Basal-bolus Insulin Regimen Research Articles

Use of Glucagon-like Peptide 1 Receptor Agonist to Sustain Patients off Basal-Bolus Insulin Regimens

BackgroundThe 2024 Standards of Care in Diabetes recommend initiation of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) prior to starting basal insulin and to reconsider initiating a GLP-1 RA before starting bolus insulin if not already initiated. GLP-1 RA addition leads to improved glycemic benefits as well as risk reduction of cardiovascular and renal outcomes in patients with a history of these events. While there is evidence demonstrating the trends of insulin reduction or discontinuation following GLP-1 RA initiation, data regarding longer-term durability of GLP-1 RA use to sustain patients off bolus insulin is lacking. ObjectiveThis retrospective study aimed to assess the percentage of patients remaining off bolus insulin after transitioning from a basal-bolus regimen to GLP-1 RA therapy with basal insulin over a period of three years. MethodsWe conducted a single centered, retrospective study analyzing patient data from July 2018 through July 2023. Patients were included if they had a diagnosis of type 2 diabetes, were on a basal-bolus insulin regimen, had a GLP-1 RA initiated followed by bolus insulin discontinuation within 90 days, and remained on a GLP-1 RA for at least six months. The primary outcome was the percentage of patients who were sustained off bolus insulin after three years following GLP-1 RA initiation. ResultsThere were 252 patients included. At three years, 82.6% of patients were sustained off bolus insulin. The mean change in weight at three years was -8.5 kg. The mean A1c initially decreased from 8.6% to 7.8%, but then increased slightly to 8.1% at the end of the study timeframe. ConclusionThis trial demonstrated the majority of patients on basal-bolus regimens where bolus insulin was replaced with a GLP-1 RA were sustained off bolus insulin for a three year period of time. These results highlight the promising durability of converting bolus insulin to GLP-1 RAs.

The Emerging Role of GLP-1 Agonists in Burn Care: What Do We Know?

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. GLP-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on burn patients is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management.

6985 Intravenous Immunoglobulin induced Type 1 diabetes remission

Abstract Disclosure: N. Shahid: None. D. Newbern: None. Introduction: Intravenous immunoglobulin [IVIG] is an immunomodulatory agent used for treatment of autoimmune and inflammatory conditions. However, it is not indicated in patients with type 1 diabetes [T1D] as its efficacy has not been established. Clinical Case: A 9-year-old previously healthy boy presented to the Emergency Department with several days of unexplained bruising and mucosal bleeding with no prior history of trauma, bleeding disorders or other systemic symptoms. Physical examination showed generalized petechiae, ecchymosis and purpura. Vitals were normal including weight and BMI. Initial labs confirmed Immune thrombocytopenic purpura [ITP] as his platelets were less than 1K/µL with otherwise normal peripheral blood cell counts and smear. Concomitantly, labs showed significant hyperglycemia [260mg/dL] with glycosuria and trace ketonuria. Glycated hemoglobin [Hba1c] was elevated at 10.5% and ultimately Pancreatic autoantibodies [GAD65, Zinc transporter-8 and islet cell antibody] came back positive confirming T1D. Other autoimmune disorders such as adrenal insufficiency, thyroiditis, and celiac disease were ruled out. For the treatment of ITP, he the patient received 1 dose of IVIG 1g/kg and responded well with a rise in platelets to 6K/µL. The morning following the infusion, due to fasting hyperglycemia, the patient was started on basal-bolus insulin regimen. By 2nd day post IVIG, he had hypoglycemia, so insulin was discontinued with normalization of blood sugars. He is now 7 months post IVIG with no recurrent episodes of thrombocytopenia. He also remains off insulin with Hba1c in the 5.9-6.5% range. He eats a regular diet with avoidance of simple carbohydrates. He wears onwears a a continuous glucose monitor, which shows that blood sugars are in range 93% of the time He remains euglycemic overnight with transient self-resolving mild post-prandial hyperglycemia. Pancreatic autoantibodies have been reassessed and remain positive Conclusions: This case demonstrates that IVIG used for the treatment of ITP has induced a state of remission in our patient with newly diagnosed with T1D. IVIG is not a standard of treatment for T1D, however, when given for other autoantibody- or T-cell-mediated autoimmune conditions, it may reduce the insulin need in patients with known diabetes or induce remission in patients with newly diagnosed diabetes.

