bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Liraglutide, Metformin, and Gliclazide on Body Composition in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease—A Randomised Trial
Authors: FENG WENHUAN , BI YAN , LI PING , YIN TINGTING , GAO CAIXIA , SHEN SHANMEI , GAO LIJUN , JIANG CAN , ZHU DALONG 
Published: June 2018

Objective: To compare the effects of gliclazide, liraglutide, and metformin on body composition in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD).
Methods: Eighty-five subjects were randomly allocated and received gliclazide (n=27), liraglutide (n=29), or metformin (n=29) monotherapy for 24 weeks. Body composition was measured using dual-energy x-ray absorptiometry.
Results: Liraglutide and metformin reduced weight and total, trunk, limb, android, and gynoid fat mass. However, no significant changes in weight or fat mass occurred with gliclazide. In the liraglutide and metformin arms, weight loss was mainly due to reductions in total, trunk, limb, android, and gynoid fat mass. The stable weight obtained with gliclazide resulted from identical reductions in fat mass and increases in lean tissue mass. Blood glucose concentrations and glycated haemoglobin A1c (HbA1c) levels improved in all treatment arms, but lower HbA1c levels were found with liraglutide and metformin. Serum alanine aminotransferase (ALT) concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase (AST) concentrations reduced with liraglutide and metformin only. For all subjects, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with reductions in serum ALT and AST concentrations, and reductions in waist circumference were positively correlated with reductions in serum ALT concentrations.
Conclusions: As compared with gliclazide monotherapy, liraglutide and metformin monotherapies resulted in greater weight loss, reductions in body fat mass, and improvements in liver function and blood glucose control among patients with T2DM and NAFLD.

Disclosure
W. Feng: None. Y. Bi: None. P. Li: None. T. Yin: None. C. Gao: None. S. Shen: None. L. Gao: None. C. Jiang: None. D. Zhu: None.
Longitudinal Predictors of Insulin Sensitivity and Secretion during Puberty
Authors: KELSEY MEGAN M. , PYLE LAURA , HILKIN ALLISON M. , JOHNSON AIMEE , NADEAU KRISTEN J. , ZEITLER PHIL 
Published: June 2018

All youth experience a transient reduction in Si during puberty, but little is known about the associated physiology. We previously demonstrated cross-sectionally that insulin-like growth factor 1 (IGF-1) and leptin are associated with Si early in puberty. We now aim to evaluate longitudinal predictors of Si and acute insulin response to glucose (AIRg) during puberty.
Methods: Forty-five (47% female) normal-weight (mean BMI %ile 44±22%) ethnically mixed youth entered the study in early puberty (Tanner [T] 2-3). Study visits, including an IV glucose tolerance test (IVGTT), fasting laboratory studies, and DXA, were performed at T2-3, T4, and T5, based on breast development and testicular volume. Physical activity (PA) was assessed by the 3DPAR (3-Day PA Recall). Repeated measures models were used to test if changes over time in potential predictors (IGF-1, leptin, estradiol, total testosterone, dehydroepiandrosterone-sulfate, PA, and urinary gonadotropins) were associated with changes over time in the outcomes, with and without adjustment for sex and % body fat.
Results: Si (p=0.04) decreased and AIRg increased (p=0.12) from T2/3-T5. IGF-1 and leptin were the only significant predictors of change in Si and AIRg over time. IGF-1 was associated with both Si (β=-0.016, p=0.0004) and AIRg (β=1.40, p=0.002), and remained so after adjusting for sex and % fat (p=0.0007 and 0.004, respectively). Leptin was associated with Si in univariate analysis (p=0.003) and with both Si (β=-0.238, p=0.003) and AIRg (β=38.4, p=0.043) after adjustment for sex and % fat.
Conclusions: This is the first study to show a longitudinal relationship between leptin and Si and AIRg during puberty independent of sex and body fat, and confirms previous reports of associations between IGF-1 and Si and AIRg. These results suggest that leptin and IGF-1 may be driving factors for changes in Si and AIRg during puberty. Knowledge of normal pubertal metabolism may contribute to understanding of diseases of pubertal onset, such as type 2 diabetes.

