bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between HbA1c and Haemoglobin of Healthy Adults Visiting a Tertiary Care Hospital in India
Authors: BHARGAVA AMIT , SINGH PARAS , WAGHDHARE SWATI , SIDDIQUI SAMREEN , JHA SUJEET 
Published: June 2018

Objective: To correlate Hemoglobin (Hb) and Glycosylated hemoglobin (HbA1c) levels and to study interquartile differences in HbA1c values of subjects having low Hb (first quartile) vs. High hemoglobin (last quartile).
Methods: We conducted a retrospective study on 1,040 normal healthy adults (Indians and Afghanis) attending a tertiary care hospital to assess the correlation between Hb and HbA1c. Data of past 5 years (2010-2015) was extracted from hospital records. The cohort was divided into 4 groups according to the quartiles of the Hb level (QI = &lt;13 g/dl, QII = 13-14.1 g/dl, QIII = 14.1-15.4 g/dl, QIV &gt;15.4 g/dl). We studied interquartile differences in HbA1c values of subjects having low hemoglobin (first quartile) vs. High hemoglobin (last quartile) values.
Results: The mean of hemoglobin and HbA1c among the Indian subgroup was (13.49 g/dl ± 1.39) and (5.52% ± 0.45) respectively. On the other hand, the mean hemoglobin and HbA1c among Afghani subjects was (14.80 g/dl ± 1.47) and (5.34% ± 0.43), respectively. Mean Hb of Indian males was 14.04±1.28 g/dL and females was 12.56±1.g/dL vs. 15.38±1.16 g/dL in Afghani males and 13.24±1.07 g/dL in Afghani females. Further analysis revealed that HbA1c declines by an average of 0.03% when Hb increases by 1 g/dl in combined dataset. The difference in average FBS level of subjects in quartile 1 of Hb level (99.42 mg/dL) was significantly different from subjects of 4th quartile (95.14 mg/dL), (t = 2.414 and p-value = 0.016).
Conclusion: In our study we had found that Indians have higher BMI, FBS and HbA1c, inspite of having lower Hb as compared to Afghani population. The findings of our study show that with an increase in hemoglobin levels, there is a decrease in Hb1Ac levels. However the same is not clinically significant. Larger studies of subjects with IDA would be useful in examining the impact of IDA on measurement of HbA1c.

Disclosure
A. Bhargava: None. P. Singh: None. S. Waghdhare: None. S. Siddiqui: None. S. Jha: None.
Visiting the Dentist May Help Diagnose Prediabetes
Authors: CZUPRYNIAK LESZEK , SZYMANSKA-GARBACZ ELEKTRA , BIJOS PAWEL 
Published: June 2018

Diabetes is a well known risk factor for periodontal and dental diseases. Despite increasing diabetes awareness, up to a third of diabetes cases remain undiagnosed. We assumed that a visit at the dentist’s is an opportunity to assess one’s glucose tolerance. We conducted a nationwide cross-sectional study evaluating whether a dentist can help diagnose diabetes in at-risk subjects. The study was performed between March and June 2017. Thirty dental surgeries across the country participated in the study. Each surgery was given 20 laboratory referral notes for free fasting plasma glucose (FPG) measurement to be handed over to 20 consecutive eligible individuals who gave their consent to take part in the study. The referred patients were asked to perform FPG test during the following 4 weeks. The study inclusion criteria were: age ≥18 years, any degree of any dental or periodontal disease, presence of at least one diabetes risk factor (i.e., BMI ≥25 kg/m2, family history of diabetes, sedentary lifestyle, past gestational diabetes, hypertension, dyslipidemia, cardiovascular disease, policystic ovary syndrome) and negative history of any glucose intolerance. Out of 600 referred patients, 469 (78.2%, 330 [70.4%] women, mean [±SD] age 53.7±15.4 years) had FPG assessed. Mean FPG in all subjects was 97.2±20.9 mg/dl (range 63-377 mg/dl). In 140 subjects (29.9% of those tested and 23.3% of those referred) impaired fasting glucose (IFG; i.e., FPG ≥100 and &lt;126 mg/dl) was diagnosed. 19 subjects had FPG ≥126 mg/dl. IFG subjects were older than those with normal FPG: 60.1±12.6 vs. 50.9±15.7 years (p&lt;0.001), and were more often men (40% vs. 27%; p&lt;0.01). Odds ratio for IFG in subjects aged ≥60 vs. those &lt;60 years was 3.413 (95% CI 2.215-5.264).
In conclusion, approx. every fourth patient with at least one diabetes risk factor visiting the dentist’s presents with IFG. Dentists should be concerned about prediabetes particularly in their male patients aged ≥60. Increasing diabetes awareness among the dentists may help diagnose prediabetes and thus further prevent diabetes.

