insulin pens, and mobile applications). Drug treatment for DM1 consists of intensive insulin therapy using multiple dose injection (MDI) or continuous subcutaneous insulin infusion (CSII). The choice of treatment regimen should be based on patient characteristics and other clinical considerations (e.g., pregnancy, presence of undetected hypoglycemia, or variable insulin requirements). There are currently no other insulin adjuvant therapies approved for use in DM1, although DM2 drugs such as GLP-1 analogs or SGLT2 inhibitors that may provide benefits in blood glucose control or weight loss have been used. Kidney-pancreas or pancreatic islet transplantation is considered a final option in patients with end-stage chronic kidney disease together with or following renal transplantation or in individuals with undetected or severe recurrent hypoglycemia that does not respond to optimized management.

EFFECTIVENESS OF CONTINUOUS GLUCOSE MONITORING IN UNCONTROLLED TYPE-2 DIABETICS IN TERTIARY HEALTHCARE CENTRE

Long term diabetic complications can be prevented or reduced by achieving good metabolic control, reflected by HbA1c <6.5–7.0%.1-3 Glucose excursions might also contribute to the development of diabetic complications.4,5 Fear of hypoglycemia limits the ability to reach strict glycemic control, because it is usually accompanied by reluctance of the patient to intensify insulin therapy. Indeed, the goal of intensive therapy is to normalize HbA1c and control fasting and postprandial glycemia, while concurrently limiting the number and severity of hypoglycemic events. To reach tight glycemic control, frequent self- monitoring of blood glucose (SMBG) must be performed.6 SMBG devices provide the patient with accurate but discreet blood glucose levels. They do not provide trend information nor do they reflect glycemic fluctuations, which is possible by using continuous glucose monitoring (CGM) systems. Thus, implementation of strict glycemic control may be facilitated by a CGM device. This manuscript critically reviews the proposed benefits and indications of CGM and the current evidence of CGM on health outcomes in diabetic patients.

A Glycemic Threshold Above Which the Improvement of β-Cell Function and Glycemia in Response to Insulin Therapy Is Amplified in Early Type 2 Diabetes: The Reversal of Glucotoxicity.

Alleviation of unrecognized glucotoxicity, with resultant recovery of β-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-cell function and glycemia is amplified. IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-cell function between those at/above the indicated glucose level and those below it. The relationship between baseline fasting glucose and the differential change in β-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified. The respective improvements in β-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity.

Real-time continuous glucose monitoring vs. self-monitoring of blood glucose: cost-utility in South Korean type 2 diabetes patients on intensive insulin

Aims This study investigated the cost-utility of real-time continuous glucose monitoring (rt-CGM) versus self-monitoring of blood glucose (SMBG) in people with type 2 diabetes (T2D) receiving intensive insulin therapy in South Korea. Methods The IQVIA Core Diabetes Model (CDM v9.5) was used, with clinical effectiveness data obtained from a large-scale real world study. Costs were obtained from South Korean sources and inflated to 2022 South Korean Won (KRW). A South Korean payer perspective was adopted over a lifetime horizon, with future costs and effects discounted at 4.5% per annum. Baseline characteristics included a mean baseline HbA1c level of 8.6% (71 mmol/mol), and a mean age of 64.4 years. A willingness-to-pay (WTP) threshold of KRW 46.0 million was used. Results Rt-CGM led to an increase of 0.683 quality-adjusted life years (QALYs) versus SMBG (7.526 QALYs for rt-CGM versus 6.843 QALYs for SMBG). An increase in costs of KRW 16.4 million (from KRW 90.4 million to KRW 106.8 million) was associated with rt-CGM. The incremental cost-utility ratio was KRW 24.0 million per QALY gained, significantly lower than the KRW 46 million threshold. Conclusions For individuals with T2D managed by intensive insulin therapy in South Korea, rt-CGM is cost-effective relative to SMBG.

Metabolic health in people living with type 1 diabetes in Belgium: a repeated cross-sectional study.

Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities. We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data. The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c. Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

Impact of Intensive Insulin Therapy on Clinical Outcomes of Traumatic Brain Injury Patients with Pre-Existing Diabetes

Impact of Intensive Insulin Therapy on Clinical Outcomes of Traumatic Brain Injury Patients with Pre-Existing Diabetes

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

ObjectivesTo 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. MethodsThe 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 β-cell function recovery after CSII therapy. ResultsA 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). ConclusionsDrug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better β-cell function recovery.

Evaluation of a structured pharmacist-led intervention on glycemic control in underprivileged diabetic patients: a randomized open-label trial

Abstract 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/).

Association of Changes in A1C Following Continuous Glucose Monitoring Acquisition in People with Sub-Optimally Treated Type 2 Diabetes Taking GLP-1 RA Therapy.