8348 A Rare Case Of Liraglutide-Associated Angioedema Requiring Emergent Intubation

Abstract Disclosure: T. Amin: None. A. Mararenko: None. J. Cheng: None. R. Ong: None. S. Holland: None. K. Hu: None. Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the management of type 2 diabetes mellitus to enhance glycaemic control. While generally considered safe, recent reports indicate an increasing frequency of adverse drug reactions, with gastrointestinal symptoms such as pancreatitis becoming more prevalent. This case report highlights a rare occurrence of angioedema induced by the GLP-1 receptor agonist, Liraglutide. Case A 58-year-old Type 2 diabetic male presented with rapidly progressing tongue swelling, abdominal discomfort, and watery diarrhea, six hours after initiating Liraglutide therapy. On presentation, he was hemodynamically stable, afebrile, maintaining adequate oxygenation on room air. On examination, the patient was in moderate distress with generalized tongue swelling protruding out, with no swelling of eyelids or lips. No rashes were noted on exposed skin and clear breath sounds without wheezing on lung examination. Due to concern for an impending airway compromise, the patient was intubated. Chart review showed he had an episode of self-resolving tongue swelling a few months back, at which time he was taken off his Angiotensin receptor blocker. 2 weeks ago, he was started on a new brand of GLP-1 receptor agonist (Liraglutide) to achieve optimal glycemic control. No other drug allergies or allergic reactions were reported. C1-Esterase panel, eosinophil count, and inflammatory markers were within normal limits.On admission, Liraglutide was discontinued, he was placed on a basal-bolus insulin regimen, received methylprednisolone, famotidine, and diphenhydramine Subsequent improvement allowed for extubation on the third day, and the patient was discharged with plans to discontinue Liraglutide and an epinephrine pen for precautionary use. Conclusion: This case represents a rare and severe manifestation of angioedema associated with Liraglutide use in a diabetic patient. While angioedema has been infrequently reported with other GLP-1 receptor agonists such as Exenatide and Dulaglutide , our case underscores the importance of clinicians' awareness regarding this potential life-threatening complication with Liraglutide. Post-marketing surveillance data suggest that anaphylactic reactions with Liraglutide may occur rarely, emphasizing the need for vigilance among healthcare providers. Presentation: 6/2/2024

7378 Glargine Induced Neuroglycopenia in Patients with End-Stage Renal Disease: Importance of Insulin Regimen Optimization in Haemodialysis Patients

Abstract Disclosure: M. Shrivastava: None. L. Kaur: None. B. Armendariz: None. R. Kaur: None. A. Shetty: None. In patients with end stage renal disease (ESRD), hypoglycemia accounts for up to 3.6% of all the admissions with mortality rates of up to 30%. A combination of impaired insulin clearance, changes in glucose metabolism and dialysis process makes the patients with end stage renal disease vulnerable to neuroglycopenia.Case description:53 year old female with past medical history of insulin dependent type 2 diabetes mellitus, ESRD secondary to diabetes, on hemodialysis(HD) thrice weekly since two years, presented to the emergency with altered mental status, respiratory distress, tachycardia. Lab work revealed blood glucose(BG) of 23 mg/dl, HbA1c of 8.4%, eGFR of 6, and arterial blood gas showed hypercapnic respiratory acidosis. Patient received dextrose, with no improvement of symptoms. Eventually she developed acute hypercapnic respiratory failure requiring endotracheal intubation with mechanical ventilation, and was transferred to the ICU. As per family, a night prior to presentation, last recorded BG after dinner was 253 mg/dl, she took her night time glargine, which was recently increased by her primary care for poorly controlled HbA1c levels. Brain MRI and long term EEG monitoring findings were consistent with underlying extensive brain injury secondary to prolonged hypoglycemia. Unfortunately, the patient's condition did not improve despite HD and BG correction, eventually she underwent compassionate extubation. Case Discussion:The insulin requirements in ESRD patients are reduced by approximately 50%, regardless of residual insulin secretion. Malnutrition and acidosis reduce hepatic glycogen stores and availability of gluconeogenic precursor, expected compensatory renal gluconeogenesis is compromised by decreased renal function causing hypoglycemia, which is further worsened by inappropriately high plasma insulin levels caused by reduced renal insulin breakdown. Diabetes mellitus patients with ESRD are frequently managed with basal-bolus insulin regimen, and HD up to thrice weekly, leaving them without HD for up to 3 days especially over the weekend. This can result in accumulation of insulin metabolites causing delayed insulin clearance as seen in our patient. In such cases even long acting insulin, such as glargine, can have compounding effects, which could possibly cause fatal complications such as neuroglycopenia. In such patients continuous glucose monitor use with tapering dose glargine regimen may help eliminate this compounding effect. Conclusion: Neuroglycopenia is a rare manifestation of diabetes mellitus with ESRD. Compromised renal gluconeogenesis and impaired insulin clearance can cause inappropriately high plasma levels of insulin. In such patients continuous glucose monitoring along with tapering dose of long acting insulin should be utilized for proper glycemic control to limit compounded effect of insulin metabolite accumulation. Presentation: 6/3/2024