Disclosure
L. Czupryniak: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Merck & Co., Inc., Polpharma, Servier. E. Szymanska-Garbacz: Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Merck & Co., Inc. P. Bijos: Employee; Self; Teva Pharmaceutical Industries Ltd..
Lunapark, a Novel Target to miR-126—Its Potential Role in Maintenance of ER and Glucose Homeostasis
Authors: FARIA JULIANA DE A. , GUIMARAES DANIELLA DUQUE , PANTALEAO LUCAS , ONG THOMAS P. , OZANNE AUSAN 
Published: June 2018

Strong evidence suggests that an adverse in utero and/or early postnatal environment impacts on long-term risk of developing type 2 diabetes. We showed previously that miR-126 is increased in adipose tissue of mouse offspring born to obese mothers which leads to impaired insulin signaling pathway by silencing IRS-1 at the translational level. However, the full spectrum of targets of miR-126 and consequently the consequences of its overexpression for adipose tissue function are unknown. The aim of the current study was therefore to identify novel targets of miR-126 using the proteomic technique, known as Pulsed Stable Isotope Labeling by Amino Acids (pSILAC). 3T3-L1-cells were transfected with miR-126 and their proteome compared to those transfected with a scrambled sequence. We detected 4567 proteins that were translated in adipocytes and of these 401 demonstrated a &gt;1.3 fold decrease following over-expression of miR-126. Bioinformatic analysis revealed that 43 of these contained a miR-126 seed sequence in their 3’un-translated region. This included known miR-126 targets such as IRS-1 and VCAM-1 as well as novel targets. One of the largest changes in expression was observed for Lunapark and through the use of luciferase assays and western blotting we independently confirmed this was a direct target of miR-126. Lunapark is a key component for stabilization of nascent three-way junctions in the endoplasmic reticulum (ER). Consistent with this role we observed altered levels of mTOR and XBP1 in cells treated with miR-126, reflecting the presence of ER stress. Together, the results suggest that overexpression of miR-126 can lead to both ER stress and Insulin Resistance and therefore represent a novel link between two pathways that contribute to development and progression to T2DM.

Disclosure
J.A. Faria: None. D. Duque Guimaraes: None. L. Pantaleao: None. T.P. Ong: None. A. Ozanne: None.
Loss of Hypothalamic Somatostatin (SST) Contributes to Bone Marrow (BM) Dysfunction and Diabetic Retinopathy (DR) in Type 2 Diabetic Rats
Authors: LONGHINI ANA LEDA , THINSCHMIDT JEFFREY , BOULTON MICHAEL , KING MICHAEL A. , GRANT MARIA B. 
Published: June 2018