Disclosure
M.M. Kelsey: Other Relationship; Self; Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp.. L. Pyle: None. A.M. Hilkin: None. A. Johnson: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH.
Increased Glucagon, but Reduced GIP Secretion, in Adolescents with Obesity and T2DM
Authors: KRISTINSSON HJALTI , MANELL HANNES , VILHELMSSON MONICA , PRESTO JENNY , GÄREDAL CAROLINA , RITZÉN HANNA , FORSLUND ANDERS H. , BERGSTEN PETER 
Published: June 2018

We have previously reported that insulin and glucagon levels at fasting and during OGTT are increased in obese adolescents as glucose intolerance develops. In adults incretin hormone GIP has been coupled with enhanced glucagon secretion. We hypothesized that the observed elevated glucagon levels in obese adolescents were associated with increased levels of GIP. Total GIP in plasma samples from obese (NGT=7, IGT=9, T2DM=4) and lean (n=8) adolescents was measured at fasting and during OGTT with a newly developed ELISA (Mercodia AB, Uppsala, Sweden). Newly secreted GIP and glucagon were defined as GIP and glucagon area under curve AUC during the first 30 min, AUC30. Ethical approval was obtained from the Uppsala Ethical Review Board. Fasting GIP levels ± SEM were 4.7 ± 2.8, 3.6 ± 2.0, 2.9 ± 1.7 and 2.2 ± 0.9 pM in lean, obese NGT, obese IGT and obese T2DM adolescents, respectively. During OGTT GIP concentrations peaked at 30 min for all groups (Figure). Highest concentrations were observed throughput the OGTT in lean, followed by obese NGT, obese IGT and obese T2DM adolescents. GIP AUC30 ± SEM was 1181 ± 197, 920 ± 22, 707 ± 146 and 699 ± 211 pmol/L *min in lean, obese NGT, obese IGT and obese T2DM, respectively. For the same groups glucagon AUC30 ± SEM was -73 ± 21, -39 ± 43, -3 ± 30 and 91 ± 80 pmol/L *min. Hyperglucagonemia in adolescents developing T2DM does not seem to be driven by enhanced GIP secretion.

Disclosure
H. Kristinsson: None. H. Manell: None. M. Vilhelmsson: Employee; Self; Mercodia AB. J. Presto: Employee; Self; Mercodia AB. C. Gäredal: None. H. Ritzén: None. A.H. Forslund: None. P. Bergsten: None.
Perceptions of Physical Activity in American-Indian Youth at Risk for Diabetes
Authors: KIMBLEY HEATHER , CHADWICK JENNIFER , COLEMAN CHARLOTTE L. , TULLIER MARY A. , WOLBERT LISA D. , COPELAND KENNETH C. , SHORT KEVIN R. 
Published: June 2018

American Indians (AI) have high prevalence of diabetes, which might be reduced through targeted lifestyle changes. We conducted an exercise program for AI adolescents at risk for diabetes. We tested whether the participants’ perceptions of physical activity were related to their physical characteristics or exercise participation. Overweight (OW) AI youth (n = 75), 11-20 years old, with low physical activity, were instructed to exercise 3d/week for 16 weeks at tribal centers. Another 39 normal weight (NW) peers from the same communities served as a reference group but did not enter the exercise program. Perceived comfort and enjoyment of physical activity was measured on a 15-item, 5-point scale. Clinical tests included body composition, aerobic fitness (VO2pk), and physical activity (daily steps). Mean perception score was higher (more positive outlook) for NW than OW/Ob (4.1 ± 0.5 vs. 3.5 ± 0.6, p &lt; 0.001) and for boys than girls (3.9 ± 0.5 vs. 3.5 ± 0.6, p &lt; 0.02). Perception was negatively correlated with body mass index (r = -0.52), percent body fat and total fat free mass (r = -0.54 and -0.23, respectively), and positively correlated with VO2pk and daily steps (r = 0.53 and 0.38). OW participants completed 27 ± 15 exercise sessions, lasting 34 ± 7 minutes per session. Participants who completed at least 24 sessions had higher perception scores than those with less than 24 sessions (3.6 ± 0.6 vs. 3.3 ± 0.6, p=0.04). More OW participants reported perceived limitations to exercise (64%) and life stressors (85%) than the NW group (51% and 74%, respectively), but these barriers did not explain variance in exercise compliance. In AI adolescents, perception of physical activity varies with body weight, physical activity, and aerobic fitness, and may contribute to rates of participation in a wellness-center based exercise program. Thus, physical activity programs to reduce diabetes risk in this population must be tailored to address additional barriers related to one’s perceptions in order to to optimize participation.

