bluuebunny/crossref_metadata_2025 huggingface dataset:
1253-P: Markers of Beta-Cell Death and Insulin Secretion in Ketosis-Prone Diabetes (KPDM)
Authors: VELLANKI PRIYATHAMA , OLADEJO OMOLADE , FAYFMAN MAYA , DAVIS GEORGIA , MIGDAL ALEXANDRA , STAIMEZ LISA R. , SMITH ALICIA K. , UMPIERREZ GUILLERMO E.
Published: June 2021

Approximately 50% of obese Black individuals present with diabetic ketoacidosis (DKA) at new-onset of diabetes undergo remission from insulin (fasting blood glucose [FBG <130 mg/dl, random BG < 180 mg/dl and HbA1c < 7% and off insulin therapy > 1 week) with intensive insulin treatment due to improved pancreatic beta(β)-cell secretion. Controversy exists whether KPDM is type 1 or type 2 diabetes and whether β-cell death contributes to DKA and β-cell secretion. Circulating unmethylated to methylated insulin DNA ratio (unMeth/MethINS) levels were found to correlate with β-cell death and β-cell secretion in patients at high risk for type 1 diabetes. In this exploratory study, we hypothesized that increased circulating unMeth/MethINS ratio at presentation of DKA correlates with decreased β-cell secretion in KPDM. Obese Black individuals presenting with DKA without GAD-65 antibodies were recruited 3-4 days after discharge from the hospital (Visit 1, n=22) and at insulin remission (Visit 2, n=19). Serum circulating unMeth/MethINS levels were measured at Visit 1. β-cell secretion was measured with glucagon stimulation tests (GST) performed at Visit 1 and Visit 2 and calculated as 6-min (maximum[Max]) and Delta (Max-baseline) C-peptide levels. At Visit 1, mean age was 38 ± 12 years and 7 (32%) were female. Mean BMI was 39.4 ± 10.6 kg/m2 with mean baseline HbA1c of 12.4 ± 1.8%. C-peptide levels increased significantly from Visit 1 to Visit 2 and expressed as median with minimum and maximum: Max (Visit 1: 2.94 [0.65, 12.07] vs. Visit 2: 5.87 [1.83, 12.11] ng/ml, p=0.011) and Delta (Visit 1: 1.57 (0.24, 6.88) vs. Visit 2: 2.80 [0.46, 9.01], p=0.047). UnMeth/MethINS ratio at Visit 1 was not significantly correlated (Spearman) with C-peptide levels at Visit 1 (Max: r=0.02, p=0.93, Delta: r=0.04, p=0.84) or at Visit 2 (Max: r=-0.07, p=0.79, Delta: r=0.03, p=0.89). Our data shows that in patients with KPDM, markers of β-cell death are not correlated with insulin secretion indicating that KPDM is consistent with type 2 diabetes.

Disclosure

P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. O. Oladejo: None. M. Fayfman: None. G. Davis: None. A. Migdal: None. L. R. Staimez: None. A. K. Smith: None. G. E. Umpierrez: Research Support; Self; AstraZeneca, Dexcom, Inc., Novo Nordisk.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024, UL1TR002378, K23DK11324-01A1)
1262-PUB: Observational Study to Evaluate the Presence of Tubulopathy and Glomerulopathy in Indian T2DM Patients and to Correlate Their Presence with Established Risk Factors for Nephropathy
Authors: HANS PANKAJ , KUMAR MANISH
Published: June 2021

Objective: Urinary cystatin C (UCC) is an emerging marker of DN. UCC has recently been suggested as an alternative marker in eGFR due to its favorable properties. This study was conducted to evaluate the presence of glomerulopathy and tubulopathy in patients with type 2 diabetes mellitus (T2DM) and to correlate them with established risk factors for nephropathy. We aimed at evaluating the level of UCC as a marker of tubulointerstitial damage in patients with T2DM in relation to the level of albuminuria and other parameters.

Methods: Sixty eight patients with T2DM (mean age, 47.44 ± 10.40 years) age- and sex-matched subjects were evaluated for UCC, serum creatinine (SCr), and urinary albumin-creatinine ratio (UACR) along with other parameters.

Results: Of the 68 patients enrolled in the study, 49 were male (72%) and 19 were female (28%). The mean duration of diabetes was 7.21 ± 4.03 years, mean HbA1c was 9.1 ± 1.3%, and mean body mass index (BMI) was 23.21 ± 3.11 kg/m2. Microalbuminuria was found in 17 (25%) cases and macroalbuminuria was found in 8 (11.8%) cases. The mean UACR of the study group was 113.42 ± 252.31 mg/g creatinine and mean UCC was 741.26 ± 1523.46 ng/ml. There was a statistically significant association between rising albumin excretion and BMI, duration of diabetes, SCr, UCC, and SBP and DBP. A significant negative correlation between eGFR and age of the patient and SCr and significant positive correlation between eGFR and BMI was noted. However, a negative correlation between eGFR and UCC failed to achieve statistical significance.

Conclusion: We thus conclude that UCC may be one of the early biomarkers of DN. the use of UCC measurement for early evaluation of renal involvement and may help initiation of timely treatment and prevent/delay renal complications of diabetes.

