bluuebunny/crossref_metadata_2025_split huggingface dataset:
39-LB: The Greater the Increase in Physical Activity and Exercise after Metabolic Bariatric Surgery, the Greater the Loss of Fat Mass in Obese Korean Subjects
Authors: NA JANG HAN , SUK PARK YOUNG , HO MOON JOON , CHOI SUNGHEE , MIN CHO YOUNG , CHUL JANG HAK , JUNG OH TAE 
Published: June 2023

Object: Exercise after metabolic bariatric surgery (MBS) is known to be more effective in reducing weight, maintaining muscle strength, and improving insulin sensitivity than MBS alone. In this study, we investigated the influence of increment in physical activity and exercise on clinical outcomes after MBS in obese Korean subjects.
Method: We recruited 94 patients who underwent MBS from April 2019 to December 2021 prospectively. The levels of physical activity and exercise were collected with self-report questionnaires before and 1 year after MBS. Physical activity- and exercise-related energy expenditure (MET-min/week) was calculated by multiplying the frequency, intensity, and duration of the activities. Patients were classified into non-improved and improved groups according to changes in energy expenditure relative to before surgery.
Result: The mean age was 41.4 ± 10.4 years, 38 (40.4%) were male, BMI was 36.9 [32.6, 40.6] kg/m2, and energy expenditure was 438.0 [87.0, 1105.3] MET-min/week at baseline. The improved group had significantly higher BMI (38.0 [34.4, 41.1] vs 33.2 [32.1, 38.8], P = 0.031) and lower MET-min/week (369.8 [174.0, 601.1] vs 761.3 [65.3, 1414.5] METS-min/week, P = 0.045) before surgery. The reduction of BMI and fat mass was significantly greater in the improved group compared with the non-improved group (BMI, 10.2 [8.6, 13.2] vs 9.0 [6.7, 10.9] kg/m2, P = 0.030; fat mass, 25.9 ± 11.1 vs 20.3 ± 9.6 kg, P = 0.016). However, the change in muscle mass was not different between the groups. A greater increase in MET-min/week after MBS was associated with a greater reduction in fat mass after MBS (β = -0.217, P = 0.007), but not with the change in muscle mass.
Conclusion: Patients with higher BMI and lower degree of physical activity and exercise were likely to increase their physical activity after MBS. This improvement in physical activity and exercise was associated with more fat mass loss while maintaining muscle mass.

Disclosure
H. Jang: None. Y. Park: None. J. Moon: None. S. Choi: None. Y. Cho: Consultant; LG Chem. H. Jang: None. T. Oh: None.
393-P: Acute Hypoglycemia Alters Serum Immune Mediators Associated with Macrophage and T-Cell Activation in Type 2 Diabetes
Authors: MOIN ABU S. , SATHYAPALAN THOZHUKAT , ATKIN STEPHEN , BUTLER ALEXANDRA E. 
Published: June 2023

Objective: Hypoglycemia complicates intensive glycemia regimens in type 2 diabetes (T2D). Hyperglycemia induces macrophage priming and dysregulates T-cell activation/function. Immune cell response to acute hypoglycemia has not been investigated in T2D. Thus, immune mediators associated with macrophage/T-cell activation in response to insulin-induced hypoglycemia were studied.
Methods: Hypoglycaemia (&lt;2.2mmol/l; &lt;40mg/dl) was achieved in T2D (n=23) and controls (n=23) by intravenous insulin infusion. Somalogic analysis of plasma proteins related to macrophage/T-cell activation was performed at baseline, hypoglycemia and post-hypoglycemia to 24 hours.
Results: IL-4 and IL-13 (promotors of alternative macrophage activation (M2 macrophages)) decreased 2hours post-hypoglycemia in T2D (p&lt;0.05). Co-stimulatory molecules of T-cell activation expressed in antigen presenting cells (APCs), CD80 and CD86, were decreased at 2h post-hypoglycemia (CD86 in T2D, p&lt;0.05; CD80 in controls and T2D, p&lt;0.05). Hypoglycemia did not affect ligands of co-stimulatory molecules, CTLA4 (ligand of CD80, expressed in APCs) and CD40LG (ligand of CD40, expressed in dendritic cells). The negative regulator of T-cell activation, IL-10, was decreased at 2h (p&lt;0.001) and increased at 4h post-hypoglycemia (p&lt;0.01). Elevation of CD80 (p&lt;0.05) and CD86 (p&lt;0.05), with increased T-cell proliferator IL-6 (p&lt;0.05) was seen in T2D at 4h post-hypoglycemia. Positive correlations of IL10 with IL6, IL4, were observed at 2h post-hypoglycemia in T2D, suggesting a role for IL10 in altering immune cell activation mediators following hypoglycemia in T2D. No correlations with glucagon suggest changes are independent of glucose counter-regulation.
Conclusion: Induced hypoglycemia is associated with decreases in macrophage and T-cell activation mediators (cytokines) in T2D. Thus, this study reveals a novel link between hypoglycemia and inefficient immune system activation.

