bluuebunny/crossref_metadata_2025_split huggingface dataset:
512-P: The Concomitant Insulin Treatment with Sodium–Glucose Cotransporter 2 Inhibitors Influenced the Renal Composite Outcome in Japanese Type 2 Diabetes Patients with Chronic Kidney Disease
Authors: KOBAYASHI KAZUO , TOYODA MASAO , SAKAI HIROYUKI , TAMURA KOUICHI , HATORI NOBUO 
Published: June 2020

Background and Aim: Some large clinical trials using SGLT2 inhibitor revealed the superiority in the renal outcome in patients with type 2 diabetes mellitus (T2DM) patients. We already reported that SGLT2 inhibitor improved urinary albumin-creatinine ratio at baseline (ACR) in Japanese T2DM patients with CKD and revealed some factors that influence to the renoprotective effects of SGLT2 inhibitor. The aim of this study is to clarify how the concomitant insulin treatment with SGLT2 inhibitor influence the renal composite outcome.
Research Design and Methods: We retrospectively assessed 624 patients with Japanese T2DM patients with CKD who underwent SGLT2 inhibitor treatment for more than 1 year. We set the renal composite endpoint that was the progression of the stage of albuminuria or the decrease in eGFR by ≥15% per year. For comparative analyses, we performed the cohort model of patients with or without insulin treatment that was used propensity score (PS) matching methods. The PS matching was using the following algorithm: 1:1 nearest neighbor match with a ±0.04 caliper and no replacement. Further, all patients were stratified into quintiles based on the corresponding PS and included in the analyses.
Results: The comparison of 149 PS-matched patients in each group were performed. The incidence of renal composite outcome was significantly higher in patients with insulin treatment than without it (n=23[15.4%] and n=10[6.7%], respectively, p=0.033). The results from the analysis depending on the quintiles of all patients by the Mantel-Haenszel method, there was a significant difference between the two groups (p=0.021) and the odds ratio for the renal composite outcome was 2.09 (95%CI,1.15, 3.80, p=0.016) in patients with insulin treatment.
Conclusion: The concomitant insulin treatment with SGLT2 inhibitor influenced the renal composite outcome in Japanese T2DM patients with CKD.

Disclosure
K. Kobayashi: None. M. Toyoda: None. H. Sakai: None. K. Tamura: Research Support; Self; AstraZeneca K.K., Ono Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; AstraZeneca K.K., Ono Pharmaceutical Co., Ltd. N. Hatori: None.
521-P: Novel Screening and Management of Fall Risk in Type 2 Diabetic Patients with Diabetic Kidney Disease
Authors: IKEJIMA SHIN , KONDO SEIYA , TAKAHASHI TOMOMI , UEMA MIKA , UMEZU JUNKO , HIRAI AIZAN 
Published: June 2020

Background: Recently, GLP-1 receptor agonists and SGLT2 inhibitors have been frequently used to reduce the risk of diabetic kidney disease (DKD). However, these therapies may cause anorexia, sarcopenia, and an increased fall-risk. Furthermore, sarcopenia frequently accompanies chronic renal disease. The following study describes a novel method of screening to identify patients at an increased fall-risk in type 2 diabetic patients with DKD.
Methods: The procedure was tested in type 2 diabetic outpatients at our hospital. We measured outpatient one-leg standing (OLS) times with eye open and the timed up and go test (TUG), which were fall-risk assessment tools. OLS times of less than 20 seconds or TUG score of more than 11 seconds were predictive of a greater fall-risk. Furthermore, we used the ten time sit to stand test (TTSST) and toe grip strength test (TGST), grip strength, skeletal muscle mass index (SMI), and evaluated diabetic neuropathy. We also analyzed their dietary surveys about Salt and protein intake. We planned a novel exercise program for patients with a high fall-risk. Result: A total of 247 cases (147 males; 100 females) were included in this study. The prevalence of patients with OLS times of less than 20 seconds was 45.3%. Interestingly, 56.6% of patients who scored less than 11 seconds on the TUG also scored less than 20 seconds on their OLS time. The OLS time was significantly associated with impaired renal function. In patients with short OLS times (OLS time&lt;5 seconds) and those with normal OLS times (OLS time≥20), eGFR (ml/min/1.73 m2) was 45.3 and 64.1 respectively. Short OLS times were also significantly associated with TTSST, TGST, SMI and DPN. Salt and protein intake was 7.4 g/day and 50.5 g/day. We are currently analyzing the effects of the exercise program.
Conclusion: In summary, a patient’s OLS time, which can be quickly measured in the doctor’s office, was significantly shorter in type 2 diabetic patients with DKD, and was a useful screening procedure to predict fall-risk.

