Basal Bolus Research Articles

Insulin edema, a little known entity.

Insulin edema is an entity that should be considered in any patient who starts or intensifies an insulin regimen to improve metabolic control. Heart, liver, and kidney problems should always be ruled out beforehand. The exact mechanism is not clear. It is usually self-limiting within a few days and rarely requires specific therapy. It could be prevented with a more progressive improvement in glycemic control avoiding rapid increases in insulin dose. We present the case of two female adolescents with a new diagnosis of type 1 diabetes mellitus with ketoacidosis. A few days after starting treatment with a basal bolus regimen with subcutaneous insulin, edema started and limited to the lower extremities. In both cases, the symptoms resolved spontaneously.

Prolonged remission in latent autoimmune diabetes of adults (LADA): Is insulin resistance a major influence?

Abstract Introduction Type 1 diabetes mellitus (T1DM) is a chronic inflammatory disease that courses with high serum glucose levels as a result of pancreatic beta cell destruction and subsequent insulinopenia. LADA is a type of autoimmune diabetes where damage to the beta cell occurs much slower. The natural history of type 1 diabetes is very heterogeneous and variable. This is especially true for LADA with several possible different clinical courses due to a wider variety of pancreatic cell destruction and insulin resistance. Clinically overt diabetes ensues when more than 80% of pancreatic cell mass is loss. After treatment initiation partial disease remission is common, especially in children. However complete remission is rare, and remission lasting for over a year is even rarer, with few reports published in literature. Some agents such as vitamin D and DPP4 inhibitors have been presented has having potential immunomodulatory effects. Clinical Case A 36-year-old man with grade 1 obesity (BMI 33 kg/m2) presented at the emergency department with symptoms of insulinopenia (polyuria and polydipsia in the previous 3 months) and hyperglycemia (capillary blood glucose >500mg/dL). Ketonemia was negative and pH was normal on blood gas analysis The diagnosis of diabetes mellitus was made and insulin therapy was instituted on a basal-bolus regimen. At the first follow-up appointment, due to his morphotype and familiar history of type 2 diabetes (mother diagnosed at 52 years of age), he stopped short-acting insulin and was started on metformin and SGLT2 inhibitor. A week later he was admitted in the hospital in euglycemic ketoacidosis. Initial workup revealed positive anti-GAD 41.8 U/mL, HbA1C 9.8%, C-peptide 1.83 ng/mL, serum insuline 17.4 uU/mL. Consequently, metformin and SGLT2 inhibitor therapy was stopped, and the patient resumed basal bolus insulin regimen. He then remained under a basal insulin without need of meal-time insulin bolus, progressively lowering the basal insulin dose until suspension four months later. Simultaneously, lifestyle changes were implemented with significant weigh loss (BMI 33 > 26.4 kg/m2 at the time of insulin suspension). After 3 years of follow-up the patient remains without need of antidiabetic therapy, with normal Hba1c 5.3%. Anti-GAD antibodies remain positive (39.4 U/mL) but C-peptide and serum insulin are within the reference range (1.69 ng/mL [1.1–4–4], 6.9uU/mL [2.6–25], respectively). Conclusion Prolonged disease remission in type 1 diabetes is rare. This case highlights an especially long “honeymoon” period in a patient with LADA. Obesity and insulin resistance probably played a role in the initial patient presentation, and its improvement probably helps to justify this prolonged remission. In spite of the family history of diabetes, other types of diabetes seem unlikely due to positive antibodies and SGLT2 inhibitor associated euglycemic ketoacidosis.

INSULIN THERAPY IN T2DM PATIENTS IN DIABETES OUTPATIENT CLINIC, DR. SOETOMO GENERAL ACADEMIC HOSPITAL, SURABAYA, INDONESIA

Highlights1. The occurrence of macrovascular and microvascular problems is strongly associated with high mortality in type 2 diabetes mellitus (T2DM).2. Combinations of rapid-acting and long-acting insulin were the most frequent kind of insulin. AbstractBackground: High mortality in type 2 diabetes mellitus (T2DM) has a strong correlation with the presence of macrovascular and microvascular complications. The risk of these complications can be reduced through good glycemic control. As the disease progresses, patients may need to add or switch to insulin therapy rather than oral antihyperglycemic drugs to achieve desirable glycemic control. Objective: To determine the pattern of insulin therapy and glycemic control in T2DM patients. Material and Method: Data for this study were obtained from the medical records of the Diabetes Outpatient Clinic at the Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. This study was an observational descriptive. In June-July 2016, total samples were collected from 124 patients who received insulin therapy between February 2015 and March 2015. Result: According to the data obtained, the most commonly used insulin was a combination of rapid-acting and long-acting insulin (75.8%). While basal bolus insulin (75.8%) accounts for the most common regimen used to administer insulin, only 27.4% and 45% of total patients achieved good glycemic control based on FPG and PPG testing, respectively. HbA1c testing was done on 44 out of 124 people, with 9 people (20.5%) met the target of HbA1c <7%. Conclusion: Glycemic control in T2DM patients who received insulin therapy was relatively low.

