bluuebunny/crossref_metadata_2025 huggingface dataset:
1283-P: Pilot Study Reveals Excellent Agreement between the Newly Developed Pastry Sugar Tolerance Test and the OGTT in the Diagnosis of Diabetes
Authors: SCHENK BLAYNE R. , HURSTON JAMAIICA , DE DIEU GATETE JEAN , DUBOSE CHRISTOPHER , MABUNDO LILIAN , YANG SHANNA , WORTHY CHARLITA , COURVILLE AMBER B. , JAGANNATHAN RAM , SUMNER ANNE E.
Published: June 2023

Achieving early diagnosis of type 2 diabetes (T2D) in Africans is challenging. The Glucola used in the OGTT is expensive and unavailable in most African countries. Alternatives to the OGTT are fasting plasma glucose (FPG) and A1C, but they have a low diagnostic sensitivity in Africans. As an alternative to the Glucola (75g glucose) used in the OGTT, we developed the Pastry Sugar Tolerance Test (PSTT) with pastry sugar (75g glucose powder) dissolved in hot water. Pastry sugar is inexpensive and widely available in Africa. Hence, our aim was to determine the diagnostic agreement between (1) OGTT and PSTT; (2) OGTT and A1C; (3) OGTT and FPG in the detection of T2D in 48 African-born Blacks living in America (male: 67%; age: 41±10y (mean±SD)). At Visit 1, an OGTT, A1C and FPG were performed. At Visit 2, which occurred 8±3 days later, a PSTT was performed (Fig). ADA criteria were used for the OGTT, A1C≥6.5% and FPG≥126 mg/dL. Agreement between tests was determined by κ-statistic. T2D, prediabetes and normal glucose tolerance occurred in 8% (4/48), 31% (15/48) and 61% (29/48), resp. All individuals with T2D were detected by both the OGTT and PSTT (κ=0.99). Yet, A1C only detected 50% (2/4) (κ=0.65), and FPG only detected 25% (1/4) (κ=0.38) of Africans with T2D. This pilot study suggests that in the detection of T2D, agreement between the PSTT and the OGTT may be both excellent and superior to A1C and FPG.

Disclosure

B.R.Schenk: None. A.E.Sumner: None. J.Hurston: None. J.Gatete: None. C.Dubose: None. L.Mabundo: None. S.Yang: None. C.Worthy: None. A.B.Courville: None. R.Jagannathan: None.
1289-P: Predictors of New-Onset Type 2 Diabetes after Infection with COVID-19 in the COVID-OUT Randomized Trial
Authors: NICKLAS JACINDA M. , LEMUS WIRTZ ESTEBAN J. , MURRAY THOMAS A. , LIEBOVITZ DAVID , FENNO SARAH , ANDERSON BLAKE , AVULA NANDINI , REDDY NEHA , BRAMANTE CAROLYN
Published: June 2023

Background: There are mixed data on whether COVID-19 infection is associated with increased incidence of type 2 diabetes (T2DM). The majority of data have been derived from retrospective datasets. We sought to identify predictors of new onset T2DM in a prospective cohort enrolled in the multi-site phase 3 randomized quadruple-blinded placebo-controlled COVID-OUT clinical trial.

Methods: Adults with overweight or obesity aged 30-85 were enrolled within 3 days of a positive SARS-CoV-2 test and <7 days of symptoms. Participants were randomized to 1 or 2 of 3 oral medications (immediate-release metformin increasing over 6 days to 1500 mg daily for a total of 14 days; ivermectin 430mcg/kg/day for 3 days; fluvoxamine 50mg day 1 then 50mg twice daily through 14 days) or placebo using a two by three parallel treatment factorial design. Starting 60 days after randomization we sent automated email surveys every 30 days through 300 days about new diabetes diagnoses, as well as changes in weight and sleep. We conducted univariable analyses to determine predictors of T2DM diagnosis.

Results: Among 1093 subjects, 25 reported a new diagnosis of diabetes within 300 days of COVID-19 infection. There were no significant differences in incidence by treatment arm or vaccination in univariate analysis. Participants with new onset T2DM had a higher baseline BMI (OR 1.08, 95% CI 1.03 to 1.13), and were more likely to report weight gain between the start of the pandemic and their first infection and more likely to report difficulty sleeping, OR 1.04 (95% CI 1.01 to 1.07) and OR 2.86 (95% CI 1.16 to 7.06), respectively. Multivariate analysis is pending.

Conclusions: Patients with higher BMIs at baseline, those who gained weight between the onset of the pandemic and their first COVID-19 infection, or had difficulty sleeping were more likely to develop T2DM. Covid treatment with metformin, ivermectin, and fluvoxamine and vaccination status were not significant predictors of new T2DM.

Disclosure

J.M.Nicklas: None. E.J.Lemus wirtz: None. T.A.Murray: None. D.Liebovitz: None. S.Fenno: None. B.Anderson: None. N.Avula: None. N.Reddy: None. C.Bramante: None.

Funding

Rainwater Foundation; Parsemus Foundation; United Health Foundation; National Center for Advancing Translational Sciences (KL2TR002492, UL1TR002494); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK124654-01-A1); National Heart, Lung, and Blood Institute (K23HL133604)
129-OR: Effect of Tirzepatide on the Counterregulatory Response to Hypoglycemia during a Hypoglycemic Clamp in People with Type 2 Diabetes
Authors: PIEBER THOMAS , SVEHLIKOVA EVA , URVA SHWETA , HAUPT AXEL , ZHOU CHUNMEI , COSKUN TAMER , MILICEVIC ZVONKO , PRATT EDWARD J.
Published: June 2023

