Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study.

Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing's disease (CD). Hyperglycemia during treatment can occur because of the drug's mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 µg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.

Role of Insulin Use and Social Determinants of Health on Non-melanoma Skin Cancer: Results From the Behavioral Risk Factor Surveillance System.

BACKGROUND: Non-melanoma skin cancer (NMSC) is a frequent type of malignancy with a steadily increasing incidence rate worldwide. Although NMSC was shown to be associated with diabetes, no studies have addressed the extent to which insulin use influences the risk of NMSC in light of social determinants of health (SDOH). We conducted a quantitative study that examined the interplay between insulin use, SDOH, additional covariates, and NMSC among individuals with diabetes. METHODS: We based our analysis on the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a national survey conducted yearly in the US. We performed weighted chi-squared test, logistic regression, and survival analyses on 8685 eligible participants with diabetes enrolled in the BRFSS. RESULTS: Kaplan Meier survival curves showed higher probability of NMSC event-free survival for participants with diabetes using insulin compared to participants with diabetes not using insulin (log-rank test P < .001). Significant associations were detected between insulin use and reduced odds of NMSC (OR .56; 95% CI: .38-.82), and decreased hazard (HR .36; 95% CI: .21-.62), along with indices of SDOH. CONCLUSIONS: Our findings suggest that socioeconomic differences related to the healthcare system and behavioral patterns are linked to discrepancies in the use of insulin and the development of NMSC.

Profiles of disordered eating behaviour in type 1 diabetes using the DEPS-R and behaviour and glycaemic outcomes in a real-life setting.

AIMS: The Diabetes Eating Problems Survey - Revised (DEPS-R) is commonly used to assess disordered eating behaviour (DEB) in individuals with type 1 diabetes and has advantages compared to other measures not specifically tailored to diabetes. A score ≥20 on the DEPS-R is used to indicate clinically significant DEB; however, it does not distinguish between eating disorder (ED) phenotypes necessary to guide treatment decisions, limiting clinical utility. METHODS: The current study used latent class analysis to identify distinct person-centred profiles of DEB in adults with type 1 diabetes using the DEPS-R. Analysis of Variance with Games Howell post-hoc comparisons was then conducted to examine the correspondence between the profiles and binge eating, insulin restriction and glycaemic control (HbA1c, mean blood glucose, and percent time spent in hyperglycaemia) during 3 days of assessment in a real-life setting. RESULTS: Latent class analysis indicated a 4-class solution, with patterns of item endorsement suggesting the following profiles: Bulimia, Binge Eating, Overeating and Low Pathology. Differences in binge eating, insulin restriction and glycaemic control were observed between profiles during 3 days of at-home assessment. The Bulimia profile was associated with highest HbA1c and 3-day mean blood glucose. CONCLUSIONS: There are common patterns of responses on the DEPS-R that appear to reflect different ED phenotypes. Profiles based on the DEPS-R corresponded with behaviour in the real-life setting as expected and were associated with different glycaemic outcomes. Results may have implications for the use of the DEPS-R in research and clinical settings.

Semaglutide as a potential therapeutic alternative for HNF1B-MODY: a case study.

Maturity-onset diabetes of the young (MODY) is a grouping of monogenic disorders. It is characterized by dominantly inherited, non-insulin-dependent diabetes. MODY is relatively rare, encompassing up to 3.5% in those diagnosed under 30 years of age. Specific types are most commonly treated with sulfonylurea, particularly those identified as HNF4A-MODY and HNF1A-MODY. HNF1B-MODY is another type that is most frequently managed with insulin therapy but lacks a defined precision treatment. We present an 18-year-old, non-obese female patient diagnosed with HNF1B-MODY. She displays complete gene deletion, a renal cyst, and hypomagnesemia. Her treatment plan includes both long- and short-acting insulin, though she frequently encountered hypoglycemia and hyperglycemia. Semaglutide, a GLP-1RA, was administered weekly over 4 months. The patient's glucose level was continuously tracked using Dexcom's Continuous Glucose Monitoring system. The data suggested a notable improvement in her condition: time-in-range (TIR) increased from 70% to 88%, with some days achieving 100%, and the frequency of hypoglycemic episodes, indicated by time-below-range values, fell from 5% to 1%. The time-above-range values also dropped from 25% to 10%, and her HbA1c levels declined from 7% to 5.6%. During the semaglutide therapy, we were able to discontinue her insulin treatment. Additionally, her body mass index (BMI) was reduced from 24.1 to 20.1 kg/m2. However, the semaglutide treatment was halted after 4 months due to side effects such as nausea, vomiting, and reduced appetite. Other contributing factors included exam stress and a COVID-19 infection, which forced a switch back to insulin. Her last recorded HbA1c level under exclusive insulin therapy rose to 7.1%, and her BMI increased to 24.9 kg/m2. In conclusion, semaglutide could potentially replace insulin to improve glucose variability, TIR, and HbA1c in patients with HNF1B-MODY. However, more extensive studies are required to confirm its long-term safety and efficacy.