Disclosure

P. Hans: None. M. Kumar: None.
1280-PUB: The Impact of Proactive and Personalized Strategies in the Self-Monitoring of Blood Glucose in Women with Diabetes in Pregnancy: The Experience of the Cohort Cuido Mi Embarazo in Mexico
Authors: MARTINEZ-JUAREZ LUIS ALBERTO , LOMELIN-GASCON JULIETA , ORTEGA-MONTIEL JANINNE , BENITEZ-HERRERA ALEJANDRO EFRAÍN , REYES-GÓMEZ DIANA , CARMONA-RAMOS MA. CONCEPCIÓN , HERNÁNDEZ-GONZÁLEZ LAURA , REYES-MUÑOZ ENRIQUE , GALLARDO-RINCÓN HECTOR , TAPIA-CONYER ROBERTO
Published: June 2021

Women with Diabetes in Pregnancy (DP) have a higher risk of maternal-fetal complications, unfortunately in Mexico, its detection is only carried out in 1% of cases, and glucometers and glucose strips are not available for self-monitoring of blood glucose (SMBG). The cohort Cuido mi Embarazo (CME) ensures supplies for the Oral Glucose Tolerance Test (OGTT) and glucose screening through MIDO Embarazo®. Educational strategies have been implemented for health personnel focused on prevention, diagnosis and management. Patients with DP have been offered medical and nutritional counseling, and digital glucometers and glucose strips for SMBG. Up to now, 854 women are actively monitored and have performed the OGTT. 117 women have been found with diabetes, of which 96 (82.05%) are Gestational Diabetes (GDM) and 21 (17.95%) are pre-gestational diabetes, finding a prevalence of GDM of 11.2%. Regarding the SMBG in 84 women with diabetes that completed their pregnancy, 62 (73.8%) completed glucose measurements, representing a higher figure than the international literature. From those patients that completed their pregnancy with complete SMBG according to international standards, 39 (62.9%) women achieved control, 23 (37.1%) did not achieve control. No cases of children with macrosomia were detected. In the framework of the CME Cohort, it is demonstrated that: 1) Performing the OGTT and capillary glucose screening through MIDO Embarazo® allow the timely detection of DP. 2) Providing digital glucometers and glucose strips for SMBG, guarantees measurement, increases adherence and glucose control, and improves the health of the newborn and the mother. 3) The systematic approach that also includes the proactive participation of health professionals in the health center is a key element for success for the timely and adequate diagnosis of DP. These conclusions represent a significant public health lesson in Mexico.

Disclosure

L. Martinez-juarez: Research Support; Self; Lilly Global Health Partnership. R. Tapia-conyer: None. J. Lomelin-gascon: None. J. Ortega-montiel: Research Support; Self; Lilly Global Health Partnership. A. Benitez-herrera: None. D. Reyes-gómez: None. M. Carmona-ramos: None. L. Hernández-gonzález: None. E. Reyes-muñoz: Consultant; Self; Nestlé, Research Support; Self; Nestlé. H. Gallardo-rincón: None.

Funding

Eli Lilly and Company
1285-PUB: A Retrospective Observational Study to Find Out the Association between NAFLD, Diabetes, and Obesity in Indian Patients
Authors: SARAN MOHIT , SHARMA JUGAL K. , RANJAN AASTHA , DEKA SAURAV , SABHARWAL MUDIT , PALUKURI SRIVANI , CHANDOLIA BETINA
Published: June 2021

Background: Nonalcoholic fatty liver disease (NAFLD) is present in the body with metabolic disorders such as type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease. However, no significant evidence has been found till date exhibiting their association epidemiologically in Indian patients.

Objective: To assess the association among NAFLD, T2DM, and obesity, and to validate the scoring system with grades of fatty liver (severity of liver disease) estimated by ultrasound vs. NAFLD fibrosis score, BARD score, and APRI score.

Methodology: A retrospective, observational study was conducted out in patients with NAFLD (n=316) where diagnosis and grades of fatty liver were established via ultrasound reports. The patients were divided into two groups, Group A (n=114, NAFLD with T2DM) and Group B (n=202, NAFLD without T2DM). R 4.0.0 was used for statistical analysis.

Results: The mean age (in years) of the patients was 54.08 ± 10.78 in Group A and 48.10 ± 15.36 in Group B. The mean BMI in Group A was found to be slightly higher as compared to Group B, 27.49 ± 4.94 and 26.56 ± 4.68 respectively, and the difference was found to be statistically significant (p-value <0.05). The overall predictive ability of the NAFLD scoring system matched that to ultrasonography liver grading fibrosis report for approximately 53% of patients. The BARD scoring system was found to be matched with ultrasonography reported Grade-1 fatty liver (198/316). In the case of the APRI scoring system, the association was not observed with ultrasonography reports in any grades of fatty liver.

Conclusion: BMI might be an independent risk factor for NAFLD. NAFLD fibrosis score appears to be a reliable non-invasive tool to determine the severity of liver fibrosis in NAFLD patients. BARD score may predict Grade 1 liver fibrosis. However, APRI scores do not correlate with imaging evidence of fibrosis like NAFLD and BARD scores.

Disclosure

M. Saran: None. J. K. Sharma: None. A. Ranjan: None. S. Deka: None. M. Sabharwal: Employee; Self; Health Arx Technologies Pvt. Ltd. S. Palukuri: None. B. Chandolia: None.
137-LB: An Audit on the Management of Diabetic Ketoacidosis during the COVID-19 Pandemic in St. Vincent’s University Hospital, Dublin, Ireland
Authors: MCCARTHY A. MARY , CROWLEY RACHEL
Published: June 2021

DKA is a complication of type 1 diabetes with a 5% mortality rate. Patients with diabetes who test positive for COVID-19 have a higher mortality rate than the general population.

In this audit, patients treated for DKA in SVUH in March-April 2020 were identified and their records were reviewed to assess adherance to the DKA protocol. Patients treated for DKA during March-April 2019 were used as a comparison population.

There were 10 cases of DKA in SVUH in March-April 2020. 10% were under the care of the Endocrinology team. 50% were prescribed appropriate basal insulin. 60% were prescribed appropriate fluids. 60% were admitted via the COVID pathway. 50% were prescribed appropriate fluids, compared to 75% of patients who were admitted via the non-COVID pathway. 50% of patients on both pathways were prescribed appropriate basal insulin.

In March-April 2019 there were 9 cases of DKA in SVUH. 66% were directly under the care of the Endocrinology team. 88% were prescribed appropriate insulin. 77% were prescribed appropriate fluids.