We explored the effects of tirzepatide (TZP) on counter-regulatory response during a hypoglycemic clamp. Patients with type 2 diabetes (N=42) were randomized to TZP (15 mg) or placebo (PBO) for 12 wk, in a crossover design, with a wash-out period of 8 to 12 wk. The primary objective was the change in glucagon (GCG) during clamp-induced hypoglycemia (HG) from plasma glucose (PG) 100 mg/dL to nadir PG (45 mg/dL). Secondary measures were changes in other counter-regulatory hormones, insulin, and C-peptide during clamp-induced HG and PG recovery from nadir PG to 72 mg/dL. Time to recovery and HG symptom scores were assessed. At 12 wk, HbA1c change from baseline was -1.5% with TZP vs +0.5% with PBO. Increases in GCG from PG 100 mg/dL to nadir PG and during recovery did not differ between treatments (p=0.756 and p=0.565, respectively) (Table). Growth hormone and adrenaline responses did not differ between treatments, while increases in cortisol and noradrenaline responses were delayed with TZP, which explains a lower HG symptom score with TZP vs PBO at nadir (p=0.007). The proportion of patients aware of HG did not differ between treatments. Mean time to recovery from HG was 47 min with TZP and 43 min with PBO (p=0.002); however, nadir PG was lower with TZP (44 vs 47 mg/dL; p=0.015). In conclusion, the response of glucagon to hypoglycemia is maintained with TZP.

Disclosure

T.Pieber: Advisory Panel; Arecor, Novo Nordisk A/S, Consultant; Lilly, Research Support; AstraZeneca, Novo Nordisk A/S, Sanofi, Speaker's Bureau; Roche Diagnostics. E.Svehlikova: Other Relationship; Mylan. S.Urva: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. C.Zhou: Employee; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Z.Milicevic: Employee; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
1298-P: Independent Associations of GAD65, IA2, and ZnT8 Autoantibody (Ab) Positivity with C-Peptide (CPep) in a Diverse Cohort of Youth with Diabetes (DM)
Authors: REDONDO MARIA J. , HARRALL KYLIE K. , GLUECK DEBORAH H. , TOSUR MUSTAFA , UYSAL SERIFE , MUIR ANDREW , VEHIK KENDRA , BRUSKO TODD M. , ATKINSON MARK A. , ORAM RICHARD A. , DABELEA DANA , HAGOPIAN WILLIAM ,   DISCOVER STUDY GROUP
Published: June 2023

The current DM classification does not fully enable precision medicine in DM due to heterogeneity between and within DM types, especially in racially diverse populations. Insulin deficiency (ID) is one of the most clinically actionable DM outcomes and, while its association with islet autoimmunity is known, the influence of Ab type and number after DM onset is uncertain. Thus, we assessed the effect of Ab characteristics on ID (measured as Cpep loss) in youth with established DM. We studied 151 youth with DM (median [IQR] age 15.0 [4.2] yrs, DM duration 5.4 [3.4] yrs), 61% female, 53% Hispanic and 17% non-Hispanic African American. We measured postprandial serum Cpep, glucose and Ab (GAD65, IA2 and ZnT8) and collected clinical/demographic data. Cpep loss was pre-specified as postprandial CPep <0.6 ng/ml. We found 0, 1, 2, or 3 +Ab in 34%, 22%, 31% and 13% of participants, respectively (Figure, left panel). A Breslow-Day statistic suggested homogeneity of the risk ratios across the 3 Ab types for CPep loss (p = 0.42), which were all larger than 1 (Figure, right panel). Cpep loss was significantly associated with ≥1 (vs 0) Ab+ (p < 0.0001) but not with single (vs multiple) Ab+ (p = 0.60). In sum, each of GAD65, IA2 and ZnT8 Ab are significantly associated with ID among diverse youth with DM. This suggests that models predicting ID post-onset should include each of GAD65, IA2 and ZnT8 Ab.

Disclosure

M.J.Redondo: None. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. D.Dabelea: None. W.Hagopian: Research Support; Janssen Research & Development, LLC, Provention Bio, Inc., Randox R & D. Discover study group: n/a. K.K.Harrall: None. D.H.Glueck: None. M.Tosur: Advisory Panel; Provention Bio, Inc. S.Uysal: None. A.Muir: None. K.Vehik: None. T.M.Brusko: Consultant; Repertoire Immune Medicines, Quell Therapeutics, Research Support; Immunocore, Ltd., Adaptive Biotechnologies. M.A.Atkinson: None.

Funding

National Institutes of Health (R01DK124395)
1331-P: Association of Short-Term and Long-Term Glycemic Variability and the Renal Complications in the ACCORD Trial
Authors: OKUNO TOMOKI , REAVEN PETER , ZHOU JIN
Published: June 2023

Recent studies have shown that long-term and short-term glycemic variability (measured by low concentrations of the biomarker 1,5-anhydroglucitol (1,5-AG)) were associated with incident diabetes complications; yet, none have assessed their relative importance. Using the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, we measured 1,5-AG 12 months from randomization (when HbA1c was stable) in 4,000 randomly selected samples and assessed the risk of short-term and long-term glycemic variability for incident renal complications. The coefficient of variation of fasting glucose (CV-FG) was used to measure long-term variability. Primary outcomes were time (after 12 months) to 1) microalbuminuria and 2) macroalbuminuria. Risks were estimated using Cox proportional hazard models. Both CV-FG and lower 1,5-AG were independently associated with microalbuminuria even after adjusting for other risk factors (Table). Only CV-FG was a significant risk factor for macroalbuminuria. After adjusting for average glycemic control, the CV-FG association remained. Subgroup analysis indicated that CV-FG and 1,5 AG were more harmful in those receiving less intensive glucose control. The secondary outcome analysis supported the main conclusion (Table). This post hoc analysis indicates that long-term and short-term glucose variability may play a role in developing renal diseases in T2D.

Disclosure

T.Okuno: None. P.Reaven: Research Support; Dexcom, Inc. J.Zhou: None.