Disclosure
H. Kimbley: None. J. Chadwick: None. C.L. Coleman: None. M.A. Tullier: None. L.D. Wolbert: None. K.C. Copeland: Other Relationship; Self; Novo Nordisk Inc.. K.R. Short: None.
Complement C3 and C4 Genetics and Cardiometabolic Risk in Adolescents
Authors: HOFFMAN ROBERT P. , COPENHAVER MELANIE M. , YU CHACK-YUNG 
Published: June 2018

Background: Although not usually manifest until adulthood, evidence indicates that cardiometabolic disease has its origins in pediatrics. If we are truly to decrease cardiometabolic disease we must understand the pathophysiology of cardiometabolic risk in childhood. Individuals with the F polymorphism of the complement C3 gene have increased rates of myocardial infarction and athereosclerosis. Individuals with increased gene copy number of the complement C4 long and A genes have decreased longevity.
Methods: C3 F vs. S genotype and C4A, C4B, C4L and C4s gene copy number were measured in 59 non-Hispanic white subjects (29 female, age=15.3±1.7 years, BMI=22.4.1±5.9 kg/m2,, mean±SD). Endothelial function (reactive hyperemia (RH), venous occlusion plethysmography), arterial stiffness (augmentation index (AI), arterial tonometry), lipids, interleukin-6 (IL-6), c-reactive protein, plasminogen activator inhibitor 1 (PAI1) insulin sensitivity and secretion (oral glucose tolerance test) were used to assess cardiometabolic risk. BMI percentile, waist circumference and percent body fat (air displacement) were measured to assess adiposity.
Results: Forty percent of subjects had at least one C3F allele. These subjects were found to have increased waist circumference (78±18 vs. 70±11 cm, p=0.029) and higher HDL levels (55±14 vs. 46±11 mg/dl, p=0.024) compared to those with only the S allele. Increased C4L (r=0.34, p=0.017) and C4A (r=0.33, p=0.019) gene copy number were associated with decreased endothelial function. Multiple linear regression including percent body fat and either C4L or C4A showed that both relationships became more significant.
Conclusions: In adolescent the C3 F polymorphism gene is associated with increased central obesity but surprisingly increased HDL. Increased C4L and C4A gene copy are associated with decreased endothelial function. This could explain their association with deceased longevity.

Disclosure
R.P. Hoffman: None. M.M. Copenhaver: None. C. Yu: None.
Paternal Bisphenol A Exposure Alters Offspring Glucose Tolerance in a Time, Dose, and Sex-Specific Manner
Authors: RASHID CETEWAYO S. , BANSAL AMITA , SIMMONS REBECCA A. 
Published: June 2018

