Multiple Daily Insulin Injections Research Articles

The Official Journal of ATTD Advanced Technologies & Treatments for Diabetes Conference 22‐25 February 2023 I Berlin & Online

The Official Journal of ATTD Advanced Technologies & Treatments for Diabetes Conference 22‐25 February 2023 I Berlin & Online

Time-Action Profile of Technosphere Insulin in Children with Type1 Diabetes.

Technosphere insulin (TI) is aninhaled dry powder ultra-rapid-acting insulin. This report describes the results of the first study of TI in children with type1 diabetes (T1D). Pharmacokinetics (PK) of TI and the effect of TI on circulating glucose concentrations were evaluated in a single-arm study that enrolled children ages 8-17years with T1D for more than 1year, on a stable multiple daily insulin injection (MDI) regimen, and meeting pre-defined pulmonary function testing criteria (at least 70% predicted). To assess PK, subjects received an individualized single preprandial dose of TI (4-12U, in 4-U increments) via oral inhalation, basedon their usual meal-time subcutaneously injected rapid-acting insulin dose and meal content. Serum insulin and blood glucose were measured at -30 to 250min relative to dosing. Twenty-seven children with T1D participated in this single-dose PK study. Mean subject age was 13.3years (59% female; 81.5% White). Meanserum insulin Cmax (maximum concentration) was 77.3, 119.15, and 207.7µU/mL for doses of 4, 8, and 12U, respectively. Tmax occurred at 10.5, 13.9, and 14.6min post-dose for 4, 8, and 12U.Glucose lowering 30-60min post-dose was consistent with the PK profile. Serum insulin rapidly increased post-dose and returned to baseline by 120min. The data suggests the PK of TI in youth with T1D ages 8-17years was similar to that seen in previous adult studies. ClinicalTrials.gov identifier, NCT02527265.

Efficacy of Low-dose Dapagliflozin in Young People with Type 1 Diabetes.

Objective Young people with type 1 diabetes are likely to gain body weight and not achieve optimal glycemic control with only high doses of insulin. This study examined the efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin as an adjunct-to-insulin therapy in young Japanese subjects with type 1 diabetes who had been diagnosed before 15 years old, were overweight, and had inadequate control despitereceiving intensive insulin therapy. Methods Twenty-two patients with type 1 diabetes (12 boys and 10 girls 16.0-33.9 years old) were involved in the study. All patients had a body mass index (BMI) >25 kg/m2, glycated hemoglobin (HbA1c) level >7.0%, and daily insulin dose >0.5 units/kg. They were treated with a low dose of dapagliflozin (5.0 mg/day) as an adjunctive therapy to insulin. Fourteen patients were treated with multiple daily injections of insulin, while eight used an insulin pump. Results The body weights and BMIs were significantly reduced during the 12-month study period (change of -4.4 kg and -1.7 kg/m2, p<0.001, respectively). Their insulin dose was significantly decreased (-0.17 units/kg, P <0.001), and glycemic control was significantly improved (fasting plasma glucose: -18.7 mg/dL, HbA1c: -0.62%, p<0.001) during the study period. There was one episode of diabetic ketoacidosis, with no other problematic adverse events, including severe hypoglycemia, observed. Conclusion The use of low-dose dapagliflozin as an adjunct therapy may be beneficial in overweight young people with poorly controlled type 1 diabetes.

Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.

Dual-basal-insulin regimen for the management of dawn phenomenon in children with type 1 diabetes: a retrospective cohort study.