This work was re-audited to assess adherance to the DKA protocol in September-October 2020, when community rates of COVID-19 were lower and staff had been re-educated on DKA management. 8 patients were treated for DKA in September-October 2020. All of these patients were admitted via the non-COVID pathway. 87.5% were under the care of the Endocrinology team. 75% received appropriate basal insulin and 87.5% received appropriate fluids.

In conclusion, adherence to the DKA protocol was suboptimal in the early months of the COVID-19 pandemic. Adherance to the DKA protocol improved to baseline in September-October 2020. This was largely attributed to the fact that patients were not admitted through the COVID pathway, and that they were directly under the care of Endocrinology. It is imperative that patients with speciality specific problems are managed by the appropriate discipline, as COVID-19 remains a significant public health crisis.

Disclosure

A. Mccarthy: None. R. Crowley: None.
143-OR: Financial Incentives to Promote Adolescent Adherence to Type 1 Diabetes Self-Care: A Discrete Choice Experiment
Authors: WRIGHT DAVENE , CHALMERS KRISTEN , LEBLANC JESSICA L. , YI-FRAZIER JOYCE , SHAH SEEMA K. , GARVEY KATHARINE , SENTURIA KIRSTEN , PIHOKER CATHERINE , MALIK FAISAL
Published: June 2021

Purpose: Adolescents with type 1 diabetes (T1D) often struggle with diabetes self-care tasks and achieving optimal glycemic control. Financial incentive (FI) programs may improve T1D self-care and health outcomes. We aimed to quantify adolescent preferences for the structure of FI.

Methods: We performed a discrete choice experiment with 12-18 year-olds with T1D from two pediatric hospital endocrinology clinics in Seattle (n = 185) and Boston (n = 141). We used a literature review and focus groups to identify key attributes of FI: (1) monthly value of the reward, (2) payment structure (positive vs. negative reinforcement), and (3) difficulty of behaviors being incentivized. Using these three attributes, we generated a balanced set of profiles representing hypothetical FI using a fractional factorial design. In twelve choice questions, adolescents were shown a pair of profiles and chose the FI option more likely to motivate them to increase adherence to recommended self-care. The options presented were tailored to adolescents’ modes of insulin administration and glucose monitoring and to adolescents’ individual rating of the difficulty of completing each behavior. We used a multinomial logit choice model to analyze data.

Results: The value of the reward was the primary driver of preferences, accounting for 50% of preferences. Adolescents significantly preferred FI with a positive vs. negative reinforcement payment structure ($5.17 (95% CI: $4.11, $6.25)) and preferred higher FI for performing hard vs. easier behaviors ($6.95 (95% CI: $4.57, $8.33)). Preferences were associated with respondent age and HbA1c (p<0.05).

Conclusions: Adolescent stated preferences should inform the design of a T1D FI intervention, which can then be tested in randomized controlled trials to determine the impact of FI on T1D self-care adherence and health outcomes. Latent class analyses can identify subgroups with differential preferences and will explore subgroup characteristics.

Disclosure

D. Wright: None. K. Chalmers: None. J. L. Leblanc: None. J. Yi-frazier: None. S. K. Shah: None. K. Garvey: None. K. Senturia: None. C. Pihoker: None. F. Malik: None.

Funding

American Diabetes Association (1-18-ICTS-100 to D.W.)
147-OR: Use of Closed-Loop Insulin Therapy in Older Adults with Type 1 Diabetes: Real-World Experience
Authors: TOSCHI ELENA , SLYNE CHRISTINE , ATAKOV-CASTILLO ASTRID , MUNSHI MEDHA
Published: June 2021

Background: Closed-loop control insulin delivery systems (CLC) have been available to adults with type 1 diabetes (T1D) for many years. However, for older adults with T1D, Tandem Control IQ is the first CLC available through Medicare. We evaluated the use of CLC in older adults with T1D in a real-world scenario.

Methods: We retrospectively analyzed electronic health record (EHR) data for older adults (>65) with T1D started on CLC in a single tertiary center between January and December 2020. Continuous glucose monitoring (CGM) data from the 2 weeks prior (baseline) and 2 weeks post CLC system (post-CLC) initiation were analyzed. We evaluated glycemic measures, including coefficient of variation (CV) for glucose variability and glucose management indicator (GMI) for overall glycemic control. Demographic, clinical and diabetes technology data were gathered from EHR.

Results: We present interim data from 25 older adults (Mean age 69±4 yrs, duration of diabetes 43±13 yrs) who started using CLC over the 12 month period. Overall, 23/25 were prior pump users, and 23/25 were prior CGM users. Only 2/25 discontinued CLC use. Comparison of CGM metrics measured at baseline vs. post-CLC showed an increase in Time in Range (TIR) from 63±13% to 77±9% (p<0.001) and a reduction in time >180 mg/dL from 30±12% to 18±9% (p=0.004). While there was a trend in decrease of time <70 mg/dL from baseline to post-CLC, this change was not statistically significant (2.8±2.4% vs. 2.2±2.5% (p=0.5)). CV improved from 0.33±0.04% to 0.30±0.04% (p=0.04) and GMI decreased from 7.0±0.5% to 6.7±0.4% (p=0.06). CLC use averaged 92% of the time over 2 weeks.

Conclusion: In a small cohort of older adults with T1D using CLC in a real-world scenario, the majority of the cohort was able to use the system successfully, resulting in a higher TIR and improved glycemic variability, as seen by a decrease in CV over a 3 month period. Thus, CLC has the potential to improve glycemic outcomes in this elderly population.

