Insulin Requirements Research Articles

ODP214 INSULIN REQUIRING DIABETES MELLITUS(IRDM) and CAD

Abstract Background Several studies have shown a higher risk of coronary artery disease(CAD) in insulin-requiring T2 diabetes mellitus(IRDM) patients which could be linked with DNA methylation(proinflammatory cytokines),histone deacetylase activity(mitochondrial function-oxidant stress) and micro RNAs impacting insulin secretion and action, endothelial function and atherosclerotic process. [1,2,3,4,5]. Insulin therapy has been shown to be associated with atherosclerosis. [3]Clinical Study: A retrospective study of twenty T2 DM patients was done to observe the association of IRDM and CAD. There was equal sex distribution with mean age of 55 years in males and 50 years in females. Ten (50%)patients were insulin requiring(IRDM),having a mean insulin requirement of 0.57 units/kg in males and 0.98 units/kg in females. Seven(35%) patients had CAD;five(50%)of IRDM and two(20%)of non-insulin requiring patients. The mean insulin dose of IRDM patients with CAD was 0.74 units/kg in males and 1.3 units/kg in females and those without CAD was 0.30 units/kg in males and 0.73 units/kg in females. There was no significant difference in the prevalence of hypertension, dyslipidemia and nephropathy between the patients with or without CAD. All the three IRDM males with CAD had BMI less than 25 kg/m 2 where as both the IRDM females with CAD had BMI greater than 25 kg/m 2 . Both the IRDM females with CAD had CAD before institution of insulin therapy, though they ultimately required higher insulin dose denoting higher degree of insulin resistance(IR) and suggesting non-contribution of insulin therapy in the pathogenesis of CAD. Conclusion This study highlights a)higher incidence of CAD in IRDM patients, b)higher insulin requirement in CAD patients,c)higher insulin dose in females as compared to males and d)females(all obese)having CAD earlier than males,having CAD before insulin therapy but requiring higher dose than non-CAD females. These could be due to a) insulin deficiency and predominantly IR impacting IRDM[3];b)IR enhancing atherosclerosis((through proinflammatory cytokines, oxidant stress and procoagulant activity (not measured)promoting CAD[2,3,4,]);c)higher BMI[6] and associated greater IR[3] contributing to higher insulin dose in females, though,they required insulin much later;some studies have shown female gender having a protective effect on insulin initiation[5];d)the overlap of traditional CV risk factors viz. dyslipidemia,hypertension, nephropathy in IRDM and non-IRDM patients with or without CAD points towards the predominant contribution of proinflammatory cytokines viz CRP and procoagulants viz . PAI in the aetiopathogenesis of CAD[4]. Further studies on larger patient population are required to substantiate these observations.

PMON101 Fluctuating Insulin Requirements in Untreated Acromegaly: From 200-to-0

Abstract Introduction Acromegaly is a clinical disorder that occurs from autonomous production of growth hormone (GH). Diabetic ketoacidosis (DKA) is an uncommon and late complication of acromegaly. Acromegaly presenting in DKA prognosticates glycemic management with insulin-based regimens. Cessation of insulin therapy, however, can be achieved in patients with acromegaly after proper medical and/or surgical interventions. Our case highlights a unique outcome in a patient with newly-diagnosed acromegaly that initially presented in DKA with very high insulin requirements and was ultimately de-escalated off all anti-hyperglycemic therapy with significant glycemic improvement prior to any treatment for acromegaly. Clinical Case A 32 year-old male with a past medical history of colorectal cancer and no known history of diabetes presented to the emergency department for evaluation of generalized weakness, epigastric pain, nausea, and vomiting and was admitted for DKA. Hemoglobin A1c was 11.6% (reference range < 5.7%), confirming the diagnosis of newly-diagnosed diabetes. C-peptide was 1.4 ng/mL (reference range 0.5-3.3 ng/mL) and anti-glutamic acid decarboxylase, anti-islet cell, and anti-zinc transporter 8 antibodies were all negative. He was initiated on intravenous insulin infusion, with rates achieving > 200 units of insulin per day. Given severe insulin resistance in conjunction with acromegalic features on physical exam and a unique history of colorectal cancer at a young age without any family history, evaluation for acromegaly was initiated. Human GH level was 68.60 ng/mL (reference range 0.05-3.00 ng/mL) and insulin-like growth factor-1 (IGF-1) level was 1,036 ng/mL (reference range 82-242 ng/mL). MRI brain revealed a hypoenhancing 1.3 cm lesion enlarging the left lateral pituitary gland. Diagnosis of acromegaly due to a GH-secreting macroadenoma was established. The patient was discharged on a high-dose insulin regimen in addition to metformin therapy with de-escalation off of all anti-glycemic therapy within a few weeks of diagnosis; at his 3 month follow-up visit, his repeat hemoglobin A1c was 6.1 with repeat GH level of 28.8 ng/mL and IGF-1 level of 1602 ng/mL, despite not yet undergoing any treatment for the underlying condition. Conclusion DKA as an initial presentation of acromegaly has been previously reported in literature, however, not with a concomitant history of colon cancer. Moreover, no previous cases of acromegaly have reported glycemic normalization off of anti-hyperglycemic therapy prior to any treatment for acromegaly. Our case highlights that evaluation for secondary causes, including acromegaly, should be considered in patients with severe insulin resistance and emphasizes the dramatic range of insulin requirements that patients with acromegaly may have. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP243 Severe Sustained Hyperglycemia in Setting of Simultaneous Dobutamine and Insulin Infusions - Drug Interaction

