bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Sleep Disturbances Are Predictive of Incident Diabetes in Older AdultsߞVariations by Gender and Race/Ethnicity
Authors: GUYER HEIDI 
Published: June 2018

Study Objectives: The current study was conducted to determine whether self-reported chronic sleep disturbances are predictive of incident diabetes in older adults, as well as to determine variations by gender and race/ethnicity.
Methods: 7446 participants from the Health and Retirement Study, a nationally-representative longitudinal cohort study of U.S. adults, were followed for eight years, between 20and 2014. Chronic sleep disturbance was defined as self-reported trouble falling asleep or staying asleep “most of the time.” Diabetes was based on self-reported doctor’s diagnosis or a Hemoglobin A1C value &gt;=6.5mg/dl. Hazard ratios were calculated for baseline and on-going sleep disturbances.
Results: The average age of participants was 63.5 years. Close to 30% of men and 40% of women reported having a chronic sleep disturbance at baseline. The cumulative incidence of diabetes was 17.7% among men and 15.2% among women. Both men and women who developed diabetes were more likely to report chronic sleep disturbances at baseline than those who did not develop diabetes (men: 32.2% vs. 27.3%; women: 44.2% vs. 36.0%). Women were more likely to develop diabetes within eight years than men after adjustment for demographic covariates (women: HR 1.40 95% CI 1.19-1.63; men HR 1.27 95% CI 0.98-1.66). Black and Hispanic men and women with chronic sleep disturbances had a greater likelihood of developing diabetes within eight years than white men and women.
Conclusions: Self-reported chronic sleep disturbance is an independent predictor of incident diabetes in women. The likelihood of developing diabetes among those with chronic sleep disturbances is greater for women than men and greater for blacks and Hispanics than non-black/Hispanic older adults. This finding has both public health and clinical relevance in an aging society.

Disclosure
H. Guyer: None.
Lower Hepatic Insulin Sensitivity in a Family with a Recently Described Glucokinase Gene Variant
Authors: BÓDIS KÁLMÁN , ZAHARIA OANA P. , KARUSHEVA YANISLAVA , BOBROV PAVEL , MARKGRAF DANIEL F. , KNEBEL BIRGIT , KUPRIYANOVA YULIYA , HWANG JONG-HEE , BURKART VOLKER , MÜSSIG KARSTEN , RODEN MICHAEL , SZENDROEDI JULIA 
Published: June 2018

Mutations in the gene encoding glucokinase (GCK) cause maturity-onset diabetes of the young (MODY) 2, characterized by impaired prandial insulin secretion and hepatic glycogen storage. Recently diagnosed patients with type 1 diabetes (T1D) exhibit impairment of both beta cell function and hepatic energy metabolism. Thus, this study aimed at examining the effect of MODY 2 on hepatic insulin sensitivity and energy metabolism. Carriers of one recently described GCK mutation (D124N; c.370, GAC&gt;AAC in exon 4) were compared to controls (CON) with similar sex, age and body mass index (BMI) (female/male: 1/2 vs. 3/6; 36±4 vs. 35±2 years; 20.1±1.6 vs. 25.7±1.5 kg/m2) from the German Diabetes Study (Registration_Clinicaltrials.gov NCT01409330). Whole body and hepatic insulin sensitivity (IS) were assessed by Botnia-clamp tests with [6,6-2H2]glucose. Beta cell function was determined from incremental AUC(C-peptide)0-60min/δAUC(glucose)0-60min during intravenous glucose tolerance test. Hepatocellular lipid content (HCL), γATP and inorganic phosphate (Pi) were measured with by 1H/31P magnetic resonance spectroscopy. MODY 2 patients had higher hemoglobin A1c (6.1±0.1 vs. 5.2±0.1%, p&lt;0.001) along with approximately 62% lower glucose-stimulated C-peptide secretion than CON (p&lt;0.05). They also had lower hepatic IS (1.8±0.1 vs. 2.3±0.1 mg/(kg*min), p&lt;0.05), but similar whole body IS (12.6±1.9 vs. 13.1±1.5 mg/(kg*min), p=0.87) compared to CON. However, HCL (1.0±0.9 vs. 0.5±0.2%, p=0.46), γATP (3.5±0.3 vs. 3.5±0.6 mmol/l, p=0.99) and Pi (1.9±0.5 vs. 2.9±0.7 mmol/l, p=0.45) in the liver were comparable between both groups.
In conclusion, these data show that lower hepatic IS, but not abnormal hepatic energy metabolism, underlies the previously reported reduction in prandial hepatic glycogen synthesis. Moreover, impairment of hepatic IS is not necessarily associated with hepatic mitochondrial function.

