bluuebunny/crossref_metadata_2025 huggingface dataset:
LBODP029 Pseudohypobicarbonatemia In The Setting Of Diabetic Ketoacidosis And Severe Hypertriglyceridemia
Authors: Lamb Seth , Wee Erica , Halpin Kelsee
Published: November 2022

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 <5 mmol/L, anion gap of >23 mmol/L, and triglycerides of >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
ODP138 Age-related Associations of LDL Cholesterol and Atherosclerotic Cardiovascular Disease: A Nationwide Population-based Cohort Study
Authors: Kim Min-Ju , Kim Min-Seon , Min Se Hee , Na Jung Han , Jung Chang Hee , Kim Ye-Jee
Published: November 2022

Background

No completed randomized trial exclusively incorporating the elderly has addressed the benefit of statin treatment for primary prevention until now. Therefore, consensus of major international lipid management guidelines has not been made upon lowering LDL cholesterol (LDL-C)to prevent primary atherosclerotic cardiovascular disease (ASCVD)in the older population. Question: This study aimed to investigate whether ASCVD risk according to increasing LDL-C differs between age groups.

Methods

Data was provided by the Health Screening Cohort of the Korean National Health Insurance Service, which is a nationwide health screening program covering the whole population with alow attrition rate. Subjects with preexisting cardiovascular disease or taking lipid-lowering drugs were excluded. Participants were followed up from January1,2011 to December31, 2015. Multivariable Cox proportional hazard regressions were performed to evaluate the relationship between LDL-C and ASCVD. Subgroup analyses were also conducted in patients with T2DM.

Results

The final cohort was composed of 285,119 participants with a mean age of 58.4 years and 55.2% of men. The average baseline LDL-C level was 121.5 mg/dL (standard deviation, 36.4). The proportion of individuals was 2.4% (n =6,718),9. 0% (n = 25,687), 26.6% (n = 75,981), 37.2% (n = 105,952), 20.2% (n = 57,562), and 4.6% (n = 13,219) in LDL-C ≥190, 160–189, 130–159, 100–129, 70–99, and<70 mg/dL, respectively. Patients with T2DM comprised 7.5% (n = 21,258) of the entire population. During a median follow-up of 6.44 years, the first ASCVD developed in8,996 participants (3.2%). All age groups showed positive associations between LDL-C and ASCVD risk, mostly with statistical significance from LDL-C of 160 mg/dL onward. ASCVD risk did not differ significantly between the age groups (P for interaction =0.62). Compared with ASCVD risk in LDL-C of 70–99 mg/dL, the risk in the highest LDL-C(≥190 mg/dL)was similar between groupsaged<50 and ≥70 years (adjusted hazard ratio [aHR], 1.90 [95%confidence interval (CI),1.52–2.38] and aHR, 1.86 [95% CI, 1.30–2.68], respectively). Subgroup analysis in patients with T2DM showed that 7.2% of subjects experienced incident ASCVD. Age-specific association of ASCVD risk and LDL-C in T2DM patients displayed no difference in line with the total participants(P for interaction = 0.31).

Conclusions

A large-scale, population-based cohort study of adults who had no previous CVD history and were not prescribed lipid-lowering drugs demonstrated that elevated LDL-C was significantly correlated with a greater risk of ASCVD in people aged≥70 years, which was comparable with the risk in younger adults. This finding spotlights the necessity of settling intensive guidance on LDL-C levels for primary CVD prevention in the elderly.

Presentation: No date and time listed
ODP143 Cushing Syndrome - A Potential Risk Factor For Atrial Fibrillation
Authors: Konindala Navya , Park Kyeeun , Enriquez Leidy Plaza , Aung Pyi Phyo
Published: November 2022

Introduction

Cushing syndrome (CS) is a systemic disorder characterized by prolonged exposure to high cortisol hormones. Our study analyses the association of Cushing syndrome as a risk factor for atrial fibrillation (A-fib), its effect on associated complications and mortality.