Growth Hormone and Growth Retardation in Autoimmune Type-1 Diabetes. Insulin an Important Endocrine Growth Factor

Growth hormone (GH) secretory alterations and dysregulations with insulin-like growth factor-I (IGF-1) axis among type-1 diabetic children and adolescents is well established. In this poorly controlled abnormal metabolic state, GH hypersecretion is observed with decreased levels of Insulin-like Growth Factors (IGFs), IGF binding proteins-3 (IGFBP-3), and growth hormone binding protein (GHBP). These all factors results in decreased growth velocity and growth retardation in type-1 diabetic children and adolescents. Insulin is the most important metabolic regulator of this system. Absolute insulin deficiency, as observed in type-1 diabetics, is the primary cause of this dysregulation and alterations. Several published studies have shown that elevated HbA1c and poor glycaemic control are the main factors of this abnormal metabolic state. Conversely, studies have also demonstrated that good glycaemic control with basal bolus insulin regimens or insulin pump can improve diabetic state with restoration of normal growth. Hence this perspective review focuses on these important aspects of growth abnormalities in type-1 diabetic patients and concludes that health care policy makers should develop a close monitoring program and system with multi-disciplinary team approach to prevent further diabetes related growth complications.

Role of New Insulin Analogs in the Management of Diabetes. A Clinical Review

This paper has reviewed different insulin analogs currently available in the market and pharma industry, their safety, efficacy and their roles in the diabetes management, comparing with human regular and NPH insulin. Traditional insulins (human regular and NPH insulins) do not have constant or smoother pharmacokinetic and pharmacodynamic profiles and are usually associated with erratic blood glucose profiles with hypoglycemia or hyperglycemia when compared with analog insulins. Similarly they do not match physiologic insulin profiles with basal bolus format. According to the medical literature, current insulin analogs are more efficacious and also it has been documented in research trials that recent insulin analogs are better and safer as compared to human regular and NPH insulin in terms of hypoglycemia and HbA1c reductions. Hence this paper has reviewed these insulins analogs (longer acting basal and rapid acting insulin analogs) for their safety and efficacy in terms of hypoglycemia and HbA1c control, for the management of both type-1 and type-2 diabetics in hospitals and clinics.

Study of clinical profile and treatment of type 1 diabetes mellitus in pediatric patients at a tertiary care centre

Background: Type 1 diabetes mellitus (T1DM) is multifactorial autoimmune disease that leads to destruction of insulin-producing pancreatic β cells. Although exact etiology of T1DM is still unknown, researchers believe there is genetic predisposition, with strong link with specific HLA (DR and DQ2W) alleles. Treatment is directed at replacing missing hormone, insulin. After availability of more medical facilities, improvement in diagnosis and increasing awareness of diabetes, more cases of T1 DM have been diagnosed and treated. Aim of study were to study clinical profile of T1 DM in hospitalized children and to study effect of various insulin regimens in children with T1 DM.Methods: Study design was of prospective observational, carried out at paediatric ICU and pediatric wards of civil hospital Ahmedabad, conducted from 01 August 2017 to 31 July 2021 (4 years) and study population was 150. Results: Maximum numbers of patients (50.0%) were diagnosed as T1 DM in the age group of 5‐10 years in the present study. Diabetic ketoacidosis was the most common cause of hospitalization in 111 patients (74.3%). Most common presenting symptom in present study was polyuria and polydipsia (81.4%). In the present study, 88.6% patients were discharged. With basal bolus regimen, better glycaemic control was achieved. Incidence of hypoglycaemic events was also lesser (37.5%) with basal bolus regimen compared to split mix regimen (62.5%).Conclusions: Diabetic ketoacidosis was the most common cause of hospitalisation. Better glycemic control was achieved through Basal Bolus Regimen.

