bluuebunny/crossref_metadata_2025_split huggingface dataset:
1018-P: Chronic Limb-Threatening Ischemia in Individuals with Type 1 Diabetes: The Impact of Diabetic Nephropathy and Severe Diabetic Retinopathy
Authors: HARJUTSALO VALMA , KALLIO MILLA , FORSBLOM CAROL , GROOP PER-HENRIK ,   GROUP THE FINNDIANE STUDY
Published: June 2021

The aim was to explore the prevalence and incidence of chronic limb threatening ischemia (CLTI) in individuals with type 1 diabetes (T1D) and to assess risk factors, especially the independent and joint association of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR). The study population comprised 4,694 individuals with T1D from the nationwide Finnish Diabetic Nephropathy Study (FinnDiane). CLTI events were ascertained from medical records. There were 319 events of CLTI; 102 at baseline visit and 217 during follow-up of 11.9 (IQR 9.3-13.8) years. End-stage renal disease (ESRD) increased the risk of CLTI 12.3-fold (95% CI 5.2-28.9) compared to normoalbuminuria at baseline. Odds ratio (OR) for micro- and macroalbuminuria was 1.2 (0.4-3.6) and 2.9 (1.2-7.1), respectively. SDR increased the risk with an OR of 3.4 (1.4-8.6). Other risk factors were age, duration of diabetes, lower HDL cholesterol and estimated glucose disposal rate. The 15-year cumulative incidence of CLTI was 5.8% (5.0-6.5). Risk factors included DN, SDR, age, duration of diabetes, HbA1c, SBP, triglycerides and smoking. Hazard ratios (HRs) by combinations of DN status and with (+) or without (-) SDR were 4.1 (1.6-10.1) for normo/SDR+, 3.5 (1.3-9.6) for micro/SDR-, 10.4 (4.8-22.6) for micro/SDR+, 8.2 (3.2-21.2) for macro/SDR-, 14.3 (6.8-30.2) for macro/SDR+ and 32.6 (15.1-70.4) for ESRD compared to normo/SDR-. The 15-year risk of coronary artery disease and stroke after the diagnosis of CLTI was 48.1% (41.0-55.0) and 24.4% (19.1-30.1), respectively. Median survival time after CLTI was 5.7 (4.3-7.1) years.
In conclusion, there was a graded association between the combined effect of DN and SDR on the risk of CLTI, especially strong in individuals with ESRD. Early interventions to prevent severe forms of DN and diabetic retinopathy may help to decrease the risk of CLTI in individuals with T1D. In such individuals early detection and treatment of foot ulcers is mandatory.

Disclosure
V. Harjutsalo: None. M. Kallio: None. C. Forsblom: None. P. Groop: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Mundipharma International. The finndiane study group: n/a.

Funding
Folkhälsan Research Foundation Academy of Finland (299200, 316664); Wilhelm and Else Stockmann Foundation; Liv och Hälsa Society; Novo Nordisk Foundation (NNF OC0013659); Finnish Foundation for Cardiovascular Research; Diabetes Research Foundation
1021-P: Mortality and Length of Hospitalisation amongst Diabetic and Nondiabetic COVID-19 Critical Patients: A Retrospective Cohort Study
Authors: SINHA AJAY K. , PANDEY DIVYANSHU , MADHUKAR MAJOR , TOPNO ROSHAN K. , KUMAR RISHIKESH , SINHA SANJAY K. 
Published: June 2021