Disclosure
S. Ikejima: None. S. Kondo: None. T. Takahashi: None. M. Uema: None. J. Umezu: None. A. Hirai: None.
527-P: Risk Factors for Nephropathy among Children and Young Adults with Type 1 Diabetes: A Swedish Cohort
Authors: AHMADI SHILAN S. , PIVODIC ALDINA , SVENSSON ANN-MARIE , WEDEL HANS , LUDVIGSSON JOHNNY , LIND MARCUS 
Published: June 2020

Background: Persons with diabetic nephropathy have an increased risk to progress to severe renal failure and have a high cardiovascular risk. To better understand the impact of risk factors on diabetes complications information from diagnosis and onward is needed. Less focus has been on evaluating other risk factors than HbA1c following large populations from diagnosis with repeated measurements. Therefore, we aimed to evaluate risk factors for albuminuria in children and young adults.
Methods: In a population-based cohort study persons with type 1 diabetes (T1D), both children (data from SWEDIABKIDS) and adults (data from Swedish National Diabetes Registry) were included, and followed from January 1, 2001 to December 31, 2017. The association between risk factors and albuminuria was evaluated. The gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor.
Results: A total of 10398 individuals with T1D were followed, 43.4% female, mean age 14.7 years and mean HbA1c 8.0% (63.4 mmol/mol). HbA1c was the strongest risk factor with an odds ratio (OR) of 1.51 (95% 1.39-1.64, p&lt;0.0001). After adjustment for age, sex and mean HbA1c the OR per 1 SD increase were for mean diastolic blood pressure (DBP) 1.27 (95% 1.16-1.39, p&lt;0.0001), mean triglycerides 1.21 (95% 1.14-1.28, p&lt;0.0001), mean systolic blood pressure (SBP) 1.21 (95% 1.10-1.33, p&lt;0.0001), mean cholesterol 1.16 (95% 1.07-1.25, p=0.0002) and mean LDL 1.12 (95% 1.03-1.21, p=0.0051). Risk for albuminuria increased at the following levels: SBP 140 mmHg, DBP 80 mmHg, triglycerides &gt;89 mg/dL (&gt;1.0 mmol/L), total cholesterol &gt;193 mg/dL (&gt;5.0 mmol/L), LDL &gt;135 mg/dL (&gt;3.5 mmol/L) and BMI &gt;30 kg/m2. Smoking showed no association.
Conclusion: For individuals with type 1 diabetes, higher HbA1c, blood pressure, triglycerides, LDL and cholesterol were the most prominent risk factors for albuminuria. Blood pressure levels 140/80 mmHg were associated with increased risk of albuminuria.

Disclosure
S.S. Ahmadi: None. A. Pivodic: None. A. Svensson: None. H. Wedel: None. J. Ludvigsson: None. M. Lind: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Dexcom, Inc., Novo Nordisk Inc.

Funding
Swedish Child Diabetes Foundation
529-P: Insulin Replacement Therapy Does Not Fully Prevent Peripheral Neuropathy in Type 1 Diabetic Mice
Authors: EID STEPHANIE , HINDER LUCY M. , HAYES JOHN M. , MENDELSON FAYE , FELDMAN EVA L. 
Published: June 2020

Peripheral Neuropathy (PN) is one of the most common complications of diabetes worldwide, affecting up to 60% of diabetic patients. Despite strict glycemic control, the risk of PN persists in approximately 30% of type 1 diabetic (T1D) patients. Understanding the role of insulin in PN is therefore critical to designing adjunct therapies that can slow or reverse disease progression. In this study, we aimed to determine the effect of insulin replacement therapy on nerve function and identify metabolic and molecular changes in plasma and nerves of T1D mice that are not improved following euglycemia. Terminal metabolic and neuropathy phenotyping was performed in Streptozotocin (STZ)-induced T1D mice, treated with insulin for 12 weeks. Oxidative stress was quantified in plasma and sciatic nerve. DNA methylation and protein expression of key insulin signaling markers were also determined in dorsal root ganglia (DRG). T1D mice developed hyperglycemia, hypertriglyceridemia, reduced plasma insulin, PN, systemic and nerve oxidative stress. Additionally, DRG isolated from T1D mice exhibited hypermethylation and reduced insulin signaling. Insulin replacement therapy normalized glycemia and triglyceride levels, but induced hyperinsulinemia and markers of oxidative stress. While insulin treatment did not reverse large fiber neuropathy, it improved small fiber and sensory nerve function. This protective effect was accompanied with a restoration of methylation levels and insulin signaling markers in DRG. Our findings show that insulin treatment ameliorates small fiber function by correcting methylation and insulin signaling. However, we show that insulin treatment fails to rescue large fiber deficit, which is mediated at least in part by hyperinsulinemia and systemic oxidative stress. Accordingly, these results suggest that in addition to metabolic control, restoring oxidative balance may represent an adjunct therapy to fully prevent PN in T1D.