Abstract Case A 55 year old female with a history of congestive heart failure, type 1 diabetes mellitus and chronic kidney disease stage IV presented to the ED for acute on chronic progressive shortness of breath. She was admitted to the telemetry unit and treatment with diuretics was initiated. During the course of hospitalization, she was noted to have atrial fibrillation with rapid ventricular response and dronedarone was started. However, her heart rate remained elevated along with borderline hypotension and thus, she was transferred to the ICU for amiodarone infusion and continued diuresis with dobutamine support via central line. Since the day of admission, she was being managed on a subcutaneous insulin regimen; however, while in the ICU her blood glucose levels continued to rise and remained elevated at 400-500 mg/dL (normal range 70 - 99 mg/dL). As per Endocrinology, insulin drip was started. The patient had poor peripheral vasculature and it was difficult to obtain and maintain peripheral intravenous (IV) access. Therefore, the same right internal jugular central line was used to infuse both dobutamine and insulin. The insulin drip was continued on and off for just short of 3 days and with an average rate of >10 units insulin per hour, and the highest rate of insulin infusion running at 15 units/hour for more than 7 hours. Her insulin requirement declined as dobutamine was weaned off, and ultimately, she was transitioned back to a basal-bolus regimen. Discussion Hyperglycemia is a common occurrence in critically ill patients for which insulin drip is a powerful tool. There is paucity of data on insulin and its incompatibility with vasopressors, another class of very commonly used agents in the intensive care unit (ICU) setting. Research has shown that vasopressors can cause insulin resistance if infused via the same vascular channel by rendering insulin ineffective. A previously published case report detailed a patient requiring Insulin infusion as high as 450 units/hr while norepinephrine and insulin were being administered via the same central line and upon switching them to different IV access sites, the insulin requirement decreased to 14 units/hour. Another study demonstrated reduction in insulin efficacy by 70% in patients receiving simultaneous norepinephrine. There are no such studies available on interactions of insulin with dobutamine. This case report calls attention to the risk of deleterious interactions between commonly used medications in the ICU setting running through the same channel. This is an important entity to recognize as standard treatment protocols for IV insulin treatments do not typically account for other simultaneous IV medications which can have profound consequences in regards to dosing and wide range of variation from hyperglycemia to hypoglycemia if the titration based on medication interaction is not accounted for. Presentation: No date and time listed

PSUN196 Outcomes following SGLT-2 inhibitor use in 99 patients with type 1 diabetes: A single-centre, retrospective, chart-review study

Abstract Introduction Despite the numerous benefits seen with the use of SGLT-2 inhibitors in patients with T1DM, the drug class has failed approval for this indication in both the US and Australia, largely due to the increased risk of ketosis and DKA. Resultantly there is limited real-world data for its use in this patient population. Methods We completed a retrospective medical record review of 99 patients with T1DM treated with an SGLT-2 inhibitor within a single outpatient clinic between 2014 to 2021. Our primary objective was to review the change in Hba1c and weight, as well as incidence of DKA, with secondary objectives to review the reduction in insulin dose, and reasons for cessation. Results Baseline characteristics demonstrated a female predominant population (63%) with a median BMI of 30kg/m2. Around half of our patients were on concurrent CSII therapy (53%) We observed an improvement in Hba1c in 72% of our patients, with a median decrease of 0.3% (P=0.001). 80% of patients noted a decrease in weight, with a median reduction of 4.2kg (P=0.10). Five patients developed DKA requiring hospitalisation, and the most common cause for SGLT-2i cessation was genital tract infection. The insulin requirement was noted to decrease by an median of 6.6 units (P=0.04). Conclusion SGLT-2 inhibitor class medications have a valuable role in the treatment of certain patients with T1DM. Our study is one of only a handful of real-life data sets, and unique in the number of patients involved. Future areas for review involve evaluating the effect of risk mitigation measures on the incidence of DKA. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

RF19 | PSUN368 Surviving Insulinoma: Severe Insulin Resistance in the Face of Endogenous Hyperinsulinemia

Abstract Introduction Insulinoma is a rare pancreatic neuroendocrine tumor (PNET) accounting for 1-2% of pancreatic neoplasms. Usually benign, even small tumors can cause significant morbidity due to hypoglycemia. Surgical resection is preferable choice of treatment, but diagnosis is usually delayed and localization can be evasive. We present a case of insulinoma in a patient who battled his symptoms with high carbohydrate intake leading to massive weight gain associated with severe insulin resistance. Case A 70 year old male presented to the ED after being found unconscious in his home. Blood glucose was 34 mg/dl after missing a meal. He had a remote history of diabetes mellitus, which gradually resolved. Five years ago, he began experiencing sweats, tremors, headaches and confusion early in the morning or when fasting that improved with eating. He was hospitalized four years ago due to hypoglycemia where he was suspected to have endogenous hyperinsulinemia. CT abdomen at that time was unremarkable. Possibility of insulinoma was raised, but patient did not pursue further investigations. In the last 4 years, he avoided severe hypoglycemic events with frequents meals, but had gained more than 50 lbs with resultant BMI of 51 kg/m2. While admitted, he underwent a 72h fasting test showed glucose 42 mg/dl, insulin level was 84.8 IU/L (range <3), proinsulin was 105.7 (pmol/l) and C-peptide was 4.83 ng/ml (ref <0.2). EUS revealed 7 mm×4 mm mass in pancreatic body. FNAB confirmed well differentiated PNET, grade 1. CT abdomen remained unrevealing. He was started on weight based diazoxide therapy with resolution of hypoglycemic events and persistent hyperglycemia, which required high dose insulin therapy and improved with significant decrease in diazoxide dose. Hospitalization was complicated by hypoxic hypercarbic respiratory failure due to obesity hypoventilation syndrome, COVID19 infection and new onset rapid atrial fibrillation. Patient was deemed not to be a surgical candidate due to multiple comorbidities and his medical management was switched to octreotide with low dose insulin therapy, which patient tolerated well. Conclusion Diagnosis of insulinoma can be significantly delayed in cases with mild or slowly progressive course of the disease. We suggest that progressive development of severe insulin resistance in patients with baseline obesity and insulin resistance-driven DM2 can mask endogenous hyperinsulinemia for extended period of time. This gives a false sense of slower progression or even resolution of symptomatology, as well as diversion to alternative diagnoses, like postprandial hypoglycemia. We also argue that "resolution" of diabetes with significant weight gain, especially when associated with increased calorie intake through frequent meals and symptomatology suggestive of hypoglycemia should be a red flag for workup towards possible insulinoma, akin to suspecting adrenal insufficiency in diabetic patients with an unexplained decrease in insulin requirements. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