Methods

We conducted a retrospective analysis of 3 years of the National Inpatient Sample (NIS) data base from 2016 to 2018. Patients with Cushing syndrome, in association with/without A-fib were selected using ICD-10 diagnosis code. Discharge-level weight analysis was used to produce a national estimate. We conducted multivariate regression analysis to calculate odds ratio. RESULTS: During the study period 107,024,275 patient met inclusion criteria. 35,309 patient was diagnosed with CS. Mean age of Cushing patients was 52 and non-Cushing patients was 49. History of hypertension, congestive heart failure (CHF) and obstructive sleep apnea (OSA) were more prevalent in CS population (42. 03% v 29.34%, 20.99% vs 14.18, 17.29% v 5.86). Cushing patients had less prevalence of ischemic heart disease (5.10% v 5.91%). After adjusting with age, hypertension, CHF, ischemic heart disease, race and OSA, CS is related with higher prevalence of A-fib (OR 1.13, 1. 03-1.24, p = 0. 014). However it doesn't increase the complications of A-fib. While 3.70% patients with both CS and A-fib developed ischemic stroke, 3.81% patients without Cushing had the ischemic strokes. No arterial embolic events were detected in CS patients with A-fib, but 0.41% of patients without CS had arterial embolism. Univariate regressions demonstrated no significant association between CS and ischemic stroke associated with A-fib (p = 0.898). Our study also demonstrated that CS is related with high in-hospital mortality. When it was adjusted to age, sex, congestive heart failure, ischemic stroke and chronic kidney disease, CS with concomitant A-fib is associated 1.8 times higher mortality (OR 1.8, 1.27- 2.60, p = 0. 001).

Discussion

Several studies have demonstrated a possible association between serum cortisol level and the risk of A-fib. To our knowledge, this is the first study to demonstrate CS's clinical significance on A-fib. In our analysis, a statistically significant association was found between A-fib and CS with higher in-hospital mortality reported in patients with CS and concomitant A-fib. Patients with CS tend to have higher CHA2DS2-VASc Score but there is no association with higher risk of complications from A-fib. Our study prompts the need for further research to establish CS as an important risk factor for atrial fibrillation.

Presentation: No date and time listed
ODP145 Epigenesis of 11beta-hydroxysteroid dehydrogenase 1 in the adipose tissue of aldosterone-producing adenoma
Authors: Aono Daisuke , Demura Masashi , Karashima Shigehiro , Kometani Mitsuhiro , Konishi Seigo , Sawamura Takashi , Takeda Yoshimichi , Takeda Yoshiyu , Yoneda Takashi
Published: November 2022

Objective

11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) is the key enzyme of metabolic syndrome. The transcript-specific epigenetic regulation of 11b-HSD1 (HSD11B1) is reported. We examined the HSD11B1 mRNA level and methylation status of the promoter region of the HSD11B1 in the adipose tissue of patients with aldosterone-producing adenoma (APA).

Methods

We evaluated 10 adipose tissue specimens from patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 7 tissue specimens from patients with non-functioning adrenal adenoma (NFA). Primary aldosteronism was diagnosed according to the guideline of the Japanese Endocrine Society. The expression levels of HSD11B1 mRNA were quantified using a real time PCR. Isolated DNA was treated with bisulfite and amplified using primers specific for the humanHSD11B1promoter region.

Results

The glycohemoglobin level was significantly higher in patients with APA compared with those with NFA (p<0. 05). Blood pressure was significantly elevated in patients with APA compared with those with NFA (p<0. 01). TheHSD11B1 mRNA level and the enzyme activities were significantly increased in the adipose tissues of APA compared with NFA patients (p<0. 05). The methylation ratio was not significantly different between APA and NFA patients.

Conclusion

These results may suggest that adipose11beta-HSD1 contributes to metabolic abnormalities in APA. The pathophysiological significance of epigenetic control of 11beta-HSD1 gene in the adipose tissue should be further studied.

Presentation: No date and time listed
ODP151 Hypothyroidism and Cardiac Remodeling in Ischemic Strokes
Authors: Rashid Hytham , Brown Jonathan , Pansuriya Tusharkumar , Khalaf Khaled , Raza Syed
Published: November 2022