Handling of the dawn phenomenon (DP) with multiple daily insulin injection (MDII) regimen is a real challenge. We aimed to demonstrate the effectiveness of a dual-basal-insulin (a long-acting glargine and an intermediate-acting neutral protamine Hagedorn (NPH)) regimen for the management of DP in children with type 1 diabetes mellitus (T1DM). The primary efficacy outcome was to overcome morning hyperglycemia without causing hypoglycemia during the non-DP period of the night. Retrospective cohort study. Charts of 28 children with T1DM (12 female; 42.8%, mean age 13.7 ± 2.1 years) treated with MDII were retrospectively reviewed. The median duration of diabetes was 4.5 years (range 2-13.5 years). DP was diagnosed using a threshold difference of 20 mg/dL (0.1 mmol/L) between fasting capillary blood glucose at 3 a.m. and prebreakfast. NPH was administered at midnight in addition to daily bedtime (08.00-09.00 p.m.) glargine (dual-basal-insulin regimen). Midnight, 03:00 a.m., prebreakfast and postprandial capillary blood glucose readings, insulin-carbohydrate ratios, and basal-bolus insulin doses were recorded the day before the dual-basal-insulin regimen was started and the day after the titration of the insulin doses was complete. Body mass index standard deviation scores (BMI SDS) at the onset-3rd-12th month of treatment were noted. Before using dual basal insulin, prebreakfast capillary blood glucose levels were greater than those at midnight and at 03:00 a.m. (F = 64.985, p < 0.01). After titration of the dual-basal-insulin doses, there were significant improvements such that there were no statistically significant differences in the capillary blood glucose measurements at the three crucial time points (midnight, 03.00 a.m., and prebreakfast; F = 1.827, p = 0.172). No instances of hypoglycemia were reported, and the total daily insulin per kilogram of body weight did not change. The BMI SDS remained steady over the course of the 1-year follow-up. In this retrospective cohort study, the dual-basal-insulin regimen, using a long-acting glargine and an intermediate-acting NPH, was effective in overcoming early morning hyperglycemia due to insulin resistance in the DP. However, the effectiveness of the dual-basal-insulin regimen needs to be verified by prospective controlled studies using continuous glucose monitoring metrics or frequent blood glucose monitoring.

Continuous subcutaneous infusion versus multiple daily injections of insulin for type 1 diabetes in pregnancy

Continuous subcutaneous infusion versus multiple daily injections of insulin for type 1 diabetes in pregnancy

Clinical practice recommendations for diabetes in pregnancy (Update 2023)

In 1989 the St. Vincent Declaration aimed to achieve comparable pregnancy outcomes in women with diabetes and those with normal glucose tolerance. However, currently women with pre-gestational diabetes still feature ahigher risk of perinatal morbidity and even increased mortality. This fact is mostly ascribed to apersistently low rate of pregnancy planning and pre-pregnancy care with optimization of metabolic control prior to conception. All women should be experienced in the management of their therapy and on stable glycemic control prior to conception. In addition, thyroid dysfunction, hypertension as well as the presence of diabetic complications should be excluded or treated adequately before pregnancy in order to decrease the risk for aprogression of complications during pregnancy as well as maternal and fetal morbidity. Near normoglycaemia and HbA1c in the normal range are targets for treatment, preferably without the induction of frequent resp. severe hypoglycaemic reactions. Especially in women with type1diabetes mellitus the risk of hypoglycemia is high in early pregnancy, but it decreases with the progression of pregnancy due to hormonal changes causing an increase of insulin resistance. In addition, obesity increases worldwide and contributes to higher numbers of women at childbearing age with type2diabetes mellitus and adverse pregnancy outcomes. Intensified insulin therapy with multiple daily insulin injections and pump treatment are equally effective in reaching good metabolic control during pregnancy. Insulin is the primary treatment option. Continuous glucose monitoring often adds to achieve targets. Oral glucose lowering drugs (Metformin) may be considered in obese women with type2diabetes mellitus to increase insulin sensitivity but need to be prescribed cautiously due to crossing the placenta and lack of long-time follow up data of the offspring (shared decision making). Due to increased risk for preeclampsia in women with diabetes screening needs to be performed. Regular obstetric care as well as an interdisciplinary treatment approach are necessary to improve metabolic control and ensure the healthy development of the offspring.

