bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Baseline Glomerular Filtration Rate Is Associated with a More Rapid Decline in Chinese Patients with Type 2 Diabetes with Normoalbuminuria
Authors: WAN JING , CHEN HAIBING 
Published: June 2018

Aims: To investigate the association between estimated baseline glomerular filtration rate (GFR) and renal function decline in Chinese patients with type 2 diabetes with normoalbuminuria.
Main Methods: A longitudinal study was performed on 368 Chinese patients with type 2 diabetes whose estimated GFR (eGFR) was determined at baseline with a 3.12-year follow-up. The patients were divided into three groups according to baseline eGFR (mL/min/1.73 m2): G1 (eGFR ≥ 120), G2 (90 ≤ eGFR &lt; 120), G3 (60 ≤ eGFR &lt; 90). The association between baseline eGFR and the renal function decline rate was assessed using binary logistic regression. Decliners were defined as a negative change ≥ −3.3% per year.
Key Findings: Among G1 patients, the decliners were younger, had a higher baseline eGFR, shorter duration of diabetes, and lower diastolic blood pressure, compared with non-decliners. The G1 eGFR decline slope (% per year) was significantly higher than that in G2 and G3 patients. The percentage of decliners among G1 patients was significantly higher than that among G2 and G3 patients. Baseline eGFR group, HbA1c, hypertension history, and diastolic blood pressure were independent risk factors for progressive renal decline. Patients in the decliners group were more likely to progress to microalbuminuria and macroalbuminuria compared with those in the non-decliners group; however, the albuminruria progression percentage was not significantly different among G1, G2, and G3 decliners.
Significance: Patients with baseline eGFR ≥ 120 mL/min/1.73 m2 had a higher risk for more rapid eGFR decline among Chinese patients with type 2 diabetes with nomalbuminuria.

Disclosure
J. Wan: None. H. Chen: None.
Wider Peripheral Retinal Vessel Predicts Renal Dysfunction in Adolescents with Type 1 Diabetes
Authors: VELAYUTHAM VALLIMAYIL , CRAIG MARIA E. , LIEW GERALD , WONG TIEN Y. , JENKINS ALICIA , DONAGHUE KIM C. 
Published: June 2018

Objective: The renal and retinal vasculature shares similar pathophysiologic features. Retinal vasculature changes, even without typical retinopathy, can predict microvascular disease in type 1 diabetes (T1D). We hypothesise that peripheral retinal vessels are wider and predict incident renal dysfunction in adolescents with T1D.
Research Design and Methods: In this longitudinal study of 441 retinopathy free and normoalbuminuric adolescents with T1D retinal photographs were measured by computer software (Singapore I Vessel Assessment) with vessel calibres summarized in the standard “central zone” [Central Retinal Arterial and venular equivalents (CRAE and CRVE respectively)] and “extended zone” [Mean width of arterioles and venules (MWa and MWv)]. Retinal vascular geometry including length diameter ratio (LDR) and simple tortuosity (ST) was quantified. Generalised estimating equation was used to explore associations between vessel calibres, LDR, ST and incident renal dysfunction. Incident renal dysfunction was defined as Albumin excretion rate (AER) &gt; 7.5µg/min, with results expressed as odds ratio (OR) and 95% CI.
Results: Mean ± SD age was 14.1±1.5 year, median diabetes duration 4.8 year [IQR 3.3, 7.5], A1C 8.4 ±1.3% (IFCC 68 ±14.2mmol/mol). Incident renal dysfunction occurred in 186/441 (42%) over a median 4 year follow-up. Wider MWa and MWv (4th vs. 1st quartile), higher LDR (4th vs. 1st -3rd quartile) and lower ST (1st vs. 2nd-4th quartile) were associated with renal dysfunction: MWa OR 2.0 (1.2, 3.5); MWv 2.2 (1.3, 3.6), LDRa 1.5(1.07, 2.08), LDRv 1.4 (1.02, 1.9), STa 1.5(1.1, 2.2), STv 1.4 (1.1, 1.8) after adjusting for covariates (A1C, diabetes duration, gender, height and blood pressure). Central vessels were not related to renal dysfunction: CRAE: 0.9 (0.5, 1.5); CRVE: 1.3 (0.8, 2.1), all p&lt;0.05.
Conclusions: We speculate that small vessel dilatation and tortuosity are modulators of diabetic renal disease.