Disclosure
S. Eid: None. L.M. Hinder: None. J.M. Hayes: None. F. Mendelson: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation.

Funding
American Diabetes Association (7-12-BS-045 to E.L.F.); JDRF; Rose C. and Nathan L. Milstein Family Emerging Scholar Fund; A. Alfred Taubman Medical Research Institute
537-P: Dietary Reversal Improves Peripheral Neuropathy and Gut Microbiota Profile in a Murine Model of Prediabetes and Obesity
Authors: GUO KAI , FIGUEROA-ROMERO CLAUDIA , EID STEPHANIE , HINDER LUCY M. , PETIT HAYLEY J. , HUR JUNGUK , FELDMAN EVA L. 
Published: June 2020

Gut microbiota has recently emerged as a major regulator of energy utilization, glycemia and immunological function. Disturbances in gut microbiota have been widely reported in obesity and type 2 diabetes (T2D). We have previously shown that dietary reversal (DR) alleviates peripheral neuropathy (PN), a common complication of obesity and T2D. However, the crosstalk between the microbiome, nerve function, and DR in PN remains unknown. Therefore, the objective of this study was to identify the changes in gut microbiome and correlate them with PN phenotypes during disease progression and reversal in a mouse model of obesity, prediabetes, and PN. The study consisted of five groups of C57BL6/J mice: mice were fed a standard diet (10% kcal fat; SD) or a high-fat diet (60% kcal fat; HFD) from 5-16 wk. of age, mice fed a SD or HFD from 5-24 wk., and mice fed a HFD from 5-16 wk. then switched to SD from 16-24 wk. (DR). Fecal samples were collected bi-weekly and gut tissue content at 16 or 24 wk along with metabolic and neuropathy phenotypes measured at the same time. Bacterial communities were profiled by 16S rRNA gene V3-V4 sequencing from cecum, colon, ileum, and fecal samples. Amplicon sequence variants were determined and taxonomically classified against the SILVA database. We observed significant changes in the gut microbial community structure soon after HFD was introduced, which was restored following DR. These changes were driven by bacterial families belonging to the Firmicutes (Lactobacillaceae and Clostridiales Family XIII), which were increased by HFD and subsequently decreased by DR. Notably, the distinct microbiota profiles were significantly correlated with HFD-induced PN and its reversal by DR. Our results provide new insights into the role of gut microbiota in the development of PN and highlight the potential therapeutic efficacy of a dietary intervention in restoring the microbiome and improving nerve function.

Disclosure
K. Guo: None. C. Figueroa-Romero: None. S. Eid: None. L.M. Hinder: None. H.J. Petit: None. J. Hur: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation.

Funding
National Institutes of Health (R24DK082841)
539-P: Time in Glucose Target Range Indicates the Risk of DPN in Chinese Type 1 Diabetes Patients
Authors: SHEN WENQI , LIU FANG 
Published: June 2020

