bluuebunny/crossref_metadata_2025 huggingface dataset:
510-P: Serum Mac-2 Binding Protein Is Associated with Diabetic Micro- and Macroangiopathy in People with Type 2 Diabetes
Authors: HASHIMOTO YOSHITAKA , HAMAGUCHI MASAHIDE , FUKUI MICHIAKI
Published: June 2020

A close relationship between type 2 diabetes and nonalcoholic fatty liver disease, including liver fibrosis, has been reported. Mac-2 binding protein glycosylation isomer (M2BPGi) is reported as a non-invasive new serological glyco-biomarker for liver fibrosis. The purpose of this cross-sectional study was to investigate the association between serum M2BPGi levels and diabetic complications in people with type 2 diabetes. Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normo-, micro-, or macroalbuminuria. Retinopathy was divided into three groups: no- (NDR), simple- (SDR), or proliferative diabetic retinopathy (PDR). Mean age for 363 people (212 males) was 66.4 (10.6) years, the median M2BPGi level was 0.77 (0.57-1.04) C.O.I., and the median UAE was 22 (9-82.1) mg/g Cr. Serum M2BPGi level was increased with levels of diabetic microangiopathy. Furthermore, the M2BPGi levels in people with a history of cardiovascular diseases were higher than that in people without (0.82 [0.65-1.22] vs. 0.76 [0.55-1.03] C.O.I., p = 0.019). The logarithm of M2BPGi was associated with the logarithm of UAE after adjusting for covariates (β = 0.107, p = 0.031). This study reveals a close association between serum M2BPGi levels and diabetic micro- and macroangiopathy in people with type 2 diabetes.

Disclosure

Y. Hashimoto: None. M. Hamaguchi: None. M. Fukui: None.
515-P: Nonalbuminuric Diabetic Kidney Disease in Type 1 Diabetes: Incidence of Major Vascular Outcomes over a 10-Year Follow-Up
Authors: GAROFOLO MONIA , GUALDANI ELISA , CAMPI FABRIZIO , ARAGONA MICHELE , LUCCHESI DANIELA , BIANCHI CRISTINA , MICCOLI ROBERTO , FRANCESCONI PAOLO , PENNO GIUSEPPE , PRATO STEFANO DEL
Published: June 2020

Non-albuminuric diabetic kidney disease (Alb-DKD) has been associated with a raised risk of CV outcomes and all-cause mortality in T1D. We report about the association between DKD phenotypes and CV outcomes in a single-centre, prospective, 10.4±2.9 years observation of 774 T1D. Rates of outcomes and vital status were censored on December 2017. Out of 774 T1D, 692 (89.4%) had no-DKD, 53 DKD 1-2 (6.8%), 17 (2.2%) Alb-DKD and 12 (1.6%) Alb+DKD. Incidences of CV outcomes, coronary events and ESRD were available for 736 subjects (95.1%). A CV event occurred in 49 T1D (6.7%; 6.42 events x 1000 PYs), rising from no-DKD (4.2%) to DKD 1-2 (28.6%) and Alb-DKD (35.3%). In Alb+DKD, due to competition with all-cause death, only 1 event occurred. Compared to no-DKD, the adjusted HRs were 4.43 (95%CI 2.27-8.61, p<0.0001) in DKD 1-2 and 3.44 (1.34-8.81, p=0.010) in Alb-DKD. After further adjustment for prior CVD, the HR was fully preserved for DKD 1-2 (p<0.0001), but attenuated for Alb-DKD (p=0.064). A coronary event occurred in 35 T1D (4.8%; 4.54 events x1000 PYs), rising from 3.0% in no-DKD to 18.4% in DKD 1-2 and 29.4% in Alb-DKD. Compared to no-DKD, the adjusted HRs were 3.85 (1.72-8.65, p=0.001) in DKD 1-2 and 4.75 (1.66-13.56, p=0.004) in Alb-DKD. After adjustment for prior CVD, the HRs were preserved for both DKD 1-2 (p<0.0001) and Alb-DKD (p=0.016). Only 11 subjects developed ESRD (1.5%): 0.9% in no-DKD, 2.0% in DKD 1-2, 17.6% in Alb-DKD and 10.0% in Alb+DKD. Compared to no-DKD, the risk of ESRD raised only in Alb-DKD (HR 6.59, 95%CI 1.31-33.20, p=0.022). After adjustment for prior CVD, this HR was 5.26 (p=0.058). Compared to no-DKD, the risk of death was increased to the same extent of about four-five fold in Alb-DKD and Alb+DKD (p<0.0001). In T1D, Alb-DKD was independently associated to a raised rate of CV, mainly coronary, morbidity. Though preliminary, our data do not to confirm Alb-DKD does not increase risk of ESRD. This DKD phenotype deserves intensive prevention strategies.

Disclosure

M. Garofolo: None. E. Gualdani: None. F. Campi: None. M. Aragona: None. D. Lucchesi: None. C. Bianchi: None. R. Miccoli: None. P. Francesconi: None. G. Penno: None. S. Del Prato: Advisory Panel; Self; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Takeda Pharmaceutical Company Limited.
516-P: Urine Metabolite Biomarkers Predict Progression of Diabetic Nephropathy in 2,531 Individuals with Type 1 Diabetes
Authors: MUTTER STEFAN , VALO ERKKA A. , AITTOMÄKI VILJAMI , FORSBLOM CAROL , GROOP PER-HENRIK , WURTZ PETER ,   FINNISH DIABETIC NEPHROPATHY STUDY GROUP
Published: June 2020

People living with type 1 diabetes have increased risk to develop diabetic nephropathy. No targeted cure exists, but the progression can be slowed down if detected early. We tested whether metabolic biomarkers measured in urine could predict progression of diabetic nephropathy (DN) in the Finnish nationwide FinnDiane Study.

At baseline, 18 urine metabolites were measured with nuclear magnetic resonance metabolomics and scaled relative to urine creatinine. Individuals were followed for DN status for 9.0 years (± 5.1 years) until they progressed to their most severe DN status (334 events) or the latest known DN status for non-progressors. A Bonferroni-corrected P<0.003 was considered significant.