Disclosure

E. Toschi: Consultant; Self; Medtronic. C. Slyne: None. A. Atakov-castillo: None. M. Munshi: Consultant; Self; Sanofi.

Funding

National Institutes of Health (1DP3DK112214-01)
150-OR: Intermittently Scanned Continuous Glucose Monitoring and Automated Bolus Calculation in Type 1 Diabetes Treated with Multiple Daily Insulin Injections: A Randomized Controlled Trial
Authors: SECHER ANNA L. , PEDERSEN-BJERGAARD ULRIK , SVENDSEN OLE L. , GADE-RASMUSSEN BIRTHE , ALMDAL THOMAS P. , RAIMOND LINDA H. , VISTISEN DORTE , NØRGAARD KIRSTEN
Published: June 2021

In a randomized controlled multicenter trial, 170 adults with type 1 diabetes ≥1 year, multiple daily insulin injections, HbA1c >7.0% (53 mmol/mol), were randomized to usual care (n=42), carbohydrate counting with automated bolus calculation (ABC) (n=41), intermittently scanned continuous glucose monitoring (isCGM) (n=48), or ABC+isCGM (n=39). HbA1c, blinded CGM and patient-reported outcomes were recorded at baseline and after 26 weeks. Primary outcome was change in time in range (TIR) with isCGM vs. usual care. Baseline characteristics were comparable across intervention arms; median (Q1;Q3) diabetes duration 18 (10;28) years, HbA1c 8.1 (7.7;8.7) % (65 (61;72) mmol/mol) and mean (SD) BMI 26.7 (3.9) kg/m2. Changes in TIR, hypo- and hyperglycemia were similar in the intervention arms compared to usual care. Daytime TIR increased 22 (95% CI: 1;47) % with ABC and nighttime hyperglycemia increased 258 (40;814) % with isCGM compared to usual care. With ABC+isCGM, HbA1c was reduced 0.4 (0.1;0.7) % (4 (1;8) mmol/mol) and glucose coefficient of variation (CV) was reduced 11 (4;17) % compared to usual care. Treatment satisfaction improved with isCGM and ABC+isCGM. With ABC+isCGM, empowerment and present life quality also improved. Within the ABC and isCGM arms, we observed HbA1c reductions of 0.3 and 0.3% (4 and 3 mmol/mol), respectively, however not significantly different from usual care. Statistical significance was maintained after adjustment for multiple testing with regards to CV and treatment satisfaction with ABC+isCGM, and treatment satisfaction with isCGM only.

In conclusion, although no significant improvement in TIR was achieved, simultaneous intervention with ABC+isCGM improved the coefficient of variation and treatment satisfaction compared to usual care, and HbA1c was clinically relevant reduced, in adult technology-naïve persons with type 1 diabetes and suboptimal HbA1c.

Disclosure

A. L. Secher: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. O. L. Svendsen: None. B. Gade-rasmussen: None. T. P. Almdal: None. L. H. Raimond: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K. Nørgaard: Advisory Panel; Self; Medtronic, Other Relationship; Self; Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic.
153-OR: Measurement of C-Peptide at Diagnosis Informs Glycemic Control but Not Hypoglycemic Risk in Type 1 Diabetes
Authors: CARR ALICE , ORAM RICHARD A. , NARENDRAN PARTH , ANDREWS ROBERT C.
Published: June 2021

Background and Aims: High residual C-peptide in longer duration type 1 diabetes associates with fewer hypoglycemic events and reduced glycemic variability. However, little is known about the impact of C-peptide close to diagnosis. Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with type 1 diabetes, we aimed to explore if variation in C-peptide close to diagnosis influenced glycemic variability and risk of hypoglycaemia.

Materials and Methods: We studied newly diagnosed adults with type 1 diabetes who wore a Dexcom G4 CGM as part the EXTOD study. We examined the relationship between peak stimulated C-peptide in a mixed meal tolerance test and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants.

Results: Higher levels of C-peptide associated with lower glycemic variability, more time in range and less hyperglycemia. For every 100 pmol/L increase in peak C-peptide, percentage time spent in the range 3.9-10 mmol/L was increased by 2.39% [95% CI: 0.51,4.26], p=0.012) with a reduction in time spent in level 1 hyperglycaemia (> 10 mmol/L) and level 2 hyperglycemia (> 13.9 mmol/L) glucose levels by 2.64% [95% CI: -4.87, -0.41, p=0.018) and 1.33% [95% CI: -2.66, -0.0057], p= 0.041) respectively. Glucose levels were on average lower by 0.19 mmol/L ([95 % CI: -0.39,0.015], p=0.06) and standard deviation reduced by 0.14 [95% CI: -0.25, -0.023], p=0.017) for every 100 pmol/L increase in peak C-peptide. Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (p=0.967) or hypoglycemic risk (p=0.721). There was no association between peak C-peptide and insulin dose (p=0.707), HbA1C (p=0.364) or insulin dose adjusted HbA1c (IDAA1c, p=0.452).

Conclusion: C-peptide associates with time spent in normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with type 1 diabetes.

Disclosure

A. Carr: None. R. A. Oram: Consultant; Self; Janssen Research & Development, LLC. P. Narendran: Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi. R. C. Andrews: None.
162-LB: Plasma Glycated CD59 Predicts Postpartum Glucose Intolerance after Gestational Diabetes
Authors: BENHALIMA KATRIEN , MA DONGDONG , CASTILLO MICHELLE TOTH , LAENEN ANNOUSCHKA , MATHIEU CHANTAL , HALPERIN JOSE
Published: June 2021