Aim: To determine the rate of mortality in critically ill COVID-19 positive diabetic patients and association with mortality and length of hospitalization.
Methods: Retrospective Cohort Study done at Nalanda Medical College and Hospital in 670 patients. Critically ill COVID-19 positive (RT-PCR proven) (&gt;= 18yrs), either gender, attending MICU, NMCH Patna included in the study.
Results: The mortality rate of patients was 31% where as patients aged above 40 yrs were having significantly higher odds [OR(95% CL)=5.64 (1.56-20.43)] of mortality Increasing age by 10 years showed significantly higher odds [OR(95%CL)= 1.55 (1.15-2.07)] of mortality. An Insignificant association was found between diabetes and mortality in patients. The length of hospitalization in diabetic patients was higher [median =10(6,16)] than non- diabetic patients [median=7(2,12)] (p=0.036). The mean age of patients in MICU, NMCH was 51 years with 71 % patients aged more than 40 yrs. The patients had a male predominance 31 % patients were Diabetic. 106 patients were diagnosed as T2DM patients after their MICU admission. 29 % patients were Hypertensive and 23 % patients had both T2DM and HTN, 74 % patients had shortness of breath as C/F whereas only 58% patients had fever, RBS level on admission had no significant association [OR(95%CL)=0.882(0.730-1.067)] with mortality Glycemic variability had no significant association [OR(95%CL)=1.000(0.925-1.082)] with duration of hospitalization. A statistically significant association was seen between T2DM and HTN (p=0.01) in COVID-19 patients. A significant (p=0.008) proportion (90.3%) of diabetic patients were aged above 40 years as compared to nondiabetic patients.
Conclusion: COVID-19 patients attending NMCH patna have male preponderance. With increasing age, mortality increases in COVID-19 critically ill patients. Diabetes does not increase mortality in COVID-19 patients but increases the length Of hospitalization.

Disclosure
A. K. Sinha: None. D. Pandey: None. M. Madhukar: None. R. K. Topno: None. R. Kumar: None. S. K. Sinha: None.
1147-P: Pseudo Insulin Resistance: Palmitate Inactivates Insulin Signaling but Stimulates Basal Glucose Uptake in 3T3-L1 Adipocytes
Authors: PODKUYCHENKO NIKITA , MICHURINA SVETLANA , STAFEEV IURII , KHAPCHAEV ASKER Y. , SHIRINSKY VLADIMIR P. , VOROTNIKOV ALEXANDER V. 
Published: June 2021

Increased levels of circulating free fatty acids (FFA) is the major risk factor for type 2 diabetes in obesity. While the long-term effects of increased FFA on adipose tissue likely involve latent inflammation, the short-term effects on insulin-sensitive adipocytes are less clear. We treated fully differentiated 3T3-L1 adipocytes with increased concentrations (0.3-1 mM) of a typical FFA, palmitate, for 2 days, and measured insulin stimulation of 2-deoxyglucose (2-DG) uptake. The insulin cascade and AMPK activities, Glut-1 and Glut-4 levels were measured by western blots (WB). Glut-4 translocation was measured either by WB after cell membrane fractionation, or by fluorescence analysis after lentiviral transduction of adipocytes with Glut-4 construct containing C-terminal mCherry and outer Myc epitope insertion in the Glut-4 extracellular loop. While fluorescence of mCherry reported the total Glut-4, that of anti-Myc antibody revealed Glut-4 exposed on the plasma membrane. Palmitate dose dependently increased basal 2-DG uptake, whereas insulin-stimulated uptake and Glut-4 translocation to the plasma membrane were significantly reduced only by high (1 mM) palmitate. High palmitate did not alter Glut-1 and Glut-4 expression, but reduced IRS phosphorylation (Tyr612) and completely ceased that of Akt (Thr308/Ser473) and AS160 (Ser318) in the absence or presence of insulin, as well as phosphorylation of ACC (Ser-79) by AMPK. These results suggest that the short-term effects of palmitate on adipocytes are associated with “pseudo” insulin resistance, i.e., an increased basal glucose uptake likely due to the “pull” mechanism for increased triglyceride turnover, and the loss of insulin stimulation possibly due to fill-up of fat depots.

Disclosure
N. Podkuychenko: None. S. Michurina: None. I. Stafeev: None. A. Y. Khapchaev: None. V. P. Shirinsky: None. A. V. Vorotnikov: None.