Disclosure
A.S.Moin: None. T.Sathyapalan: Other Relationship; Novo Nordisk, Abbott Diabetes, Research Support; Abbott Diabetes, Novo Nordisk, Eli Lilly and Company. S.Atkin: None. A.E.Butler: None.
396-P: The Humanistic Burden of Type 1 Diabetes in U.S. Adults With or Without Recurrent Severe Hypoglycemic Events—A Qualitative Interview Study
Authors: BOATENG-KUFFOUR ADRIANA , CALLAHAN PATRICK , CHANDARANA KEVAL , GAGLIA JASON L. , PHINNEY MICHAEL , GUZMAN ORTEGA ERICK , KRUPNICK ROBERT N. , REANEY MATTHEW , POLONSKY WILLIAM H. 
Published: June 2023

Introduction: Despite advances in technology, many people with type 1 diabetes (T1D) still experience severe hypoglycemic events (SHEs). This study explored the perceived humanistic burden of T1D in adults using continuous glucose monitor (CGM) in the US with or without recurrent SHEs.
Methods: In 60-minute semi-structured interviews, adult CGM users with self-reported T1D diagnosis (≥5 yrs.) described the burden of TID on quality of life (QoL). Participants ranked the ‘top 3’ negative impacts of T1D on QoL. Subgroup analyses were conducted in participants with recurrent SHE (rSHE; ≥2 SHEs last yr.) and without recurrent SHE (nSHE; ≤1 SHEs last yr.).
Results: Participants (N=31; 42% rSHEs, 58% nSHEs) were 74% female and 81% were married. Mean age of T1D diagnosis was 28 yrs. Median SHEs in the past year in the rSHE group were 3 and in the nSHE group were 0. Both groups had mean HbA1c of 7.1%. rSHE and nSHE participants used hybrid closed loop systems (hCLS) (53.8% vs. 44.4%), multiple daily injections (23.1% vs. 33.3%) and continuous subcutaneous insulin infusion pump without hCLS (23.1% vs. 22.2%), respectively. All participants reported negative impacts on physical health, mental health, sleep, relationships, leisure activities, work/studies, and sex life. The ‘top 3’ ranked impacts for the rSHE cohort were physical health and sleep (tied at first) followed by leisure activities. Impacts to physical health, mental health, and relationships were ‘top 3’ for the nSHE cohort.
Conclusions: Recurrent severe hypoglycemia is observed to persist despite use of advanced diabetes technology. Negative impacts on physical health ranked as the primary concern in both rSHE and nSHE cohorts. However, moderate variability in ranked negative impact order was observed between the cohorts.

