Insulin Therapy Research Articles

7305 Pheochromocytoma Presenting With Resistant Hyperglycemia

Abstract Disclosure: M. Economou: None. A. Devine: None. Background: Pheochromocytoma is a rare catecholamine producing tumor arising from the adrenal gland. Impaired glucose tolerance is a well-recognized hormonal and metabolic manifestation of pheochromocytoma caused by catecholamine excess [1]. Insulin resistance requiring very high doses of insulin in association with pheochromocytoma is, however, rare. Here we report a case of pheochromocytoma in a woman with diabetes mellitus that proved difficult to control despite high-dose insulin therapy. Case presentation: A 72-year-old woman with a longstanding history of type 2 diabetes mellitus, uncontrolled hypertension, hyperlipidemia and CVA presented to the hospital after she was found to have a hemoglobin of 7.0 ng/mL on routine labs. Notably, over the past 4 years, her insulin requirement gradually increased from 20 units/day to 50 units/day despite an A1c level of 6.1%. On presentation, our patient was hypertensive to 170/90 with limited response to multiple antihypertensive medications. Additionally, her glucose was severely uncontrolled, fluctuating between 200-500 mg/dL. Within days, the patient’s total daily insulin requirement increased tremendously to as much as 300 units/day. As part of her anemia workup, she underwent a contrast-enhanced CT abdomen & pelvis which identified a left adrenal mass measuring 2.2 x 2.8 x 2.9 cm. Further evaluation with MRI confirmed an adrenal mass suspicious for pheochromocytoma. Evaluation of plasma hormone levels revealed an elevated normetanephrine level of 7.10 nmol/L (normal: less than 0.89 nmol/L). Furthermore, the 24-h urinary normetanephrine level and chromogranin A levels were elevated to 145 mcg/day and 1203 ng/mL, respectively. Initial treatment with alpha and beta blockade improved blood pressure but glucose levels remained persistently elevated. The patient underwent left laparoscopic adrenalectomy and pathology revealed pheochromocytoma, measuring, 3.2 cm in diameter, with stains positive for CD56, synaptophysin and chromogranin. Surgical resection margins were negative for tumor. Postoperatively, insulin requirements returned to roughly that of her baseline, 40 units/day. Conclusion: Impaired glucose tolerance is a known phenomenon associated with pheochromocytoma. Despite this, it is unusual to see an insulin requirement rise as abruptly and drastically as seen in this case. Our patient, with relatively controlled diabetes had an enormous increase in her insulin requirement during her hospital course as evidenced by her insulin regimen which increased sixfold. This case highlights the importance of maintaining a high degree of suspicion for pheochromocytoma in patients with a sudden rise in insulin requirement and uncontrolled hypertension. Reference: (1) Ronen JA, Gavin M, Ruppert MD, Peiris AN. Glycemic Disturbances in Pheochromocytoma and Paraganglioma. Cureus. 2019 Apr 27;11(4): e4551. Presentation: 6/3/2024

7540 Recognition of Need for Optimization of Diabetes Education for Children with Type 1 diabetes: Long term Provider Experience