Disclosure
V. Velayutham: None. M.E. Craig: None. G. Liew: None. T.Y. Wong: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. K.C. Donaghue: None.
Superior Glycaemic Control Effects with Dulaglutide (Dula), a Once-Weekly Glucagon-Like Peptide Receptor-Antagonist (GLP-1RA), to Liraglutide (Lira) in Diabetic Hemodialysis Patients Assessed by Continuous Glucose Monitoring (CGM)
Authors: FUNAKOSHI SATOSHI , HAYASHIDA MASATOSHI , SAWASE KENJI , HASHIGUCHI JYUNICHIRO , ETOH RICA , MORI YUTAKA , UTSUNOMIYA KAZUNORI , HARADA TAKASHI 
Published: June 2018

Objective: Dulaglutide (Dula) is a novel, long-acting glucagon-like peptide receptor antagonist (GLP-1RA) used in the treatment of T2D patients with or without renal impairment. In this study we compared by using CGM once-daily Lira and once-weekly Dula, each combined with various doses of insulin degludec (IDeg).
Methods: Eighteen adult HD patients with T2D (men/women, 11/7) who had been treated with once-daily Lira (0.6-0.9 mg) combined with daily IDeg (5-26 units) (Lira + IDeg) were switched to once-weekly Dula 0.75 mg combined with daily IDeg (Dula + IDeg). The dose of IDeg stayed the same in each patoent, and all patients were monitored for PG control by CGM, and the mean amplitude of glycaemic excursions (MAGE) was calculated before and after switching.
Results: A significant reduction was observed in MAGE with Dula + IDeg 4 weeks after switching to Lira + IDeg both in on-HD days (122.3±38.3 mg/dL vs. 66.7±22.1 mg/dL, p&lt;0.001) and off-HD days (88.8±24.1 mg/dL vs. 42.6±20.3 mg/dL, p&lt;0.001). No episode of hypoglycemia, and 4 out of 18 patients reported mild gastrointestinal adverse events with Dula treatment, but were thought to be transient.
Conclusions: Thus, Dula appears to be potentially superior to Lira in reducing PG fluctuations in HD patients with T2D receiving IDeg.

Disclosure
S. Funakoshi: None. M. Hayashida: None. K. Sawase: None. J. Hashiguchi: None. R. Etoh: None. Y. Mori: None. K. Utsunomiya: None. T. Harada: None.
Large-Scale DNA Methylation Profiling of Human Diabetic Peripheral Neuropathy in Subjects with Type 2 Diabetes Mellitus
Authors: GUO KAI , ELZINGA SARAH , EID STEPHANIE , FIGUEROA-ROMERO CLAUDIA , MCGREGOR BRETT A. , DE ANDA-JÁUREGUI GUILLERMO , PACUT CRYSTAL , FELDMAN EVA L. , HUR JUNGUK 
Published: June 2018