Hypothyroidism has been shown to increase the risk of developing cardiovascular disease (CVD), yet the mechanism is not well described. Previous studies correlated hyperlipidemia, diastolic hypertension, and smoking with impaired thyroid function, which serve as independent risk factors for CVD. Our study seeks to understand the prevalence of hypothyroidism in ischemic strokes. We hypothesize that hypothyroidism may exacerbate the severity of co-morbidities accelerating cardiac remodeling and risk for ischemic strokes. Our multi-center retrospective study constructed a database of 646 patients who were admitted over a three year period for a primary diagnosis of ischemic stroke. Detailed chart review excluded patients with known risk factors for ischemic strokes including: atrial-fibrillation, atrial-flutter, prior stroke, carotid artery stenosis, thromboembolic disease, and an active cancer diagnosis. Cardiac remodeling was identified by the hallmark finding of left atrial enlargement (LAE) on transthoracic echocardiogram (TTE) with severity determined as a composite measurement of either left atrial diameter (LAD) or left atrial volume index (LAVI). Inclusion criteria were met by 482 patients (75%), where 349 (54%) were female, 435 (67%) were Caucasian, 390 (60%) had hypertension, 360 (56%) had hyperlipidemia, 291 (45%) were previous or current tobacco users, and 199 (31%) had diabetes. Our preliminary analysis found that 83 (13%) of patients had a diagnosis of hypothyroidism. Of note, TTE reports available for 225 (35%) of patients, wherein 74 (33%) of patients met at least one criteria for LAE. Our initial findings support further subgroup analysis to characterize the significance of hypothyroidism as a comorbidity in the development of ischemic strokes. Further research may identify the individual contribution of hypothyroidism to the severity of cardiac remodeling, as well as the impact of treatment for hypothyroidism in stroke risk reduction. Our preliminary analysis found 74 (48%) of patients met at least one criteria for LAE.

Presentation: No date and time listed
LBODP032 Case Report Of A 13 Years Old Female With A Novel Pathogenic Variant In The Hnf1b Gene
Authors: Griffing Emily , Tsai Sarah J L
Published: November 2022

Background

MODY5 results from mutations in the gene encoding hepatocyte nuclear factor 1 homeobox B (HNF1B), a transcription factor critical in development of the pancreas, liver, intestines, and the urogenital tract (1). We report the case of a pediatric patient with a novel frameshift variant (p. Phe309SerfsTer18) in the HNF1B gene accounting for the co-occurrence of diabetes mellitus and structural renal abnormalities. Clinical case: A 13-years-old female with chronic kidney disease stage 3 (eGFR = 48 ml/min/1.73m2) secondary to congenital dysplastic-appearing left kidney and surgical removal of a cystic dysplastic right kidney was referred to our diabetes clinic for hyperglycemia. She reported long-standing polyuria and polydipsia previously attributed to her kidney disease. She required laparoscopic right nephrectomy at age 5 years due to increasing cyst size. Her left kidney also has small renal parenchymal cysts which have been monitored over time. There is no known family history of kidney disease, and grandparents have a history of diabetes. Laboratory investigation revealed a random blood glucose of 478 mg/dL and a hemoglobin A1c of 12.2%. She was not in diabetic ketoacidosis. She had a detectable insulin level of 5.1 mcIU/mL and C-peptide was 3.4 ng/mL. She was initially presumed to have Type 1 diabetes based on a relatively low insulin level and started on basal-bolus insulin (up to 0.59 units/kg of weight/day). Glycosylated hemoglobin was 8.7% one month after diagnosis. Glutamic acid decarboxylase, zinc transporter, islet cell, and insulin autoantibodies were not detected, however, and she was then suspected to have either Type 2 diabetes or MODY. Approximately one year later, she was taken off insulin due to hypoglycemia and managed only with metformin 500 mg twice daily. Next-generation sequencing revealed a de novo pathogenic variant in HNF1B causing a frameshift deletion (p. Phe309SerfsTer18). Genetic testing of parents was negative. Once her diagnosis of MODY5 was made, she was started on glipizide 2.5 mg once daily which has been titrated up to a dose of 5 mg with some success. However, she has since been re-started on insulin (up to 0.2 units/kg/day) due to hyperglycemia keeping in line with the MODY5 phenotype likely causing destruction of beta cells over time (1).

Conclusion

We report a case of MODY5 with a novel frameshift mutation (p. Phe309SerfsTer18) in the HNF1B gene. This case highlights the importance of screening for HNF-1B mutations in those patients with structural renal abnormalities and hyperglycemia, as diagnosis can guide management decisions and provide prognostic information. Reference Bellanné-Chantelot C, Chauveau D, Gautier JF, et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med. 2004;140(7): 510-517. doi: 10.7326/0003-4819-140-7-200404060-0000

Presentation: No date and time listed
LBODP063 The Benefits Of Using Cgm For Intravenous Insulin Therapy
Authors: Bublik Evgeniya , Udovichenko Oleg , Olga Vinogradskaya , Aleksandr Farmanov , Salima Deunezheva , Irina Tobianskaya , Popova Yadviga , Frolova Nadezhda
Published: November 2022

