bluuebunny/crossref_metadata_2025 huggingface dataset:
485-P: T Lymphocytes Infiltration in Kidneys of People with Type 2 Diabetes
Authors: KONG LINGYUN , ANDRIKOPOULOS SOF , MACISAAC RICHARD , TORKAMANI NILOUFAR , COUGHLAN MELINDA , POWER DAVID , MARIN EVELYN C. , MACKAY LAURA K. , EKINCI ELIF I.
Published: June 2020

Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes and is the leading cause of ESKD. The role of T lymphocytes in DKD remains unclear. We aimed to determine the distribution of T lymphocytes in renal biopsies in people with T2DM with varying degrees of kidney function and albuminuria. Fresh renal biopsy samples were provided by the Victorian Cancer Biobank at the time of surgery from individuals undergoing partial/complete nephrectomy or from people with diabetes who had a renal biopsy for clinical indications at Austin Health. Participants were divided into the following groups: Diabetic kidney disease group (DKD was diagnosed by clinical and histologic characteristics), nondiabetic and intact renal function (Control) (eGFR > 60ml/min/m2, no albuminuria) and nondiabetic kidney disease (NDKD) (eGFR < 60ml/min/m2, no history of diabetes). DKD group was further stratified into normo-, micro-, or macroalbuminuria groups. Sections were immunostained with CD3 antibody. Results showed higher level of creatinine, systolic blood pressure, and reduced level of eGFR, poor glycemic control in people with DKD and macroalbuminuria as compared with people without diabetes. T lymphocytes numbers were significantly increased in the interstitial compartment of people with T2DM and macroalbuminuria compared to those without diabetes, suggesting the immunopathologic role of T lymphocytes in the development of DKD.

Disclosure

L. Kong: None. S. Andrikopoulos: None. R. MacIsaac: None. N. Torkamani: None. M. Coughlan: None. D. Power: None. E.C. Marin: None. L.K. Mackay: None. E.I. Ekinci: None.
487-P: AI Prediction of Chronic Kidney Disease Stage Progression Combinations for Type 2 Diabetes Mellitus
Authors: MIYAMOTO KOHTAROH , KOSEKI AKIRA , KUDO MICHIHARU , MAKINO MASAKI , SUZUKI ATSUSHI
Published: June 2020

Chronic Kidney Disease (CKD) for type 2 diabetes mellitus (T2DM) is an increasingly serious issue worldwide. CKD stage is known to progress in stages where 1 is normal and 5 is the worst case of hemodialysis. We have previously reported on the accuracy of AI technology to target CKD stage 1 patients and predict the progression to stages 2 and above. Such prediction is targeted to help identify patients who require intensive care. Such study showed maximum 0.75 AUC score. In this study, we have extended our study to investigate all other stage combinations. For example, we can set our goal to answer questions such as: "Can AI technology accurately predict stage 2 patients progressing into stage 5 (hemodialysis)?"

We have investigated the EMR (Electronic Medical Record) of 64,059 type-2 diabetes patients who have visited the hospital. We have extracted 36 features, where 12 sources (e.g., Urine protein, albuminuria and eGFR) were selectively chosen by extraction from known literature and 3 types of values (mean, latest, SD) were calculated for each source. Period of 180 days range was scanned within 20% range (i.e., 180 days * 0.2 = 36 days). We balanced the label transition of each stage evenly by the number of data for each good label (no progress from current target stage) and bad label (progress from target to worse stage). We created a new prediction model for each combination (i.e., 1 to 2, 1 to 3, 1 to 4, 1 to 5, etc.) and performed cross validation by Logistic Regression to calculate the accuracy, F-Score and AUC.

All the combinations showed relatively good results. The range and average of each measurements were:

Accuracy 0.653 through 0.753 Average: 0.708.

F-Score 0.673 through 0.754 Average:0.719.

AUC 0.705 through 0.826 Average 0.770.

We applied AI techniques to create new predictive model which can detect the progression for all combinations of type-2 diabetes CKD stage progression. This model may contribute by a more effective and accurate intervention to reduce hemodialysis and cardiovascular events.

