Excellent Glycemic Control Research Articles

Simultaneous en bloc kidney and pancreas transplantation from pediatric donors: Selection, surgical strategy, management, and outcomes

Pediatric donors are underutilized for simultaneous pancreas-kidney transplantation due to concerns about technical complications and inadequate islet and/or renal mass. We analyzed our experience with simultaneous en bloc kidney and pancreas transplantation using pediatric donors on 8 consecutive adult patients from 1997-2018. En bloc kidney transplants were implanted intraperitoneally and contralaterally to right-sided pancreas grafts. All patients became insulin-independent immediately; with 1 case of delayed kidney function and 1 case of insulin resistance; there were no graft thromboses. Donor age averaged 5.0 ± 1.7 years and weight 19.8 ± 4.8 kg; recipient age averaged 46.6 ± 12.8 years and body mass index 25.2 ± 3.8 kg/m2. Postoperative creatinine, glucose, and C-peptide reflected good graft function. Simultaneous en bloc kidney and pancreas transplantation is a safe technique providing excellent long-term glycemic control and kidney function to adult recipients.

High Prevalence of A-β+ Ketosis-Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT).

A-β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A-β+ KPD within this cohort. We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A-β+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A-β+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A-β+ KPD. They manifest the key characteristics of obesity, preserved β-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A-β+ KPD.

Preoperative duration of type 2 diabetes mellitus and remission after Roux-en-Y gastric bypass: A single center long-term cohort study.

Roux-en-Y gastric bypass (RYGB) has demonstrated excellent glycemic control and type 2 diabetes mellitus (T2DM) remission for patients with obesity and T2DM. Duration of T2DM is a consistent negative predictor of remission after RYGB. However, the exact timing to offer surgical intervention during the course of the disease is not well elucidated. We performed a retrospective cohort study between 2008-2020 to establish the exact association between duration of T2DM and remission after RYGB. We divided our cohort into quartiles of preoperative disease duration to quantify the change in remission rates for each year of delay between T2DM diagnosis and RYGB. We also compared the average time to remission and changes in glycemic control parameters. A total of 519 patients (67.2% female; age 53.4±10.7y; BMI 46.6±8.4kg/m2) with a follow-up period of 6.6±3.8 years were included. Remission was demonstrated in 51% of patients. Longer duration of T2DM was a significant negative predictor of remission with an estimated decrease in remission rates of 7% for each year of delay ([OR=0.931 (95% CI 0.892-0.971)]; P<0.001). Compared to patients with <3 years of T2DM, remission decreased by 37% for patients with 3-6 years, 64% for those with 7-12 years and 81% for patients with more than 12 years (P<0.001). Half of the patients reached T2DM remission after 0.5 and 1.1 years respectively for the first and second quartiles, while patients in the other quartiles never reached 50% remission. Lastly, we noted an overall improvement in all glycemic control parameters for all quartiles at last follow-up. Patients with a recent history of T2DM who undergo early RYGB experience significantly higher and earlier T2DM remission compared to patients with a prolonged history of preoperative T2DM, suggesting potential benefit of early surgical intervention to manage patients with obesity and T2DM.

P-31 GLP1 receptor agonist in end-stage kidney disease: Are they safe and effective?

Abstract Introduction The novel antidiabetic therapies have been showing promising results in cardiovascular and renal protection besides diabetes treatment. GLP-1 receptor agonists (GLP-1RA) are well tolerated drugs with few side effects, but they are only approved for a glomerular filtration rate (GFR) higher than 15 mL/min. Anecdotal reports have been made of therapy with GLP-1RA in patients undergoing hemodialysis and intermittent hemodialysis with good results. Clinical Case A sixty-five-year-old male patient with stage 4 chronic kidney disease in the setting of hypertensive and diabetic nephropathy is accompanied at our Endocrinology Department due to non-insulin treated type 2 diabetes. His past-history was notable for atrial fibrillation, obstructive sleep apnea and chronic obstructive pulmonary disease. In what diabetes is concerned, he was under empagliflozin 10mg daily and dulaglutide 1.5mg weekly with excellent glycemic control. Despite optimized treatment and Nephrology follow-up, GFR continued to decay, standing currently at 11 mL/min, without any acute insult, acidosis or hyperkalemia. The patient is starting preparation for hemodialysis with construction of an arteriovenous fistula. At last appointment, despite the lower GFR he maintained an excellent glycemic control with HbA1c of 6% without hypoglycemia and remained clinically asymptomatic without nausea, vomiting, or abdominal pain. A pharmacokinetics study revealed a similar exposure to semaglutide independent of renal function (including severe renal impairment [10 patients] and end-stage kidney disease [10 patients]) with the drug being well tolerated in both subgroups without the need for dose adjustments. In our case, the patient maintained the weekly treatment, without reported and/or documented hypoglycemia and possible advantageous cardiovascular profile. In the future, GLP1RA may be a treatment option independently of the patient renal function.