Five out of 18 urine metabolites were robustly associated with risk for DN progression in Cox regression models adjusted for sex, year of diabetes diagnosis as well as baseline age, DN status, BMI and eGFR. Individuals with elevated urinary levels of alanine (Hazard Ratio (HR) = 1.49 [1.26, 1.77] per 1-SD creatinine-scaled metabolite concentration, , P=3×10-6), valine (HR = 1.34 [1.22, 1.48], P=4×10-9), 2–hydroxyisobutyrate (HR = 1.48 [1.30, 1.67], P=1×10-9), cis-Aconitate (HR = 1.17 [1.06, 1.28], P=9×10-4) and pseudouridine (HR = 1.45 [1.24, 1.69], P=4×10-6) showed higher DN progression rate.

We conclude that urinary biomarkers are indicative of kidney disease progression in type 1 diabetes, independently of baseline microalbuminuria and eGFR. The urinary biomarkers span multiple metabolic pathways, including microbial metabolism, citric acid cycle, and amino acids reflecting adiposity and dietary quality.

Disclosure

S. Mutter: None. E.A. Valo: None. V. Aittomäki: Employee; Self; Nightingale Health Ltd. Other Relationship; Self; Nightingale Health Ltd. C. Forsblom: None. P. Groop: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi, Sanofi. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medscape, Merck Sharp & Dohme Corp., Mundipharma International. P. Wurtz: Employee; Self; Nightingale Health Ltd. Stock/Shareholder; Self; Nightingale Health Ltd.

Funding

Folkhälsan Finland; Novo Nordisk Foundation; Academy of Finland
518-P: Association between Plasma Metabolites in the Urea Cycle and Diabetic Kidney Disease (DKD) in a Japanese Population
Authors: YAMAMOTO MASAHIKO , HARADA SEI , OKAMURA TOMONORI , FUJIHARA KAZUYA , YAGUCHI YUTA , KOMATSU TAKESHI , SATO TAKAAKI , KITAZAWA MASARU , YAMADA MAYUKO H. , KANEKO MASANORI , OSAWA TAEKO , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO , TAKEBAYASHI TORU
Published: June 2020

Some plasma metabolites in the urea cycle were reportedly associated with DKD, although results were inconsistent among studies. Also, few studies examined the association between urea cycle metabolites and DKD in community dwellers. To address this, we used the metabolite database from the Tsuruoka Metabolomics Cohort Study, which had global metabolomics in Japan, using capillary electrophoresis-mass spectrometry. Among 10,933 participants, cross-sectionally analyzed were 1,005 who had diabetes mellitus (DM) defined by HbA1c ≥6.5%, and/or fasting blood glucose ≥126 mg/dl and/or antidiabetic drug use. Of these 231 had DKD, which was defined by eGFR <60 ml/min and/or test-strip positive proteinuria. Individuals with DKD (163 men, 68 women, mean age 66 y, mean HbA1c 6.8±1.2%, mean BMI 25.4±4.0) were significantly older than those without (508 men, 266 women, mean age 64 y, mean HbA1c 6.8±0.9%, mean BMI 25.0±3.7). Univariate and multivariate logistic regression models were used to identify the association between plasma metabolites (aspartic acid [Asp], citrulline, symmetric dimethylarginine [SDMA] and ornithine) and DKD in DM patients. We found that urea cycle metabolites were associated with DKD even after adjustment for possible confounders: age, sex, BMI, alcohol intake, smoking habit, energy intake and history of hypertension or dyslipidemia. Odds ratios (ORs) per 1 SD increase in Asp, citrulline, SDMA and ornithine for DKD were 1.24 (95% confidence interval [CI], 1.01-1.53), 1.80 (1.53-2.13), 1.52 (1.30-1.79) and 1.09 (0.95-1.25) as continuous variables, respectively. For sensitivity analyses, participants were divided into quartile groups for each metabolite. Multivariate logistic regression analyses between each metabolite quartile group and DKD showed similar results as above. These results may enable early detection of DKD or clarify the pathophysiology of DKD although a prospective study remains necessary.

Disclosure

M. Yamamoto: None. S. Harada: None. T. Okamura: None. K. Fujihara: None. Y. Yaguchi: None. T. Komatsu: None. T. Sato: None. M. Kitazawa: None. M.H. Yamada: None. M. Kaneko: None. T. Osawa: None. Y. Matsubayashi: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. T. Takebayashi: None.
52-LB: Provider Communication in Black Patients with T2DM Is Associated with Glycemic Control
Authors: REID HADLEY , LIN OLIVIA , FABBRO REBECCA L. , OLSEN MAREN , CHUNG SANGYUN T. , JOHNSON KIMBERLY S. , BATCH BRYAN
Published: June 2020

Non-Hispanic Blacks (NHB) have a higher burden of T2DM and experience worse outcomes than Non-Hispanic Whites (NHW). Patient and system factors do not fully explain these disparities. We conducted a cross-sectional study of NHB and NHW with T2DM receiving care in 34 primary care practices. We examined the association between HbA1c (glycemic control), patient race, and the Interpersonal Processes of Care survey (IPC) which is divided into 7 subdomains describing the patient-provider relationship. These include hurried communication, elicited concerns and responded, explained results and medications, patient-centered decision making, compassionate and respectful, discriminated, and disrespectful office staff. We used adjusted linear regression to examine association between IPC subdomains, HbA1c and race. Due to large ceiling and floor effects we dichotomized IPC subdomains to the strongest endorsement and at least one answer that was not the strongest endorsement.

A total of 106 NHW and 115 NHB completed the study. The mean age of participants was 64.4 and 55% were female. The average HbA1c of the sample was 7.3%; 7.4% for NHB and 7.3% for NHW. There were no significant main effects of the IPC subscales; however, we found statistically significant race interactions for two of the IPC subscales. The HbA1c was on average 0.45% lower [-1, 0.1] among NHB who reported no hurried communication versus NHB who reported some hurried communication (p=0.48). Similarly, HbA1c was on average 0.64% lower [-1.19, -0.08] among NHB who fully endorsed that their providers explained results and medications compared to those who did not (p=0.01). The relationship between these subdomains and improved glycemic control was not observed in NHW.