Abstract Disclosure: J. Begum-Hasan: None. Title: Recognition of need for optimization of diabetes education for children with Type 1 diabetes: long term “On call provider experience “Janhanara Begum – Hasan, MD, PhD. Jacob school medicine. UBMD Pediatrics Context: Pediatric endocrinologist does provide on call service 24/7 to support patient care as needed for the family with children with diabetes. Complication of diabetes including DKA is preventable However, based on interaction with the family with children diabetes, the trend shows sub optimal education in this regard. Aim/Objective: To review case scenario and provide recommendation to optimize diabetes management with a goal of prevention of complications. Case discussion: 3 case scenarios are selected to review. Case 1: The father called at 2 am as his daughter’s (12 year F) Insulin pump is broken and BGs are elevated in upper 300s. Her urine is +ve for moderate ketone and she has nausea. He does not have any short acting pen or syringe to provide correction Insulin. He reports that he is not aware of her Insulin settings in the pump. Parents are separated and mother is more involved in her care. Short /long acting Insulin pen were prescribed with recommendations including correction dose as per weight with a plan for follow up. Case 2: The mother called at 9 pm and reported that by mistake, she did administer “Admelog” at 18 units instead of Basaglar, for her son, 11 year old with Type 1 diabetes. He was on Lantus and Humalog before. She gets confused with short and long acting Insulin particularly with changes. The mother was advised on close monitoring of BGs with recommendation of treatment of Hypoglycemia including Glucagon therapy. He was followed closely with stabilization of BGs with extra carbohydrate overnight. Case 3: The father calls to inform that his son, 14 year, with recent onset Typ1 diabetes, has been vomiting with high BG in 400s with large ketone. His Insulin dose was decreased recently as he was told to be in “Honeymoon phase” and planned for close follow up. However, the family missed endocrine FU >12 months now. His BGs have been high in upper 200s to 300s for last 2-3 months. The parents are in the process of divorce. He was sent to local ED with clinical impression of DKA. He was treated for his severe DKA as found after metabolic labs. He did well after 2 days hospitalization for management of his DKA. Conclusion: -Complications of Type 1 diabetes are preventable. The family needs further education on diabetes management including review of Insulin therapy when Insulin pump does malfunction, with a copy of written instruction of Insulin doses, differences in long and short acting Insulin along with psychosocial support to optimize care of children with Type 1 diabetes. Presentation: 6/2/2024

7363 Comparing the Effectiveness of Various Insulin in Insulin Naive Type 2 Diabetes Mellitus Patients: A Study from Central India

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. N. Kumari: None. A. Gwal: None. Introduction: Insulin is the cornerstone of treatment of type 2 diabetes mellitus (T2DM) and is the most efficacious treatment option. The evaluation of efficacy and safety of insulin therapy in real world setting is desirable as numerous options are currently available. This study aimed to compare the efficacy and safety of four different insulins in patients with T2DM. Methods: We conducted a retrospective observational study at our tertiary care hospital using medical records of patients with glycated hemoglobin (HbA1c) >8.5% who were not controlled on oral antidiabetic (OAD) medication and received add-on insulin treatment (Glargine U300, Lispro Biphasic 25/75, Glargine U100, IdegAsp). Glycemic control and incidence of hypoglycemia were analyzed from baseline to 6 months. Results: 101 patients were included. Mean age 56.4 years. 61.4% men. Mean duration of T2DM 13.3 years. 23 (22.8%), 27 (26.7%), 27 (26.7%), and 24 (23.8%) patients received Glargine U300, Lispro Biphasic 25/75, Glargine U-100, IdegAsp insulin respectively. At baseline, the mean (SD) HbA1c were 11.93% (1.85), 10.61% (1.55), 10.65% (1.59), and 10.58% (1.89) in patients receiving Glargine U300, Lispro Biphasic 25/75, Glargine U100, and IdegAsp, respectively. HbA1c, fasting plasma glucose (FPG) & post-prandial plasma glucose (PPG) improved significantly from baseline to 6 months across all four treatment groups (p<0.001). Glargine U300 showed a significantly greater mean reduction in HbA1c by 4.57% compared to Lispro Biphasic 25/75 (3.39%; p=0.032), Glargine U100 (2.88%; p=0.004), and IdegAsp (2.38%; p<0.001). The mean reduction in FPG, PPG, total cholesterol and triglycerides were comparable across all four treatment groups. The mean insulin doses (SD) were 15.48 (5.65) U, 23.83 (9.49) U, 20.44 (8.76) U, and 34.17 (14.57) U at baseline and 18.89 (5.39) U, 35.52 (10.37) U, 26.07 (8.92) U, and 43.58 (15.76) at 6 months, respectively. The doses of all insulins were titrated to fasting, post-meal, or pre-dinner SMBG readings as appropriate. There were no significant changes observed in the mean body weight and insulin dose in all four subgroups. The incidence of hypoglycemia (<70 mg/dL and <54 mg/dL) was numerically lower in Glargine U300 (3 and 1) group, than in Lispro Biphasic 25/75 (8 and 5), Glargine U100 (3 and 2), and IdegAsp (7 and 3) groups. As expected, biphasic insulin had a higher numerical incidence of hypoglycemia. Conclusion: All insulins demonstrated significant improvements in glycemic parameters over the study period. However, Glargine U300 demonstrated a significantly higher reduction in HbA1c with minimal hypoglycemia events compared to other insulins and can be considered in OAD uncontrolled patients. Our results should be interpreted with caution as the study was retrospective and had a small sample size. Presentation: 6/3/2024