Dietary knowledge assessment among the patients with type 2 diabetes in Madinah: A cross-sectional study .

There is a huge burden of nutrition-related non-communicable diseases, and diabetes is one of the leading chronic nutrition-related diseases affecting more than 500 million people globally. Collecting information regarding the awareness of dietary and nutrition knowledge among diabetic patients is the first step to developing a disease prevention program. Thus, this study primarily aims at assessing the dietary awareness of diabetes patients attending the diabetic centre in Madinah governorate, Saudi Arabia. The study was started in November 2020 and ended in October 2021. The study participants (315) were type 2 diabetes mellitus (T2DM) patients attending a diabetic centre in Madinah, Saudi Arabia. A self-prepared dietary knowledge questionnaire (DKQ) was used in this research. The variables include balanced diet, food type, food choice, carbohydrate, protein, and fat. Knowledge score was, and the total score was levelled/categorized into 'good', 'average', and 'poor'. Data were analysed by SPSS v.26. The study results identified the current knowledge of T2DM patients about different dietary items. The knowledge score of 62.2% of participants showed an average level of dietary knowledge, which is statistically significant. When we separately evaluated their understanding of different dietary components, we found that T2DM patients had poor knowledge of carbohydrates (30.15%), fat, food choices (47.7%), and type (34.6%). However, they had acceptable knowledge of proteins (56.5%). Our participants exhibited acceptable knowledge about proteins but poorer knowledge of other food groups. A healthy, well-balanced diet is essential for excellent glycaemic control. Educating and arranging a health education program regarding dietary knowledge is recommended, specially designed for diabetic patients so that patients can opt for a healthier lifestyle.

400.4: Insulin independence with excellent glycemic control at 17-years post-islet alone transplantation: A case report

400.4: Insulin independence with excellent glycemic control at 17-years post-islet alone transplantation: A case report

Chitosan-based injectable hydrogels with dual glucose sensors for precise control of insulin release and diabetes mellitus therapy

Chitosan-based injectable hydrogels were designed and fabricated through the dynamic crosslinking of dual-reversible covalent bonds (imine and phenylboronate ester) for precise insulin release. The hydrogels contain dual glucose-sensors/responsive elements, featuring high sensitivity and rapid responsiveness to glucose level variation in cumulative and half-hourly pulsed insulin release. The hydrogels demonstrated improved cytocompatibility against HSF cells and histological long-term analysis of tissue after implantation. Evaluation of the glycemic control ability in STZ-induced hyperglycemic mice revealed that the hydrogel system showed excellent glycemic control ability in the glucose tolerance test and maintained blood glucose levels in a normal range for up to 11 days after a single administration. Thus, the hydrogel system showed applicable potential in insulin replacement therapy for diabetes mellitus.

902-P: Patient Experience and Clinical Outcomes in Pregnant Patients with Type 1 Diabetes Using Open-Source Automated Insulin Dosing Systems