Disclosure

K. Miyamoto: None. A. Koseki: Employee; Self; IBM. M. Kudo: Employee; Self; IBM. M. Makino: None. A. Suzuki: Research Support; Self; Chugai Pharmaceutical Co., Ltd., Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
49-LB: “You Don’t Know When the Sugar’s Going to Kick In”: Experiences of People Managing Type 1 Diabetes during a Marathon
Authors: HUGHES ALLYSON , BISPHAM JEOFFREY , FULLER LILY , MCAULIFFE-FOGARTY ALICIA H.
Published: June 2020

There are many benefits of regular exercise in diabetes, but people with type 1 diabetes (T1D) also have the risk of short-term complications. There is a lack of research and information about how individuals with T1D should prepare and recover from endurance exercise. The present study had two primary objectives: 1) Understand how previous runners experienced participating in a marathon and 2) Understand their experience managing their diabetes while training for and recovering from a marathon. The study included 10 participants who had previously participated in the New York City Marathon with the Beyond Type 1 Team (mean age 33.3 ± 12.9 years, duration of T1D 13.2 ± 14.8 years, A1c 6.59 ± .7%), 80% female, 90% on insulin pump and 100% on CGM. Interviews were transcribed and thematically analyzed. Themes included (but are not limited to): methods to maintain euglycemia, preparation to reduce glycemic variability during endurance activities, and managing blood glucose variability during the marathon and recovery period. Diabetes devices were identified as a key theme given how integral they were to marathon preparation and performance. Multiple participants discussed using specific CGM and pump site placement to prevent the devices from falling off. Participants described various strategies to prevent hypoglycemia during their runs (both for training and the marathon). Some participants described frequent disruptions to their training plan due to diabetes and setting a higher target glucose to accommodate for the exercise. This data provides initial insight into the decision-making that occurs for people with T1D who participate in endurance activities - including food preparation, planning ahead for supplies and insulin manipulation, in-the-moment management decisions, and recovery period glucose management.

Disclosure

A. Hughes: None. J. Bispham: None. L. Fuller: None. A.H. Mcauliffe-Fogarty: None.
496-P: Risk Factors for Incident CKD in Prediabetes
Authors: HENNESSEY KELLY A. , DARATHA KENN B. , ALICIC RADICA Z. , JONES CAMI , NEUMILLER JOSHUA J. , DURU O. KENRIK , NICHOLAS SUSANNE , MCPHERSON STERLING M. , NORRIS KEITH C. , TUTTLE KATHERINE R.
Published: June 2020

The magnitude of risk for chronic kidney disease (CKD) in prediabetes is unclear. The study aim was to determine CKD incidence and risk factors in patients with prediabetes from the CURE-CKD registry of electronic health record data from >2.6 million patients with or at-risk for CKD.

Adults with prediabetes were identified by established criteria for %A1C, random and fasting blood glycemia, and administrative codes. CKD was defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 or urine albumin-to-creatinine ratio >30 mg/g based upon two or more measurements >90 days apart and administrative codes. Cox proportional hazards regression was used to predict incident CKD.

From 2006 to 2017, there were 544,253 patients with prediabetes and no CKD. Baseline A1C was 5.9±0.3% (mean±SD) and eGFR was 90.7±16.8 mL/min/1.73 m2. Notable medication use was: NSAIDs n=110,964 (20%), PPIs n=49,916 (9%), and ACEi/ARB n=63,738 (12%). Incident CKD occurred (n=59,583) at a rate of 25.2/1,000 person-years with mean time to CKD of 2.9 years. Older age, female gender, Hispanic/Latinx, Black, Native Hawaiian and Other Pacific Islander race/ethnicity, lower eGFR, PPI and ACEi/ARB use were associated with higher hazards of CKD in prediabetes (Table 1).

Incident CKD is common in prediabetes with risk factors similar to those in diabetes. CKD screening and detection with a focus on kidney protection may offer novel opportunities to reduce CKD risk in prediabetes.