Disclosure
K. Bódis: None. O.P. Zaharia: None. Y. Karusheva: None. P. Bobrov: None. D.F. Markgraf: None. B. Knebel: None. Y. Kupriyanova: None. J. Hwang: None. V. Burkart: None. K. Müssig: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. J. Szendroedi: None.
Incidence of Chronic Kidney Disease and Progression of Renal Dysfunction in Type 2 Diabetes-The Role of Albuminuria
Authors: NICHOLS GREGORY , DERUAZ-LUYET ANOUK , HAUSKE SIBYLLE , BRODOVICZ KIMBERLY 
Published: June 2018

Chronic kidney disease (CKD) is typically assessed by estimated glomerular filtration rate (eGFR), but the predictive value of albuminuria to worsening eGFR in routine clinical practice has not been well documented. We calculated the rate of progression of renal dysfunction measured by eGFR for clinically recognized categories of albuminuria. Using a longitudinal design and the electronic medical records of Kaiser Permanente Northwest, we identified 13,358 diabetes patients who had a serum creatinine (SCr) and urine albumin creatinine ratio (UACR) in 2006-2012 and at least one subsequent measure of each 2006-2016. From those values, we allocated each patient to a baseline eGFR and UACR category according to Kidney Disease: Improving Global Outcomes guidelines. We then calculated progression rates to each higher category of eGFR per 1,000 person-years (p-y) over 11 years of follow-up adjusted for age, sex, race/ethnicity, systolic blood pressure, and use of angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARB). We compared these rates by baseline UACR categories. Higher levels of albuminuria at baseline significantly increased the risk of progression of eGFR-based kidney dysfunction (Table). Our results from routine clinical practice demonstrate the key role of albuminuria in the worsening of renal function in a general diabetes population.

Disclosure
G. Nichols: Research Support; Self; Boehringer Ingelheim GmbH, Amarin Corporation, Janssen Pharmaceuticals, Inc., Sanofi. A. Deruaz-Luyet: Employee; Self; Boehringer Ingelheim GmbH. S. Hauske: Employee; Self; Boehringer Ingelheim GmbH. K. Brodovicz: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc..
Sex Hormones and Development of Chronic Kidney Disease in the Diabetes Prevention Program Outcomes Study (DPPOS)
Authors: KIM CATHERINE , RICARDO ANA , BOYKO EDWARD J. , CHRISTOPHI COSTAS A. , TEMPROSA MARINELLA , WATSON KAROL , PI-SUNYER XAVIER , KALYANI RITA RASTOGI ,   DPP RESEARCH GROUP
Published: June 2018

Whether endogenous sex hormones are associated with chronic kidney disease (CKD) is not known. We conducted a secondary analysis of longitudinal data from the DPPOS, the follow-up study of the Diabetes Prevention Program (DPP), a randomized trial of diabetes prevention that assigned participants to placebo, metformin, or lifestyle intervention. This analysis included overweight and glucose-intolerant men (n=889) and women (n=1281) not using exogenous sex hormones who had urine albumin-to-creatinine ratio [ACR] &lt; 30 mg/g and normal estimated glomerular filtration ratio [eGFR] ≥ 60 ml/min/1.73 m2.
Sex hormones (dehydroepiandrosterone [DHEAS], dihydrotestosterone, testosterone, estradiol, estrone, and sex hormone binding globulin [SHBG]) were measured at baseline. CKD was defined as incident low eGFR and/or albuminuria ACR ≥ 30 mg/g. eGFR and ACR were measured annually over 11 years of DPPOS follow-up. Multivariable Cox regression models adjusted for eGFR and log-ACR, age, race/ethnicity, body mass index, blood pressure, insulin resistance, high-density lipoprotein, C-reactive protein, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers at baseline.
At baseline, the mean (SD) of eGFR was 94 (15) ml/min/1.73 m2, and the median (IQR) of ACR was 4.5 (3.3-7.6) mg/g. During the follow-up period, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Fifty-four (7.1%) of men and 43 (3.9%) of women had both abnormalities. Among men, higher SHBG was associated with lower risk of low eGFR (pooled hazard ratio [HR] per SD, 95% confidence interval [CI]: 0.73 [0.57, 0.9], p=0.01) and lower risk for CKD (pooled HR per SD 95% CI: 0.78 [0.64, 0.95], p=0.01). No significant associations were observed among women.
We conclude that among overweight glucose-intolerant men, higher SHBG was associated with reduced risk of CKD.