Type 1 diabetes (T1D) in pregnancy is associated with increased obstetrical and neonatal complications; thus, stringent glycemic targets are imperative. While commercial automated insulin dosing (AID) systems represent an important development in management of T1D, a limitation is that the glycemic targets are not adjustable for pregnancy. Before commercial AID, a community of people with T1D combined CGM sensors, insulin pumps and open-source code, developing open-source automated insulin delivery systems (OSAIDS). Given customizable glycemic targets, OSAIDS may fill an important clinical gap in pregnancy. We included participants ≥18 years old with T1D who had at least one pregnancy using OSAIDS. Of 37 completed surveys, motivations for using OSAIDS included commercial AID targets being too high for pregnancy (78%), increased ownership over diabetes (53%) and transparency (44%). The INsulin Dosing Systems: Perceptions, Ideas, Reflections and Expectations (INSPIRE) questionnaire showed that 100% strongly agreed or agreed with: helped in pregnancy (89% strongly agree), better quality of life (94% strongly agree) and better sleep (83% strongly agree). With a glycemic target of 3.5-7.8mmol/L (63-140mg/dl), 86% exceeded the time-in-range (TIR) target of ≥ 70% set by the Advanced Technologies &amp; Treatments for Diabetes Congress. The majority (66%) had a more stringent TIR of ≥ 80%. The vast majority (97%) did not have severe hypoglycemia; 74% had time-below-range ≤ 4%. Of the 71% who experienced labor and delivery, 90% delivered at 37 weeks gestational age or greater; 90% did not have shoulder dystocia. Median birth weight was 3374g (SD 600g), 19% of newborns had macrosomia (&amp;gt;4000g). Neonatal hypoglycemia (&amp;lt;2.5mmol/L/&amp;lt;45mg/dl) occurred in 24% with 14% requiring NICU. OSAIDS provides excellent glycemic control, maternal quality of life and neonatal outcomes. More data is needed to validate these initial promising outcomes. Disclosure Y.Yang: None. I.Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd./Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk.

Dietary knowledge assessment among the patients with type 2 diabetes in Madinah: A cross-sectional study

Background: There is a huge burden of nutrition-related non-communicable diseases, and diabetes is one of the leading chronic nutrition-related diseases affecting more than 500 million people globally. Collecting information regarding the awareness of dietary and nutrition knowledge among diabetic patients is the first step to developing a disease prevention program. Thus, this study primarily aims at assessing the dietary awareness of diabetes patients attending the diabetic centre in Madinah governorate, Saudi Arabia. Methods: The study was started in November 2020 and ended in October 2021. The study participants (315) were type 2 diabetes mellitus (T2DM) patients attending a diabetic centre in Madinah, Saudi Arabia. A self-prepared dietary knowledge questionnaire (DKQ) was used in this research. The variables include balanced diet, food type, food choice, carbohydrate, protein, and fat. Knowledge score was, and the total score was leveled/categorized into ‘good’, ‘average’, and ‘poor’. Data were analyzed by SPSS v.26. Results: The study results identified the current knowledge of T2DM patients about different dietary items. The knowledge score of 62.2% of participants showed an average level of dietary knowledge, which is statistically significant. When we separately evaluated their understanding of different dietary components, we found that T2DM patients had poor knowledge of carbohydrates (30.15%), fat, food choices (47.7%), and type (34.6%). However, they had acceptable knowledge of proteins (56.5%). Conclusion: Our participants exhibited acceptable knowledge about proteins but poorer knowledge of other food groups. A healthy, well-balanced diet is essential for excellent glycaemic control. It is recommended to educate and arrange a health education program regarding dietary knowledge, specially designed for diabetic patients so that patients can opt for a healthier lifestyle.

Medication Adherence and Contributing Factors Among Type 2 Diabetes Patients at Adama Hospital Medical College in Eastern Ethiopia.

Good glycemic control and preventing early complications are the ultimate targets of diabetes management, which depends on patients' adherence to regimens. Even though highly potent and effective medications have been developed and manufactured with astonishing advancement over the past few decades, excellent glycemic control has remained elusive. This study aimed to assess the magnitude and factors associated with medication adherence among type 2 diabetes (T2D) patients on follow-up at Adama Hospital Medical College (AHMC) in East Ethiopia. A hospital-based cross-sectional study was conducted among 245 T2D patients on follow-up at AHMC from March 1 to March 30, 2020. Medication adherence reporting scale-5 (MARS-5) was utilized to collect information regarding patients' medication adherence. The data were entered and analyzed using SPSS (Statistical Package for Social Sciences) version 21. The level of significance was declared at a p-value of < .05. Of the 245 respondents, the proportion of respondents who adhere to diabetes medication was 29.4%, 95% CI [confidence interval] (23.7%-35.1%). After adjusting for khat chewing and adherence to blood glucose testing as confounding factors, being married (AOR [adjusted odds ratio] = 3.43, 95%CI [1.27-4.86]), government employee (AOR = 3.75, 95%CI [2.12-7.37]), no alcohol drinking (AOR = 2.25, 95%CI [1.32-3.45]), absence of comorbidity (AOR = 1.49, 95%CI [1.16-4.32]), and having diabetes health education at health institution (AOR = 3.43, 95%CI [1.27-4.86]) were the factors associated with good medication adherence. The proportion of T2D patients who adhere to medication in the study area was remarkably low. The study also found that being married, government employee, no alcohol drinking, absence of comorbidity, and having diabetes health education at a health institution were the factors associated with good medication adherence. Therefore, imparting health education on the importance of diabetes medication adherence by health professionals at each follow-up visit should be considered. Besides, awareness creation programs regarding diabetes medication adherence should be considered using mass media (radio and television).