Disclosure

K.A. Hennessey: None. K.B. Daratha: None. R.Z. Alicic: None. C. Jones: None. J.J. Neumiller: None. O. Duru: None. S. Nicholas: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Centers for Disease Control and Prevention, George Institute for Global Health, Goldfinch Bio, Inc., National Institutes of Health. S.M. McPherson: None. K.C. Norris: None. K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc.
504-P: Albuminuria Affects Prevention of Diabetic Kidney Disease Progression by Sodium–Glucose Transporter 2 Inhibitor
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: June 2020

Objective: In type 2 diabetes(T2D), prevalence of chronic kidney disease (CKD) with normoalbuminuria is increasing. We assessed the annual eGFR decline rate (slope) in Japanese patients with T2D with CKD treated by sodium glucose transporter 2 inhibitor (SGLT2i).

Methods: A total of 75 patients with T2D with CKD (eGFR<60ml/min/1.73m2) were recruited, whose initial eGFR slopes were calculated from 46±21 months period, and slopes after adding SGLT2 inhibitors (on empagliflozin 64% and others) were calculated from 21±8 months. Efficacy was compared between in patients with normo-/micro-alubuminuria (Norm/Micro) and with macroalbuminuria (Macro). Patients with Norm/Micro existed in 52% (39/75). At the time of recruitment, distribution in CKD stages are as follows, on stage 3A; eGFR 45-59 (21 vs. 8), stage 3B; eGFR 30-44, (13 vs. 15) and stage 4; eGFR<30 (5 vs. 13) respectively. Average age was 70.7±12.2 years old and duration of diabetes was 15.0±9.3 years.

Results: 1) Average initial (first month) eGFR drop values are as follows, in Norm/Micro (51.2 to 47.9ml/min/1.73m2: P<0.01), in Macro (40.7 to 39.0ml/min/1.73m2: P=0.01). 2) Annual mean eGFR slopes were improved in each group, in Norm/Micro (-4.3±4.0 to -1.2±4.1ml/min/1.73m2/year; P<0.001), and in Macro (-8.9±12.2 to -2.3±3.6ml/min/1.73m2/year; P<0.01). 3) Proportion of showing reduction of eGFR slopes after adding SGLT2i are 69.2% (27/39) and 75.0% (27/36), respectively. And even in stage 4, 80.0% (4/5) and 76.9% (10/13), respectively. 4) Rapid decliner of eGFR (>10 ml/min/1.73m2/year) existed in 12.8% (5/39) and in 25.0% (9/36) respectively. Mean eGFR slopes in these rapid decliner were all improved and as follow, -12.2±2.1 to +1.2±3.4ml/min/1.73m2/year; P<0.001 and -22.3±19.0 to -1.6±4.0ml/min/1.73m2/year; P<0.01, respectively.

Conclusion: SGLT2i could still have a remarkable renal benefit in Norm/Micro diabetic kidney disease. Slope analysis might be useful for safety and detecting rapid eGFR decliner.

Disclosure

K. Kashima: None. H. Shimizu: None. M. Yamada: None.
506-P: Hepatic Fibrosis but Not Steatosis Is Associated with Diabetic Kidney Disease in Nonobese Patients with Type 2 Diabetes
Authors: SEO DA HEA , CHO YONGIN , AHN SEONG HEE , HONG SEONGBIN , LEE YONG-HO , CHOI YOUNGJU , HUH BYOUNG WOOK , HUH KAP BUM , KIM SO HUN
Published: June 2020

Background: Recent studies investigated the association between nonalcoholic fatty liver disease (NAFLD) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) but the results are inconclusive. Here we aimed to investigate the effect of obesity on the association between NAFLD and DKD in a large cohort of participants with T2DM.

Methods: In this cross-sectional study, a total of 3,439 patients (1,710 men and 1,729 women) with T2DM were recruited from the Seoul Metabolic Syndrome cohort between 2003 and 2016. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver diseases. Advanced fibrosis was defined as FIB4 index ≥ 1.45. DKD was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2.