Objective: Previous studies have indicated that in addition to poor glycemic control, glucose variability, obesity and hypertension may also have impacts on DPN in T2DM patients. Not much researches have been taken on T1DM patients. Our study aims to use the data derived from CGMs to assess the association between DPN and glucose variety as well as to find out the potential risk factors for DPN among T1DM patients.
Methods: In this cross-sectional study, a total of 116 type 1 diabetes inpatients were recruited. Patients age range from 14 to 75 years old. All patients were screened for DPN and then divided into 2 groups, DPN and non-DPN group. A 3-day CGMs was conducted on each patient. Information regarding BMI, smoking and drinking habits, medical history were collected from the patients’ medical record book.
Results: 1. Among the type 1 diabetes patients enrolled in our study, the average age is 47.8 years old, with a known diabetes duration of 9.56 years. 40 (34.48%) presented with DPN. The prevalence of DPN increased steadily with increasing duration of diabetes, from 12.1% in those diagnosed diabetes within 5 years to 53.7% in those have diabetes longer than 10 years.
2. Compared with the control group, DPN patients are older, have longer duration, higher BMI, waist circumstance, HbA1c, GA and lower TIR (p&lt;0.05). The prevalence of hypertension, carotid artery plaque, current drinking and smoking were higher in DPN group (p &lt; 0.05). Meanwhile, glucose variability, evaluated by SD and MAGE; insulin function are comparable between two groups(p&lt;0.05)
3. Multivariate logistic regression analysis showed that TIR quartiles(Q1: &gt;71%; Q2: 56-71%; Q3: 41-56%; Q4≤41%) (OR 2.18, CI 1.35-3.51, p =0.001) and duration (OR 1.17, CI 1.08-1.27, p &lt;0.001)were significantly correlating with DPN.
Discussion: In T1DM patients, glycemic variability is not a risk factor for DPN. TIR is a significantly independent risk factor for DPN. Components of the metabolic syndrome may also play an important role in the development of DPN.

Disclosure
W. Shen: None. F. Liu: None.
546-P: Effects of Metformin on Heart Rate Variability in Adolescents with Type 1 Diabetes: A Secondary Analysis of a Randomized Crossover-Controlled Trial
Authors: YANG DAIZHI , XU WEN , DENG HONGRONG , LV JING , YAN JINHUA , YAO BIN , WENG JIANPING 
Published: June 2020

Aims: Metformin might improve glycemic control in patients with T1D, but whether it has cardiovascular benefit is controversial. We aimed to investigate whether metformin improved cardiac autonomic neuropathy, as measured by heart rate variability (HRV), in patients with T1D.
Methods: This is a secondary analysis of a crossover, randomized trial conducted in adolescents with T1D inadequately controlled with insulin. Patients were randomly received metformin added on insulin for 24 weeks followed by insulin treatment alone for a subsequent 24 weeks or vice versa. The mean amplitude of glycemic excursions (MAGE) was obtained from CGM as a measure of glucose variability, while SD of beat-to-beat (NN) intervals (SDNN), SD of the average NN intervals calculated over 5 minutes (SDANN), the percentage of the interval differences of successive NN intervals greater than 50 ms (PNN50), the square root of the mean squared differences of successive NN intervals (RMSSD), low-frequency (LF) and high frequency (HF) power were assessed by 24-h Holter monitoring as measures of HRV.
Results: Seventeen patients with age 14.4±2.3 years, BMI 18.2±1.8 kg/m2, T1D duration 5.4±3.2 years and HbA1c 9.2±1.6% were enrolled. Changes in HbA1c, BMI, lipid profiles and MAGE were similar between groups. Compared with insulin monotherapy, metformin added on insulin markedly increased SDNN (between group difference [SE], 26.96 [11.77], P=0.034), SDANN (25.62 [12.12], P= 0.049), pNN50 (10.14 [3.05], P= 0.003) and HF (236.08 [83.21], P= 0.01). Changes in RMSSD and LF were not different between groups. In a multivariable regression analysis, the increase in SDNN remained significant after adjusting for ΔHbA1c, ΔMAGE and Δ systolic blood pressure (SBP) (β= 28.62, P= 0.039), suggesting the independent effect of metformin on SDNN.
Conclusions: In adolescent patients with T1D, metformin increased HRV despite no obvious effect on improvement in metabolic parameters.

Disclosure
D. Yang: None. W. Xu: None. H. Deng: None. J. Lv: None. J. Yan: None. B. Yao: None. J. Weng: None.

Funding
National Key Research and Development Program of China (2017YFC1309602); Science and Technology Planning Project of Guangdong Province (2017A020215142); Natural Science Foundation of Guangdong Province (2019A1515010979)
55-LB: Qualitative Results from Adults with Type 2 Diabetes Using the MyDay Smartphone App
Authors: JONAS VICTORIA H. , FISHMAN SARAH R. , SEARS MALKA , FANG RAN , ASMAN ARIELLE G. , SOLON CARLY A. , MENDEZ-RODRIGUEZ HEIDY , CRESPO-RAMOS GLADYS , HOOGENDOORN CLAIRE J. , MULVANEY SHELAGH A. , CRANDALL JILL P. , GONZALEZ JEFFREY S. 
Published: June 2020