ODP237 Relation Between Long Term Glycemic Variability (LTGV) and HbA1c Time-In-Range in Diabetic Patients.

Abstract Background LTGV has become, aside with mean Hba1c level, a new measure of glycemic control. Despite the burden of information about its association to long term diabetic complications, in real-life is uncertain its relation to glycemic control. Objective to describe in real-life conditions the relation between long term LTGV and glycemic control. Methods from our clinical laboratory data base we selected those patients who attended for HPLC´s determination of HbA1c for at least two times in 2 consecutive years. We discard those results from patients with anemia or kidney failure. To evaluate LTGV in all patients that fulfill the requirements HbA1c variation coefficient (VC) were calculated ((HbA1c SD/mean HbA1c)X100). Time in control range were assessed as the percent of results below 7% during follow up. Patients were categorized in quartiles according to VC and percent of determinations of Hba1c &amp;lt;7%. (HbA1c&amp;lt; 7). We compared the frequency low vs high VC (quartile 1 vs 4) in patients divided by HbA1c&amp;lt; 7 quartiles and VC levels between hba1c&amp;lt;7 quartiles. Results we studied 193 patients (52.8% men, 61.23 (12.81) years, 925(171) days of follow up).: Percent of patients with low vs high VC quartiles (1 vs 4 respectively) divided by HbA1c&amp;lt;7 quartiles were: quartile 1: 57% vs 0. 0%, quartile 2: 19.6% vs 52.9%, quartile 3: 10.2% vs 57.1% and quartile 4: 18.3% vs 20%. (p&amp;lt;0. 05 quartile 1 vs 2,3,4 and quartile 3 vs 4). VC level were (quartiles 1 to 4 respectively, mean (SD)): 5.42(3), 22(15), 21.34(11),13(7). (p&amp;lt;0. 05 quartile 1 vs 2,3,4, quartile 2 vs 4, quartile 3 vs 4). Conclusions High glycemic variability is rare observed in patients with excellent glycemic control but seems very frequent in those with less than perfect controlled patients (quartiles HbA1c&amp;lt;7, 2 and 3) even in comparison to patients never controlled (quartile 4). VC levels are also higher in those patients in intermediate Hba1c &amp;lt;7 quartiles. It is very interesting that those patients never controlled(HbA1c&amp;lt;7 quartile 4) has no either the higher level of VC or frequency of high VC. Presentation: No date and time listed

PSUN245 Non-ketotic Hyperglycemic Hemichorea-Hemiballismus Precipitated by Antipsychotics

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

ODP255 Woman With Maturity-Onset Diabetes of the Young Type 2 (MODY2) Mistakenly Diagnosed and Treated as Type 2 Diabetes Mellitus