Modern glycemic monitoring systems make it easier for doctors and nurses to manage diabetic patients on intravenous insulin therapy in hospital wards and intensive care units (ICU). But one of the most important questions - is it safe for inpatients and usable and cost-effective for hospitals?In our study, we included 1,684 glucometer measurements and 72 cycles (1 cycle = 6 days) of the glycemic monitoring system (Guardian Connect Enlite, Medtronic) in patients on intravenous insulin therapy. Most of them were after pancreatectomy. The mean discrepancy between CGM and glucometer values was -4.1%. According to our study, 77.48% of patients were within the target glycemic range (77.4 mg/dL to 189 mg/dL / 4.3 mmol/L to 10.5 mmol/L), hypoglycemia below 50.4 mg/dL / 2.3 mmol/L was recorded in only 2 cases out of 1648. Results confirm safety and usefulness of glucose monitoring systems in-hospital even in the most severe patients, such as those who were in several days after total pancreatectomy. We compared the cost glucose control using of CGM during of one cycle (6 days) and cost glucose control using glucometer during the same period (6 days) for diabetic patients on intravenous insulin therapy in the inpatient department. We account the cost of the CGM system, batteries, smartphone, glucometer, lancets, test strips, sensors, gloves, antiseptic wipes.

Results

6 days glucose control for diabetic patients on intravenous insulin therapy of using CGM (including 3 times a day using glucometer for calibration of CGM) cost 5422 rubles (68.2 $ / 62.7 €), using only glucometer (18 times a day) cost 6696 rubles. But the most interesting results were after comparing the nurse's time, spent on the glucose control for diabetic patients on intravenous insulin therapy. During 6 days of using of CGM for this patients nurse spends (including 3 times a day using glucometer for calibration of CGM) - 71 minutes. During 6 days of using only glucometer (18 times a day) for this patients nurse spends - 324 minutes. In that way using of CGM for diabetic patients on intravenous insulin therapy save for nurse 253 minutes (nearly 4 hours) during 6 days. The cost of 1 hour of nurse for private hospitals in Moscow in ICU an average 661 rubles (8.3 $ / 7.65 €), in inpatient department - 544 rubles (6.85 $ / 6.3 €). In finally results show a significant cost-effective of using CGM. Nevertheless, well-known the other one of the most important benefit of using CGM devices is that glycemic control with CGM systems improves the quality of life of patients, because no routine finger pricking is required.

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.
Authors: Arora Gunjan , Patel Toral
Published: November 2022

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 (<=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 (<=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.
LBSUN205 Clinical Practice Guidelines With Education Make A Difference
Authors: Mohieldin Mohamed Elfatih
Published: November 2022

Diabetic ketoacidosis is a serious acute complication of diabetes. Despite the advances in management of type 1 diabetes, unfortunately there is still frequent hospital admission with it. The management of diabetic ketoacidosis was variable with no clear standards of care. We implemented clinical guidelines in September 2019. Staff education was done when the guideline was launched in the hospital. We audited our work a year after implementing the guidelines and we found issues with adherence to the fluid management (66%), fixed rate insulin infusion (69%). The overall result showed average resolution time of 27 hours. There was no mortality or serious complication reported. Extensive reeducation of staff was done. A reaudit was done which showed Signiant improvement in adherence to the guidelines. Fluid management improved (66% to 95%) and fixed rate insulin (88% to 100%). This has resulted in improvement in resolution time from 27 hours to 12.9 hours. The good outcome of this audit is reflecting the importance of proper staff education when we implement new guidelines.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN208 Patient Education And Addressal Of Social Determinants Of Health: Key To Improvement In Diabetes Care
Authors: Manas F N U , Jaiswal Pooja , Pamula John
Published: November 2022