Purpose: Since loss of retinal SST and circulating SST occurs in DR, we asked if loss of hypothalamic SST production would impact the innervation and function of the BM and influence DR in T2D rat model.
Methods: Brain sections of BBZ/Wor rats with 4 months of diabetes and age-matched nondiabetic lean BBZ rats were immuno-stained for SST, Iba-1 and Neu-N. To examine the neuronal connection between the BM and pre-sympathetic brainstem and hypothalamic areas, both control and diabetic rats were injected in a blinded manner with GFP-transgenic pseudorabies virus (PRV-152) into their femurs. Four days later rats were euthanized and brain sections prepared for colocalization of GFP with SST. DR was assessed by enumeration of acellular capillaries in trypsin-digested retinas.
Results: Injection of PRV into femur showed the presence of active virus in neurons of the paraventricular nucleus of the hypothalamus (PVN), rostral ventrolateral medulla and nucleus tractus solitarius of the brain of control rats. Colocalization studies showed that periventricular hypothalamic SST neurons were also GFP+ and directly innervated the BM. Quantitation showed that diabetic rats had significantly fewer GFP+ neurons in the PVN (n=6, *P&lt;0.05), supporting neuronal loss. SST staining of brain sections showed significant reduction in the number of SST+ cells in diabetic rats (58±5) compared with nondiabetic rats (88±6) (n=6, *P&lt;0.05). The density of Iba-1+ microglia increased, while the NeuN+ neurons decreased in the hypothalamus supporting an increase of regional inflammation and neuronal loss. Diabetic rats showed an increase in acellular capillaries compared to controls (15± 4 vs. 4±1mm2) (p&lt;0.001).
Conclusions: These studies support the notion that periventricular hypothalamic SST neurons directly innervate BM and that preservation of this small, but important population is relevant to prevention of diabetes induced-BM dysfunction and development of DR.

Disclosure
A. Longhini: None. J. Thinschmidt: None. M. Boulton: None. M.A. King: None. M.B. Grant: None.
Chronic Kidney Disease (CKD) in U.S. Adults with Type 2 Diabetes (T2D) and Cardiovascular Diseases (CVD)—A National Estimate of Prevalence by KDIGO 2012 Classification
Authors: WANG TONGTONG , XI YUZHI , LUBWAMA ROBERT N. , KORO CAROL 
Published: June 2018

Data on the prevalence of CKD among U.S. adults with T2D and CVD are limited.
The aim of this study was to provide such estimates for T2D, both overall and in those with CVD. Using the NHANES 2007-2014 data, we conducted a cross-sectional analysis of an adult sample with diagnosed and undiagnosed T2D (n=3271), aged ≥18 years. Appropriate sample weights were used to obtain a national estimate.
Results of prevalence of CKD in U.S. adults with T2D are presented in Table 1. The prevalence of moderately to severely decreased renal impairment based on eGFR &lt; 60 ml/min/1.73m2 (Stage 3-5) was 18.0%. The prevalence of mildly decreased renal impairment (Stage 2, eGFR=60-90 ml/min/1.73m2) was 36.9%, including 28.3% with UACR&lt;30 mg/g, 7.0% with UACR ≥ 30-300 mg/g and 1.6% with UACR&gt;300mg/g.
For T2D and CVD subgroup (n=837), the prevalence of moderately to severely decreased renal impairment was 33.6% (Stage 3a: 16.1%; Stage 3b: 12.3%; Stage 4 or 5: 5.2%). The prevalence of mildly decreased renal impairment (Stage 2) was 42.8%, including 29.0% with UACR&lt;30 mg/g, 11.8% with UACR≥ 30-300 mg/g and 2.1% with UACR &gt;300mg/g.
This study confirms the high prevalence of CKD in patients with multiple comorbidities: T2D and CVD. It also provides insights into prevalence of all CKD categories based on KDIGO 2012 classification for U.S. adults with T2D, both overall and those with CVD.