8439 Targeting Interferon Gamma-Mediated CXCL16-CXCR6 Chemokine-Receptor Interactions As A Strategy To Prevent Immune Checkpoint Inhibitor Autoimmune Diabetes

Abstract Disclosure: S. Wang: None. N. Huang: None. J.G. Ortega: None. J. Lee: None. K. Kimbrell: None. J. Nguyen: None. J. Olay: None. E. McCarthy: None. E. Peluso: None. H. Chen: None. M.G. Lechner: None. Autoimmune diabetes mellitus is a rare but life-threatening side effect of immune checkpoint inhibitor (ICI) cancer therapy. Checkpoint inhibitors increase immune activation by blocking regulatory molecules on T cells, including programmed death protein (PD1). As a result of this heightened immune activation, patients can develop autoimmunity in healthy tissues, known as immune related adverse events (IRAEs). ICI-associated diabetes mellitus (ICI-T1DM) is an IRAE that results in autoimmune destruction of insulin-producing pancreatic beta-cells. Patients with ICI-T1DM require life-long insulin therapy and more than half present initially with diabetic ketoacidosis. Unfortunately, the mechanism of this IRAE is not fully understood. Anti-PD1 antibody treatment (10mg/kg/dose, twice weekly, i.p.) of male and female non-obese diabetic (NOD) mice leads to autoimmune infiltrates in multiple tissues, including accelerated insulitis and DM. Single cell RNA sequencing of islet infiltrating immune cells from ICI-treated mice previously showed a role for CD8+ T cells and cytokine interferon gamma (IFNγ) in the development of ICI-T1DM. Using CellChat to perform receptor-ligand interaction analysis of these data, we identified both CD8+ and CD4+ T cells as the primary source of IFNγ in immune infiltrates and islet myeloid cells as the primary target. Furthermore, CellChat analysis showed increased receptor-ligand interactions between T cell receptor CXCR6 and its chemokine CXCL16, as well as CXCR3 and chemokines CXCL9 and CXCL10. In vitro IFNγ stimulation of myeloid cells induced strong expression of CXCL16, 9, and 10, suggesting a potential mechanism by which effector T cells are recruited to islets during ICI therapy. Immunophenotyping of islet-infiltrating immune cells indeed showed increased IFNγ+CXCR6+ effector CD8+ cells in anti-PD1 treated mice compared to isotype-treated controls. Moreover, these IFNγ+CXCR6+CD8+ T cells stained positively for the NRP-V7 mimotope tetramer, a known antigen for CD8+ T cells in spontaneous autoimmune diabetes in NOD mice, suggesting this as an antigen-specific population contributing to the immunopathogenesis of ICI-T1DM. Finally, genetic deletion of CXCR6 in NOD mice delayed the onset of autoimmune diabetes during anti-PD1 treatment in female (p=0.0162) but not male mice (p=0.3656). In summary, these data further elucidate the cellular mechanisms by which IFNγ and chemokine signaling pathways drive the development of ICI-T1DM and identify the CXCR6-CXCL16 axis as a potential therapeutic target to prevent this IRAE in checkpoint inhibitor-treated cancer patients. Presentation: 6/2/2024

6938 An Unusual Case of New-onset autoimmune insulin dependent Diabetes Mellitus Complicating Gestational Diabetes Mellitus in A Pregnant Female Diagnosed Early Postpartum - The Enigma of Autoimmunity and Diabetes During Pregnancy