These findings indicate that hurried communication and lack of explanation may contribute to worse glycemic control in NHB. Interventions aimed at improving these aspects of the patient-provider relationship may reduce racial disparities in glycemic control.

Disclosure

H. Reid: None. O. Lin: None. R.L. Fabbro: None. M. Olsen: None. S.T. Chung: None. K.S. Johnson: None. B. Batch: None.

Funding

National Center for Advancing Translational Sciences (TL1TR002555)
52-OR: Mitophagy Forms a Protective Response to Inflammatory Damage in Pancreatic ß-Cells
Authors: SIDARALA VAIBHAV , SOLEIMANPOUR SCOTT
Published: June 2020

Inflammatory damage contributes to beta cell failure in all forms of diabetes, yet few protective responses to inflammation have been described. Mitochondria are a frequent target of inflammatory β-cell damage, thus impairing bioenergetics and initiating the pro-apoptotic machinery. Thus, we hypothesized that clearance of damaged mitochondria by mitophagy is a necessary protective response for inflammatory β-cell damage. Utilizing live-cell imaging, biochemical assays, and in vivo mitophagy biosensors, we observed that pro-inflammatory cytokines promote trafficking of damaged mitochondria through the mitophagy pathway in mouse and human islets. Cytokine treatment dissipated mitochondrial membrane potential, decreased cellular respiration, induced recruitment of the mitophagy initiator Parkin, activated turnover of mitochondrial proteins, and ultimately, targeted damaged mitochondria to lysosomes for clearance. To determine if mitophagy acts as a protective response, we assessed the role of pro-inflammatory agents in mice deficient for T1D gene and mitophagy regulator Clec16a in β-cells. Indeed, Clec16a-deficient β-cells had increased cytokine-mediated apoptosis and worsening hyperglycemia after streptozotocin treatment in vivo as well as an accumulation of fragmented, damaged mitochondria. To explore mechanisms by which mitophagy contributes to cytokine-mediated toxicity, we found that reactive O2 species and nitric oxide (NO) activate mitophagy and that mitophagy-deficient mouse and human islets treated with anti-oxidants or NO inhibitors ameliorated β-cell death. Finally, we observed that adenoviral overexpression of Clec16a rescued cytokine-induced apoptosis in human islets. Together, our studies position mitophagy as a crucial protective response to inflammatory β-cell demise activated by both oxidative and nitrosative stress, which could be targeted to prevent β-cell death in diabetes.

Disclosure

V. Sidarala: None. S. Soleimanpour: None.
525-P: Impact of Extracellular-to-Intracellular Fluid Volume Ratio on Albuminuria in People with Type 2 Diabetes: A Cross-Sectional and Retrospective Cohort Study
Authors: NAKAJIMA HANAKO , HASHIMOTO YOSHITAKA , SENMARU TAKAFUMI , OKADA HIROSHI , HAMAGUCHI MASAHIDE , FUKUI MICHIAKI
Published: June 2020

Body fluid volume imbalance is common in patients with kidney failure and is associated with all-cause mortality. We hypothesized that fluid volume imbalance occurs in diabetic patients without kidney failure and is associated with albuminuria. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes without kidney failure. Body fluid imbalance was determined by measuring the extracellular water to intracellular water ratio (ECW/ICW) using bioelectrical impedance analysis. In the cross-sectional study of 432 participants, ECW/ICW increased with level of albuminuria (0.634 ± 0.002 in normo-, 0.645 ± 0.003 in micro- and 0.656 ± 0.004 in macroalbuminuria, all p <0.001 by Tukey’s HSD test). The log-transformed urinary ACR was associated with elevated ECW/ICW ratio (r =0.313, p <0.001) (Figure). In addition, there was an association between ECW/ICW ratio and logarithms urinary ACR after adjusting for covariates (β = 0.217, p <0.001) by multiple regression analysis. Moreover, in the retrospective studies of 368 participants, ECW/ICW was associated with change in the urinary ACR after adjusting for covariates (β = 0.171, p = 0.005) by multiple regression analysis. This reinforces the importance of monitoring fluid balance in diabetic patients.

Disclosure

H. Nakajima: None. Y. Hashimoto: None. T. Senmaru: None. H. Okada: None. M. Hamaguchi: None. M. Fukui: None.
530-P: Longitudinal Characterization of Peripheral Neuropathy in a Cafeteria Diet and Low-Dose Streptozotocin Rat Model of Type 2 Diabetes
Authors: HOSSAIN MD JAKIR , KENDIG MICHAEL D. , WILD BRANDON M. , MORRIS MARGARET J. , ARNOLD RIA
Published: June 2020

Diabetic peripheral neuropathy is a major complication of diabetes with complex and incompletely understood pathophysiology. We utilised a cafeteria-style diet (Caf) and low dose streptozotocin (STZ) to model varying degrees of hyperglycemia. Adult male Sprague-Dawley rats were divided into four groups: control (chow diet), prediabetic (Caf diet for 21 weeks), diet reversal (13 weeks Caf diet then 8 weeks chow; all n=12) and type 2 diabetic (T2D - Caf+STZ 25mg/kg i.p, n=24). STZ was administered after 5 weeks of diet; one week later, non-fasted blood glucose was 16.09 ± 1.19 [SEM] and 78% of T2D rats had glucose levels ≥10mmol/L. Metabolic phenotyping revealed significantly increased body weight, fat mass, fasting blood HDL cholesterol, plasma insulin and impaired glucose tolerance in both prediabetic and T2D rats compared to controls; fasting glucose and HbA1c were significantly elevated only in T2D. Neuropathy phenotyping included sensory behavioural testing (thermal and mechanical nociceptive sensibility) and electrophysiology (nerve conduction studies and nerve excitability) which were assessed at two timepoints, early (8-11 weeks of diet) and late (17-19 weeks of diet). Nerve excitability abnormalities were present in prediabetes and T2D groups at the early stage (superexcitability p<0.05) while changes in nerve conduction velocity and amplitude emerged later. Mechanical and thermal hypoalgesia was observed in prediabetic and T2D rats only at the late stage. Diet reversal improved body weight, fat mass, HDL, HbA1c, glucose clearance and mechanical nociception response, with no changes in nerve conduction and excitability. Together these data suggest that Caf diet combined with low dose STZ could be utilized to investigate the onset of neuropathological changes in T2D and assessment of subsequent peripheral neuropathy.