Funding

National Institutes of Health (R01HG006139, DMS-2054253, IIS-2205441, R21HL150374)
1335-P: The Association between Exposure to Famine in Early Life and Risks of Diabetic Complications in Adult Patients with Type 2 Diabetes in China
Authors: LIN CHU , CAI XIAOLING , JI LINONG
Published: June 2023

Background: The historical origin for the T2D pandemic in China may lie in the 1959-1961 Chinese famine. This study is aimed to exam the associations between exposure to famine in early life and risks of diabetic complications in adult patients with T2D in China.

Method: The participants in this study were selected from China National HbA1c Surveillance System (2009-2013), and further stratified according to the birth year. The participants born in 1959-1961 were classified as fetal exposed group (70852 participants). The participants born in 1956-1959 were classified as infant/toddler exposed group (93616 participants). The participants born in 1962-1964 were classified as unexposed group (72723 participants). By using the logistic regression approach, we analyzed the association between exposure to famine in early life and risks of diabetic complications.

Results: As for diabetic complications, the adjusted model indicated that, compared with T2D without exposure to famine, the risks of coronary heart disease (fetal exposed: OR=1.254, 95%CI: 1.196-1.315; infant/toddler exposed: OR=1.343, 95%CI: 1.286-1.403), cerebrovascular disease (fetal exposed: OR=1.290, 95%CI: 1.200-1.388; infant/toddler: OR=1.342, 95%CI: 1.254-1.436) and diabetic retinopathy (fetal exposed: OR=1.083, 95%CI: 1.036-1.132) were significantly increased while the reduced risk of diabetic kidney disease (infant/toddler exposed:OR=0.885, 95%CI: 0.841-0.932) was observed in adult T2D patients with early-life exposure to famine.

Conclusions: Early-life exposure to famine in patients with T2D was associated with increased risks of coronary heart disease, cerebrovascular disease, diabetic retinopathy but reduced risks of diabetic kidney disease in adulthood. Improving early-life nutritional status may promote better risk prevention and management of diabetic complications and comorbidities in patients with T2D.

Disclosure

C.Lin: None. X.Cai: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics.

Funding

National Natural Science Foundation of China (81970698, 81970708); Beijing Natural Science Foundation (7202216)
134-OR: Associations of Growth Hormone (GH) Mediators with Loss of Glycemic Control in Youth with Type 2 Diabetes (T2D)
Authors: LU CHANG , WOLFS DANIELLE , EL GHORMLI LAURE , LAFFEL LORI M. , PATTI MARY-ELIZABETH , ISGANAITIS ELVIRA M.
Published: June 2023

T2D in youth has a more severe phenotype than in adults, with puberty as a potential contributor to this difference. Pubertal changes in GH mediators (e.g., insulin-like growth factor 1 (IGF-1), growth hormone receptor (GHR), insulin-like growth factor binding protein 1 (IGFBP-1)) may impact insulin sensitivity and beta cell function. We examined associations of GH mediators with loss of glycemic control in youth with T2D using the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort (N= 310). We performed paired comparison of plasma concentrations of IGF-1, GHR, and IGFBP-1 (ELISA), between 0mo and 36mo based on TODAY primary outcome of loss of glycemic control vs. maintained glycemic control (LGC vs MGC), with LGC defined as HbA1c ≥ 8% for 6 months and/or insulin dependence. We studied associations of GH mediators with HbA1c, insulinogenic index, oral disposition index, and 1/fasting insulin. Models were adjusted for age, sex, race, treatment arm, and baseline HbA1c (linear regression). Mean plasma IGF-1 (ng/mL) was lower in LGC group at 0mo (LGC: 451 ± 141, MGC: 485 ± 155, p = 0.04), and at 36mo (LGC: 340 ± 117, MGC: 400 ± 136, p< 0.0001). Increase in IGF-1 between 0-36mo predicted lower HbA1c at 36mo (B = -3.2E-3, SE = 9.0E-4, p < 0.001). Higher GHR was associated with higher HbA1c (B = 1.2E-2, SE = 3.0E-3, p < 0.001) and lower 1/fasting insulin (B = -6.6E-4, SE = 2.1E-4, P < 0.01) at 0mo. Increase in GHR between 0-36mo predicted higher 36mo HbA1c (B = 3.0E-2, SE = 9.4E-3, p < 0.01). IGFBP-1 was positively associated with 1/fasting insulin at 0m (B = 1.1E-3, SE = 4.9E-4, p = 0.03). In exploratory analyses stratified by Tanner stage (TS) at study entry, GH mediators changed differentially between TS 1-3 (n = 31) vs TS 4-5 (n = 274). In conclusion, GH mediators differed based on primary outcome in TODAY, and were associated with HbA1c and insulin sensitivity. Whether changes in GH mediators contribute to, or are the result of, changes in glucose metabolism is a key area for future studies.

Disclosure

C.Lu: None. D.Wolfs: None. L.El ghormli: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. M.Patti: Consultant; MBX Biosciences, AstraZeneca, Hanmi Pharm. Co., Ltd., Other Relationship; Fractyl Health, Inc. E.M.Isganaitis: None.

Funding

National Institutes of Health (2T32DK007260-46); National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK061230-16)
1343-P: Decreasing Lifetime Prevalence of Diabetes-Related Foot Ulcers over 25 Years—Longitudinal Analyses of the Trøndelag Health Study (HUNT), Norway
Authors: RIISE HILDE K.R. , IGLAND JANNICKE , GRAUE MARIT , HAUGSTVEDT ANNE , OSTBYE TRULS , SØFTELAND EIRIK , HERMANN MONICA , CARLSSON SOFIA , ÅSVOLD BJØRN O. , IVERSEN MARJOLEIN M.
Published: June 2023

Background and objectives: Data on time trends in diabetes-related foot ulcer (DFU) prevalence are limited. We aimed to determine trends in the lifetime prevalence of DFU in the Trøndelag Health Study (HUNT) conducted in three waves between 1995 and 2019.