ODP232 Postoperative Glycemic Management of Children Undergoing Pancreatectomy with Islet Autotransplantation

Abstract Background Children with severe pancreatitis may require pancreatectomy, resulting in insulin-dependent diabetes. Our center has provided pediatric pancreatectomy with islet autotransplantation (PIAT) since 2003 to preserve pancreatic endocrine function and potentially prevent diabetes. We describe our experience with postoperative glycemic management after pediatric PIAT to provide guidance for future management. Method: We reviewed inpatient records for children who underwent PIAT. Data collected included age, indication for pancreatectomy, islet mass infused and details on insulin and nutritional support requirements. Descriptive analysis was performed. Results Twelve pediatric patients have undergone PIAT at our centre, with mean age 12.4 years (range 2.5-18.9) and mean duration of post-operative hospitalization 25 days (range 9-60). Indications for pancreatectomy included ten patients with chronic pancreatitis due to mutations in PRSS1, SPINK1, or CFTR, 1 patient due to trauma, and 1 patient due to tumor. Ten patients underwent total pancreatectomy, and 2 had partial pancreatectomies. Mean islet mass infused per body weight was 5867 IEQ/kg (range 1630-10276). Two patients did not receive insulin during hospitalization. The remaining ten required insulin, with mean maximum total daily dose of 0.9 u/kg/day (range 0.14-1.88). Total daily doses were higher while on parenteral nutrition (mean 0.75 versus 0.27 u/kg/day on days without parenteral nutrition). Duration of insulin therapy was also longer in patients who received parenteral nutrition (mean 25 versus 4 days). Six of the insulin-treated patients were able to discontinue insulin prior to discharge, with mean duration of insulin therapy 13 days (range 1-40). Four remained on insulin at discharge, with a mean total daily dose of 0.46 u/kg/day (range 0.12-0.82). Patients who were on insulin at discharge all had total pancreatectomies, were older (mean 17 versus 9 years), and had smaller islet mass per kilogram infused (mean 2718 versus 8116 IEQ/kg) compared to those not on insulin. Discussion We report our center's experience with PIAT. Seven of twelve patients were insulin-independent at discharge, and the remainder needed modest doses. Previous publications on islet autotransplantation have also demonstrated favourable outcomes in children, with insulin independence rates up to 82%1. Younger age and larger islet mass infused per kilogram predicted insulin independence in our cohort, similar to the findings of Chinnakotla et al2. In addition, our study suggests that feeding difficulties requiring parenteral nutrition increase daily insulin requirements and prolong the need for insulin therapy.

PSUN193 Comparing Long-Term Outcomes of Children Diagnosed with New-Onset Type 2 Diabetes in an Outpatient vs Inpatient Setting

Abstract Background Early identification and treatment of children and adolescents with Type 2 Diabetes (T2DM) is thought to improve long-term outcomes. However, it is unclear if severity of T2DM at presentation affects long-term clinical outcomes. Using the location of treatment initiation (inpatient compared to outpatient) as a proxy for severity of illness, we aimed to assess changes in dysglycemia and insulin requirements at diagnosis and after 3 years of follow-up. Methods We performed a retrospective chart review of children 8-18 years of age diagnosed with new onset type 2 diabetes and receiving diabetes care within a large tertiary care center between 1/1/2010 and 11/1/2021 for three consecutive years. Children were identified by ICD codes (ICD9 250.00, ICD10 E13.9 or E11.9). Charts were reviewed to confirm diagnosis. Exclusion criteria included medication induced diabetes, MODY, >1 positive diabetes autoantibody, BMI<85%, complicated medical history (genetic disorders, transplant, cancer, etc.), and < 3 visits in the study time frame. Chi-squared, t-tests, ANOVA, and linear regression were used for analyses. Results A total of 513 patients were identified by ICD code and, after exclusions, 116 were included in the analysis: 69 initially treated in an inpatient setting and 47 initially treated in an outpatient setting. The average A1C at presentation was higher in the inpatient group (11.02% ± 1.77) than the outpatient group (7.19% ± 0.72) (p<0.001). The BMI z-score at presentation was lower in the inpatient group (2.17%±0.58) than the outpatient group (2.41% ±0.35) (p=0.015), but at three years of follow-up the BMI z-score between the groups was not significantly different (2.05%±0.60) compared to (2.12% ±0.50) (p = 0.536). The average A1C remained higher in the inpatient group (9.58%±2.92) compared to the outpatient group (8.43% ±2.44) (p = 0.031). At treatment initiation the average total daily dose of insulin in the inpatient group (0.68±0.36 units/kg/day) was higher than the outpatient group (0.05±0.18 units/kg/day) (p<0.001). At three years of follow-up the average total daily dose of insulin remained higher in the inpatient group (0.50±0.46 units/kg/day) compared to the outpatient (0.29±0.36) (p=0.008 units/kg/day) group. Conclusion In conclusion, pediatric patients initially treated in the inpatient setting had poorer glycemic control and higher insulin requirements at baseline that persisted after three years of follow-up. These findings suggest that initial presentation may predict long-term clinical outcomes in children with T2DM. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Efficacy and Safety of Analog Insulin in Comparison With Human Insulin for Hyperglycemia in Hospitalized Patients With Acute Stroke: A Randomized, Open-Label, Single-Center Trial