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Gestation diabetes is the most common metabolic disorder in pregnancy affecting 25% of pregnancies. T1DM accounts for 0.2-0.5% of all pregnancies in the United States yearly. New-onset autoimmune insulin-dependent diabetes mellitus during pregnancy is very uncommon and it might be overlooked. Diabetes-related autoantibodies have been studied in women with GDM with prevalence of 0-10%. There is controversial data regarding the clinical significance of checking diabetes antibodies in pregnancy. Case Presentation: A 22-year-old G1P1 female with history of Hashimoto hypothyroidism presented during early second trimester for evaluation of GDM with serum glucose of 300s mg/dl in a random blood sample with multiple subsequent high values, hemoglobin A1C of 9.4% (prepartum value was 5.3%). Patient was started on insulin during pregnancy. Pregnancy was complicated with cesarian section and macrosomia. 1 week postpartum, A1c was 5.4%, Insulin was discontinued, and patient was continued on Metformin. 2 months Postpartum, patient presented with persistent high blood glucose values of 300-400 mg/dl with no signs of DKA. Glipizide and Glargine 15 units daily were added though patient continued to have hyperglycemia. Laboratory workup were remarkable for high blood glucose of 342 mg/dl, low C peptide of 0.6 ng/dl, and positive glutamic acid decarboxylase antibodies (GAD Ab) 38.8 U/ml. oral antidiabetics were discontinued and prandial insulin was added. Discussion: GDM is a risk factor for DMII after pregnancy given high insulin resistance postpartum, Data regarding new-onset DMI and diabetes autoimmunity during pregnancy is lacking. About 0-10% of women with gestational diabetes develop DM autoantibodies. GAD Ab exhibits the highest sensitivity of 63% for type 1 diabetes prediction compared to Islet cell antibodies (48%), and tyrosine phosphatase-related islet antigen 2 (34%). Pathophysiology of autoimmune DM during pregnancy is not quite understood; It is thought that when autoimmune tendency is present, GDM causes β-cells to deteriorate due to excessive insulin production in setting of insulin resistance, and the burden of third-trimester gestation may cause the insulin deficiency to be expressed sooner than non-pregnant female. So far, Literature about the predictive value or specific clinical features of checking diabetes autoantibodies is discordant and inconclusive. It is suggested to screen for autoantibodies only when array of clinical hallmarks suggestive of an autoimmune DM form of GDM present as young age, low BMI, need for insulin therapy early in pregnancy, presence of ketones, concurrent other autoimmune conditions (e.g., thyroiditis). This case is to shed light on autoimmunity in pregnancy. More data is needed with longer follow-up to better identify women at risk, their characteristics, indications for autoantibodies testing, follow and prognosis. Presentation: 6/2/2024

12599 Early Remission Of Chromosome 6 Q 24-related Neonatal Diabetes Mellitus

Abstract Disclosure: R. Pratibha: None. K. Dummula: None. Introduction: Chromosome 6q24 imprinting abnormalities represent the predominant cause of transient neonatal diabetes mellitus (TNDM), accounting for over two-thirds of cases with an estimated prevalence of 1 in 400,000. While remission typically manifests by 3 months of age, herein we detail a case of Chromosome 6q24-related TNDM exhibiting remission by 1.5 months of age. We share our clinical experience in managing this case without hypoglycemia and using C-Peptide levels as a monitoring tool to track the resolution. Case: A female infant, born at 36 weeks via elective C-section due to fetal growth restriction and oligohydramnios, was closely monitored in the nursery for potential hypoglycemia. Contrary to the expectation, she displayed escalating hyperglycemia, necessitating insulin infusion within 25 hours of birth. Apgar scores were 7 and 9, and the birth weight was 2095 g (6th percentile). Maternal history included impaired glucose tolerance in a previous pregnancy with borderline glucose tolerance during this gestation. The newborn physical exam was unremarkable except for mild macroglossia. Despite initial blood glucose (BG) of 52 mg/dl, it rose to 257 mg/dL by 16 hours. Insulin drip was started at 24 hours due to BG of 304 mg/dL. The monogenic diabetes panel obtained on day of life (DOL) #2 was negative; no acidosis was observed. The C- Peptide was low at 0.2 ng/ml. Insulin infusion was continued until DOL # 20. A trial of glyburide commenced on DOL #9 while on Insulin drip, yielded minimal response, prompting a transition to short-acting insulin for correction of hyperglycemia (>250 mg/dL). C-peptide level during sulfonylurea (SU) trial remained low (0.5 ng/mL). The infant required 2 to 3 corrections per day with 0.05 units of Lispro Insulin, with the last dose administered at 44 days. She did not receive any long-acting Insulin. As of her last follow-up at the endocrine clinic at 57 days of age, the infant is thriving well and has normal blood glucose levels. The 6q24 Methylation-MLPA study showed duplication of 6q24 on the paternally inherited chromosome 6. Significantly, she never encountered hypoglycemia during her hospital stay. The C-peptide increased to 0.8 ng/ml at DOL#37 and had normalized to 1.3 ng/mL by DOL#57 indicating remission of TNDM. Conclusion: 6q24-related TNDM may often be characterized by features such as small for gestational age (SGA), macroglossia, umbilical hernia, cardiac and renal abnormalities. Early presentation of hyperglycemia with this phenotype must prompt its diagnostic evaluation. Early resolution by 1.5 months as seen in our case is uncommon. Uniquely, we used C-peptide as a tracking tool to guide resolution and manage insulin therapy. Presentation: 6/3/2024