As per American Diabetes Association, diabetes is a 'complex chronic illness requiring continuous medical care with multifactorial risk reduction strategies beyond glycemic control'. In 2018, the prevalence of diabetes mellitus in the US population was 10.5% (34.2 million people). It is the seventh leading cause of death in the United States. The average healthcare expenditure is 2.3 times higher for diabetics than non-diabetics. The goal of diabetes care as per the American Diabetes Association and the American College of Cardiology is HbA1c less than 7%, blood pressure less than 140/90mmHg, and LDL cholesterol less than 100mg/dl. Only 19.2% of diabetic population meet all these criteria. At the Guthrie-Robert Packer Hospital, we use the 'Diabetic Bundle' as a quality metric for the standard of care for diabetic patients. It is a metric with diabetic patients seen in the past 2 years who have an active Guthrie PCP, with A1C less than 8 in the past 6 months, LDL less than 70 mg/dl (or currently prescribed a moderate or high dose statin) in the past year and age 40-75, and medical attention for nephropathy (a microalbumin test in the past year, or a nephrology visit, or are on an ACE/ARB, or have ESRD/CKD Stage 4) as a system numerator and total diabetes patients seen in the last 2 years who have an active Guthrie PCP as a system denominator. For the past few years, the resident's clinic has had lower compliance with the diabetic bundle. Multiple factors were responsible. Lack of awareness about the quality metric, discontinuity of care, failure to educate patients, poor patient involvement in diabetes care, socio-economic barriers like lack of insurance, poor family and social support, lack of transportation, poor patient compliance, and low health literacy were some of the identified factors. We conducted the prospective study to improve diabetes care by assessing 'diabetic bundle' compliance. Key interventions were focused on creating a multidisciplinary care team of the clinic director, care coordinator, informatics, nurse, resident, and faculty. Resident education regarding the diabetic bundle, patient education and involvement in diabetes care, outreach calls and mails to the non-compliant, involving the care coordinator in addressing social needs, and regular updating of the diabetes registry were some of the main interventions done during the study period. All these interventions contributed to improvement in the diabetic bundle but we believe that the most important factor in improving diabetes care was educating the patients, involving them in their diabetes care, and addressing their social determinants of health.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN210 Efficacy And Safety Profile Of Insulin Icodec Versus Insulin Glargine U100 In Type 2 Diabetes Mellitus: A Meta-Analysis Of Randomized Controlled Trials
Authors: Dimayuga Diana Colleen , Villa Michael L , Maningat Maria Patricia Deanna
Published: November 2022

In the context of diabetes, clinical inertia is defined as the failure to initiate insulin therapy or its intensification when treatment goals have not been met. Patient-related factors that contribute to this phenomenon include inability to follow complex regimens, cost of treatment and drug side effects. Icodec is a novel, investigational, ultra-long acting, once-weekly insulin analog with a potential for better treatment adherence. However, early evidence from phase 2 trials on icodec in type 2 diabetes mellitus (T2D) is conflicting. To study the efficacy and safety of insulin icodec, we conducted a meta-analysis of published randomized controlled trials (RCTs) on weekly icodec vs. daily glargine U100 in patients with uncontrolled T2D (HbA1c > 7%). A systematic search in major online databases was done to identify and review relevant RCTs. Two authors independently performed the study selection and extracted study data. Data on glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), time-in-range of 70-180 mg/dL (TIR), adverse events and hypoglycemia events were noted. Significance level of 95% was used to provide pooled estimates. Random effects model was used for analysis with significant heterogeneity (I2>50%). Three trials with 606 patients were included. Pooled analysis of available data showed that icodec resulted in a significantly greater mean reduction of HbA1c (mean difference (MD)=0.18%[0.13,0.22], p<0. 00001, I2=84% in 2 studies), mean reduction of FPG (MD=3.87mg/dl [3.18, 4.57],p<0. 00001, I2=0%), longer TIR (MD=4.39% [3.94, 4.85], p<0. 00001, I2=0%), but had significantly greater propensity to lead to level 1 hypoglycemia (Odds Ratio (OR)=1.59 [1.11,2.28], p=0. 01, I2=29%) when compared to glargine U100. Funnel plot analysis on the propensity for icodec to lead to any hypoglycemia event decreased the I2 statistic from 78% to 0% and showed significantly greater hypoglycemia events with icodec (OR=2.59 [1.67,4. 01], p<0. 001). There was no significant difference in the number of patients with end-of-trial HbA1c <7%, and any adverse event, or hypoglycemia level 2 or 3. Of note, only one hypoglycemia level 3 event was noted (patient on icodec). Once-weekly icodec had significantly better glycemic control compared to daily glargine U100, but had significantly greater hypoglycemia events. Data from ongoing trials on this novel drug can be added to the analysis as they become available.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN289 Ketonuria — A Possible Early Indicator Of Impending Euglycemic DKA In Setting Of Recent SGLT-2 Inhibitor Use And Acute Stress
Authors: Arora Gunjan , Gerais Yasmin
Published: November 2022

Introduction

- Euglycemic DKA is a notorious entity; previously thought to be primarily afflicting type 1 diabetics and rarely type 2 diabetics in a state of relative insulin deficiency, it has now become a major cause of concern and lead to the issuance of FDA warning in 2015 with regards to its link with SGLT-2 inhibitors. Although DKA is characterized by hyperglycemia, metabolic acidosis and ketogenesis, euglycemic DKA poses a diagnostic challenge as it remains disguised under the cover of euglycemia. Moreover, in the setting of recent SGLT-2 inhibitor use, this definition becomes even more of a paradox as SGLT-2 inhibitors, by the virtue of their action, promote ketogenesis thereby further adding to this enigma.