ObjectiveTo assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke. MethodsIn this single-center, open-label, randomized trial, 102 patients (age 59.4 ± 11.7 years, 54 women) admitted with acute stroke (52 ischemic, 50 hemorrhagic) and hyperglycemia were assigned to analog insulin (n = 52) or human insulin (n = 50) group during February to June 2021. Insulin was initiated and titrated according to the predefined standard protocol. The capillary blood glucose (BG) level was monitored by standardized glucometers. The primary outcomes were mean daily BG and the number of hypoglycemic events. ResultsBetween the 2 treatment groups, there was no significant difference in the mean daily BG (P >.05 for all days) or in the frequency of hypoglycemic episodes (P =.727). Four participants experienced severe hypoglycemia; all were receiving human insulin (P =.054). In the analog insulin group, there was a tendency toward lower daily total requirement for insulin (P =.053). The difference in bolus insulin dose was significantly lower in the analog insulin group (P =.029), but the difference in basal insulin dose was similar (P =.167). Between the 2 groups, there were no significant differences in the hospital mortality rate, modified Rankin Scale score on outcome, or length of hospital stay (P =.729,.658, and.918, respectively). ConclusionHospitalized patients acute stroke and hyperglycemia exhibited similar mean BG but a trend of lower incidence of severe hypoglycemia when treated with analog insulins in comparison with human insulin.

ODP581 Rapid Onset Autoimmune (non-type 1) Lean Diabetes Causing Severe Insulin Resistance and Pseudo-Cushing State

Abstract Introduction Type B insulin resistance syndrome (TBIRS) is a rare life-threatening disorder caused by autoantibodies to the insulin receptor. Suggestive clinical features include profound insulin resistance, concurrent autoimmune disease, acanthosis nigricans in lean individuals. Clinical Case 59 year old male (BMI = 21) diagnosed with diabetes 1 year prior (A1c was 8%) presents to the hospital in DKA (A1c 16.7%, pH 7.17, bicarb 8, anion gap 21, +++ketones). GAD, IA2, Islet cell, insulin antibodies were negative. Prior to admission his doctor increased his insulin (Detemir 30 units twice daily and Lispro 15 units with meals), notably high for his 60 kg frame. In the ICU an insulin drip at 8 units/h for 20 hours closed the anion gap. Glucose remained >250 mg/dL the entire time so dextrose was never required. After aggressive attempts at increasing his insulin doses over 10 days, he was discharged home on metformin, pioglitazone, U500 concentrated insulin 450 units per day (divided amongst 3 meals) and close follow up. 12 months after presentation his U500 dose peaked to 660 units per day. Spontaneously, 6 months later hypoglycemia ensued, A1c improved to 10.2%, weight increased and insulin doses were reduced. Interestingly, because he endorsed hyperpigmentation and weight loss, ACTH (RR= 6-50 pg/mL) and cortisol (RR 6-22 ug/dL) were checked and were high-normal at 8AM (53, 17.3, respectively). 8AM cortisol (RR <1.8 ug/dL) after low dose dexamethasone was not suppressed at 9.44 and 24 hour urine free cortisol (RR <50) was elevated to 114. 8AM ACTH and cortisol were trended at 6 months and peaked at 65 and 20. However, a year after his initial presentation, they spontaneously normalized to 30 and 8 as his insulin requirements decreased suggesting resolution of Pseudo-Cushings due to uncontrolled diabetes. Workup for TBIRS included: fasting insulin level (RR 1.9-23) before his AM dose = 685 uIU/mL, fasting triglycerides = 91 mg/dL, +ANA, +Ribonucleoprotein/Smith, adiponectin 34 u/mL (high), mild pancytopenia. Because of 2 grams of proteinuria after only 1 year with diabetes renal biopsy was performed which demonstrated membranous glomerulonephropathy. Proteinuria improved as A1c decreased. Patient declined immunosuppression because he wanted to see if he would continue to improve spontaneously. Discussion The prevalence of TBIRS is unknown because confirmation testing for antibodies to the insulin receptor is limited to select research laboratories (none that we are aware of in the United States). To avoid delaying treatment, diagnosis can be made clinically on the basis of high fasting insulin levels, extremely high insulin doses with refractory hyperglycemia, autoimmunity, normal triglycerides, high adiponectin and hyperpigmentation. The mortality rate is high because of sporadic hypoglycemia that develops during treatment or as spontaneous remission occurs. Close follow up and counseling can decrease morbidity and morality. Presentation: No date and time listed

PSUN245 Non-ketotic Hyperglycemic Hemichorea-Hemiballismus Precipitated by Antipsychotics

Abstract Background Non-ketotic hyperglycemic hemichorea-hemiballimus is a rare complication of uncontrolled diabetes mellitus characterized by sudden, unilateral and involuntary flailing movements. It is associated with basal ganglia lesions contralateral to the side of involuntary movements. We present a case with this complication after the initiation of olanzapine. Clinical Case A 44-year-old male with anxiety, depression and diabetes mellitus type 2 with a recent increase of glycohemoglobin from 8.0 to 14.6% over 4 months presented with a 2-week history of worsening involuntary jerky movements of his right upper extremity, which eventually progressed to his right lower extremity. He was on metformin monotherapy for his diabetes initially. Olanzapine had been prescribed in place of quetiapine 2 months prior and then he presented to a different hospital with diabetic ketoacidosis a month later. Insulin therapy was initiated at that time and olanzapine was discontinued about 2 weeks prior to the current presentation. Physical examination showed spontaneous, irregular and involuntary flailing movements in his right upper and lower extremities that subsided during sleep. Laboratory tests revealed a random plasma glucose of 124 mg/dL and a glycohemoglobin of 14.6% but otherwise diagnostic studies including heavy metal screening, C-reactive protein, cerebrospinal fluid analysis and electroencephalogram were unremarkable. A CT of brain showed increased attenuation of the left lateral basal ganglia and caudate nucleus, and an MRI of brain showed increased T1 and T2 signal within the left lateral basal ganglia, and decreased T2 signal in the left caudate nucleus. Along with a consistent carbohydrate diet, a basal-bolus insulin regimen was initiated and adjusted to optimize glycemic control between 80 to 150 mg/dL. Clonazepam and Quetiapine were prescribed for his motor symptoms. Over the span of 3 months, his motor symptoms gradually improved, his insulin requirements decreased, and eventually excellent glycemic control was achieved with metformin alone. Conclusion This case highlights a unique presentation of hemichorea-hemiballismus as a rare complication of uncontrolled diabetes mellitus precipitated by olanzapine, an atypical antipsychotic with a higher risk of metabolic adverse effects. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Assessment of Glucagon-like Peptide-1 Receptor Agonists in Veterans Taking Basal/Bolus Insulin Regimens.