Ecological momentary assessment (EMA) captures patients’ ongoing experiences in natural settings. In type 2 diabetes (T2D), EMA allows us to connect psychological experiences of illness with behavioral and biological processes. We implemented an EMA protocol to assess emotional distress, physical symptoms and diabetes self-care among predominantly ethnic minority and socioeconomically disadvantaged adults with T2D. We then collected qualitative data about patients’ experiences.
We recruited 51 English-speaking adults receiving treatment for T2D (M(SD), age = 54.3(9.7), 61% Black and 39% Hispanic, 67% female, HbA1c = 8.6(2.4%)), from an urban academic medical center. Patients completed EMA surveys (3/day) via the MyDay smartphone app and used an electronic pill cap that tracked oral medication adherence over 2 weeks. No feedback was provided from the devices. Semi-structured individual interviews were conducted upon study completion. Patients were asked about their experiences and any differences in their diabetes self-care. Interviews were audio-recorded, transcribed, and analyzed for content. A vast majority (88%) would recommend the MyDay app to others. For 90%, it took less than a few days to feel comfortable with the app. About 69% said the app positively influenced their self-care, via more consistent medication-taking and/or blood-glucose monitoring. Some participants (41%) indicated that they encountered a challenge with app use (e.g., lack of internet access, difficulty recalling instructions) and a few (14%) said they felt overwhelmed by study participation. Results suggest that the app was well-received and considered acceptable by a diverse sample who used it over 2 weeks. For some, using the app may have improved self-care. Future research may explore barriers such as limited internet access or technological literacy. This work provides support for the acceptability of technologies for assessing patients’ experience with T2D self-management.

Disclosure
V.H. Jonas: None. S.R. Fishman: None. M. Sears: None. R. Fang: None. A.G. Asman: None. C.A. Solon: None. H. Mendez-Rodriguez: None. G. Crespo-Ramos: None. C.J. Hoogendoorn: None. S.A. Mulvaney: None. J.P. Crandall: Research Support; Self; Abbott. J.S. Gonzalez: None.
550-P: Sudoscan in Combination with the Michigan Neuropathy Screening Instrument Questionnaire Is an Effective Tool for Screening for Diabetic Peripheral Neuropathy in Clinical Practice
Authors: OH TAE JUNG , KIM KYUHO , SHIN YUJIN , JANG HAK CHUL , CHOI SUNGHEE 
Published: June 2020

Background: Screening for diabetic peripheral neuropathy (DPN) is easily omitted in the busy clinical setting. SUDOSCAN is a non-invasive and convenient tool for evaluating small-fiber neuropathy, but its clinical effectiveness for screening of DPN is lacking. We investigated whether SUDOSCAN combined with a neuropathy questionnaire could be an effective tool for screening for DPN in people with type 2 diabetes.
Methods: We analysed the data for 197 people with type 2 diabetes without renal dysfunction or changes in their use of anti-hyperglycaemic medications during the past 3 months. The presence of DPN was evaluated using the Michigan Neuropathy Screening Instrument Physical Examination (MNSI-PE). Electrochemical skin conductance (ESC) of the feet was assessed using SUDOSCAN, and the MNSI Questionnaire (MNSI-Q) and 10-gram monofilament tests were conducted. We developed a scoring model including various combinations of clinical parameters and neuropathy examination results.
Results: The prevalence of DPN was 42.6%. Participants with DPN were older (59.9 ± 9.5 vs. 56.7 ± 8.8 years) and had a longer duration of diabetes than those without DPN. Feet ESC distinguished the presence of DPN, and the optimal cut-off value was 69.5 uS. The OR for the association between an abnormal feet ESC (&lt;70 uS) and the presence of DPN was 3.23 (95% CI 1.67, 6.42, p = 0.001). We made the DPN screening scores using the corresponding ORs for age, diabetes duration, and neuropathy evaluation. The MNSI-Q plus SUDOSCAN model (AUC 0.689), but not the MNSI-Q plus 10-gram monofilament model (AUC 0.668) showed better discrimination power than the MNSI-Q-only model (AUC 0.639).
Conclusions: The screening model for DPN that includes SUDOSCAN and the MNSI-Q can detect DPN with acceptable discrimination power and is more convenient than neurophysiological studies. This strategy may be useful in the busy outpatient clinical setting.

Disclosure
T. Oh: None. K. Kim: None. Y. Shin: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited. S. Choi: None.

Funding
Korean Diabetes Association (2016F-5)