Case presentation

- A 67 year old male with hypertension and diabetes mellitus type 2 (on Metformin and Empagliflozin) presented to the emergency room with dizziness. He woke up to go to the bathroom that day and felt weak, dizzy and like he was going to fall. He endorsed nausea and vomiting but denied headache, fever, chills, chest pain, shortness of breath, abdominal pain, and problems with urination/bowel movements. He was afebrile and hemodynamically stable. On examination, left sided dysmetria, loss of coordination, and axial imbalance were noted. No motor/sensory deficits. Labs were significant for WBC count 10 k/mm cu (4 - 11), Creatinine 0.78 mg/dL (0.7 - 1.3), Glucose 279 mg/dL (70 - 99), Bicarbonate 21 mmol/L (21 -31), Anion gap 19 mmol/L (6 - 14), and Lactate 3.2 mmol/L (0.7 - 2). Urinalysis showed glucosuria (glucose >500 mg/dL) and ketonuria (ketones 20 mg/dl). CT head was negative but MRI brain showed left inferior cerebellar peduncle acute ischemic infarct. Stroke protocol was initiated and he transferred to telemetry. The next day, labs showed Glucose 166, Bicarbonate 13, Anion gap 21, and Ketones 5.6 mmol/L (<0.6). Since blood glucose levels remained less than 250 mg/dl with concurrent anion gap metabolic acidosis in the setting of recent Empagliflozin use, he was transferred to ICU for insulin infusion for management of euglycemic diabetic ketoacidosis. Subsequently, he was transitioned to a basal-bolus insulin regimen and transferred to the floors.

Discussion

- SGLT-2 inhibitors reduce renal tubular glucose reabsorption, causing glycosuria, and promote ketonemia directly by enhancing ketogenesis via glucagon secretion from the pancreatic alpha cells and indirectly by decreasing the renal clearance of ketone bodies. In the setting of acute stress, such as stroke in our patient, and recent SGLT-2 inhibitor use, the presence of ketonuria should be recognized as an early ominous warning sign for euglycemic DKA. A targeted approach detailing diagnostic and therapeutic interventions should be designed to halt its progression in its track before it transforms into the dreaded euglycemic DKA.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN290 A Rare, Sordid Tale Of The Two Most Dreaded Adverse Effects Of SGLT-2 Inhibitors Occurring Concurrently - Acute Pancreatitis And Euglycemic Diabetic Ketoacidosis - Within Days Of Initiating Empagliflozin Therapy.
Authors: Arora Gunjan , Gerais Yasmin
Published: November 2022

Introduction

Empagliflozin is an anti-diabetic agent belonging to the class of SGLT-2 inhibitors, which was approved by the U. S. Food and Drug Administration (FDA) in 2013. It has emerged as a popular choice of second line diabetic therapy owing to benefits of reduction in cardiovascular adverse events and delayed progression of kidney disease. However, in 2015, FDA issued a safety warning in connection to its use with euglycemic ketoacidosis and subsequently in 2016, started investigating its link with pancreatitis. We present a case of a type 2 diabetic started on Empagliflozin therapy 4 days prior to his presentation to the ER with nausea, vomiting and diarrhea when he was found to have concurrent euglycemic DKA and acute pancreatitis.

Case presentation

A 49 year old male with a history of diabetes mellitus type 2 presented to the ER with nausea, vomiting, diarrhea and fatigue. He reported these symptoms since starting a new anti-diabetic agent Empagliflozin four days ago. He denied fever, chills, chest pain, shortness of breath, abdominal pain, and urinary symptoms. He denied heavy alcohol use or binge drinking. Lab tests showed: WBC count 18.7 k/mm cu (4 -11), Glucose 229 mg/dL (70 - 99), Bicarbonate 7 mmol/L (21 - 31), Anion gap 30 mmol/L (6 -14), Lactate 1.8 mmol/L (0.7 - 2.5), Serum beta hydroxybutyrate level >4 mM (0. 02 - 0.27), Lipase 866 IU/L (11 - 82) and Venous blood pH 6.98 (7.30 - 7.45). Repeat blood glucose measurements remained < 250 mg/dl. Urinalysis showed > 500 mg/dl glucose. CT abdomen and pelvis showed moderate fat stranding consistent with acute pancreatitis. He was started on insulin infusion and admitted to the intensive care unit. He was subsequently discharged on a basal-bolus regimen with instructions to discontinue Empagliflozin.