Effectiveness, Safety, and Appropriateness in the Use of the Fixed-Ratio Combination of Insulin Glargine and Lixisenatide in Type 2 Diabetes: The ENSURE Retrospective Real-World Study.

Pivotal trials documented glycemic benefits of fixed-ratio combination of insulin glargine 100U/mL and lixisenatide (iGlarLixi), with no weight gain and low hypoglycemia risk in type 2 diabetes (T2D). This study aimed at assessing effectiveness and patterns of use of iGlarLixi in a real-world setting. This was a retrospective, multicenter, study, based on electronic medical records. All patients initiating iGlarLixi from May 2018 to July 2020 were considered. Overall, 25 centers provided data on 675 patients initiating iGlarLixi with the following characteristics: age 66.4 ± 10.1years, 54.2% men, T2D duration 15.5 ± 11.5years, HbA1c 8.6 ± 1.4%, body mass index (BMI) 30.8 ± 5.3kg/m2, 45.1% already treated with basal insulin, and 21.9% with basal bolus (± oral hypoglycemic agents). Metformin and sodium-glucose cotransporter-2 inhibitors were used in 76.0% and 0.9% of patients, respectively. Combinations of iGlarLixi with other glucose-lowering drugs such as sulfonylureas or short-acting insulin were found in 32.4% of patients. Effectiveness of iGlarLixi (N = 184) showed that HbA1c declined by 0.77% [95% confidence interval (CI) -1.00, -0.54] after 6months. In combination with metformin and/or SGLT-2i (N = 117), HbA1c declined by -0.92% (95% CI -1.22, -0.62) and weight significantly decreased by 1.21kg. iGlarLixi dose was suboptimally titrated. Safety data (N = 171) showed incidence rates of blood glucose ≤ 70 and < 54mg/mL of 0.26 and 0.05 events per person-month during 6months, respectively, with a risk reduction of about 75% with respect the 6months before iGlarLixi initiation. No severe hypoglycemia was reported. In adults with T2D, effectiveness and safety of iGlarLixi were documented in a real-world setting; appropriateness of use and adequate titration should be urgently improved so that clinical practice outcomes become more comparable to clinical trials results. Further real-world studies on the effect of iGlarLixi therapy are warranted.

Fatigue and depression in elderly patients with poorly controlled diabetes.

In this study, it was aimed to evaluate the severity of depression and fatigue in patients with type 2 diabetes mellitus (T2DM), aged ≥ 60 years, with poor diabetes control. Between December 2018 and June 2019, 310 patients aged ≥ 60 years, with hemoglobin A1C ≥ 10%, followed-up with the diagnosis of T2DM for at least 3 years in the internal medicine outpatient clinics of Bursa Yüksek İhtisas Training and research hospital were included in the study. The geriatric depression scale (GDS) and fatigue severity scale (FSS) questionnaires were administered. Patients were analyzed according to their sociodemographic and clinical characteristics, according to their GDS and FSS scores. The GDS and FSS scores were higher in the female patients than in the male patients, those with diabetes aged ≥ 21 years than those aged < 21 years, those using premixed insulin than those using basal bolus insulin and oral antidiabetic drug for + basal insulin, and those living alone than in those living with their families. The FSS score was higher in patients with vitamin D levels < 20 ng/mL. The factors affecting the GDS score were the FGS and FSS scores in the multivariate analysis. The factors affecting the FSS score were the GDS, diabetes age, hemoglobin level, and vitamin D level in the multivariate analysis. Poorly controlled diabetes affects elderly patients more in terms of their mental and physical health. Therefore, these patients should be considered in terms of psychosocial aspects to increase treatment compliance and effects.

Management of Type 2 Diabetes With Insulin Glargine-100 in Iraq in a Real-Life Observation.