Clinical use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is well established as add-on therapy to oral medications and basal insulin. However, there is little published data regarding the use of GLP-1 RAs for longer than 12 months in patients taking basal/bolus insulin regimens. The primary goal of our study was to assess the long-term efficacy of GLP-1 RAs as add-on therapy to basal/bolus insulin regimens. This study was a retrospective record review of all patients on basal/bolus insulin regimens who received additional therapy with a GLP-1 RA. The primary outcome was the change in glycosylated hemoglobin A1c (HbA1c) at 3, 6, 12, 18, and 24 months after initiation of the GLP-1 RA. Secondary outcomes included change in weight and total daily dose (TDD) of insulin and incidence of hypoglycemia and other adverse effects (AEs). Ninety-two patient records were reviewed. Mean glycemic control changed from baseline -1.1% (95% CI, -1.3 to -0.8; P < .001) at 3 months; -1.0% (95% CI, -1.3 to -0.7; P < .001) at 6 months; -0.9% (95% CI, 1.3 to -0.6; P < .001) at 12 months; -0.9% (95% CI, -1.4 to -0.3; P = .002) at 18 months; and -0.7 (95% CI, -1.4 to 0.1; P = .07) at 24 months. A significant decrease in weight was also observed from baseline through 18 months, and a significant decrease in TDD of insulin was identified from baseline through 12 months. Hypoglycemia was documented in 29.8% of patients at any point during GLP-1 RA therapy, and gastrointestinal AEs were documented in 18.3% of patients. Adding GLP-1 RAs to complex insulin regimens may help achieve glycemic control while decreasing insulin requirements and mitigating undesirable AEs, such as weight gain.

PSUN374 Casting a Wide NET: A Case Report of Recurrent Hypoglycemia and 'Malignant' Insulinoma

Abstract Introduction Insulinomas are rare neuroendocrine tumors, with an incidence of 4 cases per one million patient-years. Malignant insulinomas are even rarer, with a paucity of data for specific treatment modalities. Surgery, the mainstay of treatment, needs to be determined by the disease extent prior to resection. Here, we describe a patient who presented to a Federally Qualified Health Center with a diagnosis of hypoglycemia and the barriers related to the evaluation and treatment of his insulinoma. Case Presentation A 40-year-old Hispanic man with no past medical history presented to the clinic with an 8-year history of syncopal episodes. Continuous glucose monitoring revealed nocturnal hypoglycemia with BG &amp;lt;50 mg/dL, but he discontinued its use due to frequent low blood glucose alerts. Physical exam was notable for central obesity and acanthosis nigricans. Labs showed a fasting glucose of 63 mg/dL, proinsulin 419.9 (&amp;lt;18.8 pmol/L), insulin 11.3 (&amp;lt;19.6 uIU/ml), C-peptide 2.24 (0.80-3.85 ng/mL), A1C 4.3%, and negative urine sulfonylurea screen. A diagnosis of insulinoma was suspected and he was started on acarbose. CT abdomen showed a centrally calcified, peripherally enhancing 24 mm lesion in the pancreatic head. 68Ga-DOTATATE PET/CT scan was recommended for further evaluation but was denied by his insurance. Biopsy of the mass using endoscopic ultrasound (EUS) was positive for neuroendocrine tumor with metastasis to a peripancreatic lymph node. Given the concern for metastatic insulinoma, he underwent a pancreaticoduodenectomy. Surgical pathology confirmed the diagnosis of insulinoma but without evidence of tumor in the lymph nodes. The most likely explanation for the tumor cells previously noted in the lymph node was the passage of the needle through the tumor during biopsy. The postoperative course was complicated by hyperglycemia requiring insulin infusion and a pancreatic fistula. The patient was followed in clinic where his repeat proinsulin level was normal. He had resolution of his hypoglycemic episodes, his fistula healed, and he is back at work. Discussion Our case reinforces the need for an accurate diagnosis and localization of neuroendocrine tumors prior to surgical intervention. A preoperative 68Ga-DOTATATE PET/CT would have demonstrated an absence of tumor outside the pancreatic mass and prompted a less invasive surgical approach. Because of insurance denial, the EUS biopsy findings suggesting metastatic insulinoma could not be confirmed and he underwent a pancreaticoduodenectomy. Patients with metastatic insulinoma are at risk for recurrence of hypoglycemia in the postoperative period. Persistence of postoperative hyperglycemia suggests either new-onset diabetes due to insulin deficiency or resistance and suppression of residual endogenous insulin secretion as a result of insulinoma-induced chronic hyperinsulinemia. Decreases in insulin requirements post-operatively can be explained by recovery of remnant pancreatic insulin production after alleviation of chronic suppression, and reduction in insulin resistance induced by surgery. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus

Abstract Canine Diabetes (CD) is identical to human T1DM. Helper T cells expressing the CD40 receptor (TH40) are prominent in human T1DM. TH40 cell expansions occur regardless of HLA haplotype or auto-antibody status and remain elevated throughout disease. TH40 cells from T1DM respond to human islets, TH40 from healthy controls do not. At a Veterinary Hospital 6 female and 2 male dogs that met clinical criteria for T1DM were recruited. Physical exam, blood panels and CBC were done. Dogs were dosed with a OPT501 a drug targeting CD40 mediated inflammation by IV infusion. Doses were 2 and later 4 mg/kg, given on days 1, 4, 7, then weekly for 8 weeks. Diabetic dogs had significantly elevated TH40 numbers compared to non-diabetic dogs (p &amp;lt; 0. 0001). OPT501 reduced TH40 cell numbers to normal, following which insulin requirements reduced on average by 75% and up to 90%. The canine equivalent of HbA1c reduced 40.2% on average; 3 subjects were normal range. Daily blood glucose reduced significantly, 3 subjects maintained normal glucose levels. Time-in-range (TIR) increased to up to 90%, from a previous 10%. Increased c - peptide levels were universally detected after 8 weeks of treatment. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN223 The Three Different Clinical Phenotypes of Checkpoint Inhibitor-Induced Diabetes Mellitus

Abstract Checkpoint inhibitor-induced diabetes mellitus (CIADM) is a rare but morbid complication of cancer immunotherapies. The most common presentation is acute hyperglycemia and severe insulin deficiency. Our experience managing 25 patients in our new Immune-Related Adverse Events (IRAE) clinic indicates that there are three distinct CIADM phenotypes. Many of our patients required admission for diabetic ketoacidosis (15/25), amongst whom we can distinguish fulminant type 1 diabetes mellitus (9/15) from ketosis-prone type 2 diabetes mellitus (T2a-CIADM) (6/15) using serum c-peptide levels. The T1-CIADM patients have decreased serum c-peptide levels that did not improve on recheck obtained 12-28 weeks following insulin initiation (mean c-peptide = 0.2 ng/mL [NR = 1.1-4.4 ng/mL], range = 0-0.5 ng/mL). In contrast, serum c-peptide levels recovered into the reference range in T2a-CIADM patients within 12 weeks of hospital discharge (mean c-peptide = 2.9 ng/mL, range 2.1-9.3 ng/mL). It does not appear sufficient to identify T1-CIADM using traditional islet cell autoantibodies (GAD-65, IA-2A, IAA and ZnT8A) as 54% of our patients (6/11) were negative. This is consistent with other published reports. None of the T2a-CIADM patients were autoantibody-positive. Three of our GAD-65-positive T1-CIADM had preexisting islet cell autoantibodies in pretreatment serum obtained through involvement in clinical trials. None of the controls for these index cases had islet cell autoantibodies and only 2/156 developed GAD-65 autoantibodies during ICI treatment. These patients had no evidence of impaired glucose tolerance or a concerning family history. This suggests that latent autoimmune diabetes in adults (LADA) is accelerated with ICI-exposure resulting in the autoantibody-positive T1-CIADM subgroup. Interestingly (but perhaps expected), there was more reported family history of diabetes in our T2a-CIADM (6/9) than T1-CIADM patients (1/11). Our third observed phenotype (T2b-CIADM) consists of five additional patients referred for significant progression of known T2DM. These patients were prescribed oral medications and had reasonable blood glucose control (HbA1c &amp;lt; 8%) before starting immunotherapy. Three patients experienced rapid deterioration in blood glucose control (manifesting as polyuria/polydipsia) and were hospitalized for severe hyperglycemia. None had laboratory evidence of DKA/HHS. All three patients were discharged on multiple daily insulin injections (MDI). The differences in total daily insulin requirements (TDD) between clinical phenotypes highlight possible dissimilarities in underlying physiology. Those patients designated T2b-CIADM have a mean TDD of 1.2 units/kg/day (range = 0.8-2.3 units/kg/day) indicating the presence of insulin resistance. The patients who have new disease (T1-CIADM and T2a-CIADM) seem to need doses more reminiscent of B-cell dysfunction (mean = 0.5 units/kg/day, range 0.2-1.3 units/kg/day). We have not observed any return of insulin secretion in four patients who discontinued ICI treatment after three years of follow-up. It is important that we continue to investigate the mechanisms contributing to CIADM as uncontrolled hyperglycemia can impact the immune system and alter the antineoplastic effects of ICIs. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT117 Lower Muscle Mass Relative to Body Weight in Pre-pubertal Children with Type 1 Diabetes