Discussion

Acute pancreatitis and euglycemic DKA are grave clinical entities, associated with significant mortality. Our patient presented with nausea, vomiting, diarrhea and fatigue; he denied the characteristic abdominal pain yet was noted to have pancreatitis by laboratory and imaging studies. It is extremely important that pancreatitis be considered and ruled out in patients presenting with non-specific symptoms while on SGLT-2 inhibitor therapy. In addition, a high radar of suspicion should be maintained in both inpatient and outpatient settings for euglycemic DKA in patients on SGLT-2 inhibitor therapy presenting with non-specific symptoms, even in the absence of a classic identifiable triggering event, especially as there is evidence to suggest that pancreatitis may actually serve as a triggering factor for euglycemic DKA suggesting that, due to a cause-effect phenomenon, these two conditions may co-exist more often than expected.

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
Authors: Wagner David , Vaitaitis Gisela , Waid Dan , Webb Craig , Webb Tracy
Published: November 2022

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 < 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.
ODP158 A Pilot Trial on the Efficacy of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness
Authors: Nakamura Yuta , Haraguchi Ai , Shigeno Riyoko , Horie Ichiro , Abiru Norio , Kawakami Atsushi
Published: November 2022

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
ODP171 Choosing GLP-1RA Over Insulin for Patients with Type 2 Diabetes and Severe Hyperglycemia
Authors: Mamtani Raashi , Cobrinik Dora , Simon Barbara
Published: November 2022

Introduction

Although insulin remains the recommended treatment in type 2 diabetes for hyperglycemia with catabolic symptoms, it is also the generally recommended treatment for persistent hyperglycemia or hemoglobin A1c (HbA1c) values above 10% 1 . Recent data has suggested that glucagon like peptide 1 receptor agonists (GLP-1RAs) are also powerful at glucose lowering while additionally offering extra-glycemic benefits such as weight loss with minimal risk of hypoglycemia. Unfortunately, data on initial use of GLP-1RA is limited in patients with very high hemoglobin A1cs. Our objective was to evaluate outcomes in patients with type 2 diabetes and a baseline HbA1c of 10% or greater treated with GLP-1RAs instead of insulin.

Methods

This study is a small retrospective case series of insulin-naïve patients with uncontrolled type 2 diabetes who were prescribed an injectable GLP-1RA. Patients included had a baseline hemoglobin A1c ≥ 10% without signs of catabolism (weight loss, ketosis, significant polyuria), a minimum of one follow-up visit after initiating GLP-1RA, and at least one HbA1c measurement within six months of initiating treatment. Patients were excluded if they had previously been on insulin or a GLP-1RA in the past 1 year. The primary endpoint was change in HbA1c after 3-6 months of GLP-1 RA use.

Results

Of the patients initially screened, 7 patients fulfilled criteria and were included in the final analysis. The age range was 45-73 with 4 female patients and 3 male patients. The number of years patients had been diagnosed with type 2 diabetes ranged from 0 to 13 with 1 patient having newly diagnosed diabetes not previously on medications. Of the 6 patients who were on medical treatment at baseline, 3 patients were on monotherapy with either metformin or a sulfonylurea and 3 patients were on 2-4 oral hypoglycemic agents. Patients were continued on their initial medication regimen with the exception of DPP-4 inhibitors which were stopped at the time of GLP-1RA initiation. Mean baseline HbA1c prior to initiation of GLP-1RA was 11.9%. Following 3-6 months of GLP-1RA use, mean HbA1c significantly improved to 7.5% (p value= 0. 0005). All patients showed improvement of HbA1c in response to GLP-1RA initiation (mean HbA1c reduction = 4.4, minimum = 1.9, maximum = 7.5). All patients remained on GLP-1RA without significant side effects.

Conclusion

In this limited case series of patients with HbA1c ≥ 10%, GLP-1RAs were well tolerated and resulted in significant improvement in HbA1c. Our results suggest that GLP-1RAs should be considered as an alternative treatment option to insulin in non-catabolic patients with very high hemoglobin A1cs. References: 1. Committee ADAPP. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2022. Diabetes Care. 2021;45(Supplement_1): S125-S143. doi: 10.2337/dc22-S009

Presentation: No date and time listed
ODP182 Diabetes types and risk of severe COVID-19
Authors: Kazlauskaite Rasa , Liu Yuanqing , Desai Pankaja , Jackson-Morris Angela M , Ngongo Carrie , Nugent Rachel
Published: November 2022

Background

Associations of diabetes (DM) types with severe COVID have not adequately been investigated in clinical databases.