Introduction: Type 2 diabetes mellitus (T2DM) management is challenging in conflict zones, such as Iraq, and insulin might not be readily prescribed or available to patients who need it. This study describes the profile of Iraqi T2DM patients treated with insulin glargine-100 (Glar-100) and their response to the treatment. Research design and methods: This observational, multicenter registry collected data over six months on demographic and medical history, insulin regimen, changes in glycemic parameters, and vital signs in patients with T2DM in Iraq. Results: Patients (N = 245) were 55.2 ± 10.2 years old, with 58.4% females. They had had diabetes for 10 years, with baseline glycated hemoglobin (HbA1c) levels of 10.3% ± 1.6% (89 mmol/mol), diabetes complications, and co-morbidities. Almost all were on oral anti-diabetics before treatment intensification with Glar-100. Over 50% of patients with prior insulin exposure were receiving basal plus or bolus regimens at baseline, versus 6% of insulin-naïve patients, though some required treatment intensification. Most were asked to self-titrate according to fasting plasma glucose (FPG), but self-titration proved challenging. Upon Glar-100 treatment, HbA1c and FPG levels significantly decreased (P < 0.001), and 20% of patients (mostly insulin-naïve) achieved HbA1c < 7% (53 mmol/mol). Vital signs improved, while weight changes were modest. Most safety events were mild, and only two patients discontinued Glar-100. Conclusion. Glar-100 safely and effectively decreased FPG and HbA1c levels, achieving HbA1c control in some patients. Glar-100 is a promising T2DM therapeutic option in Iraq.

PSUN227 A retrospective comparison of Basal Bolus using Glargine U-300 and Glulisine with Premix Insulin

Abstract Objectives The objective of this retrospective analysis was to compare the occurrence of Level 1 hypoglycaemia, Level 2 hypoglycaemia, nocturnal hypoglycaemia and mean HBA1C reduction in patients treated with premixed insulin 30/70 (Insulin Isophane/NPH 70% + Human Insulin/Soluble Insulin 30%) and after initiating a basal bolus regime using Glargine U-300 and Glulisine. Level 1 hypoglycaemia is blood glucose less than 70 mg/dL but above 54 mg/dL. Level 2 hypoglycaemia is blood glucose less than 54 mg/dL. Methodology and Data Analysis Data was collected retrospectively over 6 months on adult outpatients who were on pre mix insulin 30/70 for at least 2 years and who frequently experienced hypoglycaemic episodes and after transitioning these patients to a basal bolus regime Glargine U-300 and Glulisine. Those were having an underlying etiology which would predispose them to hypoglycaemia were excluded. The exclusion criteria included malignancy, drug induced causes except premix insulin, Chronic Kidney disease stage 4 or 5 and acute or chronic hepatic failure. Blood glucose monitoring was done by a 7 point Self Monitoring of Blood Glucose. A total of 30 cases were randomly chosen and data were sought from patients’ home glucose logs, case notes and Electronic health care records. Data were analysed by Microsoft Excel and was compared with paired-T test. Results The average number of Level 1 hypoglycaemic episodes per week on premix insulin dropped from 6.517 to 0.9655 (t = -10.807456, p&amp;lt;0.00001) after initiating the basal bolus regime. The average number of level 2 hypoglycaemic episodes per week dropped from 2.034 to 0.379 (t = -8.733497, p&amp;lt;0.00001) after changing to basal bolus regime. There was also a reduction in the occurrence of average nocturnal hypoglycaemic episodes from 2.655 on pre mix insulin to 0.2068 on the basal bolus regimen (t = -8.635475, p&amp;lt;0.00001).The mean HbA1C reduction was 3.16% in three months after commencing the basal bolus regime (t = -27.554737, p&amp;lt;0.00001). Conclusions Outpatient treatment with the basal bolus regime consisting of Glargine U -300 and Glulisine as compared to the premix insulin use showed a marked reduction in Level 1 and Level 2 hypoglycaemic episodes and nocturnal hypoglycaemic episodes per week. The decreased hypoglycaemic event rates in hypoglycaemia resulted in better compliance and adherence which was reflected as a significant reduction in HbA1C. In the future more retrospective and prospective studies will be helpful with Glargine U-300 and Glulisine. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

LBODP024 Successful Adrenal Vein Sampling Using Dexamethasone Premedication In Patients With Iodine Contrast Media Allergy