pGCD59 is an emerging biomarker for diabetes and GDM. In studies of women undergoing GDM screening either early in pregnancy (week <20) or at pregnancy weeks 24-28, pGCD59 classified GDM subjects with high sensitivity and specificity and was associated with the prevalence of large for gestational age (LGA) babies (Diabetes Care 2017 and JCEM 2020). GDM developed early in pregnancy imparts a seven-fold increased risk of subsequent glucose intolerance and diabetes. Since HbA1c is not sensitivity to detect glucose intolerance in early postpartum, professional organizations including ADA, recommend that women with GDM should undergo OGTT testing 6-12 weeks postpartum. However, the cumbersome nature of OGTT makes compliance with this requirement very low, highlighting the need for alternative biomarkers that can be used postpartum to test women with GDM for potential conversion glucose intolerance. To assess the ability of pGCD59 to identify postpartum conversion to glucose intolerance in women with GDM, levels of pGCD59 were measured in samples from participants in the Belgian Diabetes in Pregnancy (BEDIP-N, Diabetes Care 2018) cohort study who underwent OGTT testing 6-12 weeks postpartum. Among 105 samples from women with GDM, 36 subjects met OGTT criteria for glucose intolerance (cases) and 70 had normal OGTT (matched controls). Maternal age, race/ethnicity, and BMI were similar among Cases and Controls. pGCD59 was significantly higher in cases than in controls (1.5 ±0.6 SPU vs. 1.0 ±0.6 SPU, p < 0.001) and accurately predicted the postpartum conversion to glucose intolerance as indicated by an AUCROC of 0.72 (95% CI 0.62-0.83). A 0.5-unit increase in postpartum pGCD59 was associated with an OR of 2.0 (95% CI 1.34-2.95, p<0.001) for glucose intolerance. Our results indicate that pGCD59 is a simpler biomarker to assess postpartum conversion to glucose intolerance in women with GDM and represents an alternative to improve compliance with postpartum screening for glucose intolerance.

Disclosure

K. Benhalima: None. D. Ma: None. M. Toth castillo: None. A. Laenen: None. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. J. Halperin: Board Member; Self; Mellitus, LLC.

Funding

National Institutes of Health (R01DK118528, DK101442); Belgian National Lottery; Fund of Academic Studies of UZ Leuven; Yvonne and Jacques François-de Meurs of the King Boudewijn Foundation
168-OR: Five-Year Follow-up after Islet Transplantation in Nonuremic Patients with Type 1 Diabetes Mellitus and Hypoglycemia Unawareness: Favorable Long-Term Outcomes of Multicenter Trial at University of Chicago
Authors: BACHUL PIOTR J. , GENERETTE GABRIELA S. , BOREK PETER , PYDA JORDAN S. , ANTEBY ROI , BASTO LINDSAY , PEREA LAURENCIA , GOLAB KAROLINA , TIBUDAN MARTIN , PEREZ-GUTIERREZ ANGELICA , LUCANDER AARON C. , FUNG JOHN , WITKOWSKI PIOTR
Published: June 2021

Introduction: Prospective randomized multicenter trial did not find advantage of CXCR1/2 blocker (Reparixin) over placebo in islet transplantation in patients with type 1 diabetes mellitus and problematic hypoglycemia at 1 year follow-up. We note favorable metabolic outcomes at 5-year follow-up in trial cohort from our center.

Material and Methods: 12 patients with type 1 diabetes and problematic hypoglycemia received a total 19 islet transplants (max 2 per patient) within one year. Eight patients were randomly assigned and received Reparixin and 4 received placebo within first week after each transplant in addition to standard immunosuppression (anti-thymocyte globulin, tacrolimus, and mycophenolate).

Results: 11/12 patients achieved insulin independence during the study period. At 5-year follow-up 4/8 (50%) remained insulin free with HbA1c <6.0 % in Reparixin group vs. 1/4 (25%) in placebo group. One patient had partial islet function without severe hypoglycemic episodes (SHE). Diabetic neuropathy and renal function remained unchanged while retinopathy improved in 3/6 (50%) patients. 6/12 (50%) patients left the study: 3/6 proceeded with pancreas transplant and remain off insulin, the remaining 3/6 stopped immunosuppression with decline of islet graft function, deterioration of glucose control (HbA1c > 7.0 %), and recurrence of SHE. No patients experienced any cardiovascular events nor became persistently sensitized (current PRA 0%).

Conclusions: Repeat islet transplantation led to insulin independence in 91% of patients; 50% of patients in Reparixin group and 25% in placebo. Secondary diabetic complications did not progress. No patients became persistently sensitized. Subsequent pancreas transplantation was feasible and effective in patients with decline of islet graft function.

Disclosure

P. J. Bachul: None. A. Perez-gutierrez: None. A. C. Lucander: None. J. Fung: None. P. Witkowski: None. G. S. Generette: None. P. Borek: None. J. S. Pyda: None. R. Anteby: None. L. Basto: None. L. Perea: None. K. Golab: None. M. Tibudan: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK02059); Kovler Family Fund; Dompé farmaceutici S.p.A.
170-OR: Hypothalamic Gliosis Predicts Decline in Insulin Sensitivity over One Year in People with Obesity
Authors: ROSENBAUM JENNIFER L. , SCHOEN STEFAN , MELHORN SUSAN J. , LEON MARY ROSALYNN DE , WEBB MARY , UTZSCHNEIDER KRISTINA , SCHUR ELLEN
Published: June 2021

Studies demonstrate evidence of gliosis in the mediobasal hypothalamus (MBH) of people with obesity and T2D or impaired glucose tolerance (IGT), but whether MBH gliosis predicts worsening glucose homeostasis is unknown.

The study evaluated 38 subjects with obesity (68% female, 76% White). Mean age was 47±11 y and BMI was 35±3.9 kg/m2. MRI, DXA, and 75 g OGTT were performed at baseline and DXA and OGTT repeated at 1y. Mean bilateral T2 relaxation time (ms) in the MBH and 3 control regions was measured as a marker of gliosis. Serial blood samples from OGTT were used to calculate glucose area under the curve (incremental [iAUC] and total [totalAUC]) and to model insulin sensitivity (OGIS) and beta-cell function (beta-cell glucose sensitivity). Generalized estimating equations tested associations and interactions by region.