Does Insulin Treatment Affect Umbilical Artery Doppler Indices in Pregnancies Complicated by Gestational Diabetes?

Background/Objectives: Gestational diabetes mellitus (GDM) is one of the most common morbidities of pregnancy. The impact of increased maternal blood glucose on fetoplacental hemodynamics is not fully elucidated, especially in patients with uncontrolled GDM necessitating insulin therapy. The objective of this study was to assess the impact of insulin therapy on the umbilical artery dopplers in GDM pregnancies adequate for gestational-age fetuses. Methods: Retrospective observational study among 447 GDM pregnant women, divided according to their treatment (nutritional therapy (NT), long acting (LA) insulin, combined insulin) and 100 healthy controls with the same gestational age. The umbilical artery pulsatility index (UA-PI) was recorded at 28, 32 and 36 weeks. Results: UA-PI values declined in both GDM and healthy controls at all three time intervals. The combined insulin group showed reduced UA-PI values in comparison to the LA insulin group, but the difference never reached statistical significance. The combined insulin group exhibited significantly reduced UA-PI values at 32- and 36-weeks' gestation compared to the NT groups. Conclusions: A decreased impedance to blood flow in the umbilical artery of diabetic mothers on insulin therapy was observed. This was more pronounced during the last trimester. The extent to which umbilical artery PI can predict unfavorable outcomes has yet to be determined. Further additional studies are necessary to confirm the precise impact of glucose levels and medical interventions on the circulation of both the fetus and the mother.

IGlarLixi effectively reduces residual hyperglycaemia in Chinese people with type 2 diabetes on basal insulin: A post hoc analysis of the LixiLan-L-CN study.

To compare the effects of iGlarLixi versus insulin glargine 100 U/mL (iGlar) on residual hyperglycaemia in Chinese people with uncontrolled type 2 diabetes (T2D) on prior basal insulin (BI) therapy ± oral antidiabetic drugs in the LixiLan-L-CN study (NCT03798080). In this post hoc analysis, residual hyperglycaemia (i.e. HbA1c ≥ 7.0% [≥ 53 mmol/mol] and fasting plasma glucose [FPG] < 7.0 mmol/L) were assessed over 30 weeks. Outcomes were assessed at week 30 in participants with baseline residual hyperglycaemia, including changes from baseline in HbA1c, FPG, 2-hour postprandial glucose (PPG) and daily BI dose, the proportion of participants with HbA1c less than 7.0% (< 53 mmol/mol) and FPG less than 7.0 mmol/L and the incidence of hypoglycaemia. Of 421 participants, 124 (29.5%) had baseline residual hyperglycaemia (iGlarLixi, n = 64 [31.7%]; iGlar, n = 60 [29.1%]). At week 30, the residual hyperglycaemia rate decreased to 7.0% with iGlarLixi and increased to 43.3% with iGlar. Among participants with baseline residual hyperglycaemia, a greater proportion achieved both HbA1c and FPG targets at week 30 with iGlarLixi versus iGlar (43.8% vs. 16.7%), and iGlarLixi provided greater reductions in HbA1c (least squares mean [LSM] difference, -0.9% [-9.4 mmol/mol]) and 2-hour PPG (LSM difference, -4.7 mmol/L; both P < .001). Daily BI dose and incidence of hypoglycaemia were similar in the two groups. The findings of this post hoc analysis suggest that iGlarLixi had greater benefits than iGlar in reducing the rate of residual hyperglycaemia over 30 weeks in Chinese people with suboptimally controlled T2D on prior BI-based therapy.