Disclosure
T. Wang: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc.. Y. Xi: None. R.N. Lubwama: None. C. Koro: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; GlaxoSmithKline plc..
Dipstick Proteinuria as a Predictor of End-Stage Renal Disease in Japanese Adults With and Without Diabetes Mellitus (DM)
Authors: FURUYA ATSUSHI , FUJIHARA KAZUYA , OSAWA TAEKO , YAMAMOTO MASAHIKO , HARADA MAYUKO , ISHIZAWA MASAHIRO , SEIDA HIROYASU , YAMANAKA NAUTA , MATSUBAYASHI YASUHIRO , SONE HIROHITO 
Published: June 2018

Although proteinuria is an established potent predictor of the initiation of dialysis, it is unclear whether the impact and clinical relevance of widely used dipstick proteinuria on dialysis differs between adults with and without DM. To clarify this, we longitudinally analyzed a nationwide claim-based database that included 138,554 people aged 18-72 y in Japan. Urinary protein was assessed by test strip, the results of which ± corresponds to ≥15 mg/dL. During the 7-y period, there were 46 and 20 incident cases of dialysis among people with and without DM, respectively. Multivariate Cox analysis showed that, among people without proteinuria, those with DM had a 3.4-fold increased dialysis risk than those without DM whereas, even among individuals without DM, dipstick proteinuria confers a far higher risk of around 20 fold (Table, upper). DM and dipstick proteinuria seemed to additively affect (Table, middle) the initiation of dialysis although those with both DM and proteinuria did not have a significantly higher risk of dialysis than those without DM but with proteinuria (Table, lower). Proteinuria detected by dipstick confers a far higher risk of subsequent dialysis than diabetes per se, but clinicians should be aware of the greatly increased risk for dialysis in those with both DM and dipstick proteinuria, which implies the necessity of intensified interventions.Table Adjusted HRs (95% CI) for initiation of dialysis in individuals with and without DM according to presence or absence of dipstick proteinuria(events / n)Non-DM (46/128,529)DM (20/10,015)Dipstick proteinuriaHR (95% CI)P-valueHR (95% CI)P-value-ref3.37 (1.02-11.1)0.046± or moreref1.98 (0.76-5.13)0.16-ref3.51 (1.35-9.46)&lt;0.01± or more19.0 (10.5-34.3)&lt;0.0135.7 (14.1-90.1)&lt;0.01-0.(0.03-0.10)&lt;0.010.19 (0.07-0.48)&lt;0.01± or moreref1.88 (0.79-4.49)0.15Adjusted for age, sex, BMI, WC, SBP, HbA1c, smoking, HDL-C, LDL-C, TG

Disclosure
A. Furuya: None. K. Fujihara: None. T. Osawa: None. M. Yamamoto: None. M. Harada: None. M. Ishizawa: None. H. Seida: None. N. Yamanaka: None. Y. Matsubayashi: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Restoration of Insulin-Receptor Expression in Adulthood Reverses Diabetic Phenotype in Type 2 Diabetes Models
Authors: WANG YICHEN , ZHOU HEATHER , MU JAMES 
Published: June 2018

Type 2 diabetes mellitus (T2DM) is characterized by ineffective insulin action due to adult onset insulin resistance. Insulin receptor (IR) tissue content reduction in diabetes is one key contributor to the defective insulin signaling and diabetes progression. Rescuing IR levels by transgenic complementation attained beneficial effects. However, such an approach has not been considered as a treatment option since it did not always match physiological expression level or tissue selectivity and was accompanied with developmental defects as reported. In the current study, we showed that expression of human IR (hIR) via a single adeno-associated virus (AAV) administration in adult ob/ob mice normalized blood glucose and plasma triglyceride (TG) to the levels of healthy control mice and significantly lowered liver TG level with long-lasting improvement in insulin sensitivity. To further examine if this approach is applicable for treating adult onset diabetes, we generated inducible whole body IR knockout (iIRKO) mice and successfully induced hyperglycemia, hyperinsulinemia and abnormal liver TG level at 3 months of age. Injection of AAV-hIR reversed tamoxifen-induced diabetic phenotype in iIRKO mice. Western blot analysis showed that while ob/ob and iIRKO mice had IR reduction detected in all metabolic tissues, their diabetic phenotypes were largely rescued by liver tropic IR expression via AAV delivery. More interestingly, the current method had no significant effect on IR expression or metabolism in healthy animals, suggesting that the approach restores IR level only as “needed” to maintain normal energy metabolism so it does not increase the risk of excessive insulin action, such as hypoglycemia. The approach described here effectively restores IR expression and insulin signaling with long lasting efficacy and low risk, which supports its therapeutic utility in the treatment of T2DM and metabolic disorders.