Funding
Russian Foundation for Basic Research (20-015-00471)
187-LB: Leveraging Information across Multiple Related Glycaemic Traits Improves Fine-Mapping Resolution
Authors: SOENKSEN JANA , CHEN JI , ASIMIT JENNIFER L. ,   MAGIC, BARROSO INÊS 
Published: June 2021

Glycaemic traits fasting insulin (FI), fasting glucose (FG), 2-hour glucose (2hGlu) and glycated haemoglobin (HbA1c) are used to diagnose and monitor type 2 diabetes (T2D). MAGIC (Meta-Analysis of Glucose and Insulin-related traits Consortium) identified 242 loci associated with these traits in 281,416 individuals, from 6 ancestries. European (EUR) ancestry fine-mapping resulted in credible sets accounting for 99% of the posterior probability of association (99CS) with a median of 55 SNPs. Trans-ancestry (TA) fine-mapping led to 99CS with a median of 45 SNPs. Here, we investigated whether fine-mapping resolution could be improved by leveraging data across multiple related traits. We used the novel method FLexible And SHared information Fine-Mapping (flashfm), which takes advantage of sharing of information between traits. We compared its performance with single-trait FINEMAP results. We conducted EUR fine-mapping for 53 loci associated with ≥2 glycaemic traits (p&lt;10-6, N=119 loci-trait associations). EUR ancestry FINEMAP results were used as input for flashfm. Default parameters were used, except a prior odds of 80% (TOdds=0.25) of a shared causal variant across traits was used. 99CS were used to compare single-trait and flashfm results. Flashfm successfully fine-mapped 48 loci (106 locus-trait associations, 5 loci could not be run). At 40/106 locus-trait associations flashfm led to 99CS with ≤10 SNPs, of which 4 had a single SNP, prioritising SNPs for functional follow-up. Fine-mapping across ≥2 traits reduced the number of SNPs in the 99CS in 80.1% (85/106) of locus-trait associations. The median number of SNPs in the 99CS were significantly reduced from 50 to 19 (p=1.1 x10-13). In 47.3% (44/93) of locus-trait associations flashfm reduced the 99CS size compared to TA fine-mapping. Our results show that leveraging data across multiple related traits is a useful approach to improve single-ancestry fine-mapping resolution, and that it may also improve TA fine-mapping.

Disclosure
J. Soenksen: None. J. Chen: None. J. L. Asimit: None. Magic: n/a. I. Barroso: Stock/Shareholder; Self; Incyte Corporation, Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc.

Funding
Research England; Medical Research Council (MR/R021368/1)
195-LB: Lower Nonresponse Rates to 3-Antigen HBV Vaccine among Adults with Diabetes, Age 45 and Over, or Obesity Compared with a Single-Antigen HBV Vaccine: PROTECT Study
Authors: DIAZ-MITOMA FRANCISCO , VESIKARI TIMO , LANGLEY JOANNE M. , HOSSAIN ALOMGIR , MACHLUF NATHALIE , SPAANS JOHANNA , YASSIN-RAJKUMAR BEBI , ANDERSON DAVID E. , POPOVIC VLAD ,   PROTECT STUDY GROUP
Published: June 2021