Abstract Background MODY2 is a rare, monogenic form of diabetes, caused by mutations in the glucokinase gene (GCK), and is often misclassified as type 2 diabetes. Clinical case: A 37-year-old woman, during childhood, at the age of 9, was characterized as overweight and had a poor diet, despite being physically active. Her pediatrician diagnosed her with DM2 and started treatment with metformin. However, there was no improvement in fasting glucose levels, so the family decided to stop the medication on their own. In 2008, the patient became pregnant, presenting fasting glucose levels between 120-130 mg/dl (n&amp;lt;99 mg/dl), and continued without hypoglycemic treatment. In 2010, she resumed treatment for glycemic control having used: metformin, sulphonylurea, IDDP4, and basal insulin. Despite the various treatments tested, there was altered fasting glycemia, in the 130mg/dl range. In 2012, she increased her physical activity by training for a half marathon run. At the peak of her form, but maintaining hyperglycemia (always measuring while fasting), she started liraglutide 1.8mg. In 2019, she presented episodes of malaise during training, being indicated by her physician, to discontinue liraglutide, then starting dapagliflozin, but there was still no improvement of blood glucose levels. In August 2019, she was instructed to take the following medications: insulin degludec, liraglutide, and dapagliflozin. Current weight was 53kg, height 1,57cm and a BMI 21,5kg/. Laboratory exams were requested with the following results: A1C 6,6% (n: &amp;lt;5,7%), mean glycemia 143mg/dL (n: 70-99 mg/dL), fasting glycemia 127mg/dL (n: &amp;lt;100mg/dL), urea 24mg/dL (n: 13-43 mg/dL), creatinine 0,83mg/dL (n: 0,8-1,3 mg/dL), AST 16U/L (n: 10-34 U/L), ALT 17U/L (n 10-130 U/L), LDL 109mg/dL (n&amp;lt;100mg/dl), HDL 80mg/dL (n&amp;gt;60 mg/dL), TG 90mg/dL (n&amp;lt;150 mg/dL), total cholesterol 207mg/dL (&amp;lt;200 mg/dL). Faced with the suspicion of diabetes with different behavior than DM1 and DM2, genetic testing was requested for confirmation. In September 2019, the result arrived, pointing out a genetic change in heterozygosis in the GCK gene. This is a rare mutation that results in the depletion of the phenylalanine amino acid at position 150 of the protein glucokinase. This result confirmed the diagnose of MODY type 2. The patient was oriented to discontinue anti-hyperglycemic agents, maintain a low glycemic index diet, and daily physical exercises. Thus, she has been maintaining excellent glycemic control and adequate weight. Conclusion Suspicion and characterization of MODY through clinical history, and confirmation of diagnosis through genetic testing, is essential to avoid unnecessary or inefficient treatments, and to ensure a better quality of life for the patient. Presentation: No date and time listed

107-OR: Randomization to a Higher–Complex Carbohydrate or Conventional Diet in GDM Results in Equivalent Glycemic Control by Continuous Glucose Monitoring

Direct RCT evidence to support a range of nutrition options for treatment of GDM is lacking. We randomized women with diet-controlled GDM to either our CHOICE (60% complex carbohydrate (CHO) /25% fat) or a conventional diet (CONV; 40% CHO/45% fat) and previously reported equivalent newborn adiposity. We further tested the hypothesis that 6 wks on either diet would result in a similar 24-hr glucose (gluc) area-under-the-curve (AUC) by CGM. BMI-matched women were randomized to CHOICE or CONV by wk 31 (n=59; mean±SEM; BMI 32±1kg/m2) . All meals were provided, eucaloric, and simple sugars were controlled in both. A CGM was worn for 72 hrs in wk 31 and 36. Total gestational weight gain (GWG) (CHOICE vs. CONV; 9.8±0.9 vs. 10.8±1.2 kg) , GWG from 31 wks to delivery (2.0±0.4 vs. 1.8±0.3 kg) , physical activity, and days on diet were similar (48±2 vs. 54±2 days; p&amp;gt;0.all) . At wk 31 (n=23 vs. 25/group) , fasting (89±3 vs. 87±2 mg/dL) , 1-hr (127±4 vs. 127±4) and 2-hr postprandial (PP) (112±3 vs. 110±3) gluc, and time in range (TIR; 70-140mg/dL) (89±1 vs. 86±1%) , were not different on CHOICE vs. CONV as were the mean 24-hr gluc, 24-hr AUC, nocturnal and daytime AUC (p&amp;gt;0.5 all) . By wk 36, (n=22 vs. 21/group) , fasting (90±3 vs. 86±3) , 1-hr (117±4 vs. 119±3) , 2-hr PP (108±3 vs. 106±3) , 2-hr PP AUC, TIR (88±2 vs. 88±1%) , 24-hr AUC, nocturnal AUC and daytime AUC remained highly similar between diets (p&amp;gt;0.all) . In paired analyses (n=19-21/group) , women on CHOICE showed an actual reduction in 1-hr PP gluc between 31-36 wks (124±5 vs. 115±4; p=0.02) . Surprisingly, the fasting, 2-hr PP gluc, 24-hr AUC, daytime and nocturnal AUC did not increase (nor did TIR decrease) , over time in either group with the expected rise in the insulin resistance of pregnancy. These data directly support for the first time in an RCT with all provided meals that excellent glycemic control by CGM was achieved with either a higher complex CHO versus low CHO diet in GDM, with similar glycemic parameters that did not increase over time. Disclosure T.L.Hernandez: None. E.Z.Dunn: None. N.Hirsch: None. K.P.Rolloff: None. J.P.Corbett: Employee; Tandem Diabetes Care, Inc., Other Relationship; Dexcom, Inc. S.S.Farabi: n/a. J.E.Friedman: None. L.A.Barbour: None. Funding National Institutes of Health (R01DK101659) CTSA UL1 TR002535 Janssen Research and Development