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

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

An omics-based machine learning approach to predict diabetes progression: a RHAPSODY study.

AIMS/HYPOTHESIS: People with type 2 diabetes are heterogeneous in their disease trajectory, with some progressing more quickly to insulin initiation than others. Although classical biomarkers such as age, HbA1c and diabetes duration are associated with glycaemic progression, it is unclear how well such variables predict insulin initiation or requirement and whether newly identified markers have added predictive value. METHODS: In two prospective cohort studies as part of IMI-RHAPSODY, we investigated whether clinical variables and three types of molecular markers (metabolites, lipids, proteins) can predict time to insulin requirement using different machine learning approaches (lasso, ridge, GRridge, random forest). Clinical variables included age, sex, HbA1c, HDL-cholesterol and C-peptide. Models were run with unpenalised clinical variables (i.e. always included in the model without weights) or penalised clinical variables, or without clinical variables. Model development was performed in one cohort and the model was applied in a second cohort. Model performance was evaluated using Harrel's C statistic. RESULTS: Of the 585 individuals from the Hoorn Diabetes Care System (DCS) cohort, 69 required insulin during follow-up (1.0-11.4 years); of the 571 individuals in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort, 175 required insulin during follow-up (0.3-11.8 years). Overall, the clinical variables and proteins were selected in the different models most often, followed by the metabolites. The most frequently selected clinical variables were HbA1c (18 of the 36 models, 50%), age (15 models, 41.2%) and C-peptide (15 models, 41.2%). Base models (age, sex, BMI, HbA1c) including only clinical variables performed moderately in both the DCS discovery cohort (C statistic 0.71 [95% CI 0.64, 0.79]) and the GoDARTS replication cohort (C 0.71 [95% CI 0.69, 0.75]). A more extensive model including HDL-cholesterol and C-peptide performed better in both cohorts (DCS, C 0.74 [95% CI 0.67, 0.81]; GoDARTS, C 0.73 [95% CI 0.69, 0.77]). Two proteins, lactadherin and proto-oncogene tyrosine-protein kinase receptor, were most consistently selected and slightly improved model performance. CONCLUSIONS/INTERPRETATION: Using machine learning approaches, we show that insulin requirement risk can be modestly well predicted by predominantly clinical variables. Inclusion of molecular markers improves the prognostic performance beyond that of clinical variables by up to 5%. Such prognostic models could be useful for identifying people with diabetes at high risk of progressing quickly to treatment intensification. DATA AVAILABILITY: Summary statistics of lipidomic, proteomic and metabolomic data are available from a Shiny dashboard at https://rhapdata-app.vital-it.ch .

Insulin Requirement and Infrainguinal Bypass Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification. METHODS: The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure. RESULTS: A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]). CONCLUSIONS: Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

[Sodium glucose cotransporter-2 inhibitors (SGLT2i) and risk of ketoacidosis]. / SGLT2-hämmare och ketoacidos.

SGLT2i can induce euglycemic diabetic ketoacidosis (eDKA) in conditions with relative insulin deficiency, such as infections, surgery, or fasting state. In comparison with classical DKA, eDKA typically presents with lower blood glucose levels and more diffuse symptoms like tiredness, tachypnea, nausea and abdominal pain. The diagnosis is commonly delayed, and signs are often attributed to other factors. Early diagnosis and prevention are critical due to the risk of lethal outcome or prolonged hospital stay. Generous screening for ketonemia in risk situations allows identification of eDKA. To minimize the risk, we propose that SGLT2i should be discontinued 3-4 days before surgery (1-2 weeks prior to bariatric surgery) and during infections, acute disease, or poor oral intake. Postoperative slow infusion of low-dose insulin may prevent eDKA if SGLT2i could not be stopped in time or in prolonged fasting state. In this overview, the pathogenesis behind eDKA is discussed.

