bluuebunny/crossref_metadata_2025 huggingface dataset:
1329-P: Prevalence of Diabetic Burn-Out in Patients on Dialysis—A Rapid Evidence Review and Meta-analysis
Authors: COYE TYLER L. , CRISOLOGO PETER , LAVERY LAWRENCE A.
Published: June 2023

In diabetic patients on dialysis, glycemic control may improve spontaneously, leading to normal glycated hemoglobin (HbA1c) levels and termination of antidiabetic medications; this phenomenon is known as “burnt-out diabetes.” It has been previously shown that diabetic patients on dialysis with normal and less than normal glycated hemoglobin levels may have a higher risk of mortality. The aim of this systematic review and meta-analysis is to determine the prevalence of diabetic burn-out in patients with diabetic nephropathy on dialysis. Web of Science, Scopus, and PubMed were searched from inception to January 2023. Only studies that obtained samples from populations which reported the number of patients with diabetic burn-out, defined as: HgbA1c < 6.0%, cessation of antidiabetic medication, and on dialysis were included. The primary meta-analysis outcome was prevalence of diabetic burn-out. A random effects meta-analysis was carried out using RStudio software. Four studies, conducted between 2007 and 2018, met the inclusion criteria and contributed 139,690 diabetic patients (sample size range, 1296-60,019). The pooled estimation of prevalence of diabetic burn out in patients on dialysis was 28.8% (95% CI, 28.6%-29.0%). Prevalence in the included studies varied from 18.6% to 39.7%. We found a high heterogeneity (I2= 100%, p < 0.000, Q = 6641.79) in prevalence reported among studies. In conclusion, we found that the “burnt-out diabetes” phenomenon may exist in 28.8% of HD patients with diabetes in terms of HbA1c levels. Additional studies are needed to determine the optimal target for hemoglobin A1c levels in hemodialysis patients with diabetes.

Disclosure

T.L.Coye: None. P.Crisologo: None. L.A.Lavery: Research Support; AstraZeneca, Tissue tech, American Diabetes Association, PolarityTE, Inc., Microbion, Jarvis, Integra Lifesciences Holdings Corp, Smith+Nephew.
1330-P: Adverse Clinical Outcomes Attributable to Socioeconomic and Ethnic Disparities among People with Impaired Glucose Tolerance in New Zealand over 25 Years
Authors: YU DAHAI , BAKER JOHN , CUTFIELD RICHARD G. , PICKERING KAREN A. , ORR-WALKER BRANDON J. , OSUAGWU UCHECHUKWU L. , CAI YAMEI , WANG ZHENG , ZHAO ZHANZHENG , SIMMONS DAVID ,   DCSS STUDY GROUP
Published: June 2023

Aim: Future premature death and cardio-renal disease are common with impaired glucose tolerance (IGT). We aimed to quantify contributions of socioeconomic and ethnic disparities to outcomes in IGT in New Zealand (NZ).

Methods: IGT enrolments 01/01/1994-31/07/2018 into the Diabetes Care Support Service (DCSS), an NZ primary care programme linked with national databases were followed up until death or 31/12/2019. Incident outcomes included premature mortality (PM), myocardial infarction (MI), stroke, heart failure (HF), and end-stage renal disease (ESRD). Attributable fraction (AF)s for the entire population and specific groups compared with the least deprived groups or NZ Europeans (NZE) were estimated with adjustment for covariates.

Results: Among 26,031 people with IGT (mean age 57.2 years; 53.8% female), adjusted population AF to deprivation was significant for ESRD (18.90 (0.65-33.80)%) and to ethnicity was significant for MI (8.19 (0.18-15.56)%), stroke (10.33 (1.63-18.26)%), HF (12.15 (5.03-18.74)%) and ESRD (8.18 (0.65-33.80)%), respectively. Compared with NZE with the least socioeconomic deprivation, group-specific AF was higher in the most deprived NZE, Māori, and Pasifika for PM, stroke and ESRD; higher in more deprived NZE and Māori for MI and HF.

Conclusions: Ethnic and socioeconomic disparities are responsible for a substantial proportion of adverse outcomes those with IGT. Disparities were common among Māori irrespective of socioeconomic status and NZE with the most socioeconomic deprivation. Preventative policies need to address both ethnic and socioeconomic disparities.

Disclosure

D.Yu: None. D.Simmons: Consultant; Sanofi, Speaker's Bureau; Abbott Diabetes. Dcss study group: n/a. J.Baker: None. R.G.Cutfield: Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. K.A.Pickering: None. B.J.Orr-walker: None. U.L.Osuagwu: None. Y.Cai: None. Z.Wang: None. Z.Zhao: None.
1332-P: Comparison of Clinical Characteristics of People Living with Latent Autoimmune Diabetes of the Adult (LADA) and Type 1 Diabetes (T1D) in the Canadian BETTER Registry
Authors: ISSA MOHAMAD , BRAZEAU ANNE-SOPHIE , HAAG SARAH , ROY-FLEMING AMÉLIE , MESSIER VIRGINIE , TALEB NADINE
Published: June 2023

Introduction: LADA is known for a slow progression of autoimmune destruction of beta-cells with cases that span a spectrum between classic T1D and T2D phenotypes. To date, lacking a good understanding of LADA has prohibited the release of specific clinical practice guidelines and subsequently an optimal management.

Methodology: Cross-sectional analysis of online clinical questionnaires in the Canadian BETTER registry; participants can specify having received a diagnosis of LADA or T1D. Data was analyzed for the first 1464 participants; 131 (9%) reported LADA and 1333 (91%) T1D.