PS-BPR01-8: A CASE OF PHEOCHROMOCYTOMA WITH CONCOMITANT SPLENIC ARTERY ANEURYSM

A 62-year-old man with a 30-year history of headaches and a 20-year history of treatment-resistant hypertension and diabetes mellitus was referred to our hospital for evaluation of his 5 cm retroperitoneal tumor found by abdominal ultrasound examination at a medical checkup. A simple CT and MRI scan showed a heterogeneous tumor (diameter, 5 cm) in the left adrenal gland and a splenic artery aneurysm (diameter, 2 cm). Endocrine examinations revealed increased levels of plasma-free normetanephrine (NMN) (853 pg/mL), urinary noradrenaline (NA) (670 μg/day), and urinary NMN (2.6 mg/day). 123I-MIBG scintigraphy showed high accumulation in the left adrenal region. He was diagnosed with NA-dominant left pheochromocytoma. His blood pressure was controlled at around 140/90 mmHg with 16 mg of doxazosin and 10 mg of amlodipine. His insulin-dependent diabetes was treated with multiple daily insulin injections (63 units/day), metformin, and miglitol. First, he underwent splenic artery aneurysm embolization under general anesthesia, which was completed without developing a hypertensive crisis. Two months later, he underwent laparoscopic left adrenalectomy, and the resected tumor was pathologically diagnosed as pheochromocytoma with a GAPP score of 1. He did not develop postoperative hypotension. His blood pressure was well controlled with only 10 mg of amlodipine, and his insulin requirement was reduced to 23 units/day after surgery. Since few cases of pheochromocytoma with concomitant splenic artery aneurysm have been reported, we discussed the treatment plan with much consideration. Splenic artery aneurysms have a high risk of rupture due to intraoperative blood pressure elevation in pheochromocytoma, which could be fatal. Although the first choice of treatment for a splenic artery aneurysm is endovascular therapy, the use of contrast media is generally contraindicated in pheochromocytoma in Japan due to the risk of hypertensive crisis. In the present case, systemic management with a sufficiently high dose of alpha-blocker allowed the embolization to be preceded avoiding a crisis, and subsequent surgery for pheochromocytoma could be performed safely. A long history of hypertension and diabetes exacerbated by the pheochromocytoma may have contributed to the arteriosclerosis leading to the splenic artery aneurysm. Here we report a rare case of pheochromocytoma with concomitant splenic artery aneurysm and will discuss the pathogenesis and management of this case with a review of the literature.

Nighttime hypoglycemia in Japanese children with type 1 diabetes mellitus treated with multiple daily injection insulin therapy.

Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.

Effectiveness of continuous subcutaneous insulin infusion versus multiple daily injections on glycaemic control among older adults with type 2 diabetes: protocol for systematic review and meta-analysis

IntroductionInsulin therapy plays an irreplaceable role in glycaemic control among older adults with type 2 diabetes mellitus (T2DM) and can be administered by either multiple daily injections (MDI) of insulin...

ПОМПОВАЯ ИНСУЛИНОТЕРАПИЯ: ОПЫТ И ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ У ДЕТЕЙ С САХАРНЫМ ДИАБЕТОМ 1 ТИПА В АМБУЛАТОРНЫХ УСЛОВИЯХ

The study is based on the results of determining the level of HbA1c and analyzing the medical records of 47 pediatric patients with type 1 diabetes registered with a pediatric endocrinologist, when comparing groups of children on pump insulin therapy and on the regime of multiple daily insulin injections. The results showed that all 100% of patients know the features of the diet in diabetes mellitus, and only 20 patients (42.5%) adhere to the diet strictly. 15 people (83.3%) in the comparison group regularly use the XE system in the main group – 9 people (31%, p &lt; 0.001). A diary of self-control on nutrition and glucose control is regularly kept by 12 people (66.7%) in the main group and 10 patients in the comparison group (34.1%, p = 0.032). The observed averages of HbA1c were comparable in these groups Treatment with multiple insulin injections or continuous subcutaneous insulin infusion had no significant differences among different age groups of children in achieving HbA1c targets on an outpatient basis. In achieving glycemic targets in children and adolescents with T1DM, the constant use of a continuous glucose monitoring system has been proven. The clinical benefit of pump insulin therapy before therapy with multiple daily injections is to reduce the number of episodes of acute complications of T1DM: severe hypoglycemia and diabetic ketoacidosis.

Effects of initiating insulin pump therapy in the real world: A nationwide, register-based study of adults with type 1 diabetes

AimsWe aimed to estimate effects of insulin pump therapy (IPT) on HbA1c level, HbA1c variability, and risk of hospitalised diabetic ketoacidosis (DKA) and severe hypoglycaemia (SH), compared with multiple daily insulin injections (MDI). MethodsWe identified a cohort of all adults with type 1 diabetes in Denmark using national registry data and assigned each individual to either IPT (treatment) or MDI (control) from 2010 to 2020. We estimated average treatment effects on the treated (ATT) and treatment effects among population subgroups using treatment-staggered difference-in-differences. ResultsThe cohort consisted of 26,687 individuals with a collective 243,601 person-years of observation; 38,823 (16 %) were IPT person-years. We identified an ATT for HbA1c of −0.33 % (95 % CI −0.39 to −0.27; −3.6 mmol/mol [95 % CI −4.2 to −2.9]). ATTs were larger among women and individuals who were older, had highest baseline HbA1c, and used continuous glucose monitoring. ATT for HbA1c variability (−0.016 % [−0.028 to −0.0041); −0.17 mmol/mol [95 % CI −0.30 to −0.045]) corresponded to a 6.5 % decrease in the standard deviation of HbA1c. ATTs for DKA and SH corresponded to 0.52 additional and 0.11 fewer hospitalisations per 1,000 person-years, respectively. ConclusionsIPT significantly reduced HbA1c level and variability, compared with MDI. However, it also marginally increased the risk of hospitalised DKA.