Disclosure

M. Hossain: None. M.D. Kendig: None. B.M. Wild: None. M.J. Morris: None. R. Arnold: None.

Funding

National Health and Medical Research Council of Australia (1126929, 1091006); Rebecca L. Cooper Foundation (RG160627)
534-P: The Association between Glycemic Variability and Cardiovascular Autonomic Neuropathy in Patients with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy
Authors: NATTERO-CHÁVEZ LÍA , SILVA JHONATAN QUIÑONES , BENGOA NURIA , ARGÜESO MARÍA FERNÁNDEZ , MONTANEZ LAURA , DURÁN ELENA FERNÁNDEZ , DORADO BEATRIZ , ZAMORANO BELÉN ARIAS , LECUMBERRI EDURNE , RAMÍREZ MANUEL LUQUE
Published: June 2020

Aim: Describe the relationships between cardiovascular autonomic neuropathy (CAN) and glucose variability (GV) in patients with DM1 on continuous subcutaneous insulin infusion therapy (CSII).

Methods Observational retrospective study (n=89). CAN was assessed by heart rate variability (HRV) in response to deep breathing, standing, Valsalva’s maneuver, and the amplitude of the low (LFa) and high (HFa) frequency of HRV. The standard deviation (SD), the coefficient of variation (CV) and time in range (TIR) were calculated from the capillary blood measurements downloaded of CSII (the mean of glucose capillary assessments was 5.8/day).

Results The mean age was 38±13 and their average duration of DM1 was 22±10 years. The prevalence of CAN was 36% (95%CI: 27-46). The population characteristics according to the presence of CAN are summarized in Table 1. The age and the duration of diabetes correlated negatively with LFa (r= -0.496, P < 0.001) and HFa (r= -0.510, P < 0.001). Separate multivariate binary logistic models were constructed for clinical and GV parameters introducing CAN as dependent variable. Only the age (expB 1.1; CI 1.04-1.15. P < 0.001) was associated with CAN in the fully adjusted model.

Conclusions Age and duration of diabetes, but not GV parameters, appear to be associated with CAN in our cohort of patients with DM1 on CSII.

Disclosure

L. Nattero-Chávez: None. J. Quiñones Silva: None. N. Bengoa: None. M. Fernández Argüeso: None. L. Montanez: None. E. Fernández Durán: None. B. Dorado: None. B. Arias Zamorano: None. E. Lecumberri: None. M. Luque Ramírez: None.

Funding

Menarini Group
536-P: Protein Tyrosine Phosphatase 1B Inhibitor MSI-1436 Promotes M2 Macrophage Polarization and Decreases Oxidative Stress in Human Monocytes under High-Glucose Conditions
Authors: FIGUEIREDO ANA , LEAL ERMELINDO C. , SANTOS DIANA , GASIUNAITE GERDA , DELIBEGOVIC MIRELA , CARVALHO EUGENIA
Published: June 2020

Peripheral neuropathy plays a role in chronic diabetic foot ulcers (DFUs), also leading to an imbalance in inflammation, as pro-inflammatory macrophages (M1) have difficulty switching to an anti-inflammatory phenotype (M2) contributing to a chronic inflammatory phase and healing impairment. Protein tyrosine phosphatase 1B (PTP1B), in the skin, is over expressed in diabetes and DFUs. We aimed to evaluate the role of PTP1B inhibition in macrophage under high glucose conditions. THP-1 monocytic cells were differentiated into macrophages, treated with the PTP1B inhibitor MSI-1436 (1 µM) and stimulated with LPS for 24h, under high glucose (25 mM) or normoglycemic conditions (5.5 mM). Cell viability was measured by MTT assay. The numbers of M1 and M2 macrophages were evaluated by immunocytochemistry by double staining with CD68 and TNF-α for M1 macrophages, and CD68 and CD163 for M2 macrophages. In addition, pro-inflammatory cytokine expression was analyzed by qRT-PCR. Oxidative stress was assessed by the DCFH-DA assay, heme oxygenase-1 (HO-1) enzyme levels were also measured by immunocytochemistry and Western blot. The treatment with MSI-1436 did not alter THP-1 cell viability. In inflammatory conditions (LPS), THP-1 cells grown under HG and treated with MSI-1436 showed an increase in M2 macrophages and a reduction in M1 macrophages (246 ± 26% and 102 ± 9%, p<0.05, of LPS treated cells, respectively). In addition, PTP1B inhibition induced a decrease in pro-inflammatory cytokine expression, IL-6, IL-1β and MCP-1, a decrease in ROS levels (78 ± 10% of LPS treated cells) and an increase in HO-1 expression (290 ± 23%, p<0.05, of LPS treated cells). Inhibition of PTP1B in macrophages, under high glucose conditions, promotes a significant reduction in the inflammatory environment and oxidative stress via increase of HO-1 expression, suggesting that PTP1B is a potential therapeutic target for the treatment of chronic DFUs.