8114 The Need For Autoantibody Screening And Diagnostic Criteria For Immune-Checkpoint Inhibitor-Induced Type 1 Diabetes

Abstract Disclosure: A. Gupta: None. H. Sanekommu: None. A.B. Ravin: None. M. Akula: None. J. Cheng: None. Background: Immune-checkpoint inhibitors (ICIs) such as Nivolumab have been extensively studied, especially in relation to their side-effect profiles. Patients on Nivolumab are prone to immune-related adverse events (irAEs) including type 1 diabetes mellitus, thyroiditis, and hypopituitarism. Prior studies have indicated that ICIs can unmask existing diabetic autoimmunities, but currently no specific guidelines exist for autoantibody screening prior to initiating treatment. We report a unique case of a young patient with newly diagnosed immune-checkpoint inhibitor-induced type 1 diabetes (ICI-T1DM) who was found to have mixed autoantibody results. Clinical Case: This is a 31-year-old male who was diagnosed with fibrolamellar hepatocellular carcinoma (pT23N0) and underwent partial hepatic resection later that year. Repeat imaging showed new hepatic lesions, thus Nivolumab was initiated. He received a total of three cycles, after which he presented to the hospital with symptoms of fever and nausea; labs were consistent with diabetic ketoacidosis (DKA) for which he was treated with IV insulin and aggressive hydration with successful resolution. Nivolumab was stopped and the patient was discharged on a basal-bolus insulin regimen. Further outpatient workup was significant for A1c 5.9% (n<5.7%), C-peptide (with glucose 220mg/dL) 0.7 (n=0.8-3.9ng/mL), glutamic acid decarboxylase autoantibody (GAD Ab) 11 (n<5.0U/mL). Insulin antibody and islet cell antibody IgG were negative. Due to the acute onset in the presentation and the recent use of Nivolumab, the patient was diagnosed with ICI-T1DM. He remained insulin-dependent after discharge. Unfortunately, soon after, he began showing signs of liver failure and ultimately underwent liver transplantation. Conclusion: This case highlights two crucial aspects - the importance of screening for autoantibodies prior to initiating an ICI and the necessity for guidelines in diagnosing ICI-T1DM. Given the evidence linking positive GAD Ab to a higher risk of developing DKA and earlier onset ICI-T1DM, it is beneficial to screen patients for these autoantibodies prior to ICI initiation to identify those more susceptible to developing ICIDM1. It may also be beneficial to obtain a C-peptide level prior to initiation to evaluate for endogenous insulin production. Additionally, while several factors support the diagnosis of ICI-T1DM such as recent ICI use, acute DKA presentation, low C-peptide levels, and the need for exogenous insulin, there is currently no specific criteria for the formal diagnosis of ICI-T1DM. Consequently, the decision to continue an ICI remains uncertain until specific diagnostic criteria are established for healthcare providers. Presentation: 6/2/2024