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 6months after initiation of FreeStyle Libre (FSL) in adults with sub-optimally controlled T2D already on GLP-1 RA therapy. 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, ≥ 18years, 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 90days 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 6months after initial FSL acquisition. The study cohort included 1454 adults with T2D (age 55 ± 10years, 52% male, 38% with intensive insulin therapy, median 471days 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 > 24months before FSL acquisition also showed improvements in A1c (n = 478; - 1.3 ± 1.7%, p < 0.001). 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.

Advances in Nanomedicine for Precision Insulin Delivery.

Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of β-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management.

1036-P: Cost-Effectiveness of Real-Time CGM vs. Self-Monitoring of Blood Glucose in People with Type 2 Diabetes on Intensive Insulin Therapy in Australia

1036-P: Cost-Effectiveness of Real-Time CGM vs. Self-Monitoring of Blood Glucose in People with Type 2 Diabetes on Intensive Insulin Therapy in Australia

Insulin Inertia Among People With Type 2 Diabetes Mellitus in Qatar: The INERT-Q Study.

Achieving and maintaining adequate glycaemic control is critical to reduce diabetes-related complications. Therapeutic inertia is one of the leading causes of suboptimal glycaemic control. To assess the degree of inertia in insulin initiation and intensification in people with Type 2 diabetes mellitus (DM-2). We performed a retrospective longitudinal cohort study and followed DM-2 2 years before and 2 years after the start of insulin. The primary outcome was the proportion of patients who achieved glycaemic targets (HBA1c ≤ 7.5%) at 6th month, 1st year and 2nd year. We included 374 predominantly male subjects (62%). The mean age was 55.3 ± 11.3 years, the mean duration of DM-2 was 12.0 ± 7.3 years, 64.4% were obese, 47.6% had a microvascular disease, and 24.3% had a macrovascular disease. The mean HBA1c at -2nd year and -1st year was 9.2 ± 2.1% and 9.3 ± 2.0%, respectively. The mean HbA1C at the time of insulin initiation was 10.4 ± 2.1%. The mean HBA1c at 6th month, 12th month and 2nd year was 8.5 ± 1.8%, 8.4 ± 1.8% and 8.5 ± 1.7%, respectively. The proportion of subjects who achieved HBA1c targets at 6th month, 12th month and 2nd year was 32.9%, 31.0% and 32.9%, respectively. Multivariate logistic regression analysis showed that achieving HBA1c targets at 6th month and 1st year increases the odds of achieving HBA1c targets at 2nd year (OR 4.87 [2.4-9.6] p < 0.001) and (OR 6.2 [3.2-12.0], p < 0.001), respectively. In people with DM-2, there was an alarming delay in starting and titrating insulin. The reduction in HBA1c plateaued at 6th month. Earlier initiation and intensification of insulin therapy are critical to achieving glycaemic targets. More studies are needed to examine the causes of therapeutic inertia from physicians', patients' and systems' points of view.

Sustaining the benefits of structured education: Participants' experiences of receiving structured individual support during a programme (DAFNEplus) informed by behavioural science.

The DAFNEplus programme seeks to promote sustained improvements in glycaemic management by incorporating techniques from behavioural science. It includes five sessions of structured individual support delivered over 12 months following group education. As part of a broader evaluation, and to inform decision-making about roll-out in routine care, we explored participants' experiences of, and engagement with, that individual support. We interviewed DAFNEplus participants (n = 28) about their experiences of receiving individual support and the impact they perceived it as having on their self management practices. We analysed data thematically. Participants described several important ways individual support had helped strengthen their self management, including: consolidating and expanding their understandings of flexible intensive insulin therapy; promoting ongoing review and refinement of behaviour; encouraging continued and effective use of data; and facilitating access to help from healthcare professionals to pre-empt or resolve emergent difficulties. Participants characterised themselves as moving towards independence in self management over the time they received individual support, with their accounts suggesting three key stages in that journey: 'Working with healthcare professionals'; 'Growing sense of responsibility'; and, 'Taking control'. Whilst all portrayed themselves as changed, participants' progress through those stages varied; a few continued to depend heavily on DAFNEplus facilitators for advice and/or direction at 12 months. While all participants benefited from individual support, our findings suggest that some may need, or gain further benefit from, longer-term, tailored support. This has important implications for decision-making about roll-out of DAFNEplus post-trial and for the development of future programmes seeking to bring about sustainable changes in self management practices.

De-intensification as a new trend in the treatment of type 2

Currently, a trend towards deintensification of sugar-lowering therapy has emerged in the domestic and international clinical practice of type 2 diabetes mellitus management. And while recently reducing the intensity of antidiabetic therapy was considered primarily for elderly patients in terms of reducing the risk of hypoglycemia, it is now recognized that many other patients could benefit especially by conversion from intensive insulin therapy regimens to simpler regimens (e. g., fixed combinations of GLP-1 RA and BI). Regimen simplification and reduced number of injections have been shown to improve adherence to therapy without compromising the quality of glycemic control.