Disclosure

A. Figueiredo: None. E.C. Leal: None. D. Santos: None. G. Gasiunaite: None. M. Delibegovic: None. E. Carvalho: None.

Funding

Diabetes UK; Portuguese Foundation for Science and Technology; European Foundation for the Study of Diabetes; Portuguese Society of Diabetology
54-LB: Control Yourself: Impact of Self-Regulation on Diabetes Management in Adolescents
Authors: ALBRIGHT DANA , RILEY HURLEY O. , FREDERICKS EMILY , STURZA JULIE , LO SHARON , CLARK KATY M. , LEE JOYCE M. , MILLER ALISON L.
Published: June 2020

Adolescents have the poorest blood sugar control compared to other age groups (Foster et al., 2019). Adolescence is also a period of developing self-regulation (SR) abilities, defined as the ability to manage thoughts, emotions, and actions to achieve a desired outcome (Eisenberg, 2019). The attention, planning, and decision making required for optimal T1D management is both cognitively and emotionally draining on the developing system of adolescents, which may be contributing to difficultly with diabetes management and glycemic control (Duke & Harris, 2014). This project examines the relationship between specific aspects of SR, including executive functions and affect; and T1D outcomes, including diabetes management behaviors and HbA1c. As part of an ongoing clinical trial (NCT03688919), adolescents (13-17 yo) diagnosed with T1D for ≥ 6 months with HbA1c ≥ 7.0 were recruited from diabetes clinics (n = 56). They completed baselines measures of self-regulation including the Behavior Rating Inventory of Executive Functioning, Positive and Negative Affect Schedule for Children, and self-reported diabetes management behaviors. HbA1c was also collected.

Parent reported cognitive aspects of SR were negatively related to number of insulin boluses per day, specifically attentional shift, task completion and planning, (r(47)= -.36, -.31, -.33 respectively, all p < .05); however, no association was found between inhibition, self-monitoring, and working memory and diabetes outcomes (p >.05). With regard to emotional aspects of SR, positive affect, including excitement, enthusiasm, pride, determination, and activation (r(47)= .34, .33, .36, .31, .29 respectively, all p < .05) were positively related to number of insulin boluses per day. No aspects of SR were related to blood glucose testing behaviors or HbA1c. SR in adolescents may be an important factor in successful T1D management. With evidence-based approaches, SR may be an optimal target for intervention.

Disclosure

D. Albright: None. H.O. Riley: None. E. Fredericks: None. J. Sturza: None. S. Lo: None. K.M. Clark: None. J.M. Lee: Advisory Panel; Self; Goodrx. Consultant; Self; T1D Exchange. Research Support; Self; Lenovo. A.L. Miller: None.

Funding

National Institutes of Health (NCT03688919)
543-P: A Randomised Control Trial to Evaluate the Efficacy of Chinese Traditional Medicine for the Treatment of Diabetic Peripheral Neuropathy
Authors: GUANJIE FAN , LIN YUPING , PAUL SANJOY K. , HUANG HAOYUE , XIANYU TANG , YUEHONG ZHOU , ZHAOHUI FANG , XIAOTANG QIU , FANG DAI , WANG SHI-DONG , WANG MEI , WEI HUA , LING ZHAO , ZHENJIE LIU , FU YU , WU MINGHUI , ANXIANG LI , JINZHU HUANG , LI QINGBO
Published: June 2020

Background: Diabetic peripheral neuropathy (DPN) is a common complication in patients (pts) with diabetes. However, multinational data do not support any convincing efficacy of the current therapies for treating DPN. This necessitated the evaluation of safety and efficacy of alternative medicine to tackle DPN.

Methods: A double-blinded RCT was conducted in 8 Chinese medicine hospitals in China, evaluating the safety and efficacy of 190 g Tangbi Waixi decoction (TW, intervention (Int)) compared with 19 g TW (control (Cont)). Change in Toronto Clinical Scoring System - Total Score (TCSS-TS) at 12 and 24 weeks follow-up was the primary outcome, with treatment ceasing at 12 weeks. Secondary outcomes included change in bilateral motor velocity (BMV) and sensory nerve conduction velocity (SNCV) of the common peroneal nerve (CPN). All pts received standard care for glycaemic management. The pts in the Int (n=317) and Cont (n=315) groups were analysed on ITT principle. All adverse events (AEs) were recorded.

Results: The pts were mean 60 years old with median 10 yrs and 2 yrs of diabetes and DPN duration respectively at randomisation. With median TCSS-TS of 10 at randomisation in both groups, the median (95% CI) reduction in Int and Cont: at 12 weeks 2 (1.7, 2.3) and 3 (2.7, 3.3) respectively (median between group difference (MBGD): 1.0, p=0.011); at 24 weeks 3 (2.6, 3.4) in both groups. At 12 weeks, median (95% CI) CPN velocity increased in both Int and Cont - BMV Int vs. Cont: 2.7 (1.9, 4.9) m/s vs. 4.9 (2.7, 5.5) m/s, MBGD - 2.5 m/s (p=0.044); SNCV Int vs. Cont: 1.4 (0, 2) m/s vs. 2.7 (1.9, 4.9) m/s, MBGD - 0.7 m/s (p=0.26). Similar increase in CPN velocity was observed at 24 weeks in both groups. Overall 12% pts experienced at least one AE, with no difference between groups.

Conclusion: Treatment of DPN with TW decoction significantly benefitted the pts and is safe, while lower dose of TW appears to be more effective than the higher does.

Disclosure

F. Guanjie: None. Y. Lin: None. S.K. Paul: Advisory Panel; Self; Sanofi. Research Support; Self; AstraZeneca, Genentech, Inc. H. Huang: None. T. Xianyu: None. Z. Yuehong: None. F. Zhaohui: None. Q. Xiaotang: None. D. Fang: None. S. Wang: None. M. Wang: None. H. Wei: None. Z. Ling: None. L. Zhenjie: None. Y. Fu: None. M. Wu: None. L. Anxiang: None. H. Jinzhu: None. Q. Li: None.