Research Design and Methods: This longitudinal population-based study consists of individuals ≥20 years with diabetes who participated in at least one of the three HUNT surveys from 1995-2019. Type 2 diabetes was defined as glutamic acid decarboxylase antibodies (GADA) <5 IU/mL (<0.09 ai) and age at diagnosis ≥30 years. Type 1 diabetes was defined as GADA ≥5 IU/mL (≥ 0.09 ai) and/or age at diagnosis <30 years. We used the following question to assess prevalence of DFU: “Have you had a foot ulcer that required more than three weeks to heal?”. The lifetime prevalence of DFUs was evaluated using cross-sectional data.

Results: The total diabetes population was 1630 in HUNT2, 1824 in HUNT3 and 2393 in HUNT4. Approximately 85% of the participants had type 2 diabetes. Among those with type 2 diabetes, the lifetime prevalence (95% confidence interval (CI)) of a DFU requiring three or more weeks to heal was 10.1% (8.5-11.8) in HUNT2, 7.4% (6.2-8.8) in HUNT3 and 5.0% (4.1-6.0) in HUNT4. Corresponding numbers in those with type 1 diabetes were 14.9% (11.1-19.8), 8.5% (5.4-13.3) and 7.2% (4.8-10.5), respectively. The decline in DFU prevalence persisted after adjusting for age, sex, educational level, marital status, work situation, body mass index, systolic blood pressure, smoking, and HbA1c.

Conclusion: The results of this longitudinal population-based study suggest that the lifetime prevalence of DFUs in Norway has declined substantially during the past 25 years.

Disclosure

H.K.R.Riise: None. M.M.Iversen: None. J.Igland: Research Support; Pfizer Inc., Sanofi. M.Graue: None. A.Haugstvedt: Advisory Panel; Novo Nordisk. T.Ostbye: None. E.Søfteland: None. M.Hermann: None. S.Carlsson: None. B.O.Åsvold: None.

Funding

Western Norway Regional Health Authority (F-12131)
1345-P: Proinsulin–to–C-Peptide Ratio Is Associated with the Time above the Target Glucose Range and the Duration of Type 2 Diabetes
Authors: MIYA AIKA , NAKAMURA AKINOBU , NOMOTO HIROSHI , KAMEDA HIRAKU , ATSUMI TATSUYA
Published: June 2023

Background: The proinsulin-to-C-peptide (PI:C) ratio is thought to be an index of pancreatic β-cell dysfunction, and in subjects with prediabetes and type 2 diabetes (T2DM), abnormally high PI:C ratios have been identified. In the present study, we investigated the relationships of the duration of diabetes and glucose variability in subjects with T2DM with the PI:C ratio.

Methods: We performed a prospective observational study of 272 Japanese outpatients with T2DM who underwent blinded professional continuous glucose monitoring (CGM) and fasting blood sample collection. Their fasting PI:C ratio and CGM-related indices were calculated. After placing all the participants into four groups on the basis of quartile (Q) of diabetes duration (Q1 <8 years, Q2 8-13 years, Q3 14-21 years, Q4 ≥22 years), the characteristics associated with PI:C ratio were identified. All of the statistical tests were two-sided and P<0.05 was considered to indicate statistical significance.

Results: The mean age of the cohort was 68.0 years, their mean HbA1c 7.1%, and their mean body mass index (BMI) 24.9 kg/m2. High PI:C ratio was associated with a short duration of diabetes (P<0.001). In each group, there was a positive correlation between PI:C ratio and the time above the target glucose range (TAR; >180 mg/dL) in Q1, Q2, and Q3. The closest correlation between PI:C ratio and TAR was found for Q1 but there was no significant correlation for Q4 (Q1: ρ=0.38, P=0.003; Q2: ρ=0.28, P=0.019; Q3: ρ=0.24, P=0.045; Q4: ρ=0.03, P=0.811).

Conclusions: We have shown that the PI:C ratio was positively associated with TAR in subjects with a short duration of T2DM. Given that insufficient pancreatic β-cell function and hyperglycemia is closely related, the PI:C ratio may play a role as the index of pancreatic β-cell dysfunction in subjects with a short duration of T2DM, but not in those with long-standing T2DM.

Disclosure

A.Miya: None. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. H.Kameda: None. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd.

Funding

Japan Society for the Promotion of Science (22K17766)
1346-P: Investigation of Changes in Urinary Titin N-terminal Fragment during Hospitalization for Glycemic Control
Authors: YOSHIDA SUMIKO
Published: June 2023

Background: Urinary titin N-terminal fragment concentration (urinary titin) has been reported to be negatively correlated with muscle mass, grip strength, and knee joint extension strength, and is considered a biomarker that reflects sarcopenia, muscle damage, and the catabolic state of muscle. Sarcopenia and skeletal muscle dysfunction occur in the person with diabetes, but it is unclear how urinary titin changes with improved blood glucose control.

Methods: One hundred and five Japanese patients with diabetes (85 type 2 and 20 type 1) who were hospitalized for glycemic control for approximately 2 weeks were included. Patients who were hospitalized with acute complications of diabetes or who had infections were excluded. Urinary titin was measured in all patients at admission and discharge, and skeletal muscle mass index (SMI) was measured in 49 patients.

Results: Patients were 55 males and 50 females. Median age was 62.0 years, BMI was 25.5, and HbA1c was 9.2%. There was no correlation between urinary titin at admission and age, BMI, SMI, and HbA1c, but it tended to be higher in men (p=0.08). Urinary titin was 2.31±5.40 nmol/gCr at admission and 1.30±1.48 nmol/gCr at discharge, showing a significant decrease (p=0.049). Body weight loss of -1.8% was observed during hospitalization, and SMI decreased by -1.4% from admission. There was no correlation between changes in urinary titin during hospitalization and age, BMI, HbA1c, and changes in body weight and SMI during hospitalization.