Abstract Background Preparation of patients with iodine contrast media (ICM) allergy who require adrenal vein sampling (AVS) to establish source of aldosterone excess in confirmed primary aldosteronism (PA) is controversial. Usual premedication with high dose prednisone can interfere with cortisol determinations, possibly altering the aldosterone-to-cortisol ratios for the identification of lateralized aldosterone excess. Objective Evaluate the efficacy and safety of premedication with high dose dexamethasone to perform AVS in patients with ICM. Methods 177 consecutive patients with confirmed PA who underwent bilateral simultaneous basal and post ACTH bolus AVS at our center between January 2010 and December 2020 were retrospectively analyzed for reported ICM allergy. A total of 7 patients (4%) with history of allergic reactions to ICM were premedicated with three doses of 7.5 mg dexamethasone rather than the usual 50 mg of prednisone. Results No breakthrough allergic reactions were reported in the 7 patients. The mean age at the time of AVS procedure was 55.1 ± 16.8 years. Patients had been hypertensive for a mean of 6.7 ± 5.9 years. The mean systolic blood pressure on the day of the procedure was 137.4 ± 4.2 mmHg and the mean diastolic blood pressure 77.1 ± 12.9 mmHg. Most patients had at least 2 anti-hypertensive medications in their drug regimen prior to AVS procedure, none being mineralocorticoid receptor antagonists. Dexamethasone suppression effect on AVS: All basal peripheral cortisol levels were suppressed, &amp;lt; 50 nmol/L, confirming lack of meaningful cortisol co-secretion. The basal and post-ACTH selectivity index were respectively &amp;gt;2 and &amp;gt; 5 bilaterally in all patients, confirming adequate cannulation of both adrenal veins. Basal peripheral plasma aldosterone concentration (PAC) was also reduced by dexamethasone administration by an average of 66 ± 30% in comparison with PAC measured before AVS. Despite basal suppression, PAC increased following ACTH bolus injection with an average rise of 698.8 ± 644.5% from baseline. AVS results: Four patients had lateralized (A/C ratio &amp;gt; 2 basally and &amp;gt;4 post ACTH), while three had bilateral source according to AVS results. Follow up data for a mean of 58 ± 41.4 months was available for 6 patients. In the three patients who underwent unilateraladrenalectomy for lateralized source, basal and post-ACTH lateralization ratios were concordant. All 3 patients had contralateral suppression, confirmed adrenocortical adenoma at histopathology and clinical (n=3) (normal blood pressure without medication) and/or biochemical cure (n=2) (direct renin concentration &amp;gt; 10 ng/dL) at follow up. Conclusion AVS using dexamethasone premedication is safe and accurate for diagnosing source of aldosterone excess in patients with PA and ICM allergy. Presentation: No date and time listed

LBSAT236 A Case of Immune Checkpoint Inhibitor Pembrolizumab Induced Simultaneous Rare Endocrinopathies, Type 1 DM (presenting As DKA) And Grave's Thyrotoxicosis, With Evidence Of Autoimmunity Development.

Abstract Introduction Pembrolizumab is a novel immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1), which has been linked to endocrinopathies. We present a rare case of type 1 DM and Grave's disease noted in setting of Pembrolizumab use. Case presentation A 56 year old female with history of Hodgkin's lymphoma (being treated with Pembrolizumab), heart failure and type 2 DM was sent to the ED from oncology infusion clinic for labs concerning for DKA. She endorsed fatigue, light-headedness, polydipsia and polyuria. She had moderate to severe DKA with bicarbonate 9 mmol/L (22 - 31), anion gap 29 mmol/L (7 -17), venous Ph 7.16 (7.30 - 7.40), beta hydroxybutyrate 9.4 mmol/L (0 - 0.3) and blood glucose 451 mg/dL (70 - 100). She was admitted to the ICU and started on insulin drip. She had a 20 year history of type 2 DM and prior to this episode had been managed on Metformin 500 mg daily alone with good glycemic control (HbA1c 5.7 - 7.1%) and had never had DKA before. Of note, she also reported recent 75 pound weight loss which she attributed to lifestyle changes. GAD65 antibody assay was positive 5.49 nmol/L (&amp;lt;=0. 02 nmol/L). She was discharged on a basal bolus insulin regimen and continues to follow up with Endocrinology. On admission, she had thyrotoxicosis with TSH 0. 06 uIU/mL (0.50 - 5.70), fT4 1.8 ng/dL (0.9 - 1.7), and total T3 99 ng/dL (80 -200) while clinically euthyroid. Repeat TFTs in one week were consistent. TSI was elevated 1.8 (&amp;lt;=1.3 TSI Index). 10 days later, labs showed improvement TSH 0. 09 uIU/mL, fT4 1.2 ng/dL and total T3 130 ng/dL. As she was clinically euthyroid and noted to have improving levels, she was managed conservatively. However, one additional one month later, tests were repeated and showed progression to hypothyroid state - TSH 44.23 uIU/mL and fT4 0.4 ng/dL. She was started on Levothyroxine supplementation. Repeat testing showed normalization of TSH. Discussion Our patient had long standing history of well controlled Type 2 DM and no history of thyroid abnormalities yet presented with moderate to severe DKA and thyrotoxicosis due to Grave's disease shortly after initiating immune checkpoint inhibitor therapy. GAD65 antibody and TSI panel were positive indicating development of autoimmunity. Although rare, development of rare endocrinopathies such as insulin deficient diabetes and Grave's disease are important side effects of immunotherapy. Patients being treated with immunotherapeutic agents should be monitored closely with serial metabolic panel testing for the first twelve weeks after starting therapy. In addition, a low threshold should be maintained for testing for additional thyroid related endocrinopathies. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSUN292 Learning Lesson From A Case of Fulminant Type 1 Diabetes Mellitus Shortly After Pembrolizumab Treatment