Abstract Introduction/Background Type 1 diabetes (T1D) is associated with decreased skeletal muscle mass (SMM) and impaired muscle function in adults. Despite the importance of skeletal muscle in insulin action and metabolic homeostasis, our understanding of skeletal muscle health in children with T1D is very limited. Here we used a novel, non-invasive methodology to compare muscle mass (MM) in children with T1D and sex and age-matched healthy children without diabetes. Objectives We hypothesized that: (a) children with T1D have lower MM than age, sex, and BMI-matched children without T1D; (b) MM in children with T1D correlates with insulin sensitivity and glycemic control. Methods Weight (BW), height, BMI%, body fat% (BF%), daily insulin requirement, CGM data, HbA1c, and total and HMW adiponectin were measured in 24 young children (15 females, 9 males; age 6-11 years) with T1D. BF% and fat-free-mass (FFM) was measured by bioelectrical impedance. Insulin sensitivity was assessed by total and HMW-adiponectin and daily insulin requirements. Glycemic control was assessed by glucose time in range, mean blood glucose, and HbA1c. MM was measured using the D3creatine dilution method in 22 of the children with T1D (14 females, 8 males) and, in a separate study, in 34 children without T1D (17 females and 17 males). This method involves an oral 10 mg dose of deuterated creatine (methyl-d3, D3Cr). Creatine is converted in vivo to creatinine, including D3Cr to D3creatinine, in muscle by an irreversible, nonenzymatic reaction and then excreted. A single fasting urine sample is collected to determine D3creatinine enrichment. MM/BW (%) was calculated to normalize for body weight. Results There were strong positive associations between MM and body weight (r=0.85, p&amp;lt;0.0001), BMI (r=0.61, p=0.0028), and FFM (r=0.72, p=0.0040). Although children with T1D were slightly older (9.2 ±1.3 vs 8.1± 1.2 yo, p=0.003) and had higher BMI (18± 2.3 vs16.0 ±2.0, p=0.001) than controls, they had lower %MM/BW than children without diabetes (37.8± 4.6 vs 43.1±4.5%, p&amp;lt;0.0001). The lower %MM/BW in T1D compared to controls was confirmed in sub-cohorts matched for age and in males and females analyzed separately. Mean daily insulin requirement and HbA1c in the children with T1D were 0.76±0.15 IU/kg/day and 7.1±1.1%, respectively. MM, FFM, %BF, FM, %MM/BW did not correlate with metrics of insulin sensitivity or glycemic control. Conclusions This is the first study to quantitate MM directly in young children with T1D. Our results demonstrate a lower %MM in 6–11-year-old pre-pubertal children with T1D with stable and reasonable glycemic control. The cause for the lower % MM in T1D is not clear; however future studies could examine the rates of muscle protein and fat synthesis and breakdown in healthy and diabetic children along with their relations to insulin administration, metabolic control, growth, and pubertal development. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP623 Life Threatening Diabetic Ketoacidosis as First Presentation of Tacrolimus-Induced Diabetes Mellitus.

Abstract Background New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients.1 Tacrolimus is an immunosuppressive agent associated with diabetogenic potential which predominantly is a result of suppression of insulin secretion from pancreatic beta cells. Diabetic ketoacidosis as the first presentation of new onset tacrolimus induced diabetes is rare. We report a case of diabetic ketoacidosis (DKA) in a patient without prior history of diabetes mellitus and receiving tacrolimus as part of immunosuppressive regime post-renal transplant. Clinical Case A 62-year-old female with past medical history of autosomal polycystic kidney disease status-post deceased donor renal transplant and hypertension presented with weakness and fatigue. She had undergone transplant 8 months prior to this presentation and her immunosuppressive regime consisted of mycophenolate mofetil and tacrolimus. The patient was encephalopathic on arrival with normal vitals. Laboratory evaluation was significant for blood glucose of 673, bicarbonate of &amp;lt;10, anion gap of 24, Beta-hydroxybutyrate &amp;gt;8 and a pH of 7.19 on arterial blood gas analysis thus confirming diagnosis of diabetic ketoacidosis (DKA). Tacrolimus level was elevated at 35.7. Intravenous fluids and insulin were initiated with resolution of symptoms and DKA. She was transitioned to a basal-bolus insulin regimen. Further labs revealed Hemoglobin A1C of 11.6% (no previous value), negative insulin antibodies and glutamic acid decarboxylase antibody, and a low C-peptide level at 0.47 (when blood glucose was 150mg/dl). Her tacrolimus dose was adjusted, and she was discharged on a basal-bolus insulin regimen. On follow up, the patient had lower insulin requirements with improvement in C-peptide level to 1.8, thus, indicating beta cell dysfunction in setting of supratherapeutic tacrolimus levels. Conclusion Tacrolimus remains the preferred immunosuppressive agent after kidney transplantation given lower incidence of acute rejections and better tolerance. However, due to its toxic effects on pancreatic beta cells it is imperative blood sugar levels should be routinely monitored in patients on tacrolimus. Appropriate monitoring can lead to timely diagnosis and successful outcomes. Further studies are required to investigate risks factors associated with tacrolimus induced DKA.

PSUN192 Therapeutic Benefit of GLP-1 Agonists in Patients with Type 1 Diabetes on Insulin Therapy: an Updated Systematic Review and Meta-analysis

Abstract Introduction Glucagon-like Peptide 1 (GLP-1) agonists are efficacious glycemic control and weight loss agents for obese patients with or without type 2 diabetes mellitus. Use of GLP-1 agonists for patients with type 1 diabetes mellitus (T1DM), on the other hand, is an evolving area of research. Our present meta-analysis aims to critically evaluate existing evidence and provide an estimated average therapeutic effect. Methods PubMed, Embase, and Cochrane libraries were searched for randomized controlled trials comparing major efficacy and safety endpoints for 12 weeks or longer administration of GLP-1 agonists compared to placebo in T1DM patients on insulin. Main endpoints for analysis included glycated hemoglobin (A1c) level, body weight, and change in total insulin dose. Study was done in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Results Of 3736 reports identified on search, 8 studies involving liraglutide 1.8mg daily (total 1415 patients) and 5 studies involving any dosage of exenatide (total 221 patients) were included. Liraglutide 1.8mg overall produced greater decrease in A1c (MD = -0.28%, 95% CI -0.41 to -0.16, I2=42%), body weight (MD = -4.84kg, 95% CI -5.25 to -4.44, I2=0%), and total daily insulin per kilogram body weight (MD = -0.08u/kg, 95% CI -0.10 to -0.06, I2=55%) compared to placebo. Exenatide regimen as a whole also overall produced decreased A1c (MD = -0.17%, 95% CI -0.38 to -0.00, I2=0%), body weight (MD = -4.05kg, 95% CI -14.3 to -3.45, I2=0%), total daily insulin (MD = -0.08u/kg, 95% CI -0.15 to -0.01, I2=0%) compared to placebo. However, 3 out of 5 exenatide trials were open label and studies used multiple doses and formations (short-release and extended release), which limited the interpretation of results in clinical practice. Conclusion Our meta-analysis supports the therapeutic benefits of GLP-1 agonists for patients with T1DM. Daily 1.8mg liraglutide injections for at least 12 weeks appear to be a promising adjunct to insulin therapy for T1DM patients, resulting in decreased A1c levels, body weight, and total daily insulin requirements. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Secondary complications of diabetes