EVALUATION OF THE GLYCOREGULATION EFFICACY BEFORE AND AFTER TREATMENT WITH INSULIN DEGLUDEC IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE REPUBLIC OF NORTH MACEDONIA

Patients with type 2 diabetes mellitus (T2DM) who have unsatisfactory glycoregulation with concurrent use of basal insulin and oral hypoglycemics, should be switched to a more intensive therapy regime. To evaluate the efficacy of newly available insulin degludec 70/insulin aspart 30 (IDegAsp), we retrospectively analyzed glycoregulation in 131 patients with T2DM treated with this insulin. All 131 patients were with unsatisfactory glycoregulations, and were switched to IDegAsp from other insulins (except basal-bolus insulin regimen). After a mean period of 11.75±5 months of the treatment with IDegAsp, we found statistically significant improvement in fasting and postprandial glucose levels, and HbA1c (12.5±4.4 vs. 8.8±3.9mmol/l, 13.2±4.6 vs. 9.6±4.1mmol/l, 9.7±1.8 vs. 8.1±1.6%, p<0.01, respectively). The total average daily dose of insulin units (IU) was the same, and there weren’t statistically significant differences in the frequency of hypoglycaemia (p<0.05). From the results, we can conclude that patients with T2DM, who switched to IDegAsp from previous antidiabetic insulin treatment (except basal-bolus insulin regimen) had improved glycaemic control without increased insulin units, and without higher risk for hypoglycemia.

De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.

Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials. Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia. All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates. Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc.

Glycemic control and adverse effects in patients with type 2 diabetes receiving basal-bolus insulin regimen versus premixed insulin regimen: An observational study

Objectives: Several studies have compared the basal-bolus (BB) and premixed (PM) insulin regimens with varying results. This study aimed to evaluate the glycemic control and occurrence of hypoglycemia with these regimens in insulin-naïve patients with type 2 diabetes mellitus (T2D) in the Indian subpopulation. Materials and Methods: This was a 12-week (wk) prospective, observational study in 60 adult patients (distributed 1:1) with &gt;7 years of T2D and uncontrolled with three oral drugs. Changes in glycemic parameters at wk4 and wk12 were assessed, and hypoglycemia events were also recorded. Results: The PM insulin showed a significant decrease in fasting plasma glucose (FPG) at wk4 from baseline (P = 0.02) and at wk12 (P &lt; 0.001), while in the BB insulin group, the change was significant only at wk12 (P &lt; 0.0001). There were greater reductions in the PM group in FPG at wk4 (PM vs. BB: P = 0.04) and wk12 (P = 0.03) compared to the BB group. The post-prandial plasma glucose in both groups significantly reduced from baseline at wk4 (PM group P = 0.034; BB group; P = 0.034) and wk12 (PM group P &lt; 0.0001 and BB group: P &lt; 0.0001). However, there were no between-group differences at wk4 (P = 0.12) but only at wk12 (P = 0.009) with greater reductions in the PM group. The PM group showed a slightly greater reduction in glycated hemoglobin versus the BB group (9.18% vs. 7.08%; P = 0.39). There was no significant difference (P = 0.49) in the incidence of hypoglycemia. Conclusion: Both treatments significantly improved glycemic control and were not associated with any severe episodes of hypoglycemia. Therefore, the choice should instead be guided by the insulin-related (posology, complexity) and patient-related (dietary habits, adherence levels) factors.

EE621 Cost-Effectiveness Analysis of iGlarLixi Compared With Basal Bolus Insulin Regimen in Triple Metabolic Goal in Type 2 Diabetes Mellitus in Latin America

EE621 Cost-Effectiveness Analysis of iGlarLixi Compared With Basal Bolus Insulin Regimen in Triple Metabolic Goal in Type 2 Diabetes Mellitus in Latin America

COVID-19 induced type 1 diabetes: A systematic review of case reports and series.