Results: At registration; LADA vs T1D were 49 ± 13 y.o. vs 42 ± 15 y.o; 61% vs. 62% females; diabetes duration 10 ± 9 vs. 24 ± 15 years. LADA vs. T1D were older at diagnosis (39 ± 12 vs. 18 ± 12 years old; p<0.001), only half started insulin in first year of diagnosis (52 vs. 97%; p<0.001), more often reported a family history of T1D (46 vs. 32%; p=0.001). For comparable glycemic control (HbA1c < 8.6 mmol/l, <7%, 38 vs. 32%), fewer cases with LADA reported at least an episode in last month of level II hypoglycemia <54 mg/dL (3.0mmol/L) 63% vs. 77%; p= 0.004, severe hypoglycemia rates were 8% vs. 12%, p=0.15. Diabetes related hospitalizations were 10% in LADA vs. 6%, p=0.11, insulin pumps and glucagon were less used in LADA. In a matched analysis for diabetes duration and gender (1:1), glycemic control was still statistically comparable in LADA vs. T1D (HbA1c <7%: 38 vs 35%, p=0.12) as well as rates of nephropathy (6% vs. 11%, p=0.22), neuropathy (12% vs. 7%, p=0.23) and retinopathy (6% vs. 9%, p=0.07) yet with more cardiovascular disease (5% vs. 2%; p=0.02) and less coeliac disease (3 vs. 5%; p=0.001). Data analysis of 3000 participants is ongoing in early 2023.

Conclusion: Reported differences may impact LADA management. This study sets the stage for building a prospective Canadian cohort of LADA to undergo deep phenotyping, genotyping and interventional trials.

Disclosure

M.Issa: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. S.Haag: Other Relationship; Omnipod. A.Roy-fleming: None. V.Messier: None. N.Taleb: Consultant; Viatris Inc.
1333-P: Diabetes Complications in Metropolitan vs. Nonmetropolitan Cities of India—Three-Year Follow-up Results of LANDMARC Trial
Authors: KALRA SANJAY , DAS ASHOK K. , JOSHI SHASHANK R. , MITHAL AMBRISH , PRASANNA KUMAR K.M. , GOPALAKRISHNAN UNNIKRISHNAN AMBIKA , THACKER HEMANT , SETHI BIPIN , CHOWDHURY SUBHANKAR , SUGUMARAN AMARNATH , SATPATHY ASHWINI , GADEKAR ARVIND , MENON SHALINI K. , NEOGI RENUKA , CHODANKAR DEEPA , TRIVEDI CHIRAG , KUMAR WANGNOO SUBHASH , ZARGAR ABDUL H. , RAIS NADEEM
Published: June 2023

Macrovascular and microvascular complications were evaluated in participants from metropolitan versus non-metropolitan cities during the three years of LANDMARC, a nationwide prospective observational study (CTRI/2017/05/008452). LANDMARC included participants with type 2 diabetes (T2D) who were on ≥2 antihyperglycemic medications. Of the total 6222 participants, 2375 and 3847 were from metropolitan and non-metropolitan cities, respectively. Age, T2D duration, and baseline A1C were similar across groups (Table). At the end of three-years, microvascular complications were significantly higher in participants from non-metropolitan than metropolitan cities (13.13% vs. 4.89%; p<0.0001). Neuropathy was the most common microvascular complication in both metropolitan and non-metropolitan cities. Among macrovascular complications, heart failure (p=0.0160) was reported more in non-metropolitan than metropolitan cities (Table). The LANDMARC data demonstrates that T2D participants from Indian non-metropolitan cities may have higher complications, particularly microvascular, and may need to be better understood through future studies. The LANDMARC results elicit a pattern of disease progression among participants with T2D.

Disclosure

S.Kalra: Speaker's Bureau; Abbott, Bayer Inc., Novo Nordisk, Sanofi. A.Sugumaran: Employee; Sanofi. A.Satpathy: Employee; Sanofi. A.Gadekar: Employee; Sanofi. S.K.Menon: Employee; Sanofi. R.Neogi: Employee; Sanofi. D.Chodankar: Employee; Sanofi. C.Trivedi: None. S.Wangnoo: None. A.H.Zargar: None. N.Rais: Advisory Panel; Bayer Consumer Care AG, Board Member; Abbott, Biocon. A.K.Das: n/a. S.R.Joshi: Advisory Panel; Biocon, Zydus Cadila, Torrent Pharmaceuticals Ltd, Franco India, Consultant; Glenmark Pharmaceuticals, Twin Health, Speaker's Bureau; Abbott Nutrition, Sanofi, Abbott, Novo Nordisk, Lupin Pharmaceuticals, Inc. A.Mithal: Advisory Panel; Eris Lifesciences Ltd., Consultant; Glenmark Pharmaceuticals, Lupin Pharmaceuticals, Inc., USV Private Limited, Research Support; Sanofi, Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim, AstraZeneca, Sun Pharmaceutical Industries Ltd., Novartis. K.Kumar: None. A.Unnikrishnan: Speaker's Bureau; Sanofi, AstraZeneca, Boehringer-Ingelheim, Intas Pharmaceuticals Ltd. H.Thacker: None. B.Sethi: None. S.Chowdhury: None.

Funding

Sanofi India
1341-P: The Improvement in Age at Mortality in Individuals with Peritoneal Dialysis Was Less Prominent in Persons with Diabetes in Korea
Authors: MIN KIM HYUN , JU SON KANG , OK SONG SUN
Published: June 2023

Backgrounds: The most prevalent underlying cause of end-stage kidney disease (ESKD) is diabetes mellitus (DM). If kidney transplantation is not possible, people with ESKD must undergo hemodialysis (HD) or peritoneal dialysis (PD). This study investigated whether the prognosis of individuals with diabetes who received PD improved recently. In addition, we analyzed the age of death and the cause of mortality to determine if there was a difference based on DM or gender from 2006 to 2018.

Methods: We Used data from the National National Health Insurance database maintained by the Korean National Health Insurance Service (NHIS) and mortality records from the National Statistical Information Service (NSIS). The NHIS claims data was merged with NSIS death records from 2006 to 2018 and then analyzed. We excluded those who underwent HD or transplanting from the 93,487 cases of ESKD-related death to include only those who underwent PD.

Results: A total of 11,174 deaths were documented (4,818 individuals with DM and 6,356 individuals without DM). Age at death increased by 0.11 and 0.44 years/year in persons with and without DM, respectively. Changes in mortality age were the biggest in females without DM (0.47 years/year) and lowest among men with DM (0.10 years/year). DM itself, cardio-cerebrovascular diseases, and cancer were the leading causes of death among people with DM receiving PD.