As it is becoming increasingly accepted that maternal exposure to the ubiquitous environmental pollutant bisphenol A (BPA) predisposes offspring to metabolic impairments, paternal contribution in this context remains unresolved. To investigate a relationship between paternal BPA exposure and offspring obesity and glucose tolerance, a mouse model was developed using dietary BPA exposure at doses comparable to human exposure levels (7% Corn Oil diet (Control), 10 μg/mg/day (Lower BPA), and 10 mg/kg/day (Upper BPA)). Two exposure windows were investigated: 1) direct exposure of male mice beginning at sexual maturation (5 weeks of age) and continuing for 12 weeks prior to mating, and 2) in utero exposure, in which dams were exposed beginning 2 weeks prior to mating and ending at weaning. F1 males were sired to unexposed females. At 16 weeks of age, offspring from both exposure windows underwent body composition analysis via NMR or DEXA scan as well as glucose tolerance testing. Paternal BPA exposure during adulthood did not affect body weight, adiposity or glucose tolerance in offspring. In utero-exposed sires produced offspring that also had no changes in body weight or adiposity. However, female offspring from the Lower BPA dose were glucose intolerant. Females with glucose intolerance were selected for islet perifusion, and interestingly, those females from Lower BPA dose exhibited enhanced glucose-stimulated insulin secretion compared to controls indicating insulin resistance. These data demonstrate that while paternal BPA exposure after sexual maturity may be metabolically innocuous, paternal BPA exposure during gestation and lactation precipitates sex-specific impairments in glucose tolerance. Further studies are required to describe precisely the glucose homeostatic impairment and elucidate epigenetic changes in sperm associated with phenotypic transmission.

Disclosure
C.S. Rashid: None. A. Bansal: None. R.A. Simmons: None.
Utility of Fibroscan in Screening Overweight and Obese Children at Risk for Nonalcoholic Fatty Liver Disease
Authors: DAYTON KRISTIN A. , BRIL FERNANDO , CUSI KENNETH 
Published: June 2018

Study Objective: Nonalcoholic fatty liver disease (NAFLD) is associated with elevated risk for metabolic syndrome, type 2 diabetes, cardiovascular disease and cirrhosis. Available diagnostic tools (plasma aminotransferases and liver ultrasound) have low sensitivity. This study screened a broad population of children from an endocrine clinic with a combination of imaging tools and biomarkers previously used only in children with known liver disease. We hypothesized that Fibroscan (an ultrasound based imaging tool for hepatic fibrosis) would correlate well with MR-elastography (MRE) and be a useful adjunct in combination with known biomarkers of fatty liver disease to screen for advanced cases of NAFLD.
Methods: Overweight patients were recruited from pediatric and endocrinology clinics. They underwent liver 1H magnetic resonance spectroscopy, magnetic resonance elastography, liver Fibroscan, and fasting lab studies. Plasma biomarkers analyzed included hemoglobin A1c, lipid panel, AST and ALT levels, cytokeratin 18 and homeostatic model of insulin resistance.
Results: Twenty seven patients were recruited and analyzed. NAFLD was present in 30% of patients based on ≥5.5% intrahepatic triglyceride content (liver fat) on 1H-MRS. Five patients (19%) showed fibrosis based on Fibroscan ≥7%, however, only one case was confirmed to have fibrosis on MRE. Two patients with positive Fibroscan were unable to undergo MRE. Metabolic markers including A1c and HOMA-IR were worse in NAFLD vs. no NAFLD patients, but only triglycerides and ALT reached statistical significance.
Conclusions: Fibroscan is useful to eliminate fibrosis, but a positive fibroscan must be further evaluated as many false positives occurred. In combination with triglycerides and ALT, this tool may be useful to stratify those patients most at risk for severe NAFLD and those patients requiring evaluation by pediatric gastroenterologists, biopsy, and more intensive intervention.

Disclosure
K.A. Dayton: None. F. Bril: None. K. Cusi: Consultant; Self; Janssen Global Services, LLC., Eli Lilly and Company. Research Support; Self; Cirius Therapeutics. Other Relationship; Self; Nordic Bioscience. Research Support; Self; Novartis Pharmaceuticals Corporation, Novo Nordisk Inc.. Other Relationship; Self; Quest Diagnostics. Research Support; Self; Zydus Pharmaceuticals (USA) Inc.. Other Relationship; Self; OWL metabolomics, Echosens. Research Support; Self; Janssen Global Services, LLC.. Consultant; Self; Tobira Therapeutics, Pfizer Inc..
Co-occurrence of 2+ Early Complications in Type 1 Diabetes—SEARCH for Diabetes in Youth
Authors: SAUDER KATHERINE A. , STAFFORD JEANETTE M. , MAYER-DAVIS ELIZABETH J. , JENSEN ELIZABETH T. , SAYDAH SHARON , MOTTL AMY K. , DOLAN LAWRENCE M. , HAMMAN RICHARD F. , LAWRENCE JEAN M. , PIHOKER CATHERINE , MARCOVINA SANTICA M. , DAGOSTINO RALPH , DABELEA DANA ,   SEARCH FOR DIABETES IN YOUTH STUDY GROUP
Published: June 2018