Disclosure
C. Kim: None. A. Ricardo: None. E.J. Boyko: None. C.A. Christophi: None. M. Temprosa: Other Relationship; Self; Merck KGaA. K. Watson: None. X. Pi-Sunyer: None. R. Rastogi Kalyani: None. D. Research Group: None.
Race and Sex Differences in Diabetic Complications in a Large Health Care System
Authors: YIN PING , SHI LIZHENG , NAUMAN ELIZABETH , KATZMARZYK PETER T. , PRICE-HAYWOOD EBONI G. , BAZZANO ALESSANDRA N. , SHEN YUN , HU GANG 
Published: June 2018

Existing studies of racial differences in diabetic complications between African Americans and whites have provided conflicting results. The objective of this study was to investigate race and sex differences in diabetic complications between African-American and white patients in Louisiana’s largest integrated health delivery system. We performed a prospective cohort study of 28,218 African Americans and 31,237 whites with diabetes. Cox proportional hazards regression was used to estimate the relative risk of each of four health outcomes between African Americans and whites. The age- and sex-adjusted incident rates per 1,000 person-years and 95% confidence intervals (CI) of coronary heart disease (CHD), heart failure, stroke, and end-stage renal disease (ESRD) for African-American patients with diabetes were 59.8 (95% CI 57.7-62.0), 43.5 (41.7-45.4), 34.0 (32.4-35.7), and 56.5 (53.8-59.3), respectively. Compared with African-American patients with diabetes, white patients with diabetes had a higher age- and sex-adjusted incident rate of CHD [63.3 (61.2-65.3)] and lower rates of heart failure [32.0 (30.6-33.4)], stroke [29.7 (28.4-31.1)] and ESRD [45.7 (44.0-47.4)]. Men with diabetes had higher age-adjusted incident rates of CHD, heart failure, and ESRD than women with diabetes. Results of the Cox proportional hazard models confirmed racial and sex differences observed in the age- and sex-adjusted incident rates. African Americans with diabetes have higher risks of heart failure, stroke and ESRD than white counterparts, whereas whites with diabetes have a higher risk of CHD than African-American counterparts.

Disclosure
P. Yin: None. L. Shi: None. E. Nauman: None. P.T. Katzmarzyk: None. E.G. Price-Haywood: None. A.N. Bazzano: None. Y. Shen: None. G. Hu: None.
Racial Variation in the Relationship of Diabetes with Pancreatic Cancer Risk
Authors: CONWAY BAQIYYAH , BLOT WILLIAM J. 
Published: June 2018

Pancreatic cancer is one of the most fatal malignancies, with a 5-year survival of &lt;8% and is the 4th leading cause of cancer death. It is also one of the cancers most tightly linked to diabetes even when recent diabetes diagnosis and reverse causation are ruled out. The highest rates of pancreatic cancer are found among blacks in the U.S., yet despite nearly twice the prevalence of diabetes among blacks compared to whites, as well as blacks’ increased prevalence of obesity, another key risk factor, little is known about the interrelationship between diabetes and pancreatic cancer among blacks and whether this accounts for the observed racial disparity. We tested the relationship of diabetes with the incidence of pancreatic cancer and whether this relationship varied between blacks and whites. Our null hypothesis was that diabetes would not differentially increase risk among blacks compared to whites. Using the Southern Community Cohort Study, we conducted a cancer follow-up (2002-2015) of a cohort of mostly low income black and white participants aged 40-79 with (n=17,644) and without diabetes (n=64,870) at cohort entry. Mean age and diabetes duration of those with diabetes was 55.0 and 9.5 years, respectively. Mean age of those without diabetes was 51.6 years. Logistic regression was used. A total of 307 incident cases of pancreatic cancer were observed. In analysis controlling for age, sex, race, current and former smoking, and BMI, diabetes was a significant risk factor for pancreatic cancer (OR=1.48, 95% CI= 1.13-2.94). In race-stratified analyses, the increases associated with diabetes were seen both among blacks (OR= 1.46, 95% CI=1.06-2.02) and whites (OR=1.60, 95% CI= 0.95-2.67). After control for diabetes, the black excess in risk of pancreatic cancer was attenuated (OR=1.25, 95% CI=0.96-1.64). The findings suggest that diabetes affects pancreas cancer risk regardless of race, but that the higher prevalence of diabetes among blacks contributes to their elevated risk of pancreatic cancer.