Conclusions: In conclusion, this study, which utilized the entire Korean population, revealed that the death age of individuals with DM receiving PD increased marginally over 12 years, but the change was much smaller than in persons without DM. Based on these results, efforts should be made to improve the prognosis of the person with DM who underwent PD. In addition, identifying the precise cause of death and the optimal management strategy in this population would be important.

Disclosure

H.Kim: None. K.Son: None. S.Song: None.
1344-P: Multiomic Signatures of Gut Dysbiosis and Diabetes in HIV Infection
Authors: LUO KAI , PETERS BRANDILYN , WANG ZHENG , HANNA DAVID B. , LANDAY ALAN L. , SCHNEIDER MICHAEL F. , GUSTAFSON DEBORAH , SHARMA ANJALI , ANASTOS KATHRYN , KAPLAN ROBERT , QI QIBIN
Published: June 2023

Introduction: Gut dysbiosis has been linked with HIV infection and diabetes. But multiomic signatures of the gut dysbiosis and diabetes in the context of HIV infection remain unknown.

Methods: We examined associations of 97 core gut bacteria genera, 378 plasma metabolites, and 74 serum proteins with prevalent diabetes in 493 women (146 with diabetes; 68% HIV+) of the Women's Interagency HIV Study from 2017 to 2019.

Results: After multivariable adjustment and correction for multiple comparison (FDR < 0.1), we identified 3 genera (Adlercreutzia, Intestinibacter, and Ruminococcus) inversely and 4 genera (Shigella, Escherichia, Megasphaera, and Lactobacillus) positively associated with diabetes. Meanwhile, 76 metabolites, including 2 microbial metabolites (phenylacetylglutamine [PAG] and imidazole-propionate [IMP]) and multiple lipid species (e.g., diradylglycerols [DGs]), and 18 proinflammatory proteins were associated with diabetes. Many metabolites and proteins were associated with the identified diabetes-related gut bacteria. Potential mediation effects of these metabolites and proteins (PAG, IMP, IL-18R1, CD6, OSM, and OPG) on the bacteria-diabetes associations were observed (mediation effects of multiple mediators ranged from 25% for Intestinibacter to 67% for Escherichia). Compared to women without HIV, those with HIV had similar abundances of the identified bacteria but higher circulating levels of many diabetes-related metabolites (PAG, IMP, and several DGs) and proteins (OSM and CD6). The associations of these multiomic features with diabetes tended to be independent of HIV status with little evidence for effect modification by HIV.

Conclusion: Among women with and without HIV, this study identified multiple gut bacteria and circulating metabolites and inflammatory proteins associated with diabetes. The observed bacteria-diabetes associations were partially explained by some microbial metabolites and proinflammatory proteins.

Disclosure

K.Luo: None. R.Kaplan: None. Q.Qi: None. B.Peters: None. Z.Wang: None. D.B.Hanna: None. A.L.Landay: None. M.F.Schneider: None. D.Gustafson: None. A.Sharma: Research Support; Gilead Sciences, Inc. K.Anastos: None.

Funding

National Heart, Lung, and Blood Institute (R01HL140976, K01HL129892); Feldstein Medical Foundation
1349-P: People with Type 2 Diabetes Have a High Prevalence of Nonalcoholic Steatohepatitis with Significant Fibrosis When Screened by NIS4 or Elastography
Authors: KALAVALAPALLI SRILAXMI , GODINEZ LEIVA EDDISON , LOMONACO ROMINA , MARANGI STEPHEN A. , VALDEZ SAENZ ENRIQUE , ORTIZ ROCHA ANDREA , BUDD JEFFREY T. , MOHSENI YASMINE , CHUN KELLY Y. , PREZANT TONI R. , CONNELLY MARGERY A. , BARB DIANA , CUSI KENNETH
Published: June 2023

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Diagnosis remains challenging as a liver biopsy is usually not feasible. NIS4 is a novel plasma diagnostic test combining the measurement of A1c and 3 biomarkers (miR-34a-5p, A2M, YKL-40) linked to NASH disease activity and higher cirrhosis risk. The aim of this study was to assess the prevalence of high-risk NASH (NASH with significant fibrosis [≥F2]) as estimated by NIS4 or elastography in the outpatient setting. A total 400 participants (age: 55±11 years; BMI: 31.6±6.6 kg/m2; T2DM: 32%; obese without T2DM [OB]: 33%), unaware of having NAFLD, were recruited from PCP and endocrine clinics and screened by: a) Elastography (Fibroscan®) for steatosis (controlled attenuation parameter or CAP ≥274 dB/m) and for fibrosis (liver stiffness measurement or LSM ≥7.0 kPa); and b) NIS4 for high-risk NASH (defined as a NIS4 >0.63; low-risk: <0.36). Among patients with T2DM or OB, 68% had steatosis compared to 35% without obesity or T2DM (CON) (p<0.01), while fibrosis (LSM≥7.0 kPa) was present in 14% of patients with T2DM (CON = 1%; p=0.02). High-risk NASH by NIS4 occurred frequently among patients with T2DM, either with (30%) or without (26%) obesity, and rare in those without T2DM (3%; p<0.001). NIS-4 correlated with steatosis (CAP) (r = 0.35) and fibrosis (LSM) (r = 0.32; both p<0.001). Patients with high-risk NASH by NIS4 compared to those with low-risk NASH, more often had steatosis (82% vs 46%), fibrosis (16% vs 4%), AST≥30 IU/L (41% vs. 8%) and ALT≥30 IU/L (36% vs. 15%), hepatic (HOMA-IR: 68% vs. 25%) and adipose tissue (adipo-IR: 80% vs 56%) insulin resistance (all p<0.01). NIS4 correlated with having metabolic syndrome (r=0.41; p<0.01) and was more often increased in people from endocrine vs. PCP clinics (34% vs. 9%; p<0.05). Conclusion: NASH with significant fibrosis is common in T2DM. Patients with elevated NIS4 often have NAFLD with fibrosis and an unfavorable cardiometabolic profile.