1328-P: COVID Associated Insulitis in Type 1 Diabetes

Recent reports suggest a potential relationship between COVID-and onset of diabetes (DM) . We present the case of a 35 yr old female with type 1 DM (T1DM) who following COVID-pneumonia (COVP) developed worsening insulitis suggesting a potential direct effect of COVID-on beta cell function. The patient is a 35 yr old Caucasian female with T1DM first diagnosed 5 yrs ago. She had some residual beta cell secretory function with fasting C-peptide; 0.51 (0-8-3.85ng/ml) . She also has hemochromatosis, thyroiditis with thyroid nodular disease and +ve history of T1DM in her older brother and maternal cousin. Since diagnosis she has been on insulin pump therapy and a CGMS device with excellent glycemic control and HBA1c of 6.7-7.1. She had not received the COVID-vaccine and had COVP in July 2021 requiring inpatient care but not intubation. She received oral steroids and Remdesivir with salutary response. She has not had post-acute sequelae of SARS-CoV (PASC) but ˜ 2 months post discharge had acute thyroiditis with no thyroid abscess, elevated sed rate, leucocytosis and peak thyroglobulin; 158 (3-40ng/ml) . Since discharge she noted persistent global hyperglycemia requiring increased basal and bolus insulin therapy with peak HBA1c of 8.3. Further evaluation showed active insulitis with reduced C-peptide 0.and increase in islet related antibodies compared to titers obtained at the time of initial diagnosis 5 yrs prior. The clinical presentation of our patient suggests a potential role of COVID-in inducing insulitis with significant implications for at risk patients including T1DM patients with preserved islet function but also type 2 DM and LADA patients. This case provides another compelling reason for advocating COVID-vaccination in at risk patients. The duration of this effect on islet function and whether beta cell functional recovery is possible over time remains to be seen. The insulitis manifests with worsening glycemic profiles as well as possibly impacting islet mediated counterregulatory glycemic responses. Disclosure G.I.Uwaifo: None.

215-OR: Once Weekly (QW) Basal Insulin Fc (BIF) Demonstrated Similar Glycemic Control to Once Daily (QD) Insulin Degludec (DEG) in Insulin-Naïve Patients with Type 2 Diabetes (T2D)

Basal Insulin Fc (BIF; LY3209590) , a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for QW administration. This randomized, parallel, open-label Ph2 study assessed safety and efficacy of BIF vs. DEG in insulin-naïve patients with T2D previously treated with oral antihyperglycemic medication. BIF was injected QW, and DEG was injected QD. Both groups were titrated to fasting blood glucose (FBG) ≤100 mg/dL. The primary endpoint was HbA1c change from baseline (CFBL) to Wk 26 (non-inferiority margin=0.4%) . Patients randomized to BIF (N=129) and DEG (N=135) had a mean age of 58.4 yrs and baseline HbA1c of 8.0%. After 26 wks, BIF showed non-inferiority vs. DEG for HbA1c CFBL with a treatment difference of 0.06% (90% CI = -0.11, 0.24; p = .56) , and both groups had &amp;gt;75% time in range (70-180 mg/dL) on average at Wk 26 (Figure) . BIF and DEG significantly reduced FBG from baseline (treatment difference BIF vs. DEG = 4.7 mg/dL [90% CI = 0.1, 9.3]; p = .09) . Rate of Level 2 hypoglycemia was low and not significantly different (BIF = 0.22; DEG = 0.15 events/pt/yr; p = 0.64) . Occurrence of treatment-emergent adverse events was similar between BIF and DEG. QW BIF achieved excellent glycemic control similar to DEG with no concerning hypoglycemia or other safety findings, supporting continued development of BIF in Ph3. Disclosure J.M. Bue-Valleskey: None. C.M. Kazda: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Ma: None. J. Chien: Employee; Eli Lilly and Company. Q. Zhang: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. E. Chigutsa: Employee; Eli Lilly and Company. W. Landschulz: Employee; Eli Lilly and Company. J. Swan: Employee; Eli Lilly and Company. A. Haupt: Employee; Lilly. Stock/Shareholder; Lilly. J. Frias: Advisory Panel; Altimmune, Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck &amp; Co., Inc., Sanofi. Consultant; 89bio, Inc., Akero Therapeutics, Inc., Altimmune, Becton, Dickinson and Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi. Research Support; Afimmune Limited, Akero Therapeutics, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi. Speaker's Bureau; Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Sanofi. Funding Funded by Eli Lilly and Company.