Abstract Background Immune checkpoint inhibitors (ICIs) in cancer treatment are considered one of the major breakthroughs in the past decade. Pembrolizumab (PBL) is one of the immune checkpoint inhibitors that targets the programmed cell death protein-1 (PD-1) receptor in order to block its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). By inhibition of these molecules, PBL helps increase T-cell activation against cancer cells. Unfortunately, this inhibition also enhances autoimmunity against normal cells, leading to immune-related adverse events (irAEs) including endocrinopathies. Unlike other irAEs, endocrinopathies are usually irreversible upon diagnosis. While hypophysitis, hypo/hyperthyroidism, and adrenal insufficiency are more commonly reported, type 1 diabetes mellitus (T1DM) is also seen around 0.9 to 1.9% of cases. Unfortunately, it can become fatal if not being promptly recognized. To raise awareness about this life-threatening adverse event, we are reporting a case of new onset T1DM, presenting with diabetic ketoacidosis (DKA) only after 22 days of the first PBL infusion. Clinical case A 19-year-old male was recently diagnosed with NUT (nuclear protein in testis) carcinoma of the left floor of mouth with high PD-L1 score. NUT carcinoma is a rare type of squamous cell cancer with chromosomal rearrangement in the nuclear protein in testis gene (NUTM1) that makes the cancer aggressive and resistant to standard therapy, hence requiring a multimodal approach. This patient underwent surgery followed by concurrent cisplatin-radiation and PBL. Two weeks after his first PBL infusion, he suddenly developed polydipsia, polyuria, and nausea. He continued to receive the second PBL dose on day 20 and developed DKA on day 21. His work-up revealed a plasma glucose of 856 mg/dL, anion gap of 20 (H), CO2 of 17 mEq/L (L), and beta-hydroxybutyrate of 3.35 mmol/L (H), while hemoglobin A1C of only 5.5% suggesting his fulminant progression. He was immediately treated with DKA protocol with clinical improvement. The patient was discharged on basal bolus insulin regimen. He had non-detectable C-peptide (&amp;lt;0.10 ng/mL) and high GAD Antibody (&amp;gt;250 IU/mL) levels, which was consistent with PBL induced T1DM. Conclusion PBL use has been linked to multiple endocrinopathies and even though rare, DKA can also be seen in setting of T-cell mediated irreversible damage to pancreas beta cells. Due to life threatening potential of DKA, clinicians should monitor patients receiving immune checkpoint inhibitors closely and should be aware symptoms of hyperglycemia for earlier intervention. | Keywords: pembrolizumab, NUT carcinoma, diabetic ketoacidosis Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSUN181 Diabetes-related outcomes following use of basal-bolus insulin vs. premixed insulin in a VA population with Type 2 diabetes: A retrospective chart review.

Abstract Background Treatment of diabetes mellitus (DM) with basal bolus insulin analogs (BB) requires up to five injections a day. The complexity of BB therapy may adversely influence patient compliance. A simpler and cheaper regimen with premixed insulin (PM) typically involves two injections a day but is perceived to be less effective in managing DM. The purpose of this research project was to compare DM-related outcomes between BB regimens (insulin detemir or glargine plus aspart, lispro or regular insulin) and PM insulin regimens (70/30 insulin NPH/regular) among our veteran population with type 2 DM. Research design and Methods This is a retrospective chart review that included 140 veterans (70 in BB group and 70 in PM group) with type2 DM. Subjects aged 18 years or above and those having A1C level ≥ 8% were included. Subjects with type 1 diabetes or who switched their insulin regimen during the follow-up period were excluded. The included subjects were followed for a year, after the start of respective insulin therapies to examine change in A1c (primary outcome) levels across groups. Data were analyzed using Chi-square/Fisher exact tests and logistic regression. All analyses were conducted using SPSS version 27 and SAS9.4. Results Out of 140 enrolled subjects, 94% were males with average age of 65.7 ± 10.1 years and DM duration of 12.9±9 years. There was no significant difference in age, gender, baseline A1c, BMI or duration of DM between the two groups. Following treatment initiation, there was no statistically significant difference between the BB and PM insulin groups for change in A1c (-1.9±1.8 vs -2.1±1.9%, p = 0.3) or for the rate of hypoglycemia (30% vs 21.4%, p = 0.3) respectively. Although the average BMI increased in both groups, the change was similar for both BB and PM groups (0.84±3.1 vs 0.4±2.2 kg/m2 respectively, p = 0.2). A logistic regression controlling for the confounders of hypoglycemia, found that the type of insulin used did not predict the development of hypoglycemia [OR 0.594, (0.251, 1.404)]. Conclusion There were no significant differences in A1c change, rate of hypoglycemia, and change in body mass index in patients treated with either BB or PM insulin among our study population. These results suggest that PM insulin is equally effective as the BB and its use can potentially improve patient compliance and reduce the cost of care. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