Funding

National Science and Technology Support Program (2015BAI04B09)
547-P: Associations between Bladder Symptoms and Diabetic Neuropathy in a Romanian Cohort of Patients with Diabetes
Authors: VONICA CAMELIA L. , BONDOR COSMINA I. , SIMA DIANA , COSMA DANIEL T. , VERESIU IOAN ANDREI , GAVAN NORINA , POP-BUSUI RODICA , SARMA ARUNA V.
Published: June 2020

Lower urinary tract symptoms (LUTS) are commonly reported by men and women with diabetes and may share a common pathogenic mechanism with diabetic peripheral neuropathy (DPN). We aimed to evaluate associations between DPN and self-reported LUTS in a cohort of Romanian patients with diabetes phenotyped for DPN with the Michigan Neuropathy Screening Instrument (MNSI). Clinical DPN was defined as MNSI exam score of >2; symptomatic DPN as MNSI questionnaire score of ≥4. LUTS was assessed with the validated American Urological Association Symptom Index and defined as 0-7 none/mild and ≥8 moderate/severe. Preliminary data is shown for 174 participants [51% men, mean age 67 years, 95% type 2 diabetes, mean diabetes duration 16 years, mean hemoglobin A1c (HbA1c 8%)]. Sixty% and 64% met the criteria for clinical and symptomatic neuropathy, respectively and 53% of men and 47% of women reported moderate/severe LUTS. MNSI questionnaire scores were significantly associated with LUTS in both men (p<0.001) and women (p<0.001) after adjusting for age and HbA1c. These data demonstrate that patients with symptomatic neuropathy are more likely to present with bladder dysfunction.

Disclosure

C.L. Vonica: Other Relationship; Self; AstraZeneca. C.I. Bondor: Consultant; Self; Wörwag Pharma. D. Sima: None. D.T. Cosma: Other Relationship; Self; Wörwag Pharma. I. Veresiu: None. N. Gavan: 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. A.V. Sarma: None.

Funding

Woerwag Pharma GmbH & Co. KG
553-P: Brain Microstructural Tissue Changes in Patients with Controlled and Uncontrolled Type 2 Diabetes
Authors: CHOI SARAH E. , ROY BHASWATI , FREEBY MATTHEW , WOO MARY A. , KUMAR RAJESH
Published: June 2020

Patients with type 2 diabetes mellitus (T2DM) show brain tissue changes in mood and cognitive control sites. However, it is unclear whether brain microstructural tissue changes differ between patients with controlled (hemoglobin A1c [A1C] <7%) and uncontrolled (A1C ≥ 7%) T2DM. Diffusion tensor imaging (DTI) based mean diffusivity (MD) measures water molecular motion within tissue and shows microstructural changes by values reduced in acute and increased in chronic pathological conditions. Methods: We collected DTI and A1C data from 37 T2DM patients (15 controlled; age 56.4±6.8 years, BMI 29.2±6.2 kg/m2, diabetes duration 6.0±4.8 years, A1C 6.2±0.4%, 7 female; 22 uncontrolled; age 57.2±7.4 years, BMI 30.5±5.1 kg/m2, diabetes duration 15.0±9.0 years, A1C 8.2±1.3%, 14 female) and 12 healthy controls (age 54.3±8.2 years, BMI 25.9±4.6 kg/m2, A1C 5.2±0.4%, 5 male) using a 3.0-Tesla magnetic resonance imaging scanner and point-of-care A1C testing. Whole-brain MD maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. healthy controls; uncontrolled T2DM patients vs. healthy controls) using ANCOVA (SPM12; covariates, age and sex; uncorrected threshold, p<0.005).

Results: No significant differences appeared between groups in age or sex. Mean duration of diabetes was significantly different between controlled and uncontrolled T2DM patients (p <0.001). Uncontrolled T2DM patients showed increased MD values in multiple brain areas, including the cingulate, insula, para-hippocampal, hippocampus, cerebellum, basal-forebrain, prefrontal, frontal, and temporal cortices over controlled T2DM patients and healthy controls.

Conclusion: Uncontrolled T2DM patients show widespread chronic brain microstructural changes in areas that are involved in mood and cognition regulation. The findings support tight glycemic control to prevent further brain tissue damages in patients with T2DM.

Disclosure

S.E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott, Novo Nordisk Inc. M.A. Woo: None. R. Kumar: None.

Funding

National Institutes of Health (R01NR017190)
558-P: Poor Oral Health Predicts Progression of Diabetic Neuropathy
Authors: JIVANESCU ANCA , BONDOR COSMINA I. , SIMA DIANA , VONICA CAMELIA L. , COSMA DANIEL T. , STEIGMANN LARISSA , VERESIU IOAN ANDREI , GAVAN NORINA , SARMA ARUNA V. , POP-BUSUI RODICA
Published: June 2020

Poor oral health (OH) manifested mainly as gingivitis/periodontitis is emerging as a serious diabetes complication. Recent reports suggest that poor OH may share pathogenic mechanisms with diabetic neuropathy (DN). We previously reported a high prevalence of poor OH in a large Romanian cohort of >1300 participants with diabetes phenotyped for OH and DN in 2016, particularly among participants with DN. This follow-up study aimed to further evaluate associations between DN and OH in this cohort over time. DN was assessed with the Michigan Neuropathy Scoring Instrument (MNSI), questionnaire (MNSIq) and clinical examination (MNSIe). Clinical DN was defined as MNSIe score of >2; symptomatic DN as MNSIq score of ≥4. OH was assessed using a validated questionnaire that includes questions about gingival pain, bleeding and complete dentures. OH was defined as good (no symptoms/signs), poor (symptoms/signs often/very often) or very poor (edentulous patients wearing complete dentures). Preliminary data is presented for 104 participants who completed a second evaluation in 2018/2019, median age (25th-75th percentile) 63 (59-70) years, 53% male, median diabetes duration 13 (8-17) years, mean A1c 7.8±1.5%. Among them 62 % presented with MNSIe>2 and 44 % with MNSIq>4. Poor and very poor OH at baseline (2016) were significantly correlated with MNSIe at follow-up (2018) (r = 0.20, p = 0.04). After adjusting for age and duration, there was a significant positive correlation between worsening in OH and DN (r = 0.26, p = 0.037) at follow-up. In multivariate analysis, after controlling for age and diabetes duration, there was a significantly higher change in the overall MNSI scores during follow-up in those with poor and very poor OH (0.97 +/- 1.9 vs. 0.16 +/- 1.8 p = 0.036). These data show that in this longitudinal cohort with diabetes DN worsened over time particularly in those with poor OH, suggesting that OH may directly affect risk of DN and other complications.