Disclosure

S.Kalavalapalli: None. T.R.Prezant: None. M.A.Connelly: Employee; LabCorp, Stock/Shareholder; LabCorp. D.Barb: 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. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. E.Valdez saenz: None. A.Ortiz rocha: None. J.T.Budd: None. Y.Mohseni: None. K.Y.Chun: None.

Funding

National Institutes of Health (R01120331-01A1)
1354-P: Level of Risk for Complications by DM2 in Urban and Rural Population in Xalapa, Veracruz
Authors: RODRÍGUEZ OSCAR E.
Published: June 2023

Background: DM2 is one of the diseases with the highest prevalence in the Mexico (10.5%), the state of Veracruz is the second with the highest number of patients. The health centers carry out the treatment of around 90% of patients which are distributed in urban and rural areas.

Aim: To determine the level of risk for the appearance of complications in patients with DM2 in urban and rural areas.

Methodology: Quantitative. Descriptive, observational and cross-sectional study. CI= 90% (n= 43 at urban center) and (n=38 at rural center). Clinical, somatometric, biochemical and risk factors were considered to create a staging scale for the level of risk for complications validated by a group of experts based on ADA recommendations (Appendix 1). The Mann-Whitney test was performed and IBS SPSS 25 program was used.

Results: Statistically significant differences were found only in 3 cases: time of diagnosis (p=0.000016), treatment time (p=0.001) and total cholesterol levels (p=0.001). In our staging proposal, most of the respondents from both groups were found in stage 3, moderate risk for complications (p=0.926) (Appendix 2).

Conclusions: The creation of different scales related to the complications of DM2 are necessary to be able to prevent, diagnose and intervene on risk groups. In our study, we found a moderate risk level for the appearance of complications in both urban and rural health center patients, and some indicators of control.

Disclosure

O.E.Rodríguez: Consultant; Adhera Health.
1362-P: The Long-Term Cardiovascular Effects of Metformin on Patients with Newly Diagnosed Type 2 Diabetes
Authors: YUE TONG , WANG XULIN , ZHAO MINZHE , WENG JIANPING , LUO SIHUI , ZHENG XUEYING
Published: June 2023

Objective: Metformin is the first pharmacological option for preventing and treating type 2 diabetes. However, the use of this drug in preventing cardiovascular disease associated with the development of newly diagnosed type 2 diabetes is unclear. We aimed to examine whether the metformin reduced the incidence of major cardiovascular events over a 20-year follow-up of patients with newly diagnosed type 2 diabetes.

Research Design and Methods: We conducted a retrospective observational cohort study of 48,338 patients with type 2 diabetes from Anhui Provincial Hospital between January 1, 2000, and June 30, 2021. Data were collected for patients with newly diagnosed T2D (within 6 months) who did not have prior cardiovascular disease and took metformin at baseline were compared with those who did not using. The primary outcome was the first occurrence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization due to heart failure (HF). The multivariate Cox proportional hazards regression with inverse probability of treatment weighting. Propensity score matching (PSM) was conducted for reducing the biases of baseline characteristics.

Results: After matching, newly diagnosed T2D patients who used metformin, compared with those who did not use, had significantly lower risk of HF (HR 0.51, 95% CI 0.28 to 0.93) and CHD (HR 0.37, 95% CI 0.13 to 1.09). No difference in the risk incident stroke (HR 0.89, 95% CI 0.68 to 1.17) was observed. In both the original and PSM groups, use of metformin can reduce the risk of CHD events from newly diagnosed T2D patients (adjusted HR 0.74; 95% CI 0.69-0.87; P = 0.029).

Conclusions: In the present retrospective study, metformin use may be beneficial for preventing CHD and HF in newly diagnosed T2D patients. Further randomized controlled trials are needed to confirm these findings.

Disclosure

T.Yue: None. X.Wang: None. M.Zhao: None. J.Weng: None. S.Luo: None. X.Zheng: None.
1373-P: The Prevalence and Risk Factors of Chronic Kidney Disease in Patients with Type 2 Diabetes in China—A Cross-Sectional Study
Authors: ZHU DALONG , MU YIMING , SHI LIXIN , XUE YAOMING , YU XUEFENG , WANG YANGANG , HONG TIANPEI , LI XIAOYING , MA JIANHUA
Published: June 2023

Chronic Kidney Disease (CKD) is a major long-term complication of diabetes and the leading cause of end-stage kidney disease worldwide. It has become very important to regularly screen for early renal disease and rationally use medicines in patients with diabetes and CKD. This was a cross-sectional study, an analysis of baseline data from an ongoing prospective multicenter cohort study, ClinicalTrials.gov ID: NCT05047471. The subjects were outpatients and inpatients from 45 hospitals participating in the endocrinology department from December 2021 to September 2022. Univariate and multivariate binary logistic regression were used to identify risk factors correlated to CKD in patients with type 2 diabetes (T2D). A total of 9886 patients with T2D met our inclusion criteria, please refer to table 1 for the baseline characteristics. The prevalence, screening rate, and awareness rate of CKD was 32.5% [95%CI 31.6, 33.4], 55.3% [95%CI 54.3, 56.3], and 26% [95%CI 24.5, 27.6], respectively. The risk factors independently associated with CKD in patients with T2D were age, duration of T2D, hypertension, LDL-C elevated, poor glycemic control, diabetic foot, diabetic retinopathy, diabetic neuropathy etc., shown in table 2. This work will be helpful in promoting the standardized diagnosis and treatment of CKD in patients with T2D in China, and in arousing the attention of patients with T2D to CKD.

Disclosure

D.Zhu: None. Y.Mu: Speaker's Bureau; Abbott Diabetes, Boehringer Ingelheim Inc., Novo Nordisk (China), Sanifit. L.Shi: None. Y.Xue: None. X.Yu: None. Y.Wang: None. T.Hong: Speaker's Bureau; Novo Nordisk (China), Sanofi China, Eli Lilly and Company, Merck Sharp & Dohme Corp., Merck & Co., Inc., Boehringer Ingelheim Inc., AstraZeneca, Bayer Inc. X.Li: None. J.Ma: None.