ODP273 Schmidt Syndrome Causing Multiorgan Failure

Abstract Introduction To our knowledge there has not been a case report published on the acute presentation of Schmidt syndrome (Polyglandular Autoimmune Syndrome Type 2) in which all three manifestations of type 1 diabetes mellitus (T1DM), primary adrenal insufficiency, and hypothyroidism were found and diagnosed at the same time. Case Description A 32-year-old male with suspected alcohol abuse presented to the hospital with nausea, vomiting, and weakness of two weeks duration after sustaining a fall. He was admitted for Diabetic Ketoacidosis (DKA) and shock requiring three pressors with unclear etiology. Labs were significant for severe hyponatremia of 113 mmol/L (136-145), elevated anion gap of 22, glucose 206 mg/dL (70-100), bicarbonate 11mmol/L (21-31), beta hydroxybutyrate 5.90 mmol/L (0. 0-0.42), and pH 7.22 (7.35-7.45) with Hemoglobin A1c 14.5% (&amp;lt;5.7). An insulin drip was instituted for DKA and the hyponatremia persisted. Cortisol was found to be suppressed at 3. 0 ug/dL (3.1-22.4) with significantly elevated ACTH 220.4 pg/mL (7.2-63.3) suggesting a new diagnosis of primary adrenal insufficiency. IV hydrocortisone 100 mg q8H was started on day 2 of hospitalization. Thyroid labs showed elevated TSH 10.10 uIU/mL (0.36-3.74) confirming hypothyroidism, prompting initiation of IV levothyroxine. His hospital course was complicated by cardiac arrest and acute respiratory failure requiring intubation. Cardiac work up was negative except for severe non-ischemic cardiomyopathy with significantly reduced ejection fraction of 20-25%. Bronchoscopy was performed and showed no evidence of obstructing pulmonary etiologies. SARS Coronavirus PCR was negative. He also had shock liver along with Disseminated intravascular coagulation (DIC). His kidney function worsened requiring continuous kidney replacement therapy (CRRT). Urine microscopy showed granular casts consistent with acute tubular necrosis. TPO antibodies, adrenal antibodies, GAD antibodies, and Zinc Transporter 8 antibodies all came back positive along with an undetectable C- peptide confirming the diagnosis of Hashimotos hypothyroidism, primary adrenal insufficiency, and T1DM respectively. He was eventually discharged on basal bolus insulin regimen, levothyroxine 75 mcg po daily, fludrocortisone 0. 05 mg po daily, and prednisone 5 mg po daily. The patient had multifactorial shock from an acute presentation of DKA, primary adrenal insufficiency, and hypothyroidism all presenting simultaneously. Conclusion This case illustrates the severe impact of having three endocrine organs affected all at once. The prevalence of Schmidt syndrome is very low at 1: 20,000 in the general population and can be associated with other non-endocrine autoimmune disorders. Prevalence of autoimmune thyroid disease is 70%, T1DM 50%, and Addison's disease is almost 100%. Due to the low prevalence, one needs a high clinical suspicion with the correct lab findings to diagnose this disease. Incorrect diagnoses or a late diagnosis can lead to life threatening consequences to the patient. The mainstay of treatment is hormone replacement, with corticosteroids given before thyroid replacement. Presentation: No date and time listed