Conclusion: Urinary titin significantly decreased in patients with diabetes who were hospitalized for glycemic control for approximately 2 weeks, and no correlation was observed with changes in SMI. The short-term changes in urinary titin suggested that skeletal muscle dysfunction was improved by improvement of blood glucose control. However, in this study, the quality of skeletal muscle such as muscle strength could not be evaluated, and additional examination is necessary.

Disclosure

S.Yoshida: None.
1377-P: The Contribution of Binge Eating to the Glycometabolic Risk Factors Is Mediated by Nutritional Status and Body Composition in People with Overweight and Obesity
Authors: LEONE ALESSANDRO , DE AMICIS RAMONA , FOPPIANI ANDREA , BERTOLI SIMONA , MENICHETTI FRANCESCA , BATTEZZATI ALBERTO
Published: June 2023

Binge eating (BE) has been associated with an increased risk of obesity and diabetes. However, it is unclear whether the relationship between BE and glycometabolic risk factors is direct or mediated by other factors, such as lifestyle, nutritional status, and body composition. To clarify this issue, we conducted a cross-sectional study of 4799 subjects free of diabetes (68% women, mean age: 47±13 years) with overweight (53.8%) and obesity (46.2%) recruited at ICANS, University of Milan. All subjects underwent a clinical examination. Anthropometric measurements (weight, height and body fat estimation by body skinfold), visceral and subcutaneous abdominal adipose tissue thicknesses measured by ultrasound, and fasting blood parameters (glucose, insulin and HOMA) were measured. Lifestyle was assessed, with particular regard to smoking, physical activity, and adherence to the Mediterranean diet (MEDAS questionnaire). BE was assessed using the Binge Eating Scale (BES) questionnaire (range score: 0-46). People with a BES score ≥18 were categorized as having BE. Overall, 18.4% of subjects presented BE, with higher prevalence in women (22.8%) than in men (9.1%, p<0.001) and in people with obesity (22.4%) than overweight (15.0%, p<0.001). In the linear regression model adjusted for sex and age, BES was significantly associated with glucose (β=0.05, 95%CI: 0.01, 0.08; p<0.013), insulin (β=0.10, 95%CI: 0.07, 0.13; p<0.001) and HOMA (β=0.03, 95%CI: 0.02, 0.04; p<0.001). The significant association between BES and glycometabolic risk factors remained after inclusion of lifestyle factors (smoking, physical activity and adherence to the Mediterranean diet). However, after inclusion of BMI, total and abdominal fat, the significance was lost. Our data do not support the hypothesis of a direct contribution of BE to the glycometabolic risk. The contribution of BE seems to be mediated by nutritional status and body composition.

Disclosure

A.Leone: None. R.De amicis: None. A.Foppiani: None. S.Bertoli: None. F.Menichetti: None. A.Battezzati: None.

Funding

Italian National Recovery and Resilience Plan Mission 4 Component 2 Investment 1.3 - Call for Proposals (341) of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU (PE00000003) Concession Decree (1550) of 11 October 2022 adopted by the Italian Ministry of University and Research (CUP D93C22000890001)
1395-P: The Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplants in the U.S.
Authors: STEPANOVA MARIA , KUMAR AMEETA , BRANDT PAMELA , GUNDURAO NAGASHREE , CUSI KENNETH , YOUNOSSI ZOBAIR
Published: June 2023

Background and Aim: Type 2 Diabetes (T2D) is a major driver of chronic diseases across the globe. The aim of this study was to assess the impact of T2D on the outcomes of solid organ transplantations.

Method: We used Scientific Registry of Transplant Recipients (SRTR) 2006-2021 to collect data for all patients ≥18 years who received a lung, heart, liver, or kidney single organ transplant in the U.S.

Results: We included 442,100 solid organ transplant recipients: 31,503 lung, 38,004 heart, 86,153 liver, 286,440 kidney transplants. The prevalence of pre-transplant T2D was 15% in lung (increased from 12% in 2006 to 15% in 2021), 26% in heart (22% in 2006 to 28% in 2021), 26% in liver (23% in 2008 to 28% in 2019), and 30% in kidney (26% in 2006 to 34% in 2021). In all organs, post-transplant mortality was significantly higher among transplant recipients with vs. without T2D [lung transplant: 14.2% vs. 13.1% (1 year), 46.4% vs. 42.6% (5 years), p<0.05; heart transplant: 11.2% vs. 9.1% (1 year), 24.4% vs. 20.6% (5 years), all p<0.0001; liver transplant: 10.3% vs. 8.4% (1 year), 25.4% vs. 21.1% (5 years), all p<0.0001; kidney transplant: 5.3% vs. 2.5% (1 year), 20.8% vs. 10.1% (5 years), all p<0.0001]. Independent association of pre-transplant T2D with higher post-transplant mortality was significant after adjustment for clinico-demographic confounders (calendar year, age, sex, race, education, insurance, functional status, obesity, history of cancer, listing diagnosis, donor-related parameters): adjusted hazard ratio (aHR) for T2D in lung transplant recipients =1.08 (1.03-1.13), in heart transplant aHR = 1.26 (1.20-1.32), in liver transplant recipients aHR = 1.26 (1.22-1.30), and in kidney transplant recipients aHR = 1.65 (1.62-1.68) (all p<0.01).

Conclusions: The prevalence of T2D is rapidly increasing in solid organ transplant candidates. In all solid organ transplants, pre-transplant T2D is independently associated with an increased risk of post-transplant mortality, the most profoundly in kidney transplants.