Unravelling the Role of Gut and Oral Microbiota in the Pediatric Population with Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease that results in the destruction of pancreatic β cells, leading to hyperglycaemia and the need for lifelong insulin therapy. Although genetic predisposition and environmental factors are considered key contributors to T1DM, the exact causes of the disease remain partially unclear. Recent evidence has focused on the relationship between the gut, the oral cavity, immune regulation, and systemic inflammation. In individuals with T1DM, changes in the gut and oral microbial composition are commonly observed, indicating that dysbiosis may contribute to immune dysregulation. Gut dysbiosis can influence the immune system through increased intestinal permeability, altered production of short chain fatty acids (SCFAs), and interactions with the mucosal immune system, potentially triggering the autoimmune response. Similarly, oral dysbiosis may contribute to the development of systemic inflammation and thus influence the progression of T1DM. A comprehensive understanding of these relationships is essential for the identification of biomarkers for early diagnosis and monitoring, as well as for the development of therapies aimed at restoring microbial balance. This review presents a synthesis of current research on the connection between T1DM and microbiome dysbiosis, with a focus on the gut and oral microbiomes in pediatric populations. It explores potential mechanisms by which microbial dysbiosis contributes to the pathogenesis of T1DM and examines the potential of microbiome-based therapies, including probiotics, prebiotics, synbiotics, and faecal microbiota transplantation (FMT). This complex relationship highlights the need for longitudinal studies to monitor microbiome changes over time, investigate causal relationships between specific microbial species and T1DM, and develop personalised medicine approaches.

Health Literacy and Adherence to Therapy in Type 2 Diabetes: A Cross-Sectional Study in Portugal.

Therapy adherence is a key factor in the control of type 2 diabetes mellitus (T2DM). Optimal self-care requires skills in health literacy (HL). This study aims to analyze the relationship between HL and adherence to therapy and to understand the possible influence of other sociodemographic and disease variables. A multicenter, cross-sectional study was conducted in Portuguese in 13 different primary health care units in both rural and urban environments. A sociodemographic questionnaire and two validated instruments, "Medical Term Recognition Test" and "Summary of Diabetes Self-Care Activities," were applied. The last value of hemoglobin A1c (HbA1c) and the number of chronic medications were collected from clinical records. Descriptive statistics and bivariate correlations were performed as well as multivariable linear regression to assess the association between HL and adherence to therapy. Participants (n = 354) were on average age 63.67 ± 10.39 years, 57.1% male and 42.9% female, 68.4% with inadequate HL and an average HbA1c of 7 ± 1.18%. Better HL was correlated with higher adherence to the total of self-care activities, nonpharmacological therapy, and foot care. In multivariable linear regression analyses, better HL (β = 0.176, p = .003), less than minimum wage (β = -0.197, p = .001) and insulin therapy (β = 0.272, p = .001) were independently associated with increased adherence to overall self-care activities. In a representative sample of people with T2DM in Portugal, HL was a key factor for greater adherence to demanding self-care activities. [HLRP: Health Literacy Research and Practice. 2024;8(4):e194-e203.].

Insulin therapy use in gestational diabetes: Frequency and predictive factors

Insulin therapy use in gestational diabetes: Frequency and predictive factors

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.

Adherence to gluten free diet and problems faced by children with celiac disease and type 1 diabetes mellitus

ABSTRACT Introduction: Celiac disease (CD) in children can be associated with Type 1 Diabetes Mellitus (T1DM) as both share autoimmune etiology. Mainstay of treatment in celiac disease is total avoidance of gluten in diet whereas treatment in child with both the diseases will be Insulin therapy, exercise along with gluten free diet (GFD). There is dearth of literature regarding adherence to GFD and barriers for children with both T1DM and CD. Methods: A questionnaire-based study was done at a tertiary care institute so as to compare the self-reported gluten adherence and the problems faced by children with dual diseases (TIDM and CD) and CD alone. Thirty children of age group 5-14 years each withType 1 DM and CD (T1DMCD group) and celiac disease (CD group) were selected consecutively. A questionnairewas filled by asking questions from either children (above 8 years) or parents (below 8 years) and the results were compiled, compared and further analysed. Results: Baseline demographic parameters were comparable in both the groups. Gluten adherence was found to be worse in T1DMCD group as compared to CD group. Greater number of problems were experienced by children with both TIDM and CD as compared to children with CD alone (P &lt; 0.05). Financial burden more so in T1DMCD group, unawareness about disease and benefits of GFD, less availability and social isolation were found to be the most significant barriers to diet adherence. Conclusion: As these children face dual diseases, they should be made more aware regarding benefits of GFD. Such information is valuable to primary care physicians for better management and rehabilitation of children suffering from these chronic diseases.