LBSUN293 Diabetic Hand Infection: A Case Report

Abstract Background Diabetes Mellitus is related to musculoskeletal and soft tissues complications in a very diverse way, and with no doubt, hands are also affected. Almost 40% of people living with Diabetes have significant problems in the hands that require medical attention. (1) Clinical Case: A 59-year-old women with history of Diabetes Mellitus diagnosed 20 years ago without control, treated with NPH and Lispro insulin (basal bolus regimen). She was admitted to the emergency room due to a third-degree boiling water burn in her right index finger. Before she came to the hospital, she was previously evaluated by a physician who prescribed antibiotics (clindamycin) for 5 days without response. At physical examination, erythema, edema, purulent secretion was found in the finger. In addition, fever and high glucose levels were also noted. During hospitalization, intravenous antibiotics such as tigecycline and oxacillin were used with no improvement. Blood samples demonstrated leukocytosis and C-reactive protein (CPR) elevated levels. Secretion culture was positive to Methicillin-sensible Staphylococcus Aureus. Electromyography revealed severe lesions at sensory-motor peripheral nerves with chronic denervation in upper limbs. Due to the poor evolution of the injury, traumatologists indicated surgical cleaning. After 2 days, leukocytosis and CPR elevated levels persisted and despite all the efforts done to save the finger, traumatologists decided to perform an amputation. After 2 weeks of antibiotic treatment, the patient was discharged with normalized hemogram and CPR levels. Conclusion Diabetic hand infection is less recognized in the literature that the diabetic foot, main reason why it is easily ignored and underestimated; resulting in increased morbidity among diabetic patients. The combination of neuropathy, peripheral artery disease and impaired glucose levels made this patient had a poor outcome, resulting in the loss of a finger. It is very important to evaluate the hands during routine controls to avoid these sad events.

IMMUNE CHECKPOINT INHIBITOR-INDUCED DIABETIC KETOACIDOSIS: A RARE SIDE EFFECT

IMMUNE CHECKPOINT INHIBITOR-INDUCED DIABETIC KETOACIDOSIS: A RARE SIDE EFFECT

De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes.

To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24months. Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. We included 156 subjects (63.5% males; age 62 ± 11years, HbA1c 70 ± 22.0mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6months after introducing a GLP-1RA and remained stable up to 24months (all p < 0.0001 vs. baseline). At 24months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.

Calibration of insulin pumps based on discrete doses at given cycle times.

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper.

Factors associated with high glucose variability in patients with type 1 diabetes

BACKGROUND: High glucose variability (GV) is recognized as a risk factor for vascular diabetic complications and hypoglycemia. Factors affecting GV in patients with diabetes needed to be clarified.AIM: To determine the factors associated with high GV in adult patients with type 1 diabetes.MATERIALS AND METHODS: We conducted a single center cross-sectional observational study. In-patients with type 1 diabetes aged 18 to 65 years on basal bolus insulin therapy were included. Day-time and nocturnal Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), Mean Absolute Glucose (MAG) were calculated from continuous glucose monitoring data. The values of CV, MAGE, MAG within the upper quartile were considered high.RESULTS: The study included 400 individuals, including 111 on continuous subcutaneous insulin infusion (CSII). Patients with high GV had lower fasting and postprandial C-peptide levels and higher insulin doses. According to ROC analysis, daily insulin dose &gt;0.69 U/kg and estimated glomerular filtration rate (eGFR) ≥90.5 ml/min×1.73 m2 were associated with high nocturnal CV values. Dose of basal insulin &gt;0.292 U/kg and bolus insulin &gt;0.325 U/day were associated with nocturnal MAGE. Body mass index (BMI) ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, HbA1c ≥8.3%, eGFR ≥89.5 ml/ min×1.73m2 increased risk of high MAG at night. High day-time CV values were associated with daily insulin dose ≥0.675 U/kg and daily dose of BI ≥0.286 U/kg. The risk of high MAGE was increased with HbA1c ≥8.24% and basal insulin dose ≥0.286 U/kg. BMI ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, daily dose of bolus and basal insulin ≥0.325 and ≥0.29 U/kg respectively, and HbA1c ≥8.33% were the risk factors for high day-time MAG. Patients on CSII had lower MAGE (p&lt;0.001) and MAG (p=0.008) compared to those on multiple daily injections.CONCLUSION: In type 1 diabetes, high GV is associated with undetectable residual insulin secretion, normal or reduced body weight, preserved kidney function, supraphysiological doses of insulin, and non-target HbA1c. Patients on CSII have a lower GV than those on multiple daily injections.