Disclosure
Y. Wang: None. H. Zhou: Employee; Self; Merck & Co., Inc.. J. Mu: None.
Epigenetics and Mitochondrial Stability in Diabetic Retinopathy
Authors: KOWLURU RENU , MISHRA MANISH 
Published: June 2018

Mitochondria constantly fuse and divide to form a cellular network, and this dynamic fusion-fission controls their function and genome stability. Although both, mitofusin 1 and 2 (Mfn1 and 2) regulate outer mitochondrial membrane fusion, Mfn2 itself is sufficient to modulate mitochondrial metabolism. In diabetes, retinal mitochondria are swollen, respiration is impaired, Mfn2 is decreased and mtDNA is damaged. Diabetes also facilitates epigenetic modifications, altering gene expressions without changing their DNA sequences. This study aims to investigate the role of DNA methylation of Mfn2 in the development of diabetic retinopathy.
Methods: Human retinal endothelial cells, incubated in normal (5mmols/L) or high glucose (20mmols/L) for four days, in the presence/absence of DNA methyltransferase (Dnmt) inhibitors (5-Azacytidine or Dnmt1-siRNA), were analyzed for methylated cytosine (5mC) at Mfn2 promoter by immunocapturing method. Mitochondrial integrity was evaluated by membrane permeability, coenzyme Q: cytochrome-c reductase (complex-III) activity, and transcripts of mtDNA-encoded cytochrome b (Cytb). Similar measurements were made in the retinal microvessels from streptozotocin-induced diabetic mice receiving 5-Aza (2.5mg/kg, i.p.) or Dnmt1-siRNA (2µg/2µl, intravitreal).
Results: High glucose increased 5mC levels at Mfn2 promoter by over 2 fold, and decreased Mfn2 expression. Dnmt inhibition ameliorated glucose-induced increase in 5mC at Mfn2 and mitochondrial membrane permeability, and decrease in Mfn2 expression, complex III activity and Cytb transcripts. Similarly, in mouse retinal microvessels, inhibition of Dnmt prevented diabetes-induced increase in 5mC at Mfn2 promoter and decrease in Mfn2 expression.
Conclusions: In diabetes, epigenetic modifications of Mfn2 promoter impair mitochondrial functional and genomic stability. Thus, targeting DNA methylation could help maintain mitochondrial homeostasis, and halt/retard the development of diabetic retinopathy.

Disclosure
R. Kowluru: None. M. Mishra: None.
Increased Hemoglobin A1c Correlates with Increased Liver Stiffness in a Mexican-American Population
Authors: WATT GORDON P. , LEE MIRYOUNG , PAN JEN-JUNG , FALLON MICHAEL , MCCORMICK JOSEPH B. , FISHER-HOCH SUSAN P. 
Published: June 2018