Disclosure

A. Jivanescu: None. C.I. Bondor: Consultant; Self; Wörwag Pharma. D. Sima: None. C.L. Vonica: Other Relationship; Self; AstraZeneca. D.T. Cosma: Other Relationship; Self; Wörwag Pharma. L. Steigmann: None. I. Veresiu: None. N. Gavan: None. A.V. Sarma: 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.

Funding

Woerwag Pharma GmbH & Co. KG
563-P: Differentially Expressed Plasma miRNAs Are Closely Associated with the Presence of Microvascular Complications in Type 2 Diabetes: The 1000 Qatar-Omics Study Cohort
Authors: AKIL AMMIRA S. , PADMAJEYA SUJITHA SUBASH , JERMAN LAILA A. , AL-KURBI ALYA , HUSSEIN AMAL M. , HARDIKAR ANAND , JOGLEKAR MUGDHA , HABIB TANWIR , ANBARI MOHAMMED EL , FAKHRO KHALID
Published: June 2020

Background: In the light of growing global epidemic of T2D and related microvascular complications, it is important to find early detection marker for the disease. Circulating miRNAs serve as a potential biomarker for monitering the progression to DR in diabetic individuals.

Hypothesis and Aims: miRNAs play a substantial role in metabolic homeostasis through regulation of multiple genes, and could serve as a prognostic biomarker in DR. This study aims to assess a functional role of selected miRNAs in the Qatari population recruited for the Qatar Genome Project through Qatar BioBank.

Methods: Plasma samples from 470 T2D subjects with and without DR and 500 matched-healthy controls has been included in this study. Total RNA was extracted and the expression profiling of 56 miRNA that previously reported as a player in the pathogenesis of DR was performed using custom open array panel. The miRNA expression data were normalized using ath-mir159a. Statistical analysis was performed to study the association between the phenotypes (HbA1c, C-peptide, age, BMI) and miRNA.

Results: The patients and controls phenotypic and miRNA expression data were analyzed to interepret the differential expression of the miRNA in DR subjects. Initial analysis by applying the generalized additive model reveals that six miRNA (hsa-miR-27a, hsa-miR-376c, hsa-miR-92a, hsa-miR-1 hsa-miR-223, and mmu-miR-451) were found to be significantly associated with DR (p>0.05). Furthermore, two differentially expressed miRNAs, (hsa-miR-1274A and hsa-miR-24) found to be associated with higher level of C-peptide in DR patients, which suggest the correlation of these miRNAs with the glucose hemostasis and DR.

Conclusion: The etiology of DR is unclear, and present treatments have limited effectiveness. The biomarkers and downstream functional studies are required to deepen the understanding of this chronic diseases and its complications.

Disclosure

A.S. Akil: None. S. Subash Padmajeya: None. L.A. Jerman: None. A. Al-Kurbi: None. A.M. Hussein: None. A. Hardikar: None. M. Joglekar: None. T. Habib: None. M. El Anbari: None. K. Fakhro: None.
57-OR: A Novel School-Based Obesity Prevention Program Improves Healthy Eating/Lifestyle among 5- to 7-Year-Olds
Authors: SENEVIRATNE SUMUDU N. , SACHCHITHANANTHAN SANATHANEE , ANGULUGAHA GAMAGE PAVITHRA S. , RAMAMOORTHY SAHANA , PEIRIS RENUKA , WICKRAMASINGHE VITHANAGE P. , SOMASUNDARAM NOEL
Published: June 2020

Background: The foundation for lifelong good health is laid in childhood. Schools can play a pivotal role in preventing obesity/type 2 diabetes with effective interventions.

Methods: We devised a novel school-based program using a sticker based food diary (FD) and colorful 12-page story book to motivate young school children to adopt a healthier diet/lifestyle. This study to conducted among 1500 grade 1 and 2 students from 4 schools between March 2018- April 2019, to evaluate its effectiveness. During the first week(W1), each child self-monitored his/her food intake daily at home for a week, using the FD, and received a Smiley Face based Score (SFS) based on the healthiness of each meal. In the second week, class teachers read the story book (illustrating the physical and psychosocial effects of obesity and benefits of healthy lifestyle in a child friendly manner). In the third week(W3) children completed the FD again. Effectiveness of the program to improve healthy eating/lifestyle was assessed by comparing mean SFS between W1 and W3, and by anonymized graded-response and open response questionnaires completed by parents and class teachers.

Results: Completed FDs were returned by 1029 students. Overall there was an improvement in healthy eating, with mean SFS increasing by 11.7% from W1 to W3 (51.3 ± 22.9 vs. 63.1 ± 24.2, p< 0.001). SFS improved >10% in all BMI categories. SFS improvement was more in boys (13.0 vs. 9.7, p=0.02), and in 2nd graders compared to 1st graders (13.1 vs. 10.3, p=0.045). Majority of responding parents (> 90%) and teachers (95%) strongly agreed/agreed that this program motivated children towards a healthier lifestyle and led to an observable improvement in food habits.

Conclusion: This novel program led to a demonstrable improvement in healthy lifestyle among 5-7 year olds and was received favorably by parents and teachers. Based on these results and positive (ongoing) longer-term follow up data, wider implementation involving 750,000 children is planned for mid 2020.

Disclosure

S.N. Seneviratne: None. S. Sachchithananthan: None. P.S. Angulugaha Gamage: None. S. Ramamoorthy: None. R. Peiris: None. V.P. Wickramasinghe: None. N. Somasundaram: None.

Funding

World Diabetes Foundation (WDF15-1291)
571-P: A Cross-Sectional Observational Study on Correlation between the Central Corneal Thickness and Diabetic Retinopathy
Authors: BAIDYA ARJUN , WAHEED QUAZI SHEHNAZ , DEY SARKAR AJOY
Published: June 2020

Introduction: In the recent years, several papers have evaluated the changes in central corneal thickness (CCT) associated with diabetes mellitus (DM) with conflicting results.