On average, measures of glucose tolerance (iAUC and totalAUC), OGIS, and beta-cell glucose sensitivity were stable over 1 y. Baseline bilateral mean MBH T2 relaxation time was not associated with changes in glucose tolerance (Δ iAUC β: -5.8 ms, 95% CI -21.0, 9.4, P=0.45; Δ totalAUC β: 1.3 ms, 95% CI -33.5, 36.0, P=0.94, adjusted for sex, age) or change in glucose sensitivity (β: 0.3 ms, 95% CI -1.0, 1.6, P=0.66) nor were interactions present. Change in OGIS over 1y was significantly negatively associated with bilateral mean MBH T2 relaxation time at baseline (β: -0.94 ms, 95% CI -1.7, -0.2, P=0.02, adjusted for sex, age); subjects with longer MBH T2 relaxation times at baseline reduced OGIS over 1 y. A formal interaction by region was not significant (chi2(7)=7.11, Pint=0.42). The relationship within the MBH was attenuated when also adjusted for change in fat mass (β: -0.70 ms 95% CI -1.4, 0.02, P=0.056).

Subjects with greater radiologic evidence for MBH gliosis exhibited declines in insulin sensitivity over 1 y which were not fully accounted for by changes in adiposity. These longitudinal findings are consistent with a role for MBH gliosis in T2D pathogenesis in people with obesity.

Disclosure

J. L. Rosenbaum: None. S. Schoen: None. S. J. Melhorn: None. M. De leon: None. M. Webb: None. K. Utzschneider: None. E. Schur: None.

Funding

American Diabetes Association (1-17-ICTS-085 to E.S.)
172-OR: Perinatal Exposure to a Western Diet Alters Hypothalamic Gene Expression and Predisposes to Diabetes in Adult Male Mice
Authors: ELGAZZAZ MONA , LAZARTIGUES ERIC D. , MAUVAIS-JARVIS FRANCK
Published: June 2021

Cardiometabolic diseases are among the most prevalent diseases worldwide. Maternal epigenetic imprinting affects gene expression in offspring, leading to increased disease susceptibility later in life. We showed previously that perinatal exposure to high fat diet (HFD) leads to obesity, fasting hyperglycemia, glucose intolerance, elevated heart rate and hypertension, exclusively in male mice. Here, we hypothesize that epigenetic maternal programming alters gene expression in the hypothalamus to promote the cardiometabolic disturbances seen in male offspring. To investigate this, C57BL6/J dams were fed a HFD or regular diet (RD) for 1 month and mated with RD-fed males. All offspring were maintained on RD after weaning. At 3 months of age, hypothalami from programmed (HFD-RD) and control (RD-RD) offspring were harvested for mRNA sequencing (Illumina NextSeq). Results show 11 differentially expressed genes (DEG) in HFD-RD males in comparison to RD-RD males. Using iPathway analysis, some of the DEGs were involved in insulin secretion and synaptic vesicle cycle pathways. Among the DEG, Snap25, coding a protein of the exocytosis machinery important for neurotransmitters, and insulin release was upregulated (p= 2.31E-06). Additionally, Nnat gene, involved in appetite suppression and regulation of synaptic plasticity in the hypothalamus, as well as insulin secretion was downregulated (p= 0.04955). MiRNA6236 (p= 2.28E-09) and Rn45s (p= 0.002), whose deficiency in islets is known to be associated with prediabetes in mice, were both downregulated in programmed males. Interestingly, with exception of Nnat gene downregulation (p= 0.001), all the male DEGs were unaltered in HFD-RD females compared to RD-RD females.

In conclusion, perinatal exposure to HFD programs sex-specific alterations in gene expression in the hypothalamus, possibly impairing the central metabolic regulation and predisposing to type 2 diabetes.

Disclosure

M. Elgazzaz: None. E. D. Lazartigues: None. F. Mauvais-jarvis: None.

Funding

American Diabetes Association (1-19-IBS-291 to E.D.L.); U.S. Department of Veterans Affairs (BX004294)
179-LB: Association of Leptin and Adiponectin with the Incidence of Type 2 Diabetes Independent of Visceral Adiposity and Liver Fat
Authors: SHIBATA IZUMI , SHIBATA MIKIKO , SATO KYOKO K. , UEHARA SHINICHIRO , NISHIDA NORIMITSU , OKAMURA KAORI , YUYAMA YOSHIHIKO , KOH HIDEO , HIKITA YONEZO , FUJIMOTO WILFRED Y. , BOYKO EDWARD J. , HAYASHI TOMOSHIGE
Published: June 2021

Leptin and adiponectin are two major adipocytokines reported to be associated with type 2 diabetes. However, it is unknown whether their associations with the risk of incident type 2 diabetes are independent of visceral adiposity and liver fat in a prospective cohort study. We included 787 Japanese men aged 28 to 77 years without type 2 diabetes at baseline. The subjects were classified into four groups based on leptin-adiponectin profile at baseline, with the median concentration value as the cut-off point (median levels of leptin and adiponectin were 4.8 ng/dL and 5.7 µg/mL, respectively): low-high, low-low, high-high, and high-low group. Visceral fat was measured by computed tomography (CT) as intra-abdominal fat area at the umbilicus level. Liver fat was assessed by liver-to-spleen attenuation ratio measured by CT. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Cox proportional hazard models were used to estimate hazard ratios (HR) for developing type 2 diabetes. During 5215 person-years of follow-up, 72 subjects developed type 2 diabetes. Incidence rates of type 2 diabetes per 1000 person-years were 3.2, 9.2, 18.6, and 26.1 for the low-high, low-low, high-high, and high-low group, respectively. After adjustment for age, smoking status, alcohol consumption, regular physical activity, family history of diabetes, visceral fat, and liver fat, multiple-adjusted HRs (95% CI) of incident type 2 diabetes were 1.87 (0.63-5.50), 2.90 (1.02-8.21), and 3.41 (1.23-9.47) for the low-low, high-high, and high-low group compared with the low-high group. In conclusion, leptin and adiponectin were associated with incident type 2 diabetes independent of both visceral fat and liver fat.