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Emerging evidence suggests that aberrant DNA methylation may play a critical role in the pathogenesis of diabetic complications. Yet, its involvement in DPN is not fully characterized. In this study, we performed a large-scale genome-wide methylation profiling of sural nerve samples obtained from subjects with type 2 diabetes mellitus (T2DM) using Reduced Representation Bisulfite Sequencing (RRBS). A total of 78 samples were sequenced and mapped to the human reference genome. Differential analysis was performed on two groups, identified by our previous transcriptomic analysis of the same samples, which showed significantly different HbA1c levels: Group 1 (=8.5%±1.6%) and Group 2 (&lt;7.0%±1.4%). Using MethylKit R package, with an adjusted p-value &lt; 0.01 and 15% methylation change as significance cutoffs, we identified 2,066 differentially methylated CpG sites and 440 regions, corresponding to 1,519 and 429 unique differentially methylated genes (DMGs). These genes were highly enriched in biological processes related to nervous system development, neuron fate specification and neuron differentiation. KEGG pathway enrichment analysis demonstrated that genes involved in cancer, ECM-receptor interaction and axon guidance pathways were significantly differentially methylated between the two groups, highlighting the importance of DNA methylation in DPN pathogenesis.
In summary, we demonstrate that type 2 diabetic patients with peripheral neuropathy and high HbA1c show distinct variations in sural nerve methylome, suggesting that DNA methylation and DPN are associated and that these associations are at least in part HbA1c-dependent. Our results provide new insights into the role of HbA1c in epigenetic variation, and identify candidate genes relevant to the pathogenesis of DPN in human sural nerves of subjects with T2DM.

Disclosure
K. Guo: None. S. Elzinga: None. S. Eid: None. C. Figueroa-Romero: None. B.A. McGregor: None. G. de Anda-Jáuregui: None. C. Pacut: None. E.L. Feldman: None. J. Hur: None.
The Effect and Molecular Mechanism of Pancreatic Kallikrein in Painful Diabetic Neuropathy Based on CX3CL1/CX3CR1 Pathway
Authors: XIANG XU , HUI JIN , LAN XU 
Published: June 2018

Objective: This study evaluated the effect and molecular mechanism of pancreatic kallikrein (PKK) in improving mechanical allodynia in STZ-induced C57 mice, an animal model of type 1 diabetes, based on CX3CL1/CX3CR1 pathway.
Methods: Male C57 mice, weighing 20-23g, were fasted overnight for 12h (20:00-8:00 next day) and injected with STZ (100mg/kg) to induce type 1 diabetes model. 24 diabetic mice were divided into PKK-1 group (PKK 6u/kg/d, ip, n=8), PKK-2 group (PKK 60u/kg/d, ip, n=8) and DNS group (0.9% NaCl 0.15ml/d, ip, n=8). Eight normal C57 mice were injected with PKK (6u/kg/d, ip) as the NPK group. The mechanical allodynia of each group was evaluated from 1h to 5 weeks after PKK injection. The expression of CX3CL1/CX3CR1 at the lumbar spinal cord was also measured at the 5th week using Western Blot analysis.
Results: 1) More than 80% of C57 mice were tested FBG&gt;11.1mmol/L at the 7th day after STZ injection and divided into the diabetic group. 2) Compared with the normal mice, we showed that the diabetic mice developed mechanical allodynia at the early stage of diabetes. Meanwhile, The intraperitoneal injection of PKK could decrease such mechanical allodynia in a dose-independent manner. 3) Compared with the DNS group, the intraperitoneal injection of PKK significantly attenuated the expression of CX3CL1/CX3CR1 at the dorsal horn.
Conclusion: Our previous study indicated that the CX3CL1/CX3CR1 pathway played an important role in the progress of painful diabetic neuropathy. These results showed that intraperitonea injection of PKK significantly decreased mechanical allodynia and attenuated the expression of CX3CL1/CX3CR1 at the dorsal horn. This study may contribute to a better understanding of the therapeutic effect and mechanism of PKK on painful diabetic neuropathy.

Disclosure
X. Xiang: None. J. Hui: None. X. Lan: None.
Effect of Diabetes on Peripheral Neuropathy in an Adult U.S. Population
Authors: OLAIYA MUIDEEN T. , HANSON ROBERT L. , KAVENA KAREN G. , SINHA MADHUMITA , NELSON ROBERT , KNOWLER WILLIAM C. 
Published: June 2018