Aims: To compare the CCT of subjects with DM with age and sex matched healthy subjects and to determine the correlation of CCT with duration of DM and severity of diabetic retinopathy (DR).

Methods: In this cross-sectional, observational study 124 subjects with DM and 65 age matched healthy controls were studied. CCT was measured by pulsair non- contact tonometer. According to retinopathy status based on the ETDRS subjects with diabetes were categorized as PDR (Gr III), NPDR (Gr II) and NO DR (Gr I). Nondiabetic healthy control subjects were categorized as Group IV.

Results: The mean CCT for the study group was 547.02±2.34 and for the control group was 504.6±3.14(p=0.02).Mean CCT in subjects with diabetes with duration >10 years was higher (557.71±19.44) as compared to those having it for less than 10 years (534.05±27.30) (p=0.178). Patients with PDR had higher mean CCT (572.13±17.50) compared to NPDR (553.78±8.80). Patients with DM but no DR had lesser mean CCT than NPDR thus implying positive correlation of CCT with severity of DR.

Conclusion: CCT is significantly greater in subjects with diabetes compared to healthy control. It is positively correlated with severity of DR and duration of DM.

Disclosure

A. Baidya: None. Q. Waheed: None. A. Sarkar: None.
572-P: Association of Sight-Threatening Diabetic Retinopathy in Type 1 Diabetes with Subclinical Atherosclerosis Disease Burden: Five-Year Indian Study
Authors: SHAH KIRAN , SUNDARAM NATARAJAN , PUROHIT LOTIKA S. , TOTH PETER P. , KOTHARI AKSHAY R. , GUPTA SUNIL
Published: June 2020

We conducted a cross sectional study in 314 T1DM patients (50% with Sight Threatening Diabetic Retinopathy (STDR). B-mode carotid ultrasound, CT coronary angiogram was done after excluding history of CV disease and CKD. Table summarizes demographic, biochemical and imaging parameters. The plaque burden, Carotid Intima Media Thickness (CIMT) and Coronary Calcium (CAC) scores were significantly higher (p<0.0001) in STDR group than No Diabetic Retinopathy (NDR) group. Prevalence of plaque burden was higher in STDR (68.7%) vs. NDR (4.45%). There was no significant correlation between age and CIMT (r= 0.0147). In STDR group, BMI and CIMT showed linear correlation (r=0.0318), there was a strong correlation between carotid plaques and triglycerides (TGs). High CAC scores correlated with higher cholesterol levels. CAC and CIMT had linear correlation with TGs but no correlation with LDL-C. Patients with high CAC scores had high CIMT and vice versa. Multivariate logistic regression analysis showed stronger correlation of carotid plaques with CIMT (p=0.0004) and TGs (p= 0.0295, r= 0.0157) than CAC (p= 0.0605 NS). STDR is an independent predictor of carotid plaques and is a marker of high atherosclerotic burden in T1DM. This association describes that T1DM patients with STDR are at higher CV risk and need aggressive, comprehensive follow up to prevent CV disease.

Disclosure

K. Shah: None. N. Sundaram: None. L.S. Purohit: None. P.P. Toth: Consultant; Self; Amarin Corporation, Amgen, Kowa Research Institute, Inc., Theravance Biopharma. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi. A.R. Kothari: None. S. Gupta: None.
58-OR: Diastolic Dysfunction, a Precursor for Heart Failure in Young Adults with Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: SHAH AMY S. , DABELEA DANA , DOLAN LAWRENCE M. , ISOM SCOTT , DAGOSTINO RALPH , WAGENKNECHT LYNNE E. , IMPERATORE GIUSEPPINA , SAYDAH SHARON , LIESE ANGELA D. , LAWRENCE JEAN M. , PIHOKER CATHERINE , URBINA ELAINE M.
Published: June 2020

Individuals with diabetes are at high risk for heart failure with preserved ejection fraction due to diabetic cardiomyopathy (DCM), defined as abnormal myocardial structure and function in the absence of overt coronary artery disease. DCM leads to myocardial fibrosis and remodeling with one of the first signs being left ventricular (LV) diastolic dysfunction. The objective was to compare the prevalence of diastolic dysfunction among young adults with type 1 diabetes (T1D) vs. type 2 diabetes (T2D) with diabetes diagnosed in childhood. Participants had T1D or T2D and were enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and diastolic function via echocardiography were measured at an in-person visit, after an average disease duration of 10.9 years (both groups). Unadjusted means were compared between those with T1D and T2D, p <0.05 indicating significance. Diastolic dysfunction was defined as abnormal LV filling volume, LV pressure, or transmitral velocity, based on published norms for age. Of 458 eligible participants, 255 had T1D (mean age 21.2±5.2 years, 60.8% non-Hispanic white, 54.1% female, mean A1c 9.0±1.9%), and 203 had T2D (mean age 24.3±4.3 years, 24.1% non-Hispanic white, 75.4% female, mean A1c 9.6±3.0%). Participants with T2D had a worse cardiovascular risk profile (higher BMI, systolic and diastolic BP, triglycerides, LDL-C, A1c and lower HDL-C) than those with T1D, all p<0.05. Participants with T2D also had lower LV filling volume, transmitral velocity and higher LV pressure, all p<0.05, than those with T1D, suggesting worse diastolic function. The unadjusted prevalence of diastolic dysfunction was high in both groups (57.7% in T2D vs. 47.2% in T1D; p<0.05). Diastolic function is worse in individuals with T2D compared to T1D, but diastolic dysfunction is high in both groups. These findings support monitoring of young adults with diabetes for development of heart-related complications.

Disclosure

A.S. Shah: None. D. Dabelea: None. L.M. Dolan: None. S. Isom: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.E. Wagenknecht: None. G. Imperatore: None. S. Saydah: None. A.D. Liese: None. J.M. Lawrence: None. C. Pihoker: None. E.M. Urbina: None.

Funding

Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)