Disclosure

I. Shibata: None. W. Y. Fujimoto: None. E. J. Boyko: None. T. Hayashi: None. M. Shibata: None. K. K. Sato: None. S. Uehara: None. N. Nishida: None. K. Okamura: None. Y. Yuyama: None. H. Koh: None. Y. Hikita: None.
186-LB: T1D Exchange Registry: Current Insights on Participant Outcomes
Authors: LEON CAROLINA , LIU JINGWEN , RAVELSON JULIA , CHAPMAN KATHERINE S.M. , HUGHES ALLYSON , WOLF WENDY
Published: June 2021

The T1D Exchange Registry was launched June of 2019 to increase participation in research and probe a diverse set of topics impacting the type 1 diabetes (T1D) population. The Registry is an online platform that recruits adults and parents/guardians of children with T1D who live in the U.S. Participants complete screening questions, sign informed consent, and answer an initial questionnaire regarding health and diabetes management. Subsequently, participants complete an annual questionnaire to track changes in diabetes management and outcomes. As of March 2021, the Registry encompasses 7630 participants who have completed their initial questionnaire and 1063 who have completed their one-year annual questionnaire. This report focuses on the cohort of participants who have completed their annual questionnaire. These participants reported an average age of 45.2 years, ranging from 4 to 85.7 years, and an average T1D duration of 25.8 years. This cohort is more technology-oriented than other reported cohorts, with 88.8% of participants using a CGM (an increase from 82.5% at their time of enrollment) and 78.6% using an insulin pump (an increase from 74.7% at their time of enrollment). Additionally, 58.2% carry a glucagon kit and 11.2% use medications other than insulin to lower blood sugar. At the time of the initial questionnaire the cohort reported an average A1c of 7.2 and subsequently 6.8 at the one-year questionnaire. However, 15.0% reported experiencing severe hypoglycemia, defined as a change in mental and/or physical functioning and needing help from another person, while 6.7% reported diabetes-related ketoacidosis (DKA) symptoms over the last 12 months. This subset of Registry participants who are highly engaged, heavy technology users, and meet target A1cs, still report severe hypoglycemia and DKA symptoms, suggesting that there is potential for improvement in diabetes management and care.

Disclosure

C. Leon: None. J. Liu: None. J. Ravelson: None. K. S. M. Chapman: None. A. Hughes: None. W. Wolf: None.
187-OR: Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes in the ACCORD Trial
Authors: KOSKA JURAJ , GERSTEIN HERTZEL C. , BEISSWENGER PAUL J. , REAVEN PETER
Published: June 2021

Individual advanced glycation end products (AGEs) have been implicated in the development of chronic kidney disease (CKD). We evaluated the prognostic utility of a comprehensive multicomponent AGE panel in predicting long-term renal function loss and CKD when added to routine clinical measures in persons with type 2 diabetes (T2D) followed for 12.5 years (including risk factor intervention and observation phases). The five key AGEs (carboxymethyl and carboxyethyl lysine, and methylglyoxal, 3-deoxyglucosone and glyoxal hydroimidazolone) were measured via LC-MS/MS in baseline serum from 1,151 the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. A composite AGE score was calculated as the mean of individual AGE z-scores. Outcomes were (1) renal function loss (≥40% decline in estimated glomerular filtration rate [eGFR]), (2) macroalbuminuria (MAU), and (3) high-risk CKD (hrCKD, KDIGO classification). Higher AGE score predicted greater risks of renal function loss (n=260 events, hazard ratio 1.49 [95%CI 1.24-1.79], p<0.0001), MAU (n=96, 1.45 [1.06-1.98], p=0.005) and hrCKD (n=128, 1.95 [1.47-2.57], p<0.0001), independent of baseline eGFR, urine albumin:creatinine, randomization arms, other standard risk factors and hemoglobin A1c. Higher AGE score predicted renal function loss even in those with normal renal function (1.40 [1.06-1.84], p=0.02). When added to routine risk factors, AGE score improved net-reclassification and integrated discrimination for renal function loss (by 19% and 17%, p=0.002) and hrCKD (by 34% and 4.9%; p=0.02), but not MAU (0.8% and 1.3%, p=0.6). There is a strong independent association between AGE burden and progression of CKD in T2D. Adding AGE measures to standard clinical parameters improves the prediction of multiple kidney outcomes, indicating its potential as prognostic biomarker of diabetes nephropathy.

Disclosure

J. Koska: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. P. J. Beisswenger: Stock/Shareholder; Self; PreventAGE Healthcare LLC. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc.

Funding

National Institutes of Health (R21HL150268)
191-LB: Impact of Subsistence and Genetics on Lipid Profiles in Ethnically Diverse Africans
Authors: MA RONG , HANSEN MATTHEW , RANCIARO ALESSIA , THOMPSON SIMON R. , BEGGS WILLIAM , MPOLOKA SUNUNGUKO W. , MOKONE GAONYADIWE G. , NYAMBO THOMAS B. , MICHAILIDIS GEORGE , LI HONGZHE , BURANT CHARLES , TISHKOFF SARAH A.
Published: June 2021