Background: Peripheral neuropathy (PN) is a diabetes complication but also occurs without diabetes. The effect of diabetes on PN is not well quantified.
Methods: Subjects ≥ 18 years old had a health exam, including an OGTT for diabetes. Distal sensory PN, assessed using 3 graded Semmes Weinstein monofilaments, was classified as none (felt all filaments), latent (insensate to 1 g filament), clinical [mild (insensate to 10 g) or severe (75 g)]. Associations with PN were assessed using ordinal logistic regression assuming equal coefficients across classes of PN.
Results: In 1564 subjects (median age 42 years, 50% women, 58% American Indians), PN was latent or worse in 68.9% (95% CI 66.7-71.2), clinical in 11.2% (CI 9.7-12.9), and associated with male sex, older age, and worse glucose regulation (Figure). Age-sex-race-adjusted prevalence was greater in people with than without diabetes (odds ratio; OR 2.2, CI 1.7-2.8), and in those with diabetes, with longer diabetes duration (OR 1.9 per decade, CI 1.5-2.4) or albuminuria, A/C ≥30 mg/g (OR 2.4, CI 1.6-3.6). In those without clinical PN, latent PN was associated with diabetes (OR 1.7, CI 1.2-2.2), longer diabetes duration (OR 2.2 per decade, CI 1.4-3.5) and albuminuria (OR 1.8, CI 1.0-3.2).
Conclusions: Although PN is common in people with no diabetes, diabetes greatly increases its risk. Use of 3 monofilaments rather than 1 adds precision and allows detection of latent PN.

Disclosure
M.T. Olaiya: None. R.L. Hanson: None. K.G. Kavena: None. M. Sinha: None. R. Nelson: None. W.C. Knowler: None.
Sensory Cutoff Value for Predicting Postural Instability in People with Peripheral Neuropathy Secondary to Diabetes
Authors: AUNG NAY LINN , MEARDON STACEY A. , LIN CHIA-CHENG , TANENBERG ROBERT J. 
Published: June 2018

People with peripheral neuropathy (PN) secondary to diabetes have higher risks of falls due to loss of the somatosensation of the feet. The purpose of this study was to investigate the cutoff values of the vibration threshold and the monofilament test to predict postural instability. Ten healthy younger adults, ten healthy older adults and ten people with PN secondary to diabetes were recruited in this study. A handheld bio-thesiometer and a set of monofilaments were used to measure the vibration threshold (VT) and tactile sensitivity (TS), respectively. VT and TS were measured at six different sites on the plantar surface, including big toe, 1st metatarsus, little toe, 5th metatarsus, middle arch, and calcaneus (heel), plus the lateral and medial malleoli. Subjects also underwent a Sensory Organization Test (SOT) to identify postural instability, defined as equilibrium scores less than age matched norms. Linear regression was used to determine which site(s) was able to predict the balance test performance. Receiver operating characteristic curves were used to compute the VT and TS cutoff values associated with postural instability. A cutoff value of 10V for lateral malleolus VT was able to predict postural abnormality with 100% Sensitivity and 54.5% Specificity. A cutoff value of 3.61 for middle arch TS was able to predict postural abnormality with 100% Sensitivity and 86.4% Specificity. Postural instability appears earlier than the current recommended clinical cutoff values for peripheral neuropathy (25V for VT and 5.07 for TS). Although current cutoff values of the vibration threshold and the monofilament test are useful for detecting a propensity for neuropathic foot ulcer, they may not be adequate for detecting early postural instability. Fall prevention strategies may be needed early in the progression of PN.

Disclosure
N. Aung: None. S.A. Meardon: None. C. Lin: None. R.J. Tanenberg: None.
OPTIFAST® Medical Weight Loss Program—Outcomes in the Endocrinology Clinics at UPMC
Authors: DETOYA KARLA B. , HAN KATRINA , REGISTER BRENNAN R. , ROMETO DAVID A. 
Published: June 2018