Diabetes mellitus (DM), older age (≥45 years) and obesity (BMI &gt;30 kg/m2) are associated with lower response to immunizations and worse outcomes of chronic hepatitis B infection. Therefore, there is a need to enhance immunogenicity of HBV vaccine for adults, especially those with DM, older age, and obesity. PROTECT study compared the immunogenicity and safety of 3-doses of 3-antigen / 3A-HBV (Sci-B-Vac) and 1-antigen / 1A-HBV (Engerix-B) HBV vaccines administered at months 0, 1 and 6. The study enrolled 1607 adults age ≥18 years in the US (42.3%), Europe (41.6%) and Canada (16.1%). Immunogenicity, measured as rate of non-response (% not achieving anti-HBs levels ≥10 mIU/mL), anti-HBs geometric mean concentration (GMC), and safety were evaluated in all adults and key subgroups of interest. Of 1607 study participants, 7.5% (3A-HBV arm) and 8.0% (1A-HBV arm) had a stable and well controlled DM (HbA1c &lt;8.5%), 81.4% were age ≥45 years and 36.7% had BMI &gt;30 kg/m2. Overall non-response rates were 23.5% (1A-HBV) and 8.6% (3A-HBV). For diabetics, non-response rates were 41.7% (1A-HBV) and 16.7% (3A-HBV), for those age ≥45 years, 34.3% (1A-HBV) and 16.4% (3A-HBV) and for BMI &gt;30 kg/m2, 31.9% (1A-HBV) and 10.8% (3A-HBV). Mean GMC of anti-HBs was higher for 3A-HBV compared to 1A-HBV (1424.5 vs. 235.4 mIU/mL) and consistently higher across key subgroups, including those with DM, age ≥45 years and BMI &gt;30 kg/m2. Safety of 3A-HBV was comparable to 1A-HBV except for higher rates of injection site pain, tenderness and myalgia of mild to moderate severity and mean duration of 1-2 days. Completion rate of all 3 vaccine doses was high at 96.8% (1A-HBV) and 95.2% (3A-HBV). Immunization with 3A-HBV achieved lower rates of non-response compared to 1A-HBV in all adults, including those with diabetes, older age, and obesity.

Disclosure
F. Diaz-mitoma: Consultant; Self; VBI Vaccines. Protect study group: n/a. T. Vesikari: Research Support; Self; VBI Vaccines. J. M. Langley: Research Support; Self; GlaxoSmithKline plc., Medicago, VIDO, Entos, Merck & Co., Inc., Pfizer Inc., Sanofi. A. Hossain: None. N. Machluf: Employee; Self; VBI Vaccines. J. Spaans: Employee; Self; VBI Vaccines Inc. B. Yassin-rajkumar: None. D. E. Anderson: Employee; Self; VBI Vaccines, Inc., Stock/Shareholder; Self; VBI Vaccines, Inc. V. Popovic: Employee; Self; VBI Vaccines.
208-OR: Fat Mass and Insulin Resistance Are Independent Risk Factors for Polyneuropathy in Non-DM Subjects Who Underwent Bariatric/Metabolic Surgery
Authors: KIM KYUHO , OH TAE JUNG , CHOI SUNGHEE , JANG HAK CHUL 
Published: June 2021

Background: Obesity is an important risk factor for polyneuropathy (PN) in subjects with DM. However, PN can be detected in subjects without overt DM but with risk factors for DM such as metabolic syndrome. Therefore, it is worthy to investigate the prevalence of PN in obese subjects and to discover the underlying mechanisms of the association between obesity and PN.
Methods: We analyzed the data of 184 subjects who underwent bariatric/metabolic surgery. PN was diagnosed when a Michigan Neuropathy Screening Instrument score was ≥ 2.5. Total body fat mass and percentage were measured by bioimpedance analysis, and visceral fat area (VFA) was quantified by computed tomography. According to DM status, obesity-related parameters were compared between subjects with PN and those without PN. The association between obesity-related parameters and PN was analyzed using logistic regression models.
Results: Of 184 subjects (mean age, 39.1 years; mean BMI, 38.6 kg/m2), 39.7% were diagnosed with DM. The prevalence of PN was 9.0% in non-DM group and 21.9% in DM group. In non-DM group, subjects with PN showed higher HOMA-IR, fat mass, and VFA compared with those without PN. HOMA-IR (OR, 1.492; 95% CI, 1.110-2.005), fat mass (OR, 1.087; 95% CI, 1.008-1.171), and VFA (OR 1.013; 95% 1.001-1.024) were significantly associated with PN even after adjustment of known risk factors of PN. In DM group, subjects with PN showed higher body weight, BMI, waist circumference, and VFA compared with those without PN. However, after adjustment of known risk factors of PN, these obesity related parameters were not significantly associated with PN.
Conclusion: Fat mass and insulin resistance might be independent risk factors in development of PN for obese subjects without DM. PN evaluation might be necessary in subjects with morbid obesity even before development of overt DM, and we need to investigate whether weight loss intervention can prevent or delay PN in obese subjects.