African Americans are at higher risk for cardiometabolic disease relative to individuals with European ancestry. Yet, populations with African ancestry are greatly under-represented in human genomics studies. To alleviate this bias and better distinguish the roles of genetics and environment on cardiometabolic traits, we conducted targeted metabolomics to measure levels of >700 lipids in 718 Africans and integrated with genomic data from >7M single nucleotide polymorphisms genotyped in the same individuals. These individuals are from 14 ethnic groups from diverse regions of Africa (Botswana, Cameroon, Ethiopia, Tanzania) and with diverse subsistence patterns (agriculturalists, pastoralists, hunter-gatherers). In contrast to US populations, most individuals were sampled from rural areas with relatively homogenous diets and, thus, we could better quantify lipids typically found at low levels in US individuals. Furthermore, several groups have similar genetic ancestry but distinct diets, and vice versa, enabling us to distinguish the role of genetic ancestry and environment on lipid variation. We identified 305 independent genetic variants associated with 103 lipid species, >50 of which have not previously been reported in similar studies of European/US populations (e.g. at ROCK2, ARHGEF28, DHODH, ALDH1A2). We observe correlations between subsistence and lipid profiles but show that genetic ancestry also plays an important role in variation within and between populations. For example, Eastern African pastoralists with a diet rich in milk and blood have relatively high levels of di-and tri-glycerides, but within each lipid class, levels are influenced by genotype. The Fulani pastoralists from Cameroon, with a high incidence of hypertension and diabetes but low BMI, also have relatively high levels of triglycerides, suggesting diet is predominantly influencing lipid levels and that genetic factors unrelated to lipid metabolism are influencing risk for disease in that population.

Disclosure

R. Ma: None. H. Li: Consultant; Self; Eli Lilly and Company. C. Burant: None. S. A. Tishkoff: None. M. Hansen: None. A. Ranciaro: None. S. R. Thompson: None. W. Beggs: None. S. W. Mpoloka: None. G. G. Mokone: None. T. B. Nyambo: None. G. Michailidis: None.

Funding

American Diabetes Association (1-19-VSN-02 to S.A.T.); National Institutes of Health (GM134957-01)
195-OR: A Comparison of Inpatient Glycemic Control Using Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Persons with Type 1 Diabetes
Authors: YE YUTING , IZARD STEPHANIE , MYERS ALYSON
Published: June 2021

Background: Continuous subcutaneous insulin infusion (CSII) therapy is increasingly being used in the outpatient setting, but there is little known information about its efficacy in the inpatient setting. This study compares inpatient glycemic control of persons with type 1 diabetes (T1D) using CSII, multiple daily injections (MDI), or both.

Method: This retrospective chart review assessed the glycemic control of adult patients with T1D who used CSII, MDI or a combination of both during their hospitalization between January 1, 2017 and December 31, 2019. Those who were pregnant and/or treated with continuous intravenous insulin infusion were excluded. Variables were summarized descriptively using means and frequencies. Continuous variables were compared across groups using the ANOVA or Kruskal-Wallis test, and categorical variables were compared using the Fisher’s Exact test.

Results: We analyzed records of 65 patients who were mostly male (53.8%) and white (72%) with a mean age of 51.7 ± 16.0 years. The mean hemoglobin A1c was 7.80 ± 1.08%. Though not statistically significant, both mean blood glucose and proportion of hyperglycemic events (proportion of blood glucose measures > 300 mg/dL) were lowest in the CSII group. Mean blood glucose for CSII, MDI, and both was 172.88 ± 40.14, 195.40 ± 43.90, and 199.50 ± 49.99 mg/dL, respectively (p=0.17). The proportion of hyperglycemic events for CSII, MDI, and both was found to be 0.11 ± 0.11, 0.26 ± 0.20, and 0.27 ± 0.27, respectively (overall p=0.0267, pairwise comparisons not significant).

Conclusion: Glycemic control of patients with CSII is not significantly different than patients with MDI or a combination of both in persons with T1D, thus suggesting that patients can remain on CSII therapy while inpatient.

Disclosure

Y. Ye: None. S. Izard: None. A. Myers: None.
196-OR: Digital Insulin Therapy Protocol in the Postoperative Period of Coronary Artery Bypass Graft Surgery: A Prospective Randomized Study
Authors: CAMARA DE SOUZA ALEXANDRE B. , TOYOSHIMA MARCOS T.
Published: June 2021

Introduction: Adequate glycemic control with intravenous insulin therapy in the postoperative period of coronary artery bypass grafting (CABG) in an intensive care unit (ICU) reduces unfavorable clinical outcomes, such as mortality, acute kidney injury (AKI), arrhythmias and nosocomial infection. After discharge from ICU, even still hospitalized, adherence to consensus on inpatient insulin therapy is low, and about 50% of patients do not receive adequate subcutaneous insulin therapy in the ward, consequently in-hospital hyperglycemia (IH) is frequent. Medical apps are increasingly facilitating the medical routine. InsulinAPP is a digital protocol for inpatient glycemic management and already validated. A 16% reduction in blood glucose (BG) has been demonstrated in clinical patients with this protocol.

Method: Prospective randomized trial was performed on diabetic patients in CABG postoperative period, after discharge from ICU. The groups were randomized according to the glycemic control protocol: InsulinAPP group (APP) or protocol defined by the assistant team (ST - standard group). The aim is to compare the groups regarding the composite outcome of AKI, nosocomial infection and atrial fibrillation.

Results: A total of 41 patients were evaluated (15 in APP and 26 in ST). There was no difference between APP vs. ST group in age (65.1±9.8 vs. 65.1±9.8 years), female gender (40 vs. 46%), body mass index (28.5±4.9 vs. 27.3±5.1 Kg/m2) and estimated glomerular function (68.0±24.1 vs. 69.1±24.5 mL/min, respectively). APP had better BG than ST group (162±28.6 mg/dL vs. 183±34.4 mg/dL, respectively; p = 0.036). Besides, in APP there was a significant reduction of the composite outcome (27% vs. 77%, p=0.002), infection (20% vs. 61%, p<0.001) and AKI (13% vs. 50%, p=0.019).

Conclusion: The InsulinAPP protocol was more effective in glycemic control and in reducing unfavorable outcomes in the postoperative period of cardiac surgery after discharge from the ICU.

Disclosure

A. B. Camara de souza: None. M. T. Toyoshima: None.