Disclosure

M.Stepanova: None. A.Kumar: None. P.Brandt: None. N.Gundurao: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. Z.Younossi: Consultant; AbbVie Inc., BMS, Gilead Sciences, Inc., Novo Nordisk, Merck & Co., Inc., Quest Diagnostics, Siemens, Intercept Pharmaceuticals, Inc., Viking Therapeutics.
14-LB: Abdominal Obesity Indices Predict Incident Renal Events in a 10-Year Cohort with Type 2 Diabetes Mellitus
Authors: MA CHIFA , YUAN MINGXIA
Published: June 2023

Background: Obesity, especially abdominal obesity, has been associated with diabetes. However, few studies focused on the association between obesity indices and diabetic nephropathy, let alone the longitudinal studies. Waist circumference (WC), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI) and lipid accumulation product (LAP) are described as abdominal obesity indices. The present study aimed to explore the associations between these indices and incident renal events in a 10-year cohort with type 2 diabetes mellitus (T2DM).

Methods: A total of 2709 participants with T2DM from the Beijing Community Diabetes Study were included. Prespecified renal outcomes included incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine, initiation of renal-replacement therapy, or renal death) and incident albuminuria. Multivariable Cox regression were applied to analyze the associations between these indices and renal events.

Results: Multivariable analyses indicated that each 1-SD increase in WC, VAI, CVAI and LAP was associated with a higher risk of renal events, with adjusted hazard ratios (HRs) being 1.236 [95% CI (confidence interval): 1.079-1.417], 1.135 (1.026-1.257), 1.295 (1.132-1.483), and 1.144 (1.036-1.263), respectively. Moreover, participants in the highest quartile of abdominal obesity indices were at higher risk of renal events compared to those in the lowest quartile (all P for trend<0.05). However, only CVAI was always significantly positively associated with incident renal events in all subgroups, including gender (male vs. female), age (< 60 years vs. ≥60 years) and ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker) treatment (no vs. yes).

Conclusion: Abdominal obesity indices could predict renal events in a 10-year cohort with T2DM, and CVAI may be more universal to predict renal events than WC, VAI and LAP in certain population.

Disclosure

C. Ma: None. M. Yuan: None.

Funding

Capital's Funds for Health Improvement and Research (2022-1-1101, 2016-1-2057)
1409-P: Association between Population Level Social Risk Factors and Prevalence of Diabetes
Authors: EGEDE LEONARD E. , WALKER REBEKAH J. , LINDE SEBASTIAN
Published: June 2023

Background: The goal of this study was to evaluate the independent effect of population social risk on the crude prevalence of diabetes.

Methods: We combined census tract level data including diabetes prevalence from the CDC PLACES 2019 database and social risk factor data from the Opportunity Insights database. A multiple linear regression model was run with diabetes prevalence as the outcome and incarceration, poverty, housing, education, employment, job environment, economic mobility, and healthcare access as independent correlates, adjusting for US population in 2020 and state fixed effects.

Results: The final analytic sample consisted of 11,457 census tracts within 157 counties in 38 states. Mean prevalence of diabetes was 11.8% +/- 4.9%. All indicator variables were significantly associated with crude prevalence of diabetes and explained 89.2% of the variance in diabetes prevalence at the national level. In the fully adjusted model, with every standard deviation (SD) increase in proportion with an annual check-up, crude prevalence increased by 0.7 SD. For every SD increase in proportion uninsured, crude prevalence increased by 0.5 SD. For every SD increase in income below the poverty line, crude prevalence increased by 0.1 SD. For every SD increase in average rent for a two-bedroom apartment, crude prevalence decreased by 0.1 SD. For every SD increase in proportion of residents with a college degree, crude prevalence decreased by 0.1 SD. For every SD increase in proportion incarcerated, crude prevalence increased by 0.05 SD. In addition, in the fully adjusted model, the crude prevalence of diabetes varied significantly across states.

Conclusions: Population level social risk factors were significantly associated with changes in prevalence of diabetes at the national level. The strongest drivers of this relationship were healthcare access, insurance, income, housing, education, and incarceration.

Disclosure

L.E.Egede: None. R.J.Walker: None. S.Linde: None.

Funding

National Institutes of Health (R01DK118038, R01DK120861, R01MD013826)
1437-P: Treatment Pattern and Glycemic Control of Adults with T2DM in Northern China
Authors: CHEN LIMING , ZHANG QIUMEI , FAN YAQING , LIU XIXI , ZHANG MINLU , WU GUANGYU , WU MENG , HUANG QIONG , HAN YANFANG , KANG LEI , LI MING
Published: June 2023

Aim: To better understand the current treatment pattern and glycemic control status in Chinese adults with T2DM.

Methods: A retrospective study was conducted among adult T2DM patients using electronic medical records from 2015 to 2019 in Tianjin, a metropolis in Northern China.

Results: From 2015 to 2019, a total of 312,203 patients from 75 hospitals were included, with mean age of 61.9 years old and BMI 26.1 kg/m2. HbA1c decreased from 8.2% to 7.9% with the percentages of HbA1c <7% increased from 28.1% to 33.7% (P<0.001). A growing proportion treated with basal insulin and GLP-1RA ± basal insulin was seen while the proportion of premixed insulin decreased (P<0.001). 44.0% of the subjects were treated with OAD only and the most frequently used OADs were α-glucosidase inhibitor (55.7%) and metformin (47.0%). The percentages of cardiovascular risk factors and macrovascular events including hypertension, dyslipidemia, obesity, cardiovascular disease and stroke were increased each year (P<0.001). During 2015-2019, 27.7% and 40.3% of the population had FPG<7 mmol/L and PPG<10 mmol/L, respectively, while 46.1% of them had both FPG ≥ 7 and PPG ≥10 mmol/L.

Conclusion: From 2015 to 2019, an increasing proportion of T2DM population achieved HbA1c target, reflecting the potential optimized treatment concept and regimen. Meanwhile, there is still room to improve the holistic management of T2DM in China for a better patient outcome.