Results: The mean age was 57.4 ± 10.3 years and duration of diabetes was 7.7 ± 7.1 years. Two hundred and fifty subjects (7.3%) had DKD and 1869 (54.3%) subjects had NAFLD. The prevalence of DKD were 7.0%, 4.5% and 11.9% in no-NAFLD group, liver steatosis only group and advanced fibrosis group respectively (p<0.001). Advanced fibrosis was independently associated with an increased risk of DKD (odds ratio [OR] 1.75; 95% confidence interval [CI] 1.08-2.86; p = 0.034) compared to no NAFLD after adjustment for potential confounders in patients with BMI < 25 kg/m2. However, the association between advanced fibrosis and DKD was not significant in those with BMI ≥ 25 kg/m2. There was no significant associated between hepatic steatosis without advanced fibrosis with DKD regardless of obesity status.

Conclusion: This study suggests that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of DKD in non-obese patients with T2DM.

Disclosure

D. Seo: None. Y. Cho: None. S. Ahn: None. S. Hong: None. Y. Lee: None. Y. Choi: None. B. Huh: None. K. Huh: None. S. Kim: None.
508-P: Single and Joint Impact of Type 2 Diabetes and of Congestive Heart Failure on Albuminuria
Authors: MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , SPRENGER LUKAS , LEIHERER ANDREAS , PURIN DANIELA , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2020

Albuminuria is a characteristic feature of diabetic nephropathy, and urine albumin excretion is also increased in patients with congestive heart failure (CHF). However, no data are available on the single and joint associations of type 2 diabetes (T2DM) and CHF with albuminuria. This issue therefore was addressed in the present study. We investigated 181 patients with CHF, of whom 84 had T2DM (CHF+/T2DM+) and 97 did not have diabetes (CHF+/T2DM-) and 413 controls without CHF, of whom 79 had T2DM (CHF-/T2DM+) and 334 did not have diabetes (CHF-/T2DM-). The albumin/creatinine ratio (ACR) was 34±117 in CHF-/T2DM- patients. Compared to this group it was higher in CHF-/T2DM+ patients (56±110; p=0,002), in CHF+/T2DM- patients (98±311; p<0,001) and in CHF+/T2DM+ patients (286±779; p<0,001), in whom in turn it was higher than in CHF-/T2DM+ (p<0,001) or in CHF+/T2DM- (p=0,001) patients. The ACR did not differ significantly between CHF-/T2DM+ and CHF+/T2DM- patients (p=0,345). In multivariate analysis of covariance, T2DM and CHF proved to be independent predictors of the ACR after adjustment for age, sex, body mass index, LDL-C, smoking and hypertension (F=6,392; p=0,012 and F=13,14; p=<0,001, respectively). We conclude that T2DM and CHF are mutually independent determinants of albuminuria.

Disclosure

M. Maechler: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Sprenger: None. A. Leiherer: None. D. Purin: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
51-LB: Young Adults with T1DM: Is Fear a Mediator between Self-Efficacy and Quality of Life?
Authors: KENT DENISE A. , PARK CHANG G. , FRITSCHI CYNTHIA , QUINN LAURIE T.
Published: June 2020

It has been reported that the many demands of young adulthood in addition to the complex treatment regimen required to manage T1DM impacts quality of life (QoL). It has also been stated in the literature that self-efficacy (SE), fear of complications (FOC) and fear of hypoglycemia (FOH) are predictive of quality of life. However, is fear a mediator in the relationship between SE and QoL? The literature to no extent has reported on whether FOC and FOH mediate the relationship between SE and QoL. Therefore, the aim of this study was to determine if fear mediates the relationship between SE and QoL in young adults with T1DM. This descriptive, cross-sectional study examined SE among young adults with T1DM. The subjects included 201 young adults (age: 27.4 ± 5; gender: 163(F) 38 (M); A1C: 7.4 ± 1.5%; age of diagnosis: 14 ± 8 years). The subjects completed a general health survey and six self-report instruments accessed via the web including the Diabetes Knowledge Test (DKT), Hypoglycemia Fear Scale (HFS), the Fear of Complications Questionnaire (FCQ), Self-Efficacy for Diabetes Self-Management (SEDM), the Diabetes Behavior Rating Scale (DBRS), the Diabetes Quality of Life Measure (DQoL). This study explored the relationship between SE and QoL and found the FOC and FOH significantly mediated the relationship between SE and QoL (p<.000). This study suggests that although the higher ones SE is, the higher the reported QoL is, FOC and FOH impact this relationship when present. The young adults in this study reported a high level of fear centered around complications from their diabetes as well as fear of hypoglycemia in trying to maintain tight glucose control. Therefore, it is important for researchers and clinicians working to improve QoL in young adults to consider mediating factors such as FOC and FOH when designing interventions aimed to impact QoL.