One-year safety and efficacy results of insulin treatment simplification with IDegLira in type 2 diabetes.

This study aimed to investigate the sustained safety and efficacy of insulin treatment simplification with IDegLira in patients with type 2 diabetes and an HbA1c ≤ 7.5% (58 mmol/mol) during a 12-month follow-up. Seventy-two adults with type 2 diabetes and an HbA1c ≤ 7.5% (58 mmol/mol) treated with multiple daily insulin injections (MDI) participated in the trial (age 63.8 ± 9.5 years, HbA1c 6.4 ± 0.7%, [46 ± 8 mmol/mol] body weight 92.95 ± 18.83 kg, total daily insulin dose: 43.21 ± 10.80 units; mean ± SD). Previous insulins were stopped, and once daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured prebreakfast plasma glucose concentration of ≥5 mmol/L to ≤6 mmol/L. After 12 months, good glycaemic control was maintained, while body weight decreased significantly. Mean HbA1c changed to 6.2 ± 0.8% (44 ± 9 mmol/mol) (p=.109) and body weight changed by -3.89 kg to 89.06 ± 18.61 kg (p < .0001). The simplified treatment was safe and well-tolerated. Percentage of patients experiencing at least one episode of hypoglycaemia was 49% during the month before simplification and 17% during the last 3months of the follow-up. Insulin treatment simplification with IDegLira in selected patients with type 2 diabetes is safe, maintains adequate glycaemic control and is associated with weight loss over 12 months.

Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion

ObjectiveTo determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH. MethodsSixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG). ResultsThe LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05). ConclusionUSG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.

A sub-analysis of the SAGE study in Italy indicates good glycemic control in type 1 diabetes

Background and aimsIntensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26–44, 45–64, and ≥65 years) of the global SAGE study. Methods and resultsThe primary endpoint was proportion of participants who achieved an HbA1c <7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m2. Mean HbA1c was 7.5% and 29.4% had HbA1c <7.0%, with the highest percentage in those 26–45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were experienced by 16.3% and 12% of patients, of which 7.1 and 9.5%, respectively, required hospitalization/emergency visits. More patients achieved HbA1c <7% with CSII (30%) than with multiple daily insulin injections (27.9%). In multivariate analysis, BMI (OR 0.94, 95% CI 0.89–0.99, p = 0.032) and adherence to diet (OR 0.36, 95% CI 0.18–0.70, p = 0.0028) were significantly associated with HbA1c <7.0%. ConclusionsGlycemic control can be considered good in the Italian SAGE cohort, especially in younger patients, who more frequently use pumps/continuous glucose monitoring. Greater patient education and use of technology may further support this achievement. Patients should be encouraged to maintain a low BMI and adhere to their diet.

Monitoring of continuous subcutaneous insulin infusion treatment in Portugal and its implications for diabetes management.

Intensive insulin therapy in the treatment of type 1 diabetes can, in place of multiple daily injections of subcutaneous insulin (MDI), be performed with continuous subcutaneous insulin infusion (CSII) systems. This method allows for better glycemic control and thus reduces the risk of complications of the disease. The aim of this study was to evaluate the results of treatment with CSII in Portugal. A retrospective analysis of the records on the national CSII platform was carried out between January 2010 and August 2021. All the registered patients are followed in certified CSII treatment centers in Portugal. Of the 7135 registered patients, 3807 were excluded due to absence of monitoring data. The reasons for treatment were analyzed and a comparison was made between patients with and without CSII. The statistical significance considered was α < 0.05. A total of 3328 patients were included in the study, 1136 under MDI and 2192 under CSII. The main reasons for CSII use were marked glycemic variability (25%) and HbA1c greater than 7% (23%). Patients under CSII had a lower HbA1c (7.7 ± 1.0% vs. 8.0 ± 1.5%, p < 0.001), as well as a lower frequency of episodes of severe hypoglycemia (1.4 vs. 3.3 per 100 patient-years, p < 0.001), and ketoacidosis (1 vs. 2.4 per 100 patient-years, p < 0.001). The present analysis validates the advantage of using CSII in metabolic control and reduction of acute complications of type 1 diabetes, both severe hypoglycemia and ketoacidosis, in the Portuguese population. CSII therapy is classically associated with an increased risk of ketoacidosis; however, in experienced centers and adequate patient education, the opposite is found.