To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection. PubMed and Scopus library databases were screened for relevant case reports published between January 2020 and June 2022. Study design, geographic region or language were not restricted. Twenty studies were identified and involved 37 patients (20 [54%] male, 17 [46%] female). Median age was 11.5 years (range 8 months-33 years) and 31 (84%) patients were aged ≤17 years. Most patients (33, 89%) presented with diabetic ketoacidosis (DKA). In total, 23 (62%) patients presented at the time of positive COVID-19 testing and 14 (38%) had symptoms consistent with COVID-19 infection or a previous positive test (1-56 days). Diabetes symptomatology was provided in 22 cases and (19, 86%) reported polyuria, polydipsia, polyphagia, fatigue, or weight loss or a combination of the aforementioned in the preceding weeks (3 days-12 weeks). Of the 28 patients that had data on acute and long-term treatment, all recovered well and most were managed with basal bolus insulin regimens. Quality assessment showed that most reports were either 'good' or 'moderate quality'. Although uncommon, new-onset T1D is a condition healthcare professionals may expect to see following a COVID-19 infection.

FRI693 Pthrp Mediated Hypercalcemia In A Patient With Recurrent Hepatocellular Carcinoma

Abstract Disclosure: D. Bondarenko: None. M. Ahmad: None. M. Mack: None. P. Ucciferro: None. Background: Humoral hypercalcemia is seen in 30 percent of cancer patients, most commonly driven by parathyroid hormone related peptide (PTHrP) production, osteolytic cytokine production, and 1,25-OH vitamin D production. The most common malignancies associated with PTHrP mediated hypercalcemia are squamous cell carcinomas and breast cancer. Less often hepatocellular cancer presents with hypercalcemia. We describe the case of a patient presenting with hepatocellular carcinoma presenting with recurrent episodes of severe hypercalcemia due to excessive PTHrP production. Clinical Case: The patient was a 68-year-old male with a past medical history of recurrent hepatocellular carcinoma with liver transplant in the past and type 2 diabetes mellitus who presented to the emergency department (ED) for one day of altered mental status. The patient was noted to be extremely agitated and confused by his home health aide and EMS was called. In the ED the patient’s vital signs were as follows: blood pressure of 196/80 mmHg, heart rate of 82 beats per minute, respiratory rate of 18 breaths per minute and temperature of 36.6 degrees Celsius. Initial lab work showed: calcium 13.5 mg/dL, albumin 4.2 g/dL, ionized calcium of 1.63 mmol/L, creatinine 0.99 mg/dL (baseline 0.5 mg/dL), glucose of 438 mg/dL, bicarbonate 23 mmol/L, anion gap 19, and beta hydroxybutyrate 51 mg/dL. Hypercalcemia workup revealed a suppressed PTH of 5 pg/mL (normal 11-67 pg), normal 25-OH vitamin D 43.6 ng/ml (normal 30-100 ng/ml), normal 1,25-OH vitamin D 38 pg/ml (normal 18-72 pg/ml), and elevated PTHrp 36 pg/ml (normal 11-20 pg/ml). The patient was started on aggressive IV fluid resuscitation with normal saline, administered a one-time dose of zoledronic acid and administered a three-day course of calcitonin. For his significant hyperglycemia the patient was started on an insulin infusion and was eventually transitioned to his home basal bolus insulin regimen. On discharge, the patient was scheduled with his oncologist to begin denosumab as an outpatient; however, he chose a palliative approach due to the terminal nature of his disease and recurrent hospitalizations for hypercalcemia. Conclusion: Hypercalcemia of malignancy is common in many different carcinomas with squamous cell cancer, renal cell cancer, breast cancer and multiple myeloma being commonly associated with this phenomenon. Reports of hepatocellular carcinoma associated with hypercalcemia are less common and occur in only 4-8 % of cases. With this case report, we hope to highlight PTHrP as a potential mechanism of humoral hypercalcemia in patients with hepatocellular carcinoma and propose denosumab as a possible treatment for patients with refractory hypercalcemia of malignancy. Presentation: Friday, June 16, 2023