Diabetes Mellitus is caused due to inconsistency in the secretion of insulin or due to defective action of insulin which can be caused by insufficient insulin or a defective pancreas. Diabetes is growing at an alarming rate with an estimation of 8.4% worldwide. Diabetes has 2 types i.e., TIDM1, in which there is excessive beta cell degradation and as result deficiency of insulin occurs in body and TIDM2 where there is insulin resistance that leads to hyperglycemia. Secondary complications of diabetes include cardiovascular damage, due to different types of glycation products, metabolites, inflammation, and endothelial dysfunction. Thyroid malfunction, as glycemic uncontrolled and insulin requirements is typically related to hyperthyroidism thus occurrence of thyroid disorder may also affect diabetes control. Effect on wound healing, as the inflammation and tissue response to wounds are unusual and endogenous growth factors (EGF) show less activity to the wounds site in diabetic patient. Diabetic neuropathy is the most recurrent complication of the diabetes. Another outcome is oxidative stress which increase with growing diabetes. The growth and development of muscles is considerably decreased along with crucial risk aspect for heart failure in type 1 diabetes. Neural and retinal cells are also affected in diabetic patients causing neuropathy and retinopathy.

Efficacy and Safety of Hydroxychloroquine in the Treatment of Type-2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Published on: October 2022Journal of Young Pharmacists, 2022; 14(4):402-407Original Article | doi:10.5530/jyp.2022.14.81 Authors:Rahul Krishna Puvvada1, Pramod Adusumilli2, Raghava Kalyan Maddukuri2, Samaksha P B1, Manohar Gopal Annam3, Krishna Undela4,*1Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, Karnataka, INDIA.2Department of Pharmacy Practice, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Chowdavaram, Guntur, Andhra Pradesh, INDIA.3Manager Pharmacovigilance, Advity Research Pvt Limited, Hyderabad, Telangana, INDIA.4Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER) Guwahati, Assam, INDIA. Abstract:Background: Type 2 diabetes is a metabolic disorder that requires continuous pharmacological treatment for its management. Due to the complexity of the treatment and increased risk of adverse reactions to the existing treatment, there is a need to demonstrate the efficacy and safety of new medications. Therefore, this study was conducted to identify the efficacy and safety of Hydroxychloroquine in people with type 2 diabetes. Materials and Methods: The Population, Intervention, Comparator, Outcome format was utilised to assess the inclusion criteria of randomized controlled trials. A total of five scientific databases were searched with the designed search terms. All the studies included were assessed for their risk of bias and a meta-analysis was performed by using RevMan. Results: A total of six randomized controlled trials were included in this systematic review. The majority of studies included hydroxychloroquine as an add on treatment for the existing treatment regimen. From the study results, it was found that hydroxychloroquine group was equally effective in lowering blood glucose levels when compared with other treatment groups. Also, it was found that there was a significant reduction in the daily insulin requirement in the hydroxychloroquine treatment group. Despite the reduction in lipid profile in hydroxychloroquine group, there was no significant reduction in body weight observed between hydroxychloroquine and non-hydroxychloroquine groups. Lastly, hydroxychloroquine was well tolerated in people living with type 2 diabetes with less severe adverse effects. Conclusion: Overall, hydroxychloroquine group was found to be safe and equally effective in reducing blood glucose levels when compared with other anti-diabetes medications groups. Keywords: Hydroxychloroquine, Type 2 diabetes, Safety, Efficacy.Keywords: Hydroxychloroquine, Type 2 diabetes, Safety, Efficacy.

CELIAC DISEASE IN SUBJECTS WITH TYPE 1 DIABETES MELLITUS AND ITS EFFECT ON GLYCEMIC CONTRO

Objective: To observe celiac disease incidence in patients with diabetes mellitus 1 and its effect on glycemic control.&#x0D; Methods: Type 1 diabetic patients presenting in the Sughra Diabetic clinic in Benazir Bhutto Hospital from 22 August 2011 till 22 February 2012 were included in this study. Medical history, including age of the patient at diagnosis of diabetes, duration of disease and daily insulin requirements was taken. Subjects with positive tTGAb levels had biopsy of 2nd part of duodenum to confirm CD according to Marsh criteria on histopathological examination.&#x0D; Results: The study included 125 patients with type 1 diabetes mellitus. The mean age was 30.08±8.9 years. 42 (33.6%) were males and 83 (66.4%) females. 5 (4%) of type 1 diabetics had celiac disease. All 5 had both a positive anti-tissue transglutaminase antibodies (&gt;24 U/ml) and all 5 also had histopathological changes confirming celiac disease. 4 had Marsh stage 3 (2 had stage 3b and 2 had stage 3c) and 1 had Marsh stage 4 changes on histopathology. All 5 CD-positive patients (100%) had poorly controlled diabetes whereas among CD-negative patients only 26 (21.6%) had well controlled diabetes; this difference was p = 0.242.&#x0D; However, mean HbA1c level CD-positive patients was significantly higher than HbA1c of CD-negative patients; p = 0.015. The mean daily insulin requirement of CD-positive patients was significantly lower than CD-negative patients; p = 0.000.&#x0D; Conclusions: The incidence of celiac disease in type 1 diabetics increases as compared to general population. Because most diabetics are asymptomatic, it is better to screen all. Moreover, CD is associated with lesser daily insulin requirement and poorer diabetes control.