Disclosure

L.Chen: None. L.Kang: Employee; Sanofi China. M.Li: None. Q.Zhang: None. Y.Fan: None. X.Liu: None. M.Zhang: Employee; Sanofi China. G.Wu: Employee; Sanofi China. M.Wu: Employee; Sanofi China. Q.Huang: Employee; Sanofi China. Y.Han: Employee; Sanofi China.

Funding

Sanofi
1443-P: Population-Based Survey Showing No Increased Incidence of Type 1 Diabetes in Association with COVID-19 Vaccination in China
Authors: LIU CHANG , XIN ZHONG , YANG JIN-KUI
Published: June 2023

Introduction: Several reports showed that COVID-19 vaccine may cause type 1 diabetes (T1D), especially fulminant T1D (FT1D). This study investigates the incidence of T1D during 2007-2021 in a general population of China, where >90% of people have received a full COVID-19 vaccination (3 injections) in 2021.

Methods: A population-based registry of T1D was performed by the Beijing Municipal Health Commission Information Center.

Results: In this population included 14.14 million registered residents, we identified 7,697 people with newly diagnosed T1D from 2007 to 2021, including 4,094 men and 3,603 women. T1D incidence [95% CI] (/100,000 persons) increased from 2.77 [2.49, 3.08] in 2007 to 3.84 [3.53, 4.18] in 2021. From 2007 to 2019 the T1D incidence increased with an annual percentage change (APC) of 3.13% (p<0.05). However, the T1D incidence was stable from 2019 to 2021 (the APC was -11.5% (p>0.05)), indicating that T1D incidence did not increase when people were vaccinated in Jan-Dec 2021. Meanwhile, the T1D with diabetic ketosis/ketoacidosis as the initial presentation incidence increased from 2007 to 2019, and it was stable from 2019 to 2021 (P>0.05) (Figure 1). The incidence of FT1D did not increase from 2015 to 2021 (APC:8.9%, P=0.53).

Conclusion: Our study indicates that COVID-19 vaccination did not increase T1D onset, at least not on a large scale.

Disclosure

C.Liu: None. Z.Xin: None. J.Yang: None.

Funding

National Natural Science Foundation of China (81930019)
147-LB: Visits in Pediatric vs. Adult Clinics for Young Adults (YA) with T1D—Prepandemic and Pandemic Care
Authors: SHAPIRA AMIT , TINSLEY LIANE J. , TOSCHI ELENA , LAFFEL LORI M.
Published: June 2023

Aim: YA with T1D have high risk of rising A1c and loss to follow up. To understand factors associated with visit frequency, we compared characteristics of YA with T1D seen in pediatric vs adult diabetes clinics in the pre- and pandemic periods.

Methods: EMR data included YA, aged 18-30 yrs, with T1D in pediatric and adult clinics during the pre- and pandemic (4/1/19 to 3/15/20 and 3/30/20 to 3/15/21, respectively), for both inperson and telehealth visits.

Results: There were 1,762 YA (54% male), aged 24.0±3.6 yrs, with T1D duration 13.4±6.3 yrs and A1c 8.2±1.6%; 61% were pump treated; 64% used CGM. Pre-pandemic, almost all visits were inperson while most pandemic visits were virtual. During the pandemic, proportion of virtual visits was greater in pediatric vs adult care (99% vs 90%, p<.001). Overall, pre-pandemic visit frequency was 3.5±3.4, reduced to 3.1±4.1 (p<.0001) during pandemic. Pre-pandemic visit frequency was higher in those with higher A1c (r =.18, p<.001) in pediatric and adult care. During pandemic, YA visit frequency was preserved across A1c groups only for those in pediatric care (Figure 1). Pandemic visit frequency was lower in adult care regardless of sex, pump, CGM or A1c.

Conclusion: Maintaining visit frequency may mitigate glycemic deterioration in YA with T1D. Pediatric care likely maintained visit frequency through use of telehealth, highlighting need for hybrid care to optimize outcomes.

Disclosure

A. Shapira: None. L. J. Tinsley: None. E. Toschi: Advisory Panel; Eli Lilly and Company. L. M. Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape.

Funding

Thomas J. Beatson, Jr. Foundation
148-OR: CGM Time Below Range Predicts Epinephrine Response to Hypoglycemia in Patients with Type 1 Diabetes
Authors: THOMAS ROBERT L. , GREGORY JUSTIN M. , GIOVANNETTI ERIN R. , BOEDER SCHAFER C. , PETTUS JEREMY
Published: June 2023

Identifying T1D patients with impaired awareness of hypoglycemia (IAH) is essential, as these patients are at ~10-fold risk of severe hypoglycemia. Defining IAH has relied on questionnaires such as Clarke score that are rarely used in clinical practice. Additional tools are needed to stratify hypoglycemia risk in patients with T1D. Here we show that CGM metrics correlate with physiologic response to hypoglycemia. We measured serum epinephrine levels in 22 subjects with T1D (ages 28-52, A1c 6.1-7.2, median Clarke score 3) during a hyperinsulinemic-hypoglycemic clamp. Baseline CGM data was collected for 2 weeks prior to clamp. These data show a novel, inverse relationship between CGM time below range (TBR, <70 mg/dL) and epinephrine response (EpiR, pg/mL/min) FIGURE. CGM TBR (ρ = -0.562, p = 0.006), Clarke score (ρ = -0.592, p = 0.03), and older age (ρ = -0.500, p = 0.015) were inversely associated with EpiR. Higher average glucose was associated with increased EpiR while time in range, coefficient of variation, BMI, and duration of T1D showed no significant association with EpiR. Our study suggests that CGM TBR predicts counterregulatory dysfunction in T1D. CGM TBR demonstrated a robust, inverse correlation with EpiR similar to the validated Clarke survey. CGM is now the gold standard for glycemic monitoring in T1D, and the percentage TBR may help identify patients at highest risk for severe hypoglycemia outcomes.