THU392 Type B Insulin Resistance: A Rare Cause Of Hypoglycemia

Abstract Disclosure: S.Z. Bhat: None. A. Sidhaye: None. A.H. Hamrahian: None. Introduction: Non-diabetic hypoglycemia in patients with diabetes mellitus is rare. Type B insulin resistance syndrome (TBIRS), caused by insulin receptor antibodies, presents with severe insulin resistance, but can uncommonly result in a hypoglycemic picture. Clinical Case: A 59-year-old woman with a history of SLE, T2DM, and primary hyperparathyroidism was admitted for acute confusion and found to have a POC glucose of 30 mg/dl. Her symptoms improved after IV glucose administration. She was on a stable basal-bolus insulin regimen of 0.8 U/kg/day and had unintentional 100-pound weight loss over 1 year. Significant exam findings included BMI of 29 kg/m2, gingival hyperplasia, and acanthosis nigricans. Aside from insulin, she took no medications strongly associated with hypoglycemia. Labs including CBC, CMP, TFTs, and morning cortisol were normal. HbA1C and adiponectin levels were 7.7%, and 28 µg/ml (5-28), respectively. Given the suspicion of exogenous insulin-mediated hypoglycemia, only correctional insulin was used during hospitalization. She had a repeat hypoglycemic episode on the 2nd day with minimal insulin use. A 72-hour fasting test showed a whole blood glucose of 44 mg/dL with concurrent serum C-peptide of 1.72 ng/mL, serum insulin 55 mIU/L and pro-insulin 21.9 pmol/L 12 hours into fasting. MRCP showed an 11 mm cystic lesion in the pancreas and widespread lymphadenopathy. The CGM noted significant fasting and post-prandial hypoglycemia. Diagnosis of insulinoma was considered unlikely due to persistent post-prandial hyperglycemia. Oral hypoglycemic panel and insulin autoantibodies were negative. The patient’s history of SLE, high-normal adiponectin, history of hyperglycemia and the presence of acanthosis nigricans favored work-up for insulin resistance syndromes. Due to the non-availability of insulin receptor antibody testing in the US, blood work was sent to Dr. Lutz Schomburg’s lab at Institute for Experimental Endocrinology, Berlin, Germany. The patient’serum was positive for insulin receptor antibodies, tested via an immunoassay technique, with elevated binding index (BI) of 248, 251 and 247 on 3 different samples of the patient, and normal binding index in the control sample, leading to the diagnosis of type B insulin resistance syndrome (BI &amp;gt;3 is positive, &amp;gt;10 indicates high positivity). The patient was treated with diet modification and CGM use, with improvement in the frequency of hypoglycemic episodes. She declined immunomodulation therapy. Conclusion: Hypoglycemia is an uncommon presentation of TBIRS and should be considered in the differential of non-diabetic hypoglycemia, particularly in patients with a history of auto-immune disease. The mechanism for hypoglycemia is purported to be an insulin-mimetic effect of insulin receptor antibodies at low titers. Presentation: Thursday, June 15, 2023

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes

PurposeTo assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial.MethodsOriginally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed.ResultsFifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (−0.8 ± 1.1%, −0.7 ± 1.1%, and −1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (−1.2 ± 1.0%, −1.2 ± 1.1%, and −1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower.ConclusionSimplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes.Clinical trial registrationClinical trial registration no. NCT04196231, clinicaltrials.gov.

In uncontrolled T2DM treated with a basal-bolus insulin regimen, weekly icodec was noninferior to daily glargine for HbA1c at 26 wk.

Mathieu C, Ásbjörnsdóttir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929-1940. 37156252.

921-P: Improved Glycemic Control in Pregnancy Using Continuous Subcutaneous Infusion of Concentrated Insulin