Disclosure
A.Boateng-kuffour: None. P.Callahan: Consultant; Rhythm Pharmaceuticals, Inc., Abbott Diabetes, HealthCore Inc., BMS, Employee; Vertex Pharmaceuticals Incorporated, Genesis Research. K.Chandarana: Employee; Vertex Pharmaceuticals Incorporated, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. J.L.Gaglia: Advisory Panel; Dompé, Consultant; Vertex Pharmaceuticals Incorporated, Abata Therapeutics, Avotres Inc., Current Health, Research Support; Avotres Inc., Dompé, Imcyse, Stock/Shareholder; Vertex Pharmaceuticals Incorporated. M.Phinney: None. E.Guzman ortega: Research Support; Vertex Pharmaceuticals Incorporated. R.N.Krupnick: Consultant; Vertex Pharmaceuticals Incorporated. M.Reaney: None. W.H.Polonsky: Consultant; Abbott Diabetes, Boehringer Ingelheim and Eli Lilly Alliance, Eli Lilly and Company, Insulet Corporation, Intuity Medical, Inc., MannKind Corporation, Provention Bio, Inc., Sanofi-Aventis U.S., Vertex Pharmaceuticals Incorporated.
401-P: Effects of Teneligliptin on Lipotoxicity in High-Fat Diet–Induced Diabetic Kidney Disease Model
Authors: KYUNG KIM HAE , KIM RYEONG-HYEON , YANG YURIM , PARK HYUNKI , JEON NARA , LEE MINYOUNG , LEE HYANGKYU , JIN LIM BEOM , YOUNG CHOI HOON , SEOK KANG EUN 
Published: June 2023

Lipotoxicity contributes to diabetic kidney disease (DKD), impairing function of glomerulus and podocyte, consequently causing albuminuria. Dipeptidyl peptidase-4 (DPP-4) inhibitors demonstrated renoprotective effects in DKD, but the mechanism for protection in DKD regarding lipid metabolism is unclear. Here, we investigated the effects of teneligliptin in high-fat diet (HFD)-induced DKD model. 5-week-old male C57BL/6J mice were supplemented with HFD for 24 weeks to develop DKD. Teneligliptin was administrated orally by pre-mixing with HFD for 16 weeks. Body weight, blood glucose levels, and glucose and insulin tolerance test were evaluated at 12 weeks and albuminuria was evaluated at 6 and 12 weeks after teneligliptin administration. Lipid panels were evaluated and the renal cortex was collected for histologic examination at 16 weeks. Body weight, random and fasting blood glucose was not significantly different but total cholesterol and triglyceride were reduced in teneligliptin group. Glucose and insulin tolerance test showed significant improvement in teneligliptin group compared with HFD group (p&lt;0.001 and p=0.009, respectively). Changes in albuminuria between 6 and 12 weeks during treatment period group were lower in teneligliptin group compared with HFD group (p=0.07). In immunohistochemistry studies, glomerular volume and mesangial expansion were attenuated in the teneligliptin group by 26.9% and 32.15% respectively (p=0.011 and p=0.043, respectively). Glomerular basement membrane thickness and foot process width were decreased by 43.2% and 9.32% in teneligliptin group (p=0.0007 and p=0.035, respectively). Teneligliptin attenuated diabetic kidney disease in HFD-induced DKD by preserving integrity of glomerulus and podocyte, with decreased albuminuria. Further investigations for detailed mechanisms about the association between DPP-4 inhibitor and lipotoxicity induced glomerulus and podocyte injury in DKD are warranted in the future.

Disclosure
H.Kim: None. E.Kang: None. R.Kim: None. Y.Yang: None. H.Park: None. N.Jeon: None. M.Lee: None. H.Lee: None. B.Lim: None. H.Choi: None.
404-P: Single-Cell RNA Profiling Changes in Glomerular Cells in Diabetic Nephropathy (DN)
Authors: FU JIALIN , LI QIAN , PARK KYOUNGMIN , HUANG QIAN , WU I-HSIEN , KING GEORGE L. 
Published: June 2023