Disclosure

D.A. Kent: None. C.G. Park: None. C. Fritschi: None. L.T. Quinn: None.
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<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<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<0.0001), mean triglycerides 1.21 (95% 1.14-1.28, p<0.0001), mean systolic blood pressure (SBP) 1.21 (95% 1.10-1.33, p<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 >89 mg/dL (>1.0 mmol/L), total cholesterol >193 mg/dL (>5.0 mmol/L), LDL >135 mg/dL (>3.5 mmol/L) and BMI >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<0.05). The prevalence of hypertension, carotid artery plaque, current drinking and smoking were higher in DPN group (p < 0.05). Meanwhile, glucose variability, evaluated by SD and MAGE; insulin function are comparable between two groups(p<0.05)

3. Multivariate logistic regression analysis showed that TIR quartiles(Q1: >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 <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 (<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)
554-P: Dapagliflozin and Measures of Cardiovascular Autonomic Function in Patients with Type 2 Diabetes
Authors: ANG LYNN , KIDWELL KELLEY M. , REISS JACOB , DILLON BRENDAN R. , MIZOKAMI-STOUT KARA R. , LEONE VIRGINIA A. , POP-BUSUI RODICA
Published: June 2020

Beneficial effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes (T2D) have been reported. We hypothesized that these benefits may be due to modulatory effects on the sympathetic/parasympathetic imbalance through blunting of the expected compensatory increase in heart rate associated with lowering blood pressure. We aimed to evaluate the effect of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN) in patients with T2D. We performed a pilot, randomized, 2-period crossover clinical trial comparing 12 weeks of glucose lowering intervention with DAPA versus glimepiride on measures of CAN [cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV)] assessed at baseline and end of each drug period. Signed rank tests and mixed models were used to evaluate the differences in CARTs and HRV indices from baseline to 12 weeks between each drug period. Preliminary data are presented for forty-one participants with T2D on metformin monotherapy (mean age 57±8 years, mean diabetes duration 7±6 years, mean HbA1c 7.8±1.3%) at baseline. Although there were no significant differences in indices of CAN in each drug period, there was a trend for higher expiration and inspiration ratio on DAPA compared to glimepiride (mean change 0.02±0.10; p=0.07). We found significant or near significant interactions between sex and treatment for the root mean square of the differences of successive RR intervals (rmsSD) (p=0.021) and Valsalva ratio (p=0.06) in women on DAPA versus glimepiride compared with men. In women, the mean 12-week change for both measures on DAPA was larger than the mean change on glimepiride, whereas in men, the mean 12-week change was larger on glimepiride than DAPA. These preliminary short-term data suggest that DAPA may have beneficial effects on measures of CAN particularly in women with T2D. These findings need to be confirmed in larger prospective studies with longer follow-up.

Disclosure

L. Ang: None. K.M. Kidwell: None. J. Reiss: None. B.R. Dillon: None. K.R. Mizokami-Stout: None. V.A. Leone: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association.
557-P: Gastric Electrical Neurostimulation Combined with Pyloroplasty for Refractory Diabetic Gastroparesis Improves Subjective and Objective Outcomes
Authors: BRIGHT TAMIS , SAROSIEK IRENE , SHANKER AARON , DAVIS BRIAN R. , PADILLA OSVALDO , DIAZ JESUS R. , ESPINO KARINA , MCCALLUM RICHARD M.
Published: June 2020

Background: Gastric electrical stimulation (GES) improves symptoms in diabetic gastroparesis (DM GP) refractory to medical therapies but does not increase gastric emptying (GE). This study investigates the clinical outcomes of GES combined with pyloroplasty (PP) to improve GE as well as the pathophysiological characteristics of the responding patients.