Identification of a novel hepatocyte nuclear factor-1 alpha (HNF1A) variant in maturity onset diabetes of the young type 3 (HNF1A-MODY).

SummaryWe identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin.Learning pointsHNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history.Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes.First-degree relatives of the affected individual should be considered for genetic testing.The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.

Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in mouse, porcine, human and human stem cell (SC)-derived beta cell (SC-beta) islets by comprehensive optimization of cryoprotectant agent (CPA) composition, CPA loading and unloading conditions and methods for vitrification and rewarming (VR). Post-VR islet viability, relative to control, was 90.5% for mouse, 92.1% for SC-beta, 87.2% for porcine and 87.4% for human islets, and it remained unchanged for at least 9 months of cryogenic storage. VR islets had normal macroscopic, microscopic, and ultrastructural morphology. Mitochondrial membrane potential and adenosine triphosphate (ATP) levels were slightly reduced, but all other measures of cellular respiration, including oxygen consumption rate (OCR) to produce ATP, were unchanged. VR islets had normal glucose-stimulated insulin secretion (GSIS) function in vitro and in vivo. Porcine and SC-beta islets made insulin in xenotransplant models, and mouse islets tested in a marginal mass syngeneic transplant model cured diabetes in 92% of recipients within 24–48 h after transplant. Excellent glycemic control was seen for 150 days. Finally, our approach processed 2,500 islets with >95% islets recovery at >89% post-thaw viability and can readily be scaled up for higher throughput. These results suggest that cryopreservation can now be used to supply needed islets for improved transplantation outcomes that cure diabetes.

Diagnosi precoce di diabete neonatale permanente conseguente a mutazione del gene KCNJ11

Neonatal diabetes mellitus (NDM) is a rare condition characterized by onset of persistent hyperglycaemia with-in the first six months of life. Heterozygous mutations in KCNJ11 gene account for about half of the cases of per-manent form of NDM and are associated with a wide range of neurocognitive disabilities. In suspected NDM, immediate molecular genetic testing is recommended because most of the cases due to mutations in KCNJ11 gene are responsive to oral sulfonylurea (SU) therapy with excellent glycaemic control at long term follow up. The present report describes a case of early detection of permanent NDM, due to KCNJ11 gene mutation, which has been successfully treated with SU oral therapy.

Low prevalence of diabetic retinopathy in patients with long-term type 1 diabetes and current good glycemic control - one-center retrospective assessment

PurposeDespite progress in type 1 diabetes (T1DM) therapy, diabetic retinopathy (DR) is still a common complication. We analysed predictors and prevalence of DR in patients with T1DM lasting 10 years or more. All of the patients were considered to be currently in excellent glycemic control and treated using modern therapies.MethodsStudy included 384 (80.7% women) T1DM patients participating in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow between the years 2014 and 2020. A retrospective analysis of medical records was conducted.ResultsThe patients were on average 34 ± 9.2 years old, had a BMI 25.0 ± 3.9 and a T1DM duration of 20.5 ± 7.9 years. The mean level of HbA1c throughout the follow-up (mean duration 4.9 ± 1.4 years) was 6.9 ± 1%. The group included 238 (62.0%) patients treated with insulin pumps and 99 (25.8%) on multiple daily injections, 47 (12.2%) used both methods; almost all patients were on insulin analogues. DR was confirmed in 150 (39.1%) patients, from which 109 (28.4%) were diagnosed de novo. Severe DR was occurred in just 31 cases (8.1%). In the multivariate logistic regression, independent risk factors for the presence of DR were T1DM duration (OR 1.13; 95% CI, 1.09–1.19), HbA1c level (OR 1.41; 95% CI, 1.08–1.84), LDL level (OR 1.79; 95% CI, 1.16–2.87), and the combined presence of non-DR micro- and macrovascular chronic complications (OR 1.86; 95% CI, 1.16–3.03).ConclusionsIn this highly-selected group of T1DM patients, mostly female, the prevalence of both DR at any stage and severe DR was lower than earlier reported results from other cohorts. Independent risk factors for the DR cohort did not differ from previously reported studies.