Disclosure
K. Kim: None. T. Oh: None. S. Choi: None. H. Jang: None.
226-OR: ADA Presidents’ Select Abstract: Exercise Training Promotes Mitochondrial Remodeling in Skeletal Muscle of Type 2 Diabetes Humans
Authors: MASTROTOTARO LUCIA , APOSTOLOPOULOU MARIA , PESTA DOMINIK , STRASSBURGER KLAUS , KARUSHEVA YANISLAVA , GANCHEVA SOFIYA , SZENDROEDI JULIA , RODEN MICHAEL 
Published: June 2021

Altered mitochondrial dynamics may contribute to impaired mitochondrial function and insulin sensitivity in type 2 diabetes (T2D). High intensity interval training (HIIT) can induce mitochondrial biogenesis in healthy humans, but its impact on mitochondrial remodeling in insulin resistant states is still unclear. To this end, this study examined the effect of HIIT on mitochondrial function and dynamics in T2D as well as in insulin resistant (IR) and sensitive (IS) glucose tolerant humans to elucidate the interplay between mitochondrial turnover and muscle insulin sensitivity. Twenty T2D, 11 IR and 12 IS humans age- and BMI-matched (HbA1c in %: 7.2 ± 0.2, 5.4 ± 0.1, 5.5 ± 0.1; M-value in mg*kg-1*min-1: 3.0 ± 0.4, 4.1 ± 0.3, 7.4 ± 0.4) performed a 12-week HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last exercise bout, whole-body insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, whereas mitochondrial respiration and dynamics were assessed by high resolution respirometry and immunoblotting of skeletal muscle biopsies. After HIIT, all participants showed improved cardiorespiratory fitness and increased muscle maximal oxygen uptake (p&lt;0.001 vs. baseline), whereas insulin sensitivity increased only in T2D and IR (M-value; 4.3 ± 0.5 and 5.7 ± 0.6; p&lt;0.01 vs. baseline). Moreover, HIIT doubled muscle citrate synthase activity in all groups, while biomarkers of mitochondrial fission (p&lt;0.01), fusion (p&lt;0.001) and mitophagy (p&lt;0.001 for phospho-Parkin(Ser65) and p&lt;0.05 for phospho-Pink(Thr257)) increased only in T2D.
In conclusion, this study suggests that mitochondrial fusion and fission synergically respond to chronic exercise training and likely contribute to the exercise training response of insulin sensitivity at least in overt T2D. Targeting these mechanisms might help to better understand muscle insulin resistance and to identify novel therapeutic strategies for tailored prevention and treatment of T2D.

Disclosure
L. Mastrototaro: None. M. Apostolopoulou: None. D. Pesta: None. K. Strassburger: None. Y. Karusheva: None. S. Gancheva: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Allergan plc, Bristol-Myers Squibb Company, Novo Nordisk A/S, Research Support; Self; Boehringer Ingelheim International GmbH, Danone Nutricia, Sanofi-Aventis Deutschland GmbH.
308-OR: Effectiveness of Telemedicine Intervention on Improving Glycemia and Reducing Pharmacologic Therapy in Older Adults with Type 2 Diabetes
Authors: ADAMS REBECCA N. , ATHINARAYANAN SHAMINIE J. , ROBERTS CAROLINE G.P. , VOLK BRITTANIE M. , FELL BRANDON , MCKENZIE AMY L. 
Published: June 2021