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.

Impact of continuous glucose monitoring on emergency department visits and all-cause hospitalization rates among Medicaid beneficiaries with type 2 diabetes treated with multiple daily insulin or basal insulin therapy.

The increasing prevalence of diabetes in the United States continues to drive a steady rise in health care resource utilization, especially emergency department visits and all-cause hospitalizations, and the associated costs. To investigate the impact of continuous glucose monitoring (CGM) on emergency department visits and all-cause hospitalizations among Medicaid beneficiaries with type 2 diabetes (T2D) treated with multiple daily insulin injections (MDIs) or basal insulin therapy (BIT) in a real-world setting. In this retrospective, 12-month analysis, we used the Inovalon Insights claims dataset to evaluate the effects of CGM acquisition on emergency department visits and all-cause hospitalizations in the Managed Medicaid population. The analysis included 44,941 beneficiaries with T2D who were treated with MDIs (n = 35,367) or BIT (n = 9,574). Primary outcomes were changes in the number of emergency department visits and all-cause hospitalizations following 6 months after acquisition of CGM (post-index period) compared with 6 month prior to CGM acquisition (pre-index period). The first claim for CGM was the index date. Inclusion criteria were as follows: aged younger than 65 years, diagnosis of T2D, claims for short- or rapid-acting insulin (MDI group) or basal insulin (not rapid-acting) (BIT group), acquisition of a CGM device between January 1, 2017, and September 30, 2022, and continuous enrollment in their health plan throughout the pre-index and post-index periods. In the MDI group, all-cause inpatient hospitalization rates decreased from 3.25 to 2.29 events/patient-year (hazard ratio = 0.12; 95% CI = 0.11-0.13; P < 0.001) and emergency department visit rates decreased from 2.15 to 1.86 events/patient-year (hazard ratio = 0.52; 95% CI = 0.50-0.53; P < 0.001). In the BIT group, all-cause inpatient hospitalization rates decreased from 1.63 to 1.39 events/patient-year (hazard ratio = 0.11; 95% CI = 0.09-0.12; P < 0.001) and emergency department visit rates decreased from 1.60 to 1.43 events/patient-year (hazard ratio = 0.47; 95% CI = 0.44-0.50; P < 0.001). Acquisition of CGM is associated with significant reductions in emergency department visits and all-cause hospitalizations among people with T2D treated with MDIs or BIT.

TNF-α inhibitors for type 1 diabetes: exploring the path to a pivotal clinical trial.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.

Exploring the “New World”: weekly basal insulins

therapeutic option today, especially in specific clinical conditions, even in type 2 diabetes. Our country is approaching a new era in the history of insulin. We are indeed close to the availability of the first weekly basal insulin formulations. The AMD annals present a unique chance to evaluate the evolution of pharmacological therapies for diabetes in recent years. The AMD annals confirm that in 2023 still more than 32% of the population with type 2 diabetes in Italy was treated with insulin, and more than 97% of subjects were treated with basal insulin. The appropriate prescription of insulin is hindered by numerous obstacles, resulting in therapeutic inertia. Among these, the non-acceptance of daily injection therapy and the difficulty in adherence justify the rationale for developing weekly basal insulin Among the weekly basal insulins in development, icodec and efsitora are the closest to being introduced into our clinical practice. The development of new biotechnological approaches has resulted in the development of insulins with a half-life of 8 and 17 days for icodec and efsitora, respectively. Icodec and efsitora, in the QWINT and ONWARDS phase 3 programs, have been shown to be effective in achieving primary and secondary efficacy endpoints. The two weekly basal insulins have shown that in the context of an oral basal regimen for people with type 2 diabetes, the risk of hypoglycemia is not different from that of daily basal insulins In studies in type 1 diabetes and in people with type 2 diabetes on basal bolus insulin therapy, the risk of hypoglycemia was found to be higher for new weekly basal insulins than for daily basal insulins, bringing up the need for more research and possibly a different prescribing approach for basal weekly insulins in this population. The reduction in the number of injections results in patients being more satisfied with the treatment, this could result in a significant improvement in quality of life and an increase in acceptance and adherence to prescribed treatment, and finally, it responds to the urgent need to counter therapeutic inertia in the care of people with diabetes.