Methods: Overall 39 DM (13 type I) GP patients with 16.6 (range 3-50) years of DM had GES with PP. Antral and pyloric biopsies were assessed for interstitial cells of Cajal (ICC) status. Depletion of ICC was defined as <10 cells/HPF. GE scintigraphy (normal <60% retention at 2h or <10% at 4 h) was performed, and GP total symptoms score (TTS) of vomiting, nausea, early satiety, bloating, fullness and epigastric pain was assessed with a 5-point Likert scale pre and post-surgery.

Results: The 39 patients, (23F) mean age 45 (25-83) years, mean 5.2 years of GP symptoms, were enrolled. TSS improvement after mean follow up of 17 (1-42) months post-surgery was 62% (19.1±3.4) vs.(7.6±6.2), while almost 70% of patients improved TTS by ≥60%. GE at 2h improved from 77% to 45%, and from 55% to 20% at 4h while 47% completely normalized their GE. Both DM1 and DM2 patients responded with improved TSS and GE. Antral ICC were depleted in 28% of DM GP with a mean number of 12 (±5.2)/HPF, while 70% of patients had <10 pyloric ICC with mean 7.4(±5.0)/HPF. Patients with <10 pyloric ICC had a 64% improvement in TSS vs. 41% if pyloric ICC was ≥10/HPF.

Conclusion: DM GP patients treated by combining GES and PP show significant symptomatic improvement with accelerated and often normalized GE. Patients with depleted pyloric ICC were the most improved, emphasizing the key role of the pylorus in GP, and explains why adding PP to GES addresses the specific pathophysiological challenges in severe diabetic GP.

Disclosure

T. Bright: None. I. Sarosiek: None. A. Shanker: None. B.R. Davis: None. O. Padilla: None. J.R. Diaz: None. K. Espino: None. R.M. McCallum: None.
567-P: The Neutrophil-to-Lymphocyte Ratio as a Biomarker of Diabetic Retinopathy: A Cross-Sectional Study
Authors: LI MEI , TANG XIXIANG , TAN YING , NIE YUANPENG , LI HAICHENG , CHEN YANMING
Published: June 2020

Aims: Diabetic retinopathy (DR) is one of the most prevalent complications, which causes visual impairment and vision loss in diabetic patients. It has been demonstrated that inflammation plays an important role in DR. Accumulating evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a novel potential marker for determining the inflammatory state. We aimed to evaluate the correlation between the NLR and DR.

Methods: We performed a cross-sectional study involving 1658 patients with type 2 diabetic mellitus (T2DM) at the Third Affiliated Hospital of Sun Yat-sen University from January 2016 to December 2018. All these subjects underwent stereo fundus photography taken by a 45° Non-Mydriatic Fundus Camera (CR6-45NM, Canon, Tokyo, Japan) through undilated pupils, and physical examinations including body mass index (BMI), systolic and diastolic blood pressures (SBP and DBP). Laboratory tests were also performed to determine the levels of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), serum creatinine (Scr), blood urea nitrogen (BUN), and glycosylated hemoglobin A1c (HbA1c). The NLR was calculated based on the absolute numbers of neutrophils and lymphocytes.

Results: 214 of the patients had DR. The age, DM duration, NLR, SBP were significantly higher in patients with DR compared with patients without DR (p < 0.01). After the adjustments by multivariable analyses, the NLR was still significantly associated with DR (P=0.048, OR=1.088, 95% CI=1.001-1.182).

Conclusion: Our finding reveals that higher NLR values are a reliable biomarker for the occurrence of DR.

Disclosure

M. Li: None. X. Tang: None. Y. Tan: None. Y. Nie: None. H. Li: None. Y. Chen: None.

Funding

Research and Development Plans in Key Areas of Guangdong Province (2019B020227003); National Natural Science Foundation of China (81770826); National Key Research and Development Program of China (2017YFA0105803)