Hyperglycemia, the main risk factor for DN, causes complex pathological damages in glomeruli. To characterize detail changes in cell differentiation and gene expressions induced by diabetes, we performed unbiased single-cell RNA sequencing (scRNA-seq) on glomerular cells from diabetic and nondiabetic mice of long duration. Glomerular cells were isolated from C57 mice after 7-months of STZ-induced diabetes, when clear glomerular pathologies have been documented. Total number of 48,337 high-qualitied glomerular cells were isolated and sequenced from WT and STZ-treated mice. Based on clustering analysis and cell-type specific markers, 12 different cell types were identified, including endothelial cells (EC), podocytes, mesangial cells (MC), proximal tubule cells, parietal epithelial cells (PEC), collecting duct cells, ascending loop of Henle, macrophages, B cells, T cells, NK cells and neutrophils. Over 90% of the cells were from glomeruli (41% EC, 34 % podocytes, 14% MC, 2% of PEC), and 6% immune cells. Interestingly, gene profiling identified 9 clusters of EC, 5 clusters of MC and 7 clusters of podocytes. Diabetes did not change the total cell numbers for EC, MC and podocytes, although macrophage and B cell numbers were increased from 2.2% to 4.8% and 0.35% to 1%, respectively. Cluster subset analysis of EC, MC and podocytes showed that diabetes induced substantial changes. For podocytes, diabetes increased those clusters (5% to 37%) with high expressions of stressed proteins such as Hspa1a, Hspa1b and Hsp90aa1, while decreased those clusters with high expressions of ECM production and CDC42 GTPase cycle, that were involved in cytoskeleton stabilization and foot process formation. Findings from scRNA-seq of glomeruli showed there were multiple subsets of podocytes, EC and MC, which appear to have different functions and their distributions were changed by diabetes. Understanding the mechanism for the distribution changes of the subsets may provide new insight in the pathogenesis of DN.

Disclosure
J. Fu: None. Q. Li: None. K. Park: None. Q. Huang: None. I. Wu: None. G.L. King: Research Support; Janssen Research & Development, LLC.
405-P: ROCK2 Activation and Its Role in Folic Acid–Induced Murine Model of Nephropathy
Authors: SEKIGUCHI KENSUKE , MATOBA KEIICHIRO , OHASHI SHINJI , MITSUYOSHI ETSUKO , NAGAI YOSUKE , TAKEDA YUSUKE , NISHIMURA RIMEI 
Published: June 2023

Over 2 million people currently receive treatment with dialysis or a kidney transplant throughout the world. Thus, developing a new strategy to treat chronic kidney diseases is significant from the perspective of a health economic and the prevention of cardiovascular death. The small GTPase Rho and its effector Rho-kinase (ROCK) are involved in the pathogenesis of diabetic nephropathy. In chronic kidney diseases including diabetic nephropathy, tubulointerstitial fibrosis is known to be highly associated with renal outcome. We have previously reported that ROCK inhibition prevented the progression of diabetic nephropathy in murine models. With regards to ROCK, there are two isoforms, which are ROCK1 and ROCK2. ROCK1 has been shown to be involved in the endocytosis of albumin in tubular epithelial cells via megalin/cubilin-dependent mechanism. However, the role of renal tubular ROCK2 remains to be elucidated. The aim of this study is to reveal the role of renal tubular ROCK2 in the pathogenesis of chronic kidney disease. To this end, we used a tubulointerstitial injury model known as folic acid-induced nephropathy (FAN). Importantly, ROCK2 was elevated at protein levels in FAN group compared with vehicle-treated group. We next generated tubular specific ROCK2 knockout mouse (TR2KO) by crossing Ksp-Cre mice with mice containing two loxP sites flanking in Exon 3 of ROCK2. In the Ksp-Cre transgenic mice, Cre recombinase has been demonstrated to be expressed in tubules, collecting ducts, and thick ascending limbs. Compared with vehicle-treated group, collagen deposition in the kidneys of FAN group was highly elevated as revealed by Masson’s trichrome staining. The increased collagen deposition was significantly improved in TR2KO. Our findings indicate that ROCK2 regulates the progression of tubulointerstitial fibrosis. ROCK2 may be a potential therapeutic target for the prevention of chronic kidney disease.