SEARCH reported a high burden of early complications in type 1 diabetes (T1DM). We examined co-occurrence of complications and related risk factors among 1327 SEARCH T1DM participants aged 10-30 years. Risk factors were assessed at baseline (mean diabetes duration and age = 0.8 and 10.9 years, respectively) and follow-up (7.8 and 18.0 years, respectively). Retinopathy (RET), diabetic kidney disease (DKD), peripheral neuropathy, cardiovascular autonomic neuropathy (CAN), and arterial stiffness (AS) were assessed at follow-up. We examined co-occurrence of ≥2 complications overall, by type, and within four demographic/metabolic risk factor clusters identified using cluster analysis. Clusters were characterized by worsening risk profiles (Table). Co-occurrence of ≥2 complications was observed in 5.9% of participants, more frequently than expected by chance (4.4%, p=0.02). Specifically, RET+DKD (0.83% vs. 0.23%), RET+AS (0.98% vs. 0.34%), and AS+CAN (1.81% vs. 1.04%) all co-occurred more frequently (all p&lt;0.05). Prevalence of ≥2 complications increased across risk clusters from 2.3% to 20.8%.
Selected characteristics and prevalence of 2+ complications at follow-up by risk factor clustersCluster 1 (n=261)Cluster 2 (n=509)Cluster 3 (n=348)Cluster 4 (n=24)p-valueNHW (n, %)217 (83.1)395 (77.6)257 (73.9)15 (62.5)0.002Private insurance (n, %)211 (80.8)386 (76.1)222 (64.2)9 (37.5)&lt;0.001A1c (%)8.5 ± 1.59.0 ± 1.79.7 ± 1.911.8 ± 2.0&lt;0.001Non-HDLc (mg/dl)79.0 ± 12.9105.7 ± 12.2147.9 ± 21.5245.5 ± 33.5&lt;0.001Waist to height ratio0.44 ± 0.050.46 ± 0.060.49 ± 0.070.50 ± 0.05&lt;0.001Mean arterial pressure (mmHg)80.0 ± 8.082.6 ± 8.682.4 ± 8.484.4 ± 10.1&lt;0.001≥2 complications (n, %)6 (2.3)32 (6.3)28 (8.0)5 (20.8)&lt;0.001
In conclusion, early T1DM complications co-occur more frequently than expected, at a young age and short diabetes duration. A cluster of risk factors including minority race/ethnicity, lack of private insurance, and poor metabolic profiles identifies groups to target with interventions to reduce complications.

Disclosure
K.A. Sauder: None. J.M. Stafford: None. E.J. Mayer-Davis: None. E.T. Jensen: None. S. Saydah: None. A.K. Mottl: None. L.M. Dolan: None. R.F. Hamman: None. J.M. Lawrence: None. C. Pihoker: None. S.M. Marcovina: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. D. Dabelea: None.
Grazing in Young Children with Type 1 Diabetes Is Associated with Higher HbA1c
Authors: SECKOLD ROWEN L. , HOWLEY PETER , KING BRUCE R. , BELL KIRSTINE , SMART CARMEL E. 
Published: June 2018