Methods

Analytical cohort of n=5713 patients with diabetes was selected from the electronic medical record-based COVID Registry in the urban academic health care system from March 2020 to March 2021. All cases in the registry tested positive for SARS-CoV-2 infection on the clinical assessments. Severe COVID was defined in cases requiring hospitalization or if fatal outcome. Demographics variables, clinic visits, vaccination status, multi-morbidity, ambulatory medication data, biochemical markers, and other diabetes characteristics were collected on or before the date of COVID diagnosis. After excluding pregnancy-related diabetes, cases were classified into type 1 (DM1), type 2 (DM2) and other/hybrid DM based on disease coding and clinical variables. Univariable and multivariable logistic regression models were used to assess the association of the three diabetes types with severe COVID after adjustment for age, sex, race/ethnicity. FindingsDiverse cohort included 37.6% Latino, 37.5% Black, 19.5% White, and 5.3% other; 53.7% were women. DM1 was identified in n=141 cases, Type 2 diabetes in n=2749, and other/hybrid diabetes in n=2823. The diabetes subtypes could not be reliably explored due to limitations of the clinical database. Compared to DM2, the odds of severe COVID were similar in DM1 (1.11, 95%CI 0.65, 1.81, p=0.700), but higher in other/hybrid DM (1.53, 95%CI 1.34, 1.76), after adjustment for sex, age, and race/ethnicity.

Other and hybrid diabetes types are not rare and are associated with a higher risk of severe COVID-19. The diabetes subtypes could not be reliably explored due to limitations of the clinical database.

Presentation: No date and time listed
ODP186 Difficulties in diagnosing MODY: clinical case
Authors: Volkova Natalya , Davidenko Ilya , Dzherieva Irina , Ganenko Lilia , Zibarev Alexander , Reshetnikov Igor , Degtyareva Julia , Brovkina Snezhana , Panenko Stanislav , Ignatiadi Anastasia
Published: November 2022

Background

MODY is one of the monogenic forms of diabetes mellitus, which includes 14 subtypes with different course and clinical picture. Final clinical diagnosis involves a molecular genetic study and is a key factor in successful treatment. Clinical case. Patient P., 33 years old, complained of aggravation of the condition after and during the dialysis procedure: general weakness, blood pressure rose to 220 mmHg, after the procedure a drop to 110-120 mmHg, lack of effect from hypertensive drugs, headaches. In 2004, type 1 diabetes mellitus was diagnosed based on complaints of polydipsia, polyuria, and fasting glycemia up to 9 mmol/l. Basic bolus insulin therapy was prescribed. Patient noted a frequent development of hypoglycemic conditions and independently canceled insulin therapy. For a long time the patient went without hypoglycemic therapy. In 2016, baseline insulin therapy was prescribed again, which resulted with frequent episodes of hypoglycemia resuming. In 2019, a diagnosis of MODY type 3 was made without medical and genetic counseling. Due to the high level of C-peptide 3057.1 pmol /L (160-1100), Repaglinide 0.5 mg was prescribed to be taken 3 times a day. Against the background of this treatment, compensation and stabilization of the condition has been observed. Family history: the mother has diabetes mellitus since the age of 22, manifested during pregnancy; receives Glibenclamide with a positive effect. Since 2011, diabetic distal sensorimotor polyneuropathy of the upper and lower extremities, diabetic foot syndrome, neuropathic form have been identified. Ulcerative defect of the I degree. Long-term non-healing trophic ulcer of the right foot for 6 years. In 2016, chronic kidney disease C5 A3 was detected. At the moment, the patient is on program dialysis. Complications of nephropathy were verified – secondary hyperparathyroidism, osteoporosis, moderate nephrogenic anemia, symptomatic nephrogenic arterial hypertension of grade 3, risk 4. In 2018, proliferative diabetic retinopathy of both eyes was detected. Total recurrent hemophthalmos of the right eye, subtotal hemophthalmos of the left eye. In 2021, autonomic neuropathy, gastrointestinal form and autonomic cardiovascular form were verified. The patient underwent a molecular genetic study for the identification of pathogenic mutations in the HNF1A gene, however, according to the study, mutations in the HNF1A gene were not detected. Thus, the diagnosis of MODY type 3 has not been confirmed. It is necessary to conduct a further diagnostic search for the type of MODY in order to make a final diagnosis.

Conclusion

This clinical case demonstrates the importance of a personalized approach to each patient, as well as conducting a molecular genetic study to make a final clinical diagnosis and prescribe timely pathogenetic therapy.

Presentation: No date and time listed