Funding

Beijing Great Physician Commonwealth Foundation (DYJ20210621)
1378-P: Habitual High Sodium Intake Is Associated with Alterations in Glucose Homeostasis Including GLP-1 Secretion
Authors: DONKERS ANNA , HUBER HANNA , SCHIEREN ALINA , MANTRI AAKASH , SEEL WALDEMAR , STOFFEL-WAGNER BIRGIT , COENEN MARTIN , KRAWITZ PETER , HOLST JENS J. , STEHLE PETER , SIMON MARIE-CHRISTINE
Published: June 2023

Objective: Although epidemiological studies robustly confirm the impact of a high sodium diet (HSD) in hypertension, the effect of HSD on glucose homeostasis and gut hormones has not been fully elucidated. We hypothesize that the metabolic effects of a HSD might be modulated by changes in the gut microbiome, as it was recently identified as a salt-sensitive compartment.

Methods: A cross-sectional analysis was carried out in 120 adults with metabolic syndrome traits (60 ± 7 years, BMI 31.1 kg/m2, 42% male). Dietary habits were assessed using a Food Frequency Questionnaire. Participants were divided into two groups (normal sodium diet (NSD) vs. HSD) with a cut off value of < 2400 mg/d for NSD and ≥ 2400 mg/d for HSD, according to the recommended maximum intake for sodium by the German Nutrition Society. Fasting and postprandial blood samples were taken after performing an oral glucose tolerance test (OGTT) over 180 min for metabolic characterization, HOMA-IR was calculated. Gut microbiome composition was analyzed using 16S rRNA amplicon sequencing. Linear models were used to test for differences between HSD and NSD in metabolic parameters.

Results: Participants of the HSD group had higher fasting GLP-1 levels (p < 0.05) in comparison to NSD, while the GLP-1 incremental area under the curve during OGTT was lower (p < 0.01). In females, HOMA-IR was higher in the HSD group compared to the NSD group. Bacterial α- and β-diversity did not differ between groups. However, several bacterial taxa correlated with metabolic parameters. In HSD, Streptococcaceae and Veillonellaceae were positively associated with HOMA-IR, and Parabacteroides were inversely correlated with fasting GLP-1.

Conclusion: This analysis provides evidence that a HSD affects insulin resistance and GLP-1 secretion possibly modulated by specific bacterial taxa. Our results add on findings indicating an adverse impact of sodium intake on the development of diabetes, possibly with sex-specific differences.

Disclosure

A.Donkers: None. P.Stehle: None. M.Simon: None. H.Huber: None. A.Schieren: None. A.Mantri: None. W.Seel: None. B.Stoffel-wagner: None. M.Coenen: None. P.Krawitz: None. J.J.Holst: Advisory Panel; Novo Nordisk A/S, Eli Lilly and Company, Board Member; Bainan Biotech, Antag Therapeutics, Consultant; Alphasights, Eli Lilly and Company, ShouTi Pharma Inc., Zealand Pharma A/S, Other Relationship; Novo Nordisk, Novo Nordisk Pharma, Mayo Clinic, Boehringer-Ingelheim, Scohia Pharma Inc., Research Support; ARLA, European Union, Novo Nordisk Foundation.
1380-P: Heterogeneity in the Association of Diet and Obesity in Asian, Pacific Islander, and Multiracial People
Authors: GIBBS SOPHIA L. , BACONG ADRIAN M. , FRANKLAND TIMOTHY B. , LI JIANG , DAIDA YIHE G. , PALANIAPPAN LATHA , FORTMANN STEPHEN P.
Published: June 2023

Background: Disaggregation of Asian, Pacific Islander (PI), and multiracial API people is needed to assess the subgroup-specific impact of diabetes. This study examined the association between diet quality and obesity.

Methods: We used CVD case-control data from two integrated healthcare systems. Diet was measured using the Rapid Eating and Activity for Patient Survey.

Results: Among all groups, Native Hawaiians had the lowest mean diet quality while Asian Indians had the highest diet quality (Table 1). Better diet was associated with lower odds of obesity in all groups except Japanese, Native Hawaiian, Other PI, and some multiracial groups after adjustment (Table 2).

Conclusion: For some race groups better diet quality was associated with lower odds of obesity. Future work should examine groups where this was not the case.

Disclosure

S.L.Gibbs: None. A.M.Bacong: None. T.B.Frankland: Research Support; Pfizer Inc., Stock/Shareholder; AbbVie Inc., Pfizer Inc., CVS Health Corp, Regeneron Pharmaceuticals Inc. J.Li: None. Y.G.Daida: Research Support; GlaxoSmithKline plc. L.Palaniappan: None. S.P.Fortmann: Research Support; Pfizer Inc.

Funding

National Heart, Lung, and Blood Institute (R01HL126172)
1385-P: Maternal Gestational Weight Gain and Children’s Genetic Susceptibility on Childhood Adiposity—A Longitudinal Cohort Study
Authors: LIU HUIKUN , LI WEIQIN , WANG LEISHEN , ZHANG SHUANG , LI WEI , YANG XILIN , LENG JUNHONG , HU GANG , WANG SHUO
Published: June 2023

Few studies have assessed the association of early-life environmental and genetic factors with the risk of childhood adiposity. The aim of the present study was to investigate the interaction between maternal gestational weight gain (GWG) and children’s genetic susceptibility on childhood adiposity. The present study included 1038 mother-child pairs. Body mass index (BMI) for age Z-score (BMI-Z) and childhood overweight were evaluated according to the World Health Organization (WHO) growth reference. Genetic risk score (GRS) was established by aggregating alleles of 10 BMI susceptibility single-nucleotide polymorphisms identified from a recent study. Children born to mothers with excessive GWG had higher BMI-Z (P<0.001), percentage of body fat (P<0.001), and prevalence of overweight (28.4% vs 15.9%, P<0.001) than those born to mothers with adequate GWG. Children’s BMI GRS was significantly and positively associated with BMI-Z, percentage of body fat and overweight risk (all P<0.05). Stratified analyses showed the positive association of children’s BMI GRS with adiposity risk was especially concentrated among mothers with pre-pregnancy normal weight but excessive GWG. The present study identified an interactive effect between maternal GWG and children’s genetic susceptibility on childhood adiposity risk. The findings provided new insight into the etiology of childhood obesity and highlighted the importance of GWG management.