Maternal and fetal complications are high in preexisting uncontrolled type 2 diabetes mellitus (T2DM). There is limited data on the use of concentrated insulin in continuous subcutaneous insulin infusion (CSII) during pregnancy. We report a case of 22-year-old woman G4P0030 with T2DM since 10 years of age who was admitted for preterm premature rupture of membrane at 26 weeks gestation. Preconception HbA1c was 12.1% on metformin, and basal bolus insulin. Severe hyperglycemia following betamethasone administration for fetal lung maturity required insulin drip initially which was transitioned to basal bolus insulin. Despite total daily insulin dose &amp;gt;480 units, glucose control was suboptimal. Decision was made to initiate CSII with basal U-500 concentrated regular insulin and U-100 prandial insulin injections. She was started on Dexcom for CGM and Omnipod Dash with basal rate 1.3 units/hour (6.5 units/hour U-500), insulin sensitivity factor 27 mg/dl (5.4 mg/dl with U-500), carb ratio 1 unit lispro to 2 g. Glycemic control improved as noted in CGM even after adjusting the pregnancy target (70-140mg/dl). Patient delivered a male infant (2090 grams) by emergency C-section at 30 weeks gestation due to preterm labor with fetal malpresentation. She was discharged home with U-100 basal bolus insulin regimen on day 3 postpartum. Concentrated insulin in CSII is effective for uncontrolled T2DM in pregnancy. Disclosure N.Mon: None. S.Krishnasamy: None.

928-P: The Use of a Novel CGM-Informed Insulin Bolus Calculator Mobile Application by People with Type 1 and Type 2 Diabetes Improves Time in Range

Background and Aims: People with diabetes on basal-bolus insulin regimens face challenges calculating bolus doses. Continuous glucose monitoring (CGM) systems can assist users with bolus dosing optimization through trend arrows. The purpose of this study was to demonstrate the safety and effectiveness of a CGM-informed insulin bolus calculator (IBC, Welldoc, Inc., Columbia, MD, U.S.A.) integrated into a mobile application that applies trend arrow and exercise adjustments to the bolus insulin dose recommendation. This investigational software also provided real-time coaching on CGM data to assist users in improving their time in range (TIR). Methods: Fifty-four participants with diabetes using CGM (Dexcom G6, San Diego, CA, U.S.A.) were enrolled in a 30-day prospective study conducted at two research sites. Participants were asked to use the mobile application to monitor their CGM data and calculate their insulin doses. TIR during the prospective 30-day period was compared to that from 30 days of baseline data. Three populations were defined: 1) the intention-to-treat (ITT) group consisted of all enrolled subjects; 2) the complete cases (CC) group had ≥90% sensor wear time; and 3) the per-protocol (PP) group used the IBC at least 30 times during the study period. Results: In the ITT group, the TIR improved from 68.4% to 71.8% (N=54, P=0.013). In the CC group, the TIR improved from 69.1% to 73.0% (N=49, P=0.005). In the PP group, the TIR improved from 69.2% to 73.0% (N=39, P=0.017). There was no increase in time with low glucose (&amp;lt;70 mg/dL) in all three populations. In a subgroup analysis, TIR increased from 74.7% to 81.4% in those with type 2 diabetes and from 64.4% to 65.2% in those with type 1 diabetes. Conclusions: Use of a novel CGM-informed insulin bolus calculator with trend arrow and exercise dose adjustment by individuals with type 1 and type 2 diabetes was associated with significant improvement in TIR. Disclosure M.Shomali: Employee; WellDoc. C.Kelly: Consultant; WellDoc, Caladrius Biosciences, Inc., Epigenomics AG, Luna, Nevro Corp., Presidio Medical, Hitachi, Ltd., Resmed, Inc., Seaspine Hldgs, Inc., ViaCyte, Inc. A.K.Iyer: Employee; WellDoc. J.Y.Park: None. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. Funding Welldoc Inc.