Disclosure
B. Conway: None. W.J. Blot: None.
Copper Is Associated with Metabolic Syndrome and Fasting Blood Glucose in Non-Hispanic Black—Results from National Health and Nutrition Examination Survey
Authors: HE XIAOWEI , YU YUN , LOU QINGLIN , TANG WEI 
Published: June 2018

Background: The metabolic syndrome is a cluster of risk factors which predicts future cardiovascular disease and type 2 diabetes. Evidences have showed that a disorder in serum Copper (Cu) level could have effects on human health. However, little data are available regarding how serum Cu affects metabolic syndrome in adults.
Method: Data from 3,375 subjects were examined from a nationally representative sample of the U.S. adults in the National Health and Nutrition Examination Survey 2011-2014. The metabolic syndrome was defined as satisfying three or more of the five criteria from the National Cholesterol Education Panel definition. Multivariate logistic and linear regression were applied to investigate the associations of serum Cu levels with metabolic syndrome prevalence and its component.
Results: In the logistic models, non-Hispanic black with the highest serum Cu levels demonstrated a greater increase in risk of metabolic syndrome (OR: 2.69, 95% CI: 1.08-6.70, P for trend= 0.001) when compared to those with the lowest serum Cu levels. Moreover, we identified a remarkable association between serum Cu levels and high fasting blood glucose condition in non-Hispanic black (OR: 2.44, 95% CI: 1.04-5.76, P for trend= 0.031). No significant associations between serum Cu level and other components of metabolic syndrome were observed, regardless of race. In the linear regressions, a strong positive association between serum Cu levels and fasting blood glucose was also observed (coefficient= 0.231, 95% CI: 0.053-0.409, P&lt; 0.001) in non-Hispanic black.
Conclusion: Our results provide the first epidemiological evidence that serum Cu concentrations may be positively associated with the prevalence of metabolic syndrome and with fasting blood glucose in non-Hispanic black. Further clinical and animal studies are urgently needed to clarify the putative causal relationships.

Disclosure
X. He: None. Y. Yu: None. Q. Lou: None. W. Tang: None.
Health Disparity in Diabetes Care—Impact of Community Health Representative–Led Patient Activation and Engagement
Authors: SHAH VALLABH , PANKRATZ VERNON S. , GHAHATE DONICA M. , BOBELU JEANETTE , NELSON ROBERT 
Published: June 2018

Objective: To compare the impact of home-based care and education delivered by community health representatives (CHRs) as part of a clinical care team vs. usual clinic-based care on measures of patient activation and risk factors for diabetes in adult Zuni Indians.
Methods: We conducted a pilot randomized controlled trial of a home-based intervention vs. usual clinic care provided by the local Zuni Indian Health Service (IHS). The study’s primary outcome was patient activation, assessed by the Patient Activation Measure (PAM). We screened 315 Zuni adults and enrolled and randomized 125 Zuni adults into the study. We used linear and logistic regression with generalized estimating equations to compare changes in the outcomes of interest over time between the two study groups.
Results: Compared to those receiving usual care at IHS, Zuni adults in the intervention group experienced significantly greater improvement in the patient activation measure, quality of life, and in several clinical measures of risk factors for diabetes at 12 months. Participants in the intervention increased their PAM total scores, on average, by 8.6 points more than participants randomized to usual care (p=0.023). BMI in the intervention group decreased by 1.kg/m2 more than was observed in the control group (p=0.007). Hemoglobin A1C levels in the intervention group decreased by 8% more than in the control group (p=0.022). The hs-CRP levels in the intervention group decreased by 62% more than in the control group (p&lt;0.001).
Discussion: Delivering culturally appropriate home-based care and education by CHRs is a promising approach for improving disease-specific knowledge, confidence, and self-management skills among rural minority populations at high risk for diabetes who experience barriers to accessing health care.