Disclosure

H.Liu: None. W.Li: None. L.Wang: None. S.Zhang: None. W.Li: None. X.Yang: None. J.Leng: None. G.Hu: None. S.Wang: None.

Funding

European Foundation for the Study of Diabetes/Chinese Diabetes Society/Lilly Programme for Collaborative Research between China and Europe; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790, R01DK132011); National Institute of General Medical Sciences (U54GM104940)
1387-P: Glutamic Acid Decarboxylase Autoantibodies (GADA) in Type 2 Diabetes Predict Glycemic Control over 16 Years
Authors: PILLA SCOTT J. , KNOWLER WILLIAM C. , BALASUBRAMANYAM ASHOK , HAMPE CHRISTIANE S. , PIETROPAOLO SUSAN , ANDERSON ANDREA M. , LI MO , ZHAO NI , ZEGER SCOTT L. , RAMELIUS ANITA , BENNET RASMUS , LERNMARK ÅKE , MATHIOUDAKIS NESTORAS N. , CLARK JEANNE , MARUTHUR NISA M.
Published: June 2023

A minority of adults diagnosed with type 2 diabetes (T2D) have islet autoantibodies that may predict diabetes progression. We investigated the association between GADA, the most prevalent islet autoantibody, and longitudinal HbA1c in Look AHEAD (Action for Health in Diabetes), a trial that randomized adults with clinically-diagnosed T2D and overweight/obesity to intensive lifestyle intervention vs. control for 9.6 years, and then followed them observationally. GADA was measured by radioligand binding assay in 87% of the cohort at baseline and categorized as negative, low-level (35-199 U/mL) or high-level (≥200 U/mL). We analyzed the association between GADA category and HbA1c (yearly through year 4, then on alternating years) using linear mixed effects regression adjusted for age, sex, race/ethnicity, calendar time and study arm. Among 4,492 participants, the median age was 59 years and diabetes duration 5 years. GADA was low-level and high-level positive in 131 (2.9%) and 85 (1.9%), respectively. Over a median follow-up of 15.9 years, the modeled mean HbA1c was 7.24% in GADA-, 7.49% in low-level GADA, and 7.67% in high-level GADA (p<0.001). GADA+ participants had consistently higher HbA1c over follow-up in both study arms (Figure). In conclusion, a substantial minority of adults with clinically-diagnosed T2D had GADA positivity that predicted worse glycemic control for more than a decade.

Disclosure

S.J.Pilla: None. A.Ramelius: None. R.Bennet: None. Å.Lernmark: Advisory Panel; Diamyd Medical. N.N.Mathioudakis: None. J.Clark: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions. W.C.Knowler: None. A.Balasubramanyam: None. C.S.Hampe: Employee; Immusoft corp. S.Pietropaolo: None. A.M.Anderson: None. M.Li: None. N.Zhao: None. S.L.Zeger: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126825, K23DK128572)
1388-P: Clinical Features Associated with Glutamic Acid Decarboxylase Autoantibodies (GADA) in Adults with Type 2 Diabetes
Authors: PILLA SCOTT J. , KNOWLER WILLIAM C. , BALASUBRAMANYAM ASHOK , HAMPE CHRISTIANE S. , PIETROPAOLO SUSAN , ANDERSON ANDREA M. , LI MO , ZHAO NI , ZEGER SCOTT L. , RAMELIUS ANITA , BENNET RASMUS , LERNMARK ÅKE , MATHIOUDAKIS NESTORAS N. , CLARK JEANNE , MARUTHUR NISA M.
Published: June 2023

Islet autoantibodies in adults classified as having type 2 diabetes (T2D) have been associated with lower adiposity and early insulin requirement. We examined the association between GADA, the most prevalent islet autoantibody, and baseline clinical features in Look AHEAD (Action for Health in Diabetes), a randomized trial of adults with clinically-diagnosed T2D and overweight/obesity from 16 geographically diverse U.S. study centers. GADA was measured by radioligand binding assay in 87% of the randomized cohort at study baseline and categorized as negative (GADA-), low-level (35-199 U/mL, GADA+) or high-level (≥200 U/mL, GADA++). We compared clinical features across GADA categories using Fisher’s exact or Kruskal-Wallis tests. There were 4,492 participants who had a median age 59 years and diabetes duration 5 years. Participants were 59% female, 67% white, 16% Black and 13% Hispanic. GADA was positive (≥35 U/mL) in 216 participants (4.8%); 131 were GADA+ (2.9%) and 85 GADA++ (1.9%). Insulin was used by 15% of GADA-, 25% of GADA+, and 40% of GADA++ (p<0.001). The median HbA1c was 7.0% in GADA-, 7.1% in GADA+, and 7.4% in GADA++ (p=0.004). There was a history of hypothyroidism in 12% of GADA-, 14% of GADA+, and 29% of GADA++ (p<0.001). There was a history of hyperthyroidism in 2% of GADA-, 2% of GADA+, and 7% of GADA++ (p=0.006). GADA level was not associated with age, sex, race/ethnicity, diabetes duration, BMI, waist circumference, or history of microvascular or macrovascular complications. In conclusion, a substantial minority of this population of adults with overweight/obesity who were clinically diagnosed as T2D have GADA positivity, and high levels were strongly associated with phenotypic differences including insulin use and thyroid disease. In contrast to prior studies, GADA was not associated with lower adiposity. These findings highlight the heterogeneity of this population and the need to further study the clinical implications of GADA positivity.

Disclosure

S.J.Pilla: None. A.Ramelius: None. R.Bennet: None. Å.Lernmark: Advisory Panel; Diamyd Medical. N.N.Mathioudakis: None. J.Clark: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions. W.C.Knowler: None. A.Balasubramanyam: None. C.S.Hampe: Employee; Immusoft corp. S.Pietropaolo: None. A.M.Anderson: None. M.Li: None. N.Zhao: None. S.L.Zeger: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126825, K23DK128572)
1391-P: National Retrospective Cohort Study of COVID-19 Infection and Incident Diabetes in American-Indian/Alaska-Native People
Authors: KECK JAMES , BRESSLER SARA , BRUCE MICHAEL , CHUKWUMA UZO , LACY MARY E.
Published: June 2023

Background: Studies report increased risk of incident diabetes following COVID-19 illness. American Indian/Alaska Native (AI/AN) people have had more frequent and severe COVID-19 illness and historically higher diabetes incidence than other racial/ethnic groups in the US. We examined the association between COVID-19 illness and incident diabetes in AI/AN people.