Introduction: Liver stiffness measured by transient elastography (TE) predicts liver fibrosis progression and risk of hepatocellular carcinoma. Studies have shown associations between liver stiffness and diabetes, insulin resistance, and obesity, independent of steatosis. In this study, we aimed to determine whether glucose control (hemoglobin A1c) was associated with liver stiffness in a sample of Mexican Americans with high rates of liver disease in south Texas.
Methods: Liver stiffness was measured in 159 participants in the community-based Cameron County Hispanic Cohort study in Brownsville, Texas. Univariable and multivariable linear regression was used to determine associations between HbA1c and log-transformed liver stiffness (log kPa) after adjusting for demographic and clinical covariates. Results are presented as Z-standardized β and p-values.
Results: One hundred fifty-nine participants underwent TE, and 6 were excluded due to unreliable results. Overall, 25% had diabetes and 44% were obese, with median age of 52 years. In univariable analysis, liver stiffness was associated with log HbA1c (β = 0.24, p = 0.0027), controlled attenuation parameter (CAP; β = 0.22, p = 0.0033), waist circumference (β = 0.30, p &lt; 0.0001), and with log insulin (β = 0.16, p = 0.0574). In multivariable analysis, log HbA1c was robustly associated (β = 0.18, p = 0.0260) with liver stiffness after adjusting for age, sex, CAP, waist circumference, and insulin levels.
Discussion: This study presents evidence of a relationship between glucose control and liver stiffness, independent of steatosis, in high-risk Mexican Americans sampled from a population-based study in the U.S. Our results suggest that HbA1c may be an important tool for prevention and management of liver disease. Longitudinal follow-up studies are needed to determine if glucose control over time modulates risk of liver-related morbidities.

Disclosure
G.P. Watt: None. M. Lee: None. J. Pan: None. M. Fallon: None. J.B. McCormick: None. S.P. Fisher-Hoch: None.
Characteristics and Impact Factors of Different Renal Glucose Thresholds in Patients with Type 2 Diabetes Mellitus in China
Authors: HUANG XIUTING , GAO XUEYING , CAI XIAOLING , JI LINONG 
Published: June 2018

Background: The aim of this study was to assess the clinical features of different renal glucose threshold (RGT) groups with type 2 diabetes (T2DM) patients.
Methods: A total of 2123 Chinese patients with T2DM hospitalized from Jan 2012 to Sep 2017 was collected in the study, including 174 patients with high RGT(defined as the absence of glycosuria when fasting plasma glucose (FPG) &gt; 10 mmol/L), 111 patients with low RGT(defined as a the absence of glycosuria when FBG &lt; 8 mmol/L) and 1838 patients with normal RGT.
Results: Compared with normal RGT, patients with high RGT showed higher HbA1c, FPG, postprandial glucose (PPG) (P&lt;0.001), triglycerides (TG) (P=0.008), total cholesterol (TC) (P=0.010) and urinary albumin creatinine ratio(UACR) (P=0.025), but lower Homeostatic Model Assessment of β cell (HOMA-β) (P=0.010), and were more likely to have diabetic peripheral neuropathy (DPN) (P=0.001). The high RGT group was composed of significantly more female patients (P&lt;0.001). A logistic regression analysis showed that FPG and TG were negatively associated with normal RGT after adjusting for age, sex and BMI. Compared with normal RGT, low RGT patients showed lower FPG (P=0.023), and lower waist to hip ratio and uric acid(UA) (P&lt;0.05) in female. A logistic regression analysis showed that FPG and UA were positively associated with normal RGT. Compared with low RGT, high RGT patients showed higher HbA1c, FPG, PPG, TG, TC (P&lt;0.05) but lower HOMA-β(P=0.016), and were more likely to have DPN (P=0.010). The high RGT group was composed of significantly more female patients (P&lt;0.001). A logistic regression analysis showed that FPG was negatively associated with low RGT.
Conclusions: Our results indicate that the presence of T2DM subtypes characterized by different RGT. Patients with high RGT have higher glucose, TG and UACR levels, but lower levels of HOMA-β. HbA1c, FPG, TG, and UA were associated with RGT.

Disclosure
X. Huang: None. X. Gao: None. X. Cai: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Eli Lilly and Company, Bristol-Myers Squibb Company, Novartis AG, Novo Nordisk A/S, Merck & Co., Inc., Bayer AG, Merck Sharp & Dohme Corp., Takeda Development Center Asia, Pte. Ltd., Sanofi, Roche Pharma, Boehringer Ingelheim GmbH. Research Support; Self; AstraZeneca, Roche Pharma, Sanofi, Merck Sharp & Dohme Corp., Novartis AG, Eli Lilly and Company, Bristol-Myers Squibb Company.