ODP158 A Pilot Trial on the Efficacy of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness

Abstract Objective Maternally inherited diabetes and deafness (MIDD) is characterized by progressive insulin secretory disorder caused by impairment of mitochondrial adenosine triphosphate (ATP) production in pancreatic beta-cells. The amino acid 5-aminolevulinic acid (5-ALA) is the first heme biosynthetic precursor and the administration of 5-ALA combined with sodium ferrous citrate (SFC) enhance heme production, leading to improvement of mitochondrial function and ATP production. Several studies showed that the treatment with 5-ALA/SFC improved glycemic tolerance in both patients with prediabetes and those with type 2 diabetes. However, no previous studies investigated the efficacy of 5-ALA in patients with MIDD. We carried out the pilot trial to investigate whether the administration of 5-ALA/SFC can improve insulin secretion and glucose tolerance in patients with MIDD. Methods We enrolled five patients with MIDD receiving multiple daily injections of insulin. The patients were administered 5-ALA/SFC 100 mg twice a day (200 mg per day) for 24 weeks as adjunctive to insulin treatment. The patients underwent a 75-g oral glucose tolerance test (OGTT) twice before (1 st -OGTT) and 24 weeks after the initiation of 5-ALA/SFC (2 nd -OGTT). We measured levels of plasma glucose, insulin, and glucagon at fasting (0 min), and 30, 60 and 120 min after glucose load (Study protocol: Nakamura Y et al. Medicine (Baltimore). 2021; 100: e25100). Results The mean levels of HbA1c tended to decrease from 8.3% to 7.9% (p = 0.36) even though total insulin doses had not changed during the 24 weeks of 5-ALA/SFC administration. In the 2nd -OGTT comparing to the 1 st -OGTT, four of the five patients showed a tendency of improvement in glucose levels with a certain degree of insulin increase, but one patient did not show any improvement. The means of area under the curve (AUC) of serum insulin from fasting to 120 min during 2nd -OGTT was 30% larger but not significant compared to that during 1st -OGTT (p = 0. 077). The late phase of glucose excursion during OGTT determined by AUC of plasma glucose from 60 to120 min during 2nd -OGTT showed 10% reduction compared to that during 1st -OGTT (p = 0. 041). The glucagon levels during OGTT were comparable between before and after 5-ALA/SFC administration. The indexes of insulin sensitivity calculated by the homeostasis model assessment of insulin resistance or Matsuda index were not significantly changed between before and after 5-ALA/SFC administration. None of the patients experienced any adverse events during the study. Conclusions The administration of 5-ALA/SFC as adjunctive to insulin therapy might be a novel effective treatment for MIDD that improves insulin secretion via amelioration of mitochondrial function. Presentation: No date and time listed