An unusual type of diabetes “not 1” and “not 2”

Type 3c diabetes mellitus (T3cDM) is a secondary form of diabetes caused by pancreatic disease, such as chronic pancreatitis, that impairs insulin and glucagon secretion and results in poor glycemic control. Often misdiagnosed as type 2 diabetes, this pancreatic diabetes requires specific management due to elevated hemoglobin A1c levels, early insulin requirements, and increased risk of hypoglycemia. This case report discusses a 24-year-old man with hereditary chronic pancreatitis associated with the PRSS1 mutation, without typical symp­toms of exocrine pancreatic insufficiency, who presented with early insulin therapy and increased glycemic variability. The complexity of diagnosing this type of diabetes highlights the importance of diabetes screening in patients with chronic pancreatitis and the risk of inappropriate diagnosis and medical treatment.

Protocolo terapéutico y seguimiento del paciente con diabetes mellitus tipo 1 y obesidad

Treatment protocol and follow-up of patients with type 1 diabetes and obesity This protocol focuses on the management of obesity in patients with type 1 diabetes mellitus (DM1), a growing problem due to factors such as lifestyle, insulin treatment, and hypoglycemia. The approach includes four key pillars: nutrition therapy, drug therapy, physical activity, and management of insulin therapy. Nutrition therapy is the first line of treatment and is based on calorie reduction and a diet rich in fiber. In addition, there are pharmacological options for the management of overweight in patients with DM1, although they have specific challenges, such as euglycemic diabetic ketoacidosis. Physical activity and the adjustment of insulin therapy also play an essential role in weight and glycemic control. In severe cases, bariatric surgery is a viable option for patients with severe obesity.

BARRIERS TO INITIATE INSULIN THERAPY AND ITS ASSOCIATION WITH DURATION OF DIABETES MELITIS AND DEMOGRAPHIC FACTORS IN UNCONTROLLED TYPE 2 DIABETIC PATIENTS, A CROSS SECTIONAL STUDY

Objectives: To determine different barriers to initiate insulin therapy and association of duration of diabetes mellitus and demographic factors with barriers in initiation of insulin therapy in Uncontrolled type 2 diabetic patients.Materials and Methods: We conducted a cross sectional study conducted among patients with type 2 diabetic patients presenting to endocrinology outpatient clinics in two Tertiary care hospitals of Peshawar ie. Khyber Teaching hospital and hayatabad medical complex Peshawar. The duration of study was 03 months after approval of synopsis. The sample size was 257.The study population was selected by consecutive non probability sampling technique. The data was collected by pre designed questionnaire. All the included patients were interviewed on pre designed questionnaire. Data was processed in SPSS version 22.Results: In study we found that patients face different barriers to initiate insulin therapy. In our study, side effects of insulin was the barrier for 97(37.7%) of the patient, difficulty in carrying insulin was barrier for 128(49.8%) patients , dose adjustment of insulin was barrier for 90(35%) patients, fear if insulin needle was barrier for 89 (34.6%) patients, self administration of insulin was barrier for 98(38.1%) patients , affordability of insulin was barrier accounting for 114(44%) patients , frightened about insulin therapy by someone was barrier for116 (45.1%) patients. The association between economic status of patient and the barrier that they are frightened by someone was statistically significant. Chi-square test was also run between duration of diabetes with all barriers in which one association was found nearly signifi cant i.e. the association of duration of diabetes with difficulty in carrying insulin with the p value of 0.064.Conclusion: The most common barrier in insulin therapy initiation of patients in the study was difficulty in carrying insulin. We found that there is near to signifi cant association between duration of diabetes and difficulty in carrying insulin. There is significant association between economic status of patient and frightened by someone. The lower the economic status the more frightened about Insulin use.