Background: The OPTIFAST® program at UPMC is a medically supervised program using very low calorie diet from Nestle products. It focuses on nutrition and lifestyle counseling, and transitioning to a low glycemic load diet to sustain glycemic benefits of weight loss. We evaluated the impact of our program on weight reduction in a 3-year period at UPMC clinics, and secondary parameters defining cardiovascular risk factors.
Methods: Patients were divided into Completer (C) and Non-Completer (NC) cohorts. For the C-group, HBA1C for diabetics, lipid profiles and systolic blood pressure (SBP) were compared at baseline and at &gt;5 months. Adjusting for weight loss, effect of DM, BP and lipid-lowering drugs on HBA1C, SBP and lipid profile, respectively, was also evaluated.
Results: A total of 215 patients (mean age=49.63, 69% female) had mean baseline and end weights of 263.7 and 222.8 pounds respectively, with mean 14.04% weight loss (p&lt;0.0001). 59% completed the program with mean 19.52% weight loss (p&lt;0.0001). For the NC-group, weight difference from baseline was not significant.
Among diabetics, there was decrease in HBA1C (7.8% to 6%, p&lt;0.0001), with a decrease in the no. of insulin units/day (71.4 to 34.6 units, p=0.015), but no significant decrease in the no. of noninsulin drugs from baseline to &gt;5 months. There was a decrease in mean baseline to end SBP (139.3 to 122.5 mmHg, p=0.0325), and no. of BP meds (1.9 to 1.2, p&lt;0.0001). There was a decrease in mean baseline to end values of: total cholesterol (TC) (192.4 to 140.7 mg/dl, p&lt;0.0001), LDL (104.3 to 84.59 mg/dl, p=0.02) and triglycerides (TG) (209.2 to 111.9 mg/dl, p&lt;0.0001). The increase in baseline to end HDL and difference in lipid lowering drugs were not significant. Adjusting for weight loss, medications had no significant association on trends of HBA1C, SBP and lipid profile.
Conclusions: Among completers, the medically supervised VLCD program at UPMC promotes significant weight loss, glycemic and SBP improvement, and lowering of TC, LDL and TG for over &gt;5 months.

Disclosure
K.B. Detoya: None. K. Han: None. B.R. Register: None. D.A. Rometo: None.
Eyekon Is a Novel Diagnostic Tool for Diabetic Neuropathy
Authors: NASR MOUFIDA BEN , GIULIANI ELENA , D'ADDIO FRANCESCA , MAESTRONI ANNA , USUELLI VERA , MARZOLI STEFANIA BIANCHI , FIORINA PAOLO 
Published: June 2018

Diabetic neuropathy (DN) is a major complication of diabetes, causing more than 50% of all hospital accesses related to type 1 diabetes (T1D). However, diagnostic criteria are not yet standardized, and diagnosis also of symptomatic DN is often underestimated. Given the medical need for an accurate non-invasive diagnostic tool, we developed a test based on tracking eye movement for early detection of DN called Eykon. SRLab -Tobii TX300 Eye tracker®, an eye-tracking device, is coupled with a series of screens on a computer to test the velocity and accuracy of gaze movement in healthy controls (CTRL, n=30), T1D patients without neuropathy (T1D, n=19) and T1D patients with neuropathy (T1D-N, n=14). The screens are divided in 5 classes: Resistance, Wideness, Pursuit, Velocity and OKN. They aim to evaluate both smooth and saccadic movement in different directions. We evaluated a total of 483 parameters and observed that 27 (5.6%) were altered in T1D patients without signs of advanced DN at the electromyography as compared to CTRL, while 29 (6%) were altered in T1D-N patients, for a total of 56 (11.6%) significantly altered parameters (T1D vs. CTRL). Our pilot study demonstrated the feasibility of this non-invasive exam and its ability to early detect DN, despite the limitations of a small number of subjects.