PSUN264 Insulin Edema: A rare side effect of Intensive Insulin Therapy

Abstract Insulin therapy associated generalized edema is a rare entity. The true incidence is unknown. It has been reported mostly in patients with poorly controlled diabetes mellitus started on intensive insulin regimens. The severity ranges from mild lower extremity swelling to anasarca. Management is primarily supportive with salt restrictions, diuretics and if possible, reduction of insulin doses. We present a case of a 39-year-old African American woman who developed generalized edema after initiation of insulin. She had history of gestational diabetes and presented to the endocrinology clinic to establish care after being hospitalized with Diabetic Ketoacidosis (DKA). She was diagnosed with diabetes mellitus initially during her pregnancy two years prior and was treated with insulin. After pregnancy, she was lost to follow up. She was then admitted to the hospital with severe DKA and was discharged on multiple daily injections of insulin. On the initial encounter in clinic, the patient endorsed developing abdominal distension and lower extremity swelling with insulin use previously so she was not using insulin consistently. Her physical examination was unremarkable. Lab work was significant for hemoglobin A1C of &amp;gt;15%, C-peptide 0.9 ng/mL (1.1-4.4 ng/mL), islet cell antibody 0.09 nmol/L (&amp;lt;0.02 nmol/L), glutamic acid decarboxylase antibody 0.40 nmol/L (&amp;lt;0.02 nmol/L). Her kidney and liver function were normal. She had normal thyroid function and cortisol levels. Her echocardiogram revealed normal cardiac function and she had non proliferative diabetic retinopathy on retinal exam. The patient was started on insulin and a continuous glucose monitor was placed to assess her glycemic patterns. Three days after starting insulin, she developed generalized body swelling involving face, abdomen, and lower extremities. The patient was advised to cut back on salt and started on low dose furosemide. On follow up one month later, her abdominal swelling had improved however she still had pitting lower extremity edema. On follow up two months later the edema completely resolved. Clinicians should be aware of the presentation and management of insulin induced edema. In most of the cases in literature, insulin induced edema started after starting insulin in newly diagnosed Type 1 diabetes or uncontrolled Type 2 diabetes. The pathophysiology is unclear. There is some evidence that insulin deficiency causes a catabolic state and hyperglycemia increases tissue capillary permeability. Re-introduction of insulin causes free water retention and renal excretion of sodium. This along with increased capillary permeability can lead to insulin edema. Water retention caused by the effect of counter regulatory hormones can also play a role. Insulin edema needs to be differentiated from other causes of diffuse edema. Management is generally supportive including temporarily decreasing insulin doses, salt restriction and diuretics as needed. Patient reassurance is important as well to aid in adherence to the prescribed insulin regimen. 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.

LBODP029 Pseudohypobicarbonatemia In The Setting Of Diabetic Ketoacidosis And Severe Hypertriglyceridemia

Abstract Background Severe hypertriglyceridemia is a rare complication of diabetic ketoacidosis (DKA); however, the resulting spuriously low measurements of serum bicarbonate ("pseudohypobicarbonatemia") are less well known. Clinical Case A healthy 15-year-old female presented to the emergency department with polydipsia, polyuria, and abdominal pain. She had a normal BMI and a sibling with type 1 diabetes (T1D). Labs demonstrated serum glucose of 351 mg/dL, serum ketones of 3.4 mmol/L, serum bicarbonate of &amp;lt;5 mmol/L, anion gap of &amp;gt;23 mmol/L, and triglycerides of &amp;gt;21,000 mg/dL. Serum lipase was normal at 70 units/L. She was admitted for protocolized DKA treatment with intravenous fluids and regular insulin drip. Hospital day 2, serum bicarbonate remained very low (7 mmol/L) despite declining ketones (1.9 mmol/L), decreasing anion gap (15 mmol/L), normal chloride (112 mEq/L), and normal lactic acid (1.3 mmol/L). A spurious lab was suspected, so bicarbonate was calculated from a venous blood gas (VBG) which showed a pH of 7.28 and a bicarbonate of 16.2 mmol/L at a time when serum bicarbonate was 7 mmol/L. Serial BMPs and VBGs were trended, with the serum bicarbonate consistently 7-10 mmol/L lower than the blood gas bicarbonate. Her ketoacidosis resolved, yet she remained hospitalized for continued IV regular insulin drip (max 0.3 units/kg/h) for treatment of severe hypertriglyceridemia. On hospital day 7, triglycerides fell below 500mg/dL. She never developed pancreatitis. She was discharged home on multiple daily injection insulin and a low-fat diet. Her triglyceride level two weeks later was 173 mg/dL. Diabetes autoantibodies returned positive, confirming a diagnosis of T1D. Clinical Lessons This case demonstrates that very high triglycerides can occur with pediatric DKA and cause a falsely low serum bicarbonate level, also known as "pseudohypobicarbonatemia". This is due to chemistry panel analyzers using absorbance to estimate bicarbonate levels, which makes them susceptible to triglyceride interference. In contrast, blood gas analyzers use the Henderson-Hasselbalch equation to calculate bicarbonate, thus, are not vulnerable to the same triglyceride interference. This is especially relevant in pediatrics, as triglyceride levels may not be routinely checked for patients in DKA, so massive elevation may be missed. It is also pertinent for centers where serum bicarbonate levels may be trended to monitor for DKA resolution, instead of blood gases. If the serum bicarbonate level remains low in a patient with DKA and resolving ketosis, a blood gas may be obtained as another way of looking at the acid/base status. If there is a discrepancy between the two measurements, triglycerides should be assessed, as this could change management and prevent complications such as pancreatitis. Presentation: No date and time listed