ONWARDS and upwards for basal insulin

In this issue of The Lancet, Chantal Mathieu and colleagues present the findings of ONWARDS 4, a phase 3 randomised, open-label, treat-to-target, non-inferiority trial comparing the novel once-weekly insulin icodec (n=291) versus once-daily insulin glargine U100 (n=291) in people with long-standing type 2 diabetes on basal-bolus insulin therapy. 1 Mathieu C Ásbjörnsdóttir B Bajaj HS et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023; (published online May 5.)https://doi.org/10.1016/S0140-6736(23)00520-2 Summary Full Text Full Text PDF Google Scholar The trial was conducted in Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA. The participants had a mean duration of type 2 diabetes of 17·1 years (SD 8·4), a mean age at baseline of 59·8 years (SD 10·0), and 304 of the 582 participants were men and 278 were women. The primary outcome in ONWARDS 4 was met, with both icodec and glargine U100 shown to be equally effective at reducing HbA1c from baseline by week 26 (estimated mean change in HbA1c −1·16 percentage points in the icodec group [baseline 8·29%] and −1·18 percentage points in the glargine U100 group [baseline 8·31%]; estimated treatment difference 0·02 percentage points [95% CI −0·11 to 0·15], p<0·0001). Given the age, duration of diabetes, and number of comorbidities of participants, the percentage of time spent with glucose concentrations within the target range of 70–180 mg/dL (3·9–10·0 mmol/L) by week 26 (ie, trial end) was impressive; 66·9% in the icodec group and 66·4% in the glargine group. In addition, the percentage of time spent with glucose concentrations less than 54 mg/dL (<3·0 mmol/L) was low, not differing significantly between the groups (0·7% for the icodec group and 0·6% for the glargine U100 group). Overall, combined level 2 and 3 hypoglycaemia rates were similar between treatment groups, there were no significant differences in weight gain, and no new safety signals emerged. These findings would suggest that once-weekly icodec is a viable therapeutic option for people with type 2 diabetes on a basal-bolus insulin regimen, and, perhaps more importantly, heralds the introduction of once-weekly insulins into clinical practice, an exciting and welcome addition to the insulin family. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trialIn people with long-standing type 2 diabetes on a basal-bolus regimen, once-weekly icodec showed similar improvements in glycaemic control, with fewer basal insulin injections, lower bolus insulin dose, and with no increase in hypoglycaemic rates compared with once-daily glargine U100. Key strengths of this trial include the use of masked continous glucose monitoring; the high trial completion rate; and the inclusion of a large, diverse, and multinational population. Limitations include the relatively short trial duration and the open-label design. Full-Text PDF

Abstract #1395490: New Onset of Type 1 Diabetes After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses the greatest threat of our times. SARS-CoV-2 vaccines are one of the most effective strategies against this infection. Diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, and new-onset diabetes as adverse effects of SARS-CoV-2 vaccination have been infrequently described in the literature. We hereby report a rare case of new-onset type 1 diabetes after SARS-CoV-2 vaccination. An 18-year-old male presented to the outpatient office for evaluation of breast pain. On routine laboratory tests, he was noted to have fasting blood glucose of 200 mg/dL. On further questioning, he reported some polyuria, nocturia, and a 10-pound weight loss over the preceding month. He received the initial dose of Pfizer-BioNTech SARS-CoV-2 vaccine in May 2022 and the second dose in June 2022, approximately one month before the onset of symptoms. He denied any earlier viral infections and had no personal or family history of autoimmune conditions. On evaluation, his body mass index was 20 kg/m2, but otherwise, he had a normal physical exam, including a breast exam. Over the next few days, his blood glucose progressively increased to over 300 mg/dl. HbA1c was noted to be elevated at 8.6%, glutamic acid decarboxylase-65 (GAD-65) antibodies were remarkably high >250 IU/ml (normal 5 IU/ml), C-peptide was 1.51 ng/ml (normal 0.80 – 3.85 ng/ml), blood glucose 156 mg/dl, islet-cell antibody titer was 320 (< 1.25 JDF units) and insulin autoantibodies were negative. He was diagnosed with autoimmune Type 1 diabetes and a basal-bolus insulin regimen was initiated to improve glycemic control. On a one-month follow-up, his insulin requirements remained low but persistent and his glycemic control was acceptable. Various viruses are known to play a fundamental role in the onset of type 1 diabetes via a variety of effects on pancreatic beta-cells because of either the direct lytic effects of viral replication or the inflammatory response to the virus, which is mediated by autoreactive T cells. The limited release of islet cell antigens induces molecular mimicry and paves the way for long-term autoimmunity and the development of type 1 diabetes mellitus. Our patient did not report any viral illnesses before the onset of his symptoms. He also did not have a family or personal history of autoimmune diseases. His onset of diabetic symptoms coincided temporally with receiving the SARS-CoV-2 vaccine. The detection of a considerable titer of GAD-65 antibodies proved autoimmunity. Clinicians must stay vigilant about this potential side effect of SARS-CoV2 vaccine so that a timely diagnosis can be made.