Disclosure

R.L.Thomas: None. J.M.Gregory: Advisory Panel; Eli Lilly and Company, vTv Therapeutics, Other Relationship; Medtronic. E.R.Giovannetti: None. S.C.Boeder: Consultant; Cecelia Health, Research Support; Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company. J.Pettus: Advisory Panel; Sanofi, Novo Nordisk, Lilly, MannKind Corporation, Consultant; Carmot Therapeutics, Inc., Diasome.

Funding

JDRF (2-SRA-2018-606-M-B, 5-ECR-2020-950-A-N); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123392)
1485-P: The Involvement of ANGPTL4 in Periodontitis and the Influence of High Glucose
Authors: KONDO SHUN , KOJIMA KENTO , NAKAMURA NOBUHISA , MIYABE MEGUMI , KIKUCHI TAKESHI , OHNO TASUKU , SAWADA NORITAKA , MINATO TOMOMI , SAIKI TOMOKAZU , ITO MIZUHO , SASAJIMA SACHIKO , MATSUBARA TATSUAKI , MITANI AKIO , NARUSE KEIKO
Published: June 2023

Periodontitis is a chronic inflammatory disease in which periodontal tissue is destroyed by bacterial infection. Periodontal disease is considered a comorbidity of diabetes due to its high prevalence and severity. However, the molecular mechanisms how diabetes aggravates periodontitis are still unclear. In this study, we investigated the involvement of Angiopoietin-like proteins (ANGPTLs) in periodontitis and the impacts of high glucose. Experimental periodontitis was induced in 6-week-old male Sprague-Dawley rats by placing a nylon suture around the neck of the maxillary second molar. Induction of periodontitis significantly increased the expression of ANGPTL4 in the gingiva. To clarify the involvement of ANGPTL4 in periodontitis, the human gingival fibroblasts (hGFs) were stimulated with LPS of Porphyromonas gingivalis (Pg-LPS), the bacterium most frequently isolated from inflamed sites of adult periodontitis. Pg-LPS significantly increased the gene and protein expression of ANGPTL4 in hGFs but not the gene expression of other ANGPTLs or ANGPTL receptors. Recombinant human ANGPTL4 significantly increased matrix metalloproteinase 13 (MMP13) gene expression in hGFs. We also confirmed that MMP13 expression was increased in the gingiva during experimental periodontitis. Pg-LPS induced MMP13 gene expression in hGFs. Next, we investigated the impacts of high glucose in Pg-LPS-stimulated hGFs. The expression of ANGPTL4 by Pg-LPS was significantly increased in high glucose condition compared with that in normal glucose condition. These results suggest the pivotal role of ANGPTL4 in periodontitis, especially under the high glucose condition.

Disclosure

S.Kondo: None. M.Ito: None. S.Sasajima: None. T.Matsubara: None. A.Mitani: None. K.Naruse: None. K.Kojima: None. N.Nakamura: None. M.Miyabe: None. T.Kikuchi: None. T.Ohno: None. N.Sawada: None. T.Minato: None. T.Saiki: None.
1490-P: Levels of Specific Antibodies (Ab) for Sars Cov2 after Vaccination and Its Relationship with Clinical and Metabolic Variables in People with Type 2 Diabetes vs. Controls without Diabetes
Authors: POMARES MARIA L. , CUZZIOL GABRIELA , LOPEZ CLAUDIO E. , KREMER SENDROS SANDRA , POMARES DAMIAN , OJEDA MARIANA , WOLFFENBUTTEL CARLOTO VICTOR , TEJADA RINA M. , OJEDA GONZALO A. , FIGUERERO ANTONELA , GOMEZ MARTIN CAROLINA , GORBAN DE LAPERTOSA SILVIA
Published: June 2023

Introduction: The COVID-19 pandemic has affected people all over the world, and even more seriously people with chronic pathologies.

Objectives: Primary: To evaluate the humoral immune response (IgG Ab specific for SARS CoV-2) in adults with DM2 versus controls. Secondary: To evaluate the relationship between Ab IgG levels and the presence of other clinical variables and comorbidities.

Materials and Methods: The study was carried out in January 2022 in Argentina. Adults with DM2 and controls who had received first and second doses of any SARS Cov-2 vaccines were included. Titers of Ac IgG were performed through the assay of IgG anti RBD (receptor binding domain in the host cell). Multiple Logistic Regression and Multiple Linear Regression were used. p value <0.05 was considered statistically significant.

Results: N 144 participants (91 with DM2 and 53 controls). Median from the second dose of a vaccine to the measurement of Ab: 141 days in controls and 144 in diabetics (p=0.451). The logarithm of the Ab titers were significantly lower in patients with DM2 vs. controls (p<0.01). Univariate analysis: Ab levels were positively and significantly related to BMI (p<0.01). They were also significantly associated with age (p<0.001) and with the presence of rheumatic diseases (p= 0.02). Multivariate analysis: Ab levels were only significantly and negatively associated with age (p<0.01) and the presence of rheumatologic bone disease (p=0.02). No differences were found between the type of vaccines used.

Conclusion: Although the Ab titers registered in DM2 were significantly lower vs. controls, the adjustment for various covariates have not allowed to sustain the significance of this association in multivariate analysis. The role of age, BMI, the presence of rheumatic diseases and other factors should be explored in other studies in order to evaluate their potential role as confounders.

Disclosure

M.L.Pomares: None. A.Figuerero: None. C.Gomez martin: None. S.Gorban de lapertosa: None. G.Cuzziol: None. C.E.Lopez: None. S.Kremer sendros: None. D.Pomares: None. M.Ojeda: None. V.Wolffenbuttel carloto: None. R.M.Tejada: None. G.A.Ojeda: None.