Disclosure
V. Shah: None. V.S. Pankratz: None. D.M. Ghahate: None. J. Bobelu: None. R. Nelson: None.
Long-Term Survival in 200 Patients with Advanced Stage of Colorectal Carcinoma and Diabetes Mellitus—A Single Institution Experience
Authors: SATEJ NIKA , BESIC NIKOLA , PAVLIC ANA , POVSIC MILENA KERIN 
Published: June 2018

Objective: Colorectal cancer surgery is often followed by postoperative complications which may impact survival. Diabetes mellitus (DM) and DM related comorbidities may initiate difficulties during cancer specific treatment and may have an impact on cancer management and outcome. The aim of our study was to find out if DM in patients with advanced colorectal carcinoma is associated with cancer-specific and overall survival.
Material and Methods: This study included 200 consecutive patients (131 males, 69 females, mean age 63 years) with elective colorectal cancer surgery at the Institute of Oncology Ljubljana from September 2010 to March 2013. Even 64% of patients had Stage 3 or 4 disease, so neo-adjuvant chemotherapy and/or radiotherapy were carried out in 59% of cases. DM was found in 39 (19.5%) patients. Data about gender, age, body mass index, presence of DM, American Society of Anesthesiologists (ASA) physical status score, stage of disease and postoperative complications were collected prospectively. Univariate survival analysis was used to identify factors correlated with disease-specific and overall survival.
Results: Patients with DM had higher ASA score and BMI than those without DM. Rectum, colon and both of them were affected by cancer in 68%, 30% and 2% of cases, respectively. Stage 3 or 4 disease was found in patients with DM and without DM in 62% and 65%, respectively. Mean follow-up period was 4.75 years. Recurrence was diagnosed in 23% of patients with DM and in 25% of patients without DM. Altogether 41 patients died of cancer and 12 patients of other causes. Three-year cancer-specific survival in patients with DM and without DM was 85% and 89%, respectively (p=0.68). Three-year overall survival in patients with DM and without DM was 82% and 84%, respectively (p=0.63).
Conclusions: Presence of DM was not associated with tumor stage, disease-specific survival or overall survival in our group of patients with advanced colorectal carcinoma.

Disclosure
N. Satej: Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi, AstraZeneca. N. Besic: Speaker's Bureau; Spouse/Partner; Novo Nordisk Inc., AstraZeneca, Sanofi. A. Pavlic: None. M. Kerin Povsic: None.
Circulating Exosomal miRNA Signature in Gestational Diabetes Mellitus Influences Glucose Metabolism in Placental Cells
Authors: NAIR SOUMYALEKSHMI , ORMAZABAL VALESKA , JAYABALAN NANTHINI , GUANZON DOMINIC , LAI ANDREW , DAVID MCINTYRE H. , LAPPAS MARTHA , SALOMON CARLOS 
Published: June 2018

There is increasing evidence that miRNA, which are enriched in small nanovesicles called exosomes, are important regulators of gene expression. In this study, we tested the hypothesis that circulating exosomes from womem with gestational diabetes mellitus (GDM) carry a specific set of miRNAs which regulate genes associated with placental glucose metabolism. Exosomes were isolated from plasma obtained from normal glucose tolerant women (NGT; n=12) and women with GDM (n=12) pregnancies at delivery by differential and buoyant density centrifugation. Exosomal RNA was extracted and an Illumina TrueSeq Small RNA kit was used to construct a small RNA library. Gene target identification and gene ontology analysis for miRNAs was performed using the Ingenuity pathway analysis (IPA). The effect of exosomes on glucose metabolism in placental cells was assessed using a human glucose metabolism array. In plasma, a total of 44 miRNAs were upregulated in exosomes from women with GDM compared to NGT pregnant women (p&lt;0.005). IPA showed that exosomal miRNAs isolated from women with GDM regulates the expression of placental genes associated with the glycolytic pathway including 6-phosphofructokinase and phosphopyruvate hydratase. Interestingly, exosomes from women with GDM increases the expression of placental genes associated with glycolysis and decrease the expression of genes associated with pentose phosphate pathway. After integration of the miRNA and mRNA data, we identified 74 differentially expressed exosomal miRNAs associated with the modulation of 10 potential target mRNAs in placental cells, which are associated with glucose metabolism. This data suggests that circulating exosomes under diabetic conditions might modulate the placental metabolic state to enhance glycogen metabolism in GDM.

Disclosure
S. Nair: None. V. Ormazabal: None. N. Jayabalan: None. D. Guanzon: None. A. Lai: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy. M. Lappas: None. C. Salomon: None.