Feline Comorbidities: Hypersomatotropism-induced diabetes in cats.

PRACTICAL RELEVANCE: Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control. CLINICAL CHALLENGES: Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests. EVIDENCE BASE: Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition.

Resolution of insulin resistance, lactic acidosis, and decrease in mechanical support requirements in patients post orthotopic heart transplant with the use of long-acting insulin glargine.

OBJECTIVE: This study investigates the efficacy of using a long-acting insulin analog, along with the infusion of regular insulin, in achieving appropriate glycemic control and correcting lactic acidosis in patients post orthotopic heart transplant who demonstrate severe lactic acidosis and insulin resistance. METHODS: This was a retrospective study of two cohorts (IRB FLA 20-003) of patients post orthotopic heart transplant with severe lactic acidosis and insulin resistance who were admitted to a tertiary intensive care unit and treated with (group 1) or without long-acting insulin analog (group 2) within the first 24 h of admission to the intensive care unit. Insulin resistance is defined as the requirement for intravenous regular insulin infusion of more than 20 units/h without the ability to achieve appropriate serum glucose level (120-180 mg /dL). Severe lactic acidosis is defined as arterial lactic acid of more than 10 mmol/L. The following parameters were investigated: time to correct lactic acidosis, duration of postoperative mechanical ventilation, the need for periprocedural mechanical circulatory support, and 28-day mortality. RESULTS: The 28-day mortality was zero in both groups. Two patients required periprocedural mechanical support in group one, and ten patients required mechanical support in group two (RR = 0.224, 95%, confidence interval 0.052-0.95, Z = 2.029, p = 0.042). Three patients required tracheostomy in group one, and four patients required tracheostomy in group two (RR 0.84, 95 confidence interval 0.20-3.48, Z = 0.23, P = 0.81). Wilcoxon rank-sum test was used to compare time to correct lactic acidosis, with lactic acid resolution being faster in group one ([Formula: see text]1 = 19.7 h, SD ± 12.6 h [Formula: see text]2 = 29.3 h, SD ± 19.6 h, Z-value - 2.02, p-value 0.043). The duration of mechanical ventilation was less in group one ([Formula: see text]1 = 29 h, SD ± 12.7 h, [Formula: see text]2 = 55.1 h, SD ± 44.5 h, Z-value: - 1.92, p-value 0.05). CONCLUSION: Administration of low-dose long-acting insulin glargine led to the resolution of the lactic acidosis, insulin resistance, and decreased requirements for pressor and inotropic support, which led to decreased need for mechanical circulatory support.

Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity.

Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has emerged. The gut-brain axis plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from ß-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.

Smart connected insulin dose monitoring technologies versus standard of care: a Canadian cost-effectiveness analysis.

Aim: There is growing interest in novel insulin management systems that improve glycemic control. This study aimed to evaluate the cost-effectiveness of smart connected insulin re-usable pens or caps for disposable insulin pens versus pens without connected capabilities in the management of adult patients with Type 1 diabetes (T1DM) from a Canadian societal perspective. Materials & methods: The IQVIA Core Diabetes Model was utilized to conduct the analyses. Applying data from a non-interventional study, the connected insulin device arm was assumed to result in greater reductions (-0.67%) in glycated hemoglobin from baseline and fewer non-severe hypoglycemic events (-32.87 events/patient annually). Macro- and micro-vascular risks were predicted using the Epidemiology of Diabetes Interventions and Complications study data. Direct and indirect costs and utilities were sourced from literature. Key model outcomes included life years and quality-adjusted life-years (QALYs). Both costs and effects were annually discounted at 1.5% over a 60-year time horizon. Uncertainty was explored in scenario and probabilistic sensitivity analyses (PSA). Results: The connected insulin pen device was associated with lower mean discounted total costs (CAD221,943 vs 266,199; -CAD44,256), improvement in mean life expectancy (25.78 vs 24.29; +1.49 years) and gains in QALYs (18.48 vs 16.74; +1.75 QALYs) over the patient's lifetime. Most scenario analyses confirmed the base case results. The PSA showed dominance in 99.5% of cases. Conclusion: For adults with T1DM in Canada, a connected insulin pen device is likely to be a cost-effective treatment option associated with greater clinical benefits and lower costs relative to a standard re-usable or disposable pen.

Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n = 207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3% vs. 60.0%, p = .036) and borderline fewer rejection episodes (25.0% vs. 40.0%, p = .066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n = 188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1% vs. 53.9%, p < .0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

Lower air ozone concentration is associated with clinical remission in type 1 diabetes diagnosed in adulthood: a prospective, observational study in Wielkopolska region, Poland.

INTRODUCTION: Clinical remission in type 1 diabetes (T1D) results from metabolic compensation after insulin implementation and is caused by various factors. OBJECTIVES: Our aim was to investigate an association between air pollution defined based on ozone concentration in the month of T1D diagnosis and the early course of the disease, that is, glucose metabolism and the occurrence of remission. PATIENTS AND METHODS: This prospective, observational analysis included 96 adult patients with newly diagnosed T1D. The study group was divided according to the occurrence of remission at 12 months after the diagnosis. The levels of ambient ozone measured within the month of T1D diagnosis were calculated using the official data of Poland's Chief Inspectorate of Environmental Protection. Remission was defined according to the following formula: actual glycated hemoglobin (HbA1c)(%) level + [4 × insulin dose (units/kg per 24 h)] - value defining partial remission ≤9. RESULTS: The remission rate after 12 months was higher in the group where ozone concentration was below or equal to the median for the study population (P <0.001). Moreover, the patients in the group where ozone levels were above the median, presented lower C­peptide levels (P = 0.01), higher HbA1c concentration (P = 0.005), and higher daily insulin requirements (P = 0.02) after 12 months from the diagnosis. Also, in the group of participants achieving remission, the ambient ozone level was lower (P <0.001). In a multivariable logistic regression analysis, the increased ozone concentration in the month of diagnosis was the variable that influenced the lack of remission after 12 months, independently of sex and smoking (P <0.001). CONCLUSIONS: Increased ozone level may exacerbate metabolic outcomes and reduce remission in T1D.

Changes in inflammatory markers and efficacy analysis of continuous subcutaneous insulin infusion in senior patients with type 2 diabetes mellitus hospitalized with community-acquired pneumonia: a randomized controlled trial.

OBJECTIVE: The purpose of this study is to analyze the changes in inflammatory markers and efficacy in the treatment of senior patients with type 2 diabetes mellitus (T2DM) and community-acquired pneumonia with continuous subcutaneous insulin infusion (CSII). METHODS: A total of 105 senior patients with T2DM and community-acquired pneumonia, were randomly divided into two groups, viz., treatment group and control group-52 patients in the treatment group were treated with CSII, and 53 patients in the control group with multiple daily insulin injections (MDI). The changes in fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin, interleukin-6 indexes, and the improvement in clinical outcome between the two groups were compared on the 5th and the 10th day of treatment. RESULTS: In the treatment group, there were 52 patients with an average age of (73.7 ± 8.5) years, which included 28 males and 24 females. In the control group, there were 53 patients, with 27 males and 26 females, with an average age of (74.8 ± 8.8) years. On the 5th and the 10th day of the treatment, the fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin and interleukin-6 of the treatment group were better than that of the control group (P < 0.05). The use of CSII was associated with a higher probability of a prompt recovery (P < 0.05). CONCLUSION: The administration of CSII in the treatment of senior patients with T2DM and community-acquired pneumonia can effectively control fasting and postprandial blood glucose, significantly reduce the levels of inflammatory markers, and improve infection treatment efficacy.

Closed-Loop Insulin Delivery May Help Prevent Metabolic Complications During Bariatric Surgery in Patients with Type 1 Diabetes: A Case Report.