Methods: Using de-identified data from the Indian Health Service, we created three cohorts spanning two periods: COVID-19 cohort and no-COVID-19 cohort (no indication of COVID-19 infection) both from 3/1/2020-12/31/2021 and pre-COVID-19 cohort from 1/1/2018-2/28/2020. We used data from the year prior to cohort entry to exclude prevalent cases of diagnosed diabetes (diagnosis codes, labs, or diabetes medications) and assess baseline characteristics. During the study period we ascertained COVID-19 infection (diagnosis codes, labs) and incident diabetes. We calculated age-adjusted diabetes incidence rates and rate ratios comparing the COVID-19 cohort to the no-COVID-19 and pre-COVID-19 cohorts.

Results: Across cohorts, age, sex, and healthcare utilization differed. Age-adjusted diabetes incidence rates and rate ratios were significantly higher in the COVID-19 cohort (Table 1).

Conclusions: Clinically confirmed COVID-19 infection was associated with increased incident diabetes rates in AI/AN people.

Disclosure

J.Keck: None. S.Bressler: None. M.Bruce: None. U.Chukwuma: None. M.E.Lacy: None.

Funding

National Institutes of Health (R34DK132548-01S1)
1393-P: Remission Incidence and Associated Clinical Factors in New-Onset Type 2 Diabetes under Standard Medical Care—A Population-Based Study
Authors: SONG KI-HO , KIM JINYOUNG , HAN KYUNGDO , KWON HYUK-SANG
Published: June 2023

The natural history of type 2 diabetes (T2D) is mostly progressive and patients often die from diabetes-related complications. However, T2D can sometimes improve enough to discontinue medications, and this phenomenon remains poorly understood. Using health examination data from the Korean National Health Insurance Service (KNHIS) for a new-onset T2D cohort, we investigated the incidence of diabetes remission and associated clinical factors. Remission was defined as normal fasting blood glucose levels < 126 mg/dL, an alternative criterion for remission based on expert consensus; patients who reached normal fasting blood glucose levels measured at 2-year intervals after discontinuation of treatment were defined as achieving remission. New-onset T2D patients (N=114,874) from 2009 to 2012 were followed until 2017, and 2,429 patients (2.1%) experienced remission during the study period. No significant difference in age was reported between the remission and non-remission groups. Compared to the non-remission group, the remission group had lower baseline body mass index (25.4 kg/m2 vs. 25.7 kg/m2), lower baseline fasting glucose levels (157.7 mg/dL vs. 177.1mg/dL), and a lower prevalence of hypertension (47.7% vs. 52.2%) and hyperlipidemia (44.4% vs. 48.2%). When investigating treatment methods, the remission rate was lower in patients who used more than three oral hypoglycemic agents including sulfonylurea (5.43% vs. 14.4%), while the rate of insulin users was higher in the remission group (10.5% vs. 8.0%). When weight change within 2 years before and after remission was reviewed through health examination results, the group that succeeded in weight loss of 5% or more had a significantly higher rate of remission.

In summary, remission was observed at rates as low as 2.1% in patients in standard medical care settings. Weight loss and insulin therapy in early T2D patients are thought to lead a favorable prognosis in terms of remission.

Disclosure

K. Song: None. J. Kim: None. K. Han: None. H. Kwon: None.

Funding

National Research Foundation of Korea (2021R1A2C2013890)
1399-P: Lipoprotein Subfractions and Type 2 Diabetes Incidence in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multiethnic Study of Atherosclerosis (MESA) Cohorts
Authors: GADGIL MEGHANA D. , HERRINGTON DAVID M. , SINGH SUKHMANI , KANDULA NAMRATHA R. , KANAYA ALKA M.
Published: June 2023

Background: Atherogenic dyslipidemia is prevalent in individuals at risk for type 2 diabetes (T2D) but less is known about composition of lipoprotein subfractions in diverse racial/ethnic groups. We examined associations between lipoprotein subfractions and incident T2D among participants of the MASALA and MESA cohorts.

Methods: Adults aged 45-84 years without T2D and with fasting serum, demographic and clinical data at baseline and 2-5 year follow-up were included. Lipoprotein subfractions were measured at baseline using NMR spectrometry on a common platform. LASSO regularized logistic regression models adjusted for age, sex, race/ethnicity, lipid-lowering agents and waist circumference assessed odds of incident T2D with adjustment for multiple comparisons.

Results: Analyses included 3839 participants with average age of 62 years, 51% women, mean BMI 28 kg/m2 and 234 incident T2D cases. Triglycerides (TG) in LDL-5, LDL-6 and HDL-3 and HDL-4 were associated with odds of incident T2D and free cholesterol in HDL-1 was inversely associated (Table). There were no interactions by race.

Conclusions: TG in small, dense HDL and LDL were positively associated, while free cholesterol in large HDL was inversely related to odds of incident T2D at first follow-up in participants of the MESA and MASALA cohort studies.