Disclosure
M. Ben Nasr: None. E. Giuliani: None. F. D'Addio: None. A. Maestroni: None. V. Usuelli: None. S. Bianchi Marzoli: None. P. Fiorina: None.
Exercise Training to Target Gait Unsteadiness in People with Diabetes
Authors: BROWN STEVEN J. , BOULTON ANDREW J. , BOWLING FRANK L. , ESQ.  , REEVES NEIL D. 
Published: June 2018

Balance impairment and an associated high fall rate in people with diabetes is common, and a huge burden to quality of life and healthcare systems. Causes of impaired balance are commonly attributed to both sensory and motor deficits, which includes impaired muscle strength and function. This study investigated the effects of resistance exercise training on balance control during walking over level ground and on stairs. Ten DM people (age: 62 years, BMI: 29kg/m2, VPT: 9V) and 6 DM people with DPN (age: 59 years, BMI: 27kg/m2, VPT: 31V) performed a 16-week intervention of weekly resistance exercise training to increase ankle and knee extensor muscle strength. Six DM controls did not take part in the intervention (age: 50 years, BMI: 26kg/m2, VPT: 12V). Balance during gait was quantified before and after the intervention, by separation between the body centre-of-mass and centre-of-pressure under the feet during both level and stair walking. Knee and ankle extensor muscle strength was assessed using a dynamometer. The exercise intervention increased strength of ankle plantar flexors (22%) and knee extensors (30%). Despite the increases in lower limb muscle strength produced by the intervention, no improvements in balance were seen post training. However, gait speed did increase by 8%, which previous research has shown to be associated with quality of life. Controls showed no training effects in any variables. Although this exercise intervention had a positive effect on gait by increasing walking speed, there was no effect on the control of balance. Previous research has identified that medio-lateral (side-to-side) balance is impaired in people with DPN. The muscles exercised in the present study mainly control the major sagittal plane (forwards-backwards) movements that occur during gait. Interventions targeting the lateral stabilising muscles of the hip and trunk, may show greater potential efficacy in redressing the balance impairment of this population.

Disclosure
S.J. Brown: None. A.J. Boulton: None. F.L. Bowling: None. N.D. Reeves: None.
Mast Cell Precursors and Diabetic Neuropathy—Is Immunity the Connection?
Authors: SAMBATARO MARIA , SAMBADO LUISA , TREVISIOL ENRICA , PACCAGNELLA AGOSTINO 
Published: June 2018

Introduction: Diabetic neuropathy and distal foot lesions are common complications of type two diabetic patients (T2DM), however the underlying pathophysiology remains uncertain. Mast cells (MCs) provide a possible link with immunity and neuroinflammation. These cells of innate immune system are found near sensory nerves or the endoneurial compartment, where they differentiate and participate in innate host defense reactions. MCs are involved in wound healing, but their role in diabetes is unknown.
Aim: To evaluate a possible connection between peripheral bone marrow derived blood MC precursors and diabetic neuropathy without and with ischemic skin lesions.
Methods: We enrolled 26 healthy controls (C), 15 T2DM with peripheral sensimotor neuropathy (N) and 14 T2DM with neuropathy, distal ischemia (allux oximetry &lt;30 mm Hg) and foot lesions (N1). Peripheral blood was analysed by flow-cytometry (CD34, CD117, lineage cocktail 1 and FcεRI antibodies).
Results: We found a significant decrease of MC precursors (LIN-, CD34+, CD117+, FcεRI+ cells) in N and N1 (0.00and 0.00051% of mononuclear cells vs. 0.0018% in C, p&lt;0.04). MC number directly correlated with total lymphocyte (p&lt;0.005, R =0.474) T-lymphocyte (p&lt;0.005, R =0.396) and CD4+ T-lymphocyte (p&lt;0.0005, R =0.515) numbers. There was an inverse but not significant correlation with monocytes (p=0.073, R =0.197).
Conclusions: Our results show a possible involvement of MC precursors in human neuropathy and neuroischemic diabetic foot lesions. Conceivably, MCs could have a protective role in favoring wound healing by interaction with cells such as fibroblasts, endothelial, immune, nervous and epithelial cells and by release mediators and neurotransmitters. The correlation with T-lymphocytes might explain the impaired wound healing in N1, suggesting a direct contact between the two populations at the lesion site. Although not significant, the inverse relation with monocytes could be i up-regulated by the decrease in MC precursors.

Disclosure
M. Sambataro: None. L. Sambado: None. E. Trevisiol: None. A. Paccagnella: None.