Background: We previously demonstrated that carbohydrate restricted nutrition therapy delivered virtually resulted in safe and sustained reduced blood glucose (BG), resulting in deprescription of antihyperglycemic medications in patients with T2D ≤65 years. Given concerns regarding polypharmacy and risk of hypoglycemia (HYPO) in older adults with T2D, this treatment approach may confer benefit.
Methods: At the time of analysis, 279 adults aged ≥65 years at enrollment (27% female, 69±1.6 years, HbA1c: 7.5±1.5%) enrolled in our clinic at least 1 year prior. Data were obtained from medical records to assess changes in BG and medication use among patients retained 1 year and incidence of HYPO in all patients enrolled. Patients provided &gt;1 BG per day on average. Glucose values and patient-reported events were used to identify level 1 (54-69 mg/dL), level 2 (&lt;54 mg/dL), and level 3 (severe requiring third-party assistance) HYPO events.
Results: Among 201 (72%) patients treated 1 year, mean glucose declined (-18.8±3.7 from 147.3±3.8 mg/dL, p&lt;0.001). Among 144 patients taking 231 medications other than metformin at enrollment, 141/231 (61%) of medications were deprescribed, including 45% of insulins and 85% of sulfonylureas. Among the 38 patients still prescribed insulin at 1 year, the average dosage decreased from 98.5±66.0 to 36.2±29.2 IU/day (p&lt;0.001). The average number of diabetes prescriptions per patient declined from 1.2±0.9 to 0.5±0.7 (p&lt;0.001). There were 149 level 1 HYPO events per 100 person-years (p-y), 28 level 2 events per 100 p-y, and no level 3 events reported.
Discussion: The majority of older adults continued treatment for at least 1 year. Improved glycemia concurrent with discontinuation of many high-risk medications and no known severe HYPO events in older adults with T2D suggests this treatment approach may reduce risk and cost associated with polypharmacy and HYPO in older adults with T2D.

Disclosure
R. N. Adams: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. S. J. Athinarayanan: Employee; Self; Virta Health Corp. C. G. P. Roberts: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. B. M. Volk: Employee; Self; Virta Health Corp., Virta Health Corp. B. Fell: None. A. L. Mckenzie: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp.
371-P: Impact of Sodium Intake on the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: Analysis of Data from the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , KAMADA CHIEMI , YOSHIMURA YUKIO , KODERA REMI , FUJIHARA KAZUYA , MORIYA TATSUMI , ARAKI ATSUSHI , SONE HIROHITO 
Published: June 2021

Excessive sodium intake is regarded as a crucial factor related to developing and worsening of cardiovascular disease (CVD). However, epidemiological studies on this topic in patients with type 2 diabetes are sparse. We investigated the associations between sodium intake and CVD risk in Japanese patients with type 2 diabetes from the analysis of pooled data from two nation-wide prospective longitudinal studies. Data were analyzed on 2428 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 6-year risk of a CVD event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean sodium intake in quartiles ranged from 2494 mg to 6166 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&lt; 2300 mg/day). After adjustment for confounders, HRs for CVD in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and CVD [Q2: 0.77 (95%CI, 0.48-1.23); Q3: 1.03 (0.65-1.63); and Q4: 1.31 (0.80-2.14), trend p = 0.131]. Results of subgroup analysis according to age showed that patients aged 39 through 59 years in the higher quartiles of sodium intake compared with the 1st quartile had a significantly higher incidence of CVD [Q2: 1.37 (0.57-3.33); Q3: 1.68 (0.70-4.03); and Q4: 4.16 (1.63-10.58), trend p = 0.004]. However, no significant association between sodium intake and CVD in participants aged over 60 years. Findings indicated that high sodium intake is associated with elevated incidence of CVD in younger patients with type 2 diabetes.

Disclosure
C. Horikawa: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. R. Aida: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. T. Moriya: None. A. Araki: None.

Funding
Japan Society for the Promotion of Science (19H04028)