Disclosure
K.Sekiguchi: None. K.Matoba: None. S.Ohashi: None. E.Mitsuyoshi: None. Y.Nagai: None. Y.Takeda: None. R.Nishimura: Speaker's Bureau; Sanofi K.K., Medicure Inc., Boehringer Ingelheim Inc., Takeda Pharmaceutical Company Limited, Kissei Pharmaceutical Co., Ltd., Novartis Pharma K.K., Eli Lilly Japan K.K., Novo Nordisk, Merck & Co., Inc., Abbott Japan Co., Ltd., Astellas Pharma Inc., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., AstraZeneca.
413-P: Intensive Insulin Therapy Delays the “Breakpoint” to Progressive Kidney Function Decline—New Findings and Implications of eGFR Trajectory Analysis in DCCT/EDIC Data
Authors: IHARA KATSUHITO , SKUPIEN JAN K. , SATAKE EIICHIRO , PERKINS BRUCE A. , KROLEWSKI ANDRZEJ 
Published: June 2023

Patterns of kidney function decline vary among those with T1D. End-stage kidney disease (ESKD) develops after progressive kidney function decline that begins when kidney function is normal, regardless of albuminuria. We aimed to determine if these findings were observed in the DCCT/EDIC cohort, which enrolled 1,441 individuals and randomly assigned them to intensive insulin therapy (n=711) or conventional insulin therapy (n=730). Baseline mean eGFR and AER were 125 ml/min/1.73m2 and 12 mg/24 hours, respectively. During 27 years of follow-up 129 individuals reached reduced eGFR &lt;60ml/min/1.73m2 or ESKD. For these individuals we applied latent class trajectory analysis minimizing sum of squares of linear spline models with varying knot placement to identify patterns of eGFR decline. We identified two patterns: i) slow decline without eGFR breakpoint (n=56) and ii) fast decline with clear breakpoint (n=73). Slow decliners reached reduced eGFR but rarely ESKD (2%), while many fast decliners progressed to ESKD (35%) within 5-15 years after the breakpoint. Fast decline was less frequent in intensive compared to conventional insulin therapy [26 (3.7%) vs 47 (6.4%), respectively, p=0.022] and had longer median time from enrollment to breakpoint (18 vs 13 years, respectively, p=0.0004). However, the slope of annual loss of eGFR after breakpoint did not differ. In conclusion, we identified a unique phenotype - the “breakpoint” to fast decline in eGFR - as the main predictor of ESKD in T1D. This breakpoint started while eGFR was normal, subsequent decline was linear, and the onset of the breakpoint was substantially delayed by intensive insulin therapy rather than the slope of decline itself. Research on biomarkers that predict the onset of the eGFR ‘breakpoint’ is needed.

Disclosure
K.Ihara: None. J.K.Skupien: None. E.Satake: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). A.Krolewski: None.
419-P: Glucose-Induced Cellular Resistance to Methylglyoxal Is Lost in Patients with Diabetes Complications and Further Deteriorated after Caloric Restriction
Authors: RAUCHHAUPT EKATERINA V. , RODEMER CLAUS , KLIEMANK ELISABETH , KOPF STEFAN , HERZIG STEPHAN , NAWROTH PETER , SZENDROEDI JULIA , ZEMVA JOHANNA , SULAJ ALBA 
Published: June 2023

Aim: Glucose stress can be protective against dicarbonyl-mediated toxicity. This study aimed to investigate cellular resistance against methylglyoxal (MG) after glucose stress in healthy humans (CON), patients with (T2D+) and without diabetes complications (T2D-) and whether this is affected by caloric restriction. Fibroblast growth factor 21 (FGF21) and β- hydroxybutyrate (β-HB) were analyzed as marker for metabolic adaptation to stress response and ketogenesis.
Methods: Peripheral blood mononuclear cells were isolated before and 2h after oGTT and incubated at each time-point with increasing MG-levels for 24hrs. Cell viability was measured with CellTiter-Glo to determine changes of MG-resistance at 2h after oGTT (ΔEC50). Experiments were repeated after a 5-day fasting-mimicking diet (FMD). FGF21 and β-HB were measured in venous blood.
Results: Thirty participants (18m/12f, age 64.6 [62.2, 67.0] y, BMI 28.6 [27.2, 30.0] kg/m2) were included. HbA1c was higher in T2D+ (7.4 [6.9, 7.9] %) and T2D- (7.0 [6.2, 7.7] %) compared to CON (5.5 [5.1, 5.8] %, p&lt;0.001), age and BMI were comparable. ΔEC50 of MG increased in CON before and after FMD (12.9% vs. 12.6%), was unaffected in T2D- (1.8% vs. -1.7%) and decreased in T2D+ after FMD (-3.9% vs. -19.0%, p&lt;0.01) and when compared to T2D- and CON (p&lt;0.05). ΔFGF21 increased in CON after FMD (7.7% vs. 115.0%, p&lt;0.05) and tended to be higher compared to T2D- and T2D+ (115.0% vs. 69.3% vs. 47.5%, p=0.5). ΔFGF21 correlated with β-HB (r = 0.48, p&lt;0.01), with strongest correlation for T2D+.
Conclusion: Acute glucose stress induces cellular resistance to MG in healthy humans, a response which is lost in T2D with diabetic complications and aggravates after caloric restriction. Our data suggest for an association between loss of capacity for handling dicarbonyl stress and the presence of diabetic complications. FGF21 might play an important role in the metabolic adaptation to dicarbonyl stress and ketosis.