Disclosure

M.D.Gadgil: None. D.M.Herrington: None. S.Singh: None. N.R.Kandula: None. A.M.Kanaya: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK119404-01A1); National Heart, Lung, and Blood Institute/National Center Research Resources/National Center for Advancing Translational Sciences (R01HL093009); National Institutes of Health (UL1RR024131); Medical Research Council/National Institute for Health and Care Research (NC-PC-12025); National Institute for Health and Care Research Imperial Biomedical Research Centre; National Heart, Lung, and Blood Institute (75N92020D00001, HHSN268201500003I, N01HC-95159, 75N92020D00005, N01HC-95160, 75N92020D00002, N01HC95161, 75N92020D00003, N01HC95162, 75N92020D00006, N01HC95163, 75N92020D00004, N01HC95164, 75N92020D00007, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169); National Center for Advancing Translational Sciences (UL1TR000040, UL1TR001079, UL1TR001420)
14-OR: Lifetime Medical Spending for Diabetes among Medicare Beneficiaries in the United States
Authors: WANG YU , SHAO YIXUE , IMPERATORE GIUSEPPINA , LUMAN ELIZABETH , HOLLIDAY CHRISTOPHER S. , ZHANG PING
Published: June 2023

Information on lifetime medical cost of type 2 diabetes mellitus (DM) among Medicare beneficiaries is needed to assess potential economic benefits of the Medicare Diabetes Prevention Program (MDPP). We estimated lifetime incremental spending for DM by age of diagnosis and sex among Medicare beneficiaries using the 2001-2019 100% Medicare fee-for-service (FFS) claims database. We identified a cohort of persons with newly diagnosed DM in 2001 using International Classification of Diseases codes (E10 and E11), used a propensity score method to construct a non-DM comparison cohort, and then followed the two cohorts until death, discontinuation of plan coverage, or end of 2019. Lifetime medical expenditures for each cohort were estimated by aggregating the expected annual medical expenditures from age at DM diagnosis to death. Annual medical costs by age at diagnosis and sex before 2019 were derived from actual spending and those after 2019 were extrapolated using age and sex-specific expenditures from 2019. The survival rate was modeled by smoothing the annual survival rate using polynomial regression. Life-years lived with and lost to DM and lifetime excess medical expenditures of DM modeled from FFS claims cost overall and by sex are presented in the table. Despite a shorter lifespan, persons with DM had higher medical costs in their lifetime. MDPP may reduce this expenditure by helping beneficiaries prevent or delay DM.

Disclosure

Y.Wang: None. Y.Shao: Employee; Biogen. G.Imperatore: None. E.Luman: None. C.S.Holliday: None. P.Zhang: None.
140-LB: Use of Apparent Glycation Ratio (AGR) to Correct Average Glucose (AG) Estimation from CGM Profiles in T1DM, T2DM, and Prediabetes
Authors: SATO IMURO SANDRA E. , KERR DAVID , BEVIER WENDY C. , SABHARWAL ASHUTOSH
Published: June 2023

Using HbA1c to reflect AG has limitations. The AGR has been proposed as a correction factor to compute a personalized estimated average glucose (peAG). Three CGM datasets with contemporary HbA1c values (mostly White individuals with T1D [REPLACE BG - RBG], and mainly Hispanic/Latinos with T2D and prediabetes [FARMING FOR LIFE-FFL and DIGITAL HEALTH - DH]) were used to estimate AGR. The RBG dataset was also used to compare peAG vs eAG. No significant differences in AGR were found across age, BMI, gender, or HbA1c in the FFL (n=105, 91% Hispanic/Latino, 32% T2D, age 54 ± 12 yr) and DH (n=26, 100% Hispanic/Latino, 39% T2D, age 50 ± 12 yr) data. However, the median AGRs (72.3 [69, 76.2] ml/g in FFL, and 75.3 [72.8, 83.8] ml/g in DH) were higher than the reference of 65.1 ml/g (p<0.005) from predominantly White individuals. Using 3-month CGM data from RBG (n=57, 90% White, 100% T1D, age 50 ± 13 yr) to compute AGR, a Bland-Altman plot showed that confidence intervals narrowed when using peAG (Figure). Also, AG had a higher correlation with peAG compared to eAG. Bias in peAG/eAG-AG lost significance when HbA1c was measured 3 months after the CGM data for AGR.Hispanic/Latinos with or at risk of T2D may have higher AGR levels than the previously suggested value, implying an overestimation of AG values from HbA1c. The use of AGR and peAG in stable glycemia can provide a more accurate representation of AG than eAG.

Disclosure

S. E. Sato Imuro: None. D. Kerr: Consultant; Sanofi-Aventis U. S. W. C. Bevier: None. A. Sabharwal: None.

Funding

U.S. Department of Agriculture (2018-33800-28404); National Science Foundation (1648451); Elsevier Foundation; Sun Life Financial
1401-P: Psychotropic Drug Use in Children and Adolescents with Type 1 Diabetes
Authors: LIU SHENGXIN , LAGERBERG TYRA , LUDVIGSSON JONAS F. , TAYLOR MARK , DONOFRIO BRIAN , LICHTENSTEIN PAUL , GUDBJÖRNSDOTTIR SOFFIA , BUTWICKA AGNIESZKA
Published: June 2023

Psychiatric disorders in children and adolescents with type 1 diabetes (T1D) have caught increasing attention. While psychotropic drugs offer great value in managing psychiatric symptoms, their adverse effects engender considerable controversy regarding their use in pediatric patients, let alone in those with T1D. Despite the topic’s high visibility, little evidence exists on the patterns of psychotropic drug use in pediatric T1D patients. We thus conducted this cohort study of 3,720,381 children and adolescents (13,191 [0.36%] had T1D) using several Swedish national registers. We examined the trends and patterns (prescription source and treatment duration) of psychotropic drug use and estimated the risk of initiating psychotropic drugs after T1D onset. We found that psychotropic drug use increased significantly in children and adolescents with T1D from 2006 to 2019 (Figure 1), with ADHD medications, SSRI, hypnotics and anxiolytics among the most used ones. The primary prescription source was psychiatric care, and treatment durations were mostly <12 months (except for ADHD medications). Children and adolescents with newly-onset T1D had a higher risk of initiating any psychotropic drug (hazard ratio 1.29, 95%CI 1.20-1.38) than their peers without T1D. Our findings highlight the need for risk/benefit studies of psychotropic drugs among young users with T1D to inform future research and guideline development.

Disclosure

S.Liu: None. T.Lagerberg: None. J.F.Ludvigsson: Research Support; Janssen Pharmaceuticals, Inc., MSD Life Science Foundation. M.Taylor: None. B.Donofrio: None. P.Lichtenstein: None. S.Gudbjörnsdottir: None. A.Butwicka: None.

Funding

Swedish Research Council (2017-00788)