Glycemic control in the young child with type 1 diabetes (T1D) has traditionally been challenging. Unpredictability in appetite and dietary intake has made the achievement of glycemic targets difficult. This study aimed to assess the nutritional quality and dietary behaviors of young children with T1D that attend a clinic that meets glycemic targets in this age group.
Carers of children aged &lt;7 years with type 1 diabetes attending a specialist Pediatric Diabetes Service in Australia completed a 3 day food diary and a survey regarding diabetes management and dietary behaviours.
Twenty one children participated (mean age: 4.7 ±1.3y, 57% male, mean BMI z score: 0.9 ± 0.9, duration since diagnosis 1.6 ±1.1y, 38% insulin pump therapy, mean HbA1c: 6.3 ± 0.7% (45±7mmol/mol)). Offering food ’whenever they are hungry’ was associated with higher HbA1c than routine meals (7.2% vs. 6.1%, p=0.02). HbA1c was not correlated with daily total CHO intake, which ranged from 126g to 236g/day. Almost all carers (95%) gave mealtime insulin before food. Most carers (55%) substituted when 6-10 grams (range 1g to &gt;15g) of CHO less than the predicted quantity was consumed. Children consumed saturated fat in excess of recommendations (15 ± 3% E) with no children meeting recommended serves of vegetables.
Young children with type 1 diabetes can achieve target glycemic control and can safely dose insulin before meals. Continuous eating episodes were positively associated with HbA1c. Dietary quality remains a concern in this age group.

Disclosure
R.L. Seckold: None. P. Howley: None. B.R. King: None. K. Bell: Other Relationship; Self; Novo Nordisk Inc.. C.E. Smart: None.
Family History of Diabetes Is Associated with Increased Risk of Recurrent DKA in Pediatric Patients in Rhode Island
Authors: VAKHARIA JANAKI D. , AGRAWAL SUNGEETA , BACIC JANINE , TOPOR LISA S. 
Published: June 2018

Factors related to recurrent DKA in pediatric patients with DM have been studied previously, with family history (FHx) of DM suggested as a protective factor. We sought to determine associations with DKA recurrence in our pediatric population as the first step in developing an intervention to reduce the frequency of DKA recurrence. In a retrospective chart review, we identified 270 patients admitted for DKA at our institution during a 5 year period. We excluded patients with new onset DM or missing data, identifying 255 DKA admissions amongst 131 patients. Patients were divided into a Recurrence group (≥ 2 admissions, n=51 (39%)) and Non-Recurrence group (1 admission). FHx was significantly associated with Recurrence in both univariate (OR 6.96, p-value &lt;0.0001) and multivariate (OR 8.32, p-value &lt; 0.001) logistic regression analyses. Older age was also significantly associated with Recurrence in both analyses. Younger age at diagnosis and public insurance was only significant in the multivariate and univariate analysis, respectively (Table 1). Family history of DM is associated with increased risk of DKA recurrence in our pediatric patients. Larger, multicenter studies are needed to study the relationship between FHx of DM and frequency of DKA admissions. At our center, this data may be used to identify patients at risk, and develop an intervention targeting all household members with DM.

Disclosure
J.D. Vakharia: None. S. Agrawal: None. J. Bacic: None. L.S. Topor: None.
Insulin Treatment and Clinical Outcomes in 67 Participants with Infancy-Onset Diabetes
Authors: LETOURNEAU LISA R. , CARMODY DAVID , DENSON ANNA M. , SANYOURA MAY , NAYLOR ROCHELLE N. , PHILIPSON LOUIS H. , GREELEY SIRI ATMA W. 
Published: June 2018

Infancy-onset diabetes occurs within the first year of life and can be monogenic or autoimmune. We investigated insulin regimens and clinical outcomes through the U.S. Monogenic Diabetes Registry. Relevant data was extracted from medical records collected from the time of diagnosis through the first two years of life. Medical records from 67 individuals were obtained. Clinical characteristics are shown in Table 1. Insulin regimens are reported in Table 2. Most participants stayed on an insulin regimen with the same intensity, ranging from staying on a pump (CSII) to staying on 2 shots of insulin per day. While 30% increased in intensity, 14% decreased (Table 2). Many different regimens appeared to be effective in infants, but further research on greater numbers of patients may show additional advantages to more intense regimens such as CSII.

Disclosure
L.R. Letourneau: Other Relationship; Self; Novo Nordisk Inc. D. Carmody: Research Support; Self; Novo Nordisk Inc.. A.M. Denson: None. M. Sanyoura: None. R.N. Naylor: None. L.H. Philipson: Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; JAEB Center For Health Research, JDRF, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc. S.W. Greeley: Research Support; Self; Novo Nordisk Inc..