Disclosure
E.V.Rauchhaupt: None. C.Rodemer: None. E.Kliemank: None. S.Kopf: Advisory Panel; Novo Nordisk, Bayer Inc., Recordati Rare Disease, Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. S.Herzig: Consultant; Novo Nordisk, Actimed, Research Support; Novo Nordisk, Boehringer-Ingelheim, Almac. P.Nawroth: None. J.Szendroedi: None. J.Zemva: None. A.Sulaj: None.

Funding
DFG; German Research Foundation (236360313-SFB, 1118DZD); German Center for Diabetes Research (82DZD07C2G)
42-LB: Low-Carbohydrate Diet Compared with Canagliflozin for the Treatment of Diabetes—A Randomized Noninferiority Trial
Authors: GU YUNJIE , XIA XINYI , XU MIAO , LI LI , YIN JUN 
Published: June 2023

Aims and Introduction: A low-carbohydrate diet (LCD) is effective for glycemic control in patients with diabetes. However, most previous studies have compared LCD with a low-fat or low-calorie diet. In this study, we used canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, as the positive control drug and aimed to establish the non-inferiority of LCD to canagliflozin in terms of blood glucose control.
Methods: We conducted a 3-month, multicenter, randomized, open-label, parallel-controlled clinical trial involving patients with type 2 diabetes. Participants were randomly assigned in a 1:1 ratio to receive canagliflozin (100 mg/day) or LCD (carbohydrate intake &lt; 20% of the total energy intake). The primary outcome was the change in HbA1c level, and the secondary outcomes were Continuous Glucose Monitoring (CGM)-measured time in the target glucose range of 3.9-10 mmol/L and the cost of antidiabetic agents.
Results: In total, 121 participants from three hospitals were enrolled; 61 were administered canagliflozin and 60 were administered LCD. After the 3-month intervention, the mean change in HbA1c levels was -1.76% with canagliflozin and -2.23% with LCD (estimated difference, -0.47%; 95% confidence interval [CI], -0.85-0.08; P = 0.0180). Time in range (TIR) increased from 48.96% at baseline to 80.21% at 3 months in the canagliflozin group and from 52.08% to 93.75% in the LCD group. The TIR in the LCD group was significantly higher than that in the canagliflozin group (P = 0.0026). Additionally, in the LCD group, 10 of 52 patients who had been using antidiabetic drugs (19.2%) discontinued one oral antidiabetic drug or reduced their insulin doses.
Conclusions: Our study showed that LCD was non-inferior to canagliflozin in glycemic control. Patients in the LCD group showed greater decline of HbA1c levels and higher TIR than those in the canagliflozin group. LCD reduced the cost of antidiabetic drugs.

Disclosure
Y. Gu: None. X. Xia: None. M. Xu: None. L. Li: None. J. Yin: None.

Funding
National Natural Science Foundation of China (82070885); Shanghai Municipal Education Commission (20172025); Xuhui Joint Research Projects on Important Diseases (XHLHGG202110)