Introduction: Obesity in patients with type 1 diabetes (T1D) may worsen their prognosis. Bariatric surgery in these patients can be associated with complications such as diabetic ketoacidosis and severe hypoglycemic episodes. Closed-loop insulin delivery could be a solution to avoid them. Case Report: A 45-year-old woman with T1D and obesity (body mass index of 38.4 kg/m2) was included in our preoperative course of bariatric surgery. Three months before surgery, a closed-loop insulin delivery was instituted due to one prior severe hypoglycemia. Patient did not have immediate or late postoperative hypoglycemia despite consuming a weak amount of carbohydrate. Three months after surgery glycemic control was on target with 86% of time in range 70-180 mg/dL and no time below 70 mg/dL. Conclusion: This case report shows that the use of a closed-loop insulin delivery made it possible to perform bariatric surgery in complete safety for our patient.

A new onset drug induced diabetes mellitus presenting with diabetic ketoacidosis in a child undergoing treatment for B cell acute lymphoblastic leukemia. A case report and review of literature.

OBJECTIVES: Hyperglycemia is a known side effect of anticancer chemotherapeutic drugs. This entity known as drug-induced diabetes mellitus usually does not present with the development of diabetic ketoacidosis (DKA). We hereby report a case of drug induced diabetes mellitus in a child with acute leukemia presenting with DKA. CASE PRESENTATION: We report a case of a teenage boy diagnosed with B cell acute lymphoblastic leukemia and was started on induction phase chemotherapy as per the Indian Collaborative Childhood Leukemia group (ICICLe) acute lymphoblastic leukemia-14 protocol. On day 12 of the induction phase, he developed hyperglycemia and presented to us with severe diabetic ketoacidosis (DKA). Serum anti glutamic acid decarboxylase 65 antibody levels were negative with low serum C peptide levels. Initially, the possibility of drug-induced acute pancreatitis was kept which was ruled out. Keeping the possibility of drug-induced hyperglycemia, the child was started on subcutaneous regular insulin which was titrated as per sugar records. Continuation of remaining chemotherapy was done by PEGylated L-asparaginase with titration of insulin as per home-based sugar records. Insulin requirement increased from 0.3 unit/kg/day to a maximum of 1 unit/kg/day during consolidation phase 1 with PEGylated L-asparaginase suggesting drug-induced hyperglycemia but subsequently insulin requirement decreased and insulin was stopped. CONCLUSIONS: Drug induced diabetes mellitus can present as DKA during induction phase of acute lymphoblastic leukemia (ALL) chemotherapy. A high index of suspicion and close monitoring are required. The insulin requirements in these patients can be very fluctuant and may become nil during the course of treatment.

The Cost-Effectiveness of an Advanced Hybrid Closed-Loop System Compared to Standard Management of Type 1 Diabetes in a Singapore Setting.

Background: Despite advances in technology, glycemic outcomes in people with type 1 diabetes (T1D) remain suboptimal. The MiniMed 780G (MM780G) advanced hybrid closed-loop (AHCL) system is the latest technology for T1D management with established safety and efficacy. This study explores the cost-effectiveness of MM780G AHCL compared against multiple daily injections (MDI) plus intermittently scanned continuous glucose monitor (isCGM). Methods: A cost-utility analysis was conducted, simulating lifetime outcomes for 1000 T1D individuals, with baseline hemoglobin A1c of 8.4%, using the IQVIA Core Diabetes Model (CDM) v9.5. A Singapore health care payer perspective was taken with 2023 costs applied. Treatment effects were taken from the ADAPT study and treatment-related events from a combination of sources. T1D complication costs were derived from local literature, and health state utilities and disutilities from published literature. Scenario analyses and probabilistic sensitivity analyses (PSAs) explored uncertainty. Cost-effectiveness was assessed based on willingness-to-pay (WTP) thresholds set to Singapore Dollars (SGD) 45,000 (United States Dollars [USD] 33,087) per quality-adjusted life year (QALY) and Singapore's gross domestic product (GDP) per capita of SGD 114,165 (USD 83,941) per QALY. Results: A switch from MDI plus isCGM to MM780G resulted in expected gains in life-years (+0.78) and QALYs (+1.45). Cost savings through reduction in T1D complications (SGD 25,465; USD 18,723) partially offset the higher treatment costs in the AHCL arm (+SGD 74,538; +USD 54,805), resulting in an estimated incremental cost-effectiveness ratio of SGD 33,797 (USD 24,850) per QALY gained. Findings were robust, with PSA outputs indicating 81% and 99% probabilities of cost-effectiveness at the stated WTP thresholds. Conclusion: MM780G is a cost-effective option for people with T1D managed in a Singapore setting.

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management.