bluuebunny/crossref_metadata_2025 huggingface dataset:
2006-P: The Role of Adipose Tissue-Resident Eosinophils in Adipocyte Metabolism and Whole-Body Energy Homeostasis
Authors: LI TING , LESUER WILLIAM , SINGH ABHILASHA , HERNANDEZ JAMES D. , ZHANG XIAODONG , JELINEK DIANE , LIU JUN , VELLA ADRIAN , JACOBSEN ELIZABETH A. , DEFILIPPIS ELEANNA
Published: June 2019

Adipose tissue resident eosinophils (AT-EOS) are thought to play a pivotal role in whole-body energy homeostasis. However, the precise role of, and the mechanisms underlying AT-EOS in the regulation of whole-body energy metabolism remains elusive. This is because of the limitations of rodent models which have been genetically engineered to either produce elevated whole-body eosinophils or knock-out models for this hematopoietic lineage. To determine the function of AT-EOS, we generated a transgenic mouse model overexpressing human eotaxin[AV1] 2 (hEo2), which is an eosinophil specific chemokine, under the control of a fat-specific aP2 promoter, to recruit circulating EOS exclusively into adipose (hEo2tg). Compared to wild type (WT) littermates of both genders, hEo2tg mice displayed a significant increase of AT-EOS in multiple AT depots including, perirenal and subcutaneous white adipose tissue (sWAT). However, EOS were not increased in brown adipose tissue (BAT). When fed a high-fat diet (HFD), hEo2tg mice gained less weight (males weight: 45.5 ±0.7g vs. 51 ±0.4g, P<0.01 hEo2tg vs. WT) and adipose tissue (males %fat: 20.8 ±0.2 vs. 31.7 ±0.6, P<0.01 hEo2tg vs. WT) compared to WT. Transgenic mice showed improved glucose tolerance (GTT) compared to WT (males GTT AUC: 300054±121 vs. 320865 ±920, hEo2tg vs. WT P<0.001). This was accompanied by increased energy expenditure and heat production compared to WT. These phenotypes were equally found in female animals. Moreover, the adipocytes in hEo2tg were smaller in both genders, and the expression of genes involved in fat oxidation in BAT and sWAT was upregulated in hEo2tg mice compared to WT mice. These data suggest that WAT-resident EOS contribute to increased BAT activation, browning of sWAT and to whole-body energy expenditure. Additional studies will be needed to evaluate the molecular mechanism(s) underling the benefits of AT- EOS.

Disclosure

T. Li: None. W. LeSuer: None. A. Singh: None. J.D. Hernandez: None. X. Zhang: None. D. Jelinek: None. J. Liu: None. A. Vella: Advisory Panel; Self; vTv Therapeutics. Research Support; Self; Novo Nordisk Inc. E.A. Jacobsen: None. E. DeFilippis: None.

Funding

National Center for Advancing Translational Sciences (KL2TR002379)
2016-P: High Dose DACRA Treatment Improves Glucose Homeostasis, without Additional Weight Loss
Authors: SONNE NINA , LARSEN ANNA T. , ANDREASSEN KIM V. , KARSDAL MORTEN ASSER , HENRIKSEN KIM
Published: June 2019

KBP is a Dual Amylin and Calcitonin Receptor Agonist (DACRA). DACRAs have shown efficacy on weight loss and glucose control in rats. However, it is unclear whether the maximum effect has been reached. High Fat Diet (HFD, 60% fat) fed male Sprague-Dawley rats entered a dose escalation regimen ending at 5 (normal dose), 50 or 500 µg/kg daily KBP (n=10/group). Male ZDF (fa/fa) rats received identical doses without dose escalation in a preventive study setup (n=9-10/group). In HFD rats, KBP treatment resulted in a transient decrease in food intake at each dose escalation step. At study end, KBP treatment resulted in a significant weight loss of 77-94 g (13-16%, P<0.0001) compared to vehicle. Furthermore, KBP reduced the weight of adipose tissues (P<0.05). Surprisingly, there was a trend of 5 µg/kg KBP causing a more pronounced adipose-specific weight loss compared to 500 µg/kg (subcutaneous 1.7 vs. 0.7 g, visceral 4.1 vs. 2.5 g adipose weight loss). During two OGTTs, KBP treatment significantly lowered blood glucose (BG) and insulin levels compared to vehicle indicating improved glucose tolerance. Lastly, 24h fecal energy loss increased by KBP treatment, though this trend was absent when accounting for food intake and total feces output.

In ZDF rats, KBP treatment significantly improved fasting BG (endpoint vehicle 29.5, endpoint KBP average 18.3 mmol/L, tAUC P<0.0001) and HbA1c (vehicle 10.2%, KBP average 6.1%, P<0.0001) compared to vehicle, with no significant difference between treatment groups. Importantly, fasting and non-fasting insulin levels of KBP-treated rats were increased compared to vehicle in a dose-dependent manner during an OGTT, resulting in lowered BG levels. Increased insulin levels suggest that KBP protects against the known β-cell degradation in the ZDF model.

Taken together, these data suggest that higher doses of KBP than previously investigated may preserve insulin secretion to a greater extent. With respect to weight loss, no additional benefit was observed from the high doses.

Disclosure

N. Sonne: None. A.T. Larsen: None. K.V. Andreassen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Employee; Self; Nordic Bioscience. K. Henriksen: Employee; Self; Nordic Bioscience. Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Nordic Bioscience. Other Relationship; Self; Nordic Bioscience.
2022-P: Neonatal IL-4 Administration Decreases Body Fat Content and Weight and Improves Glucose Tolerance in Adulthood
Authors: YING TAMMY , SIMMONS REBECCA A.
Published: June 2019

Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency is a common complication of pregnancy and leads to an increased risk for type 2 diabetes (T2D) in adulthood. We model IUGR by performing bilateral uterine artery ligation in pregnant rats at d18 of gestation (term 22 days). Offspring are growth restricted and newborn males, but not females have decreased ß-cell proliferation and impaired insulin secretion which is associated with inflammation and increased IL-4 levels. IUGR males develop obesity and insulin resistance in adulthood. Neutralizing IL-4 antibody given on postnatal days 1-6 normalizes hyperglycemia in adult IUGR animals. The aim of this study was to determine whether IL-4 is sufficient to recapitulate the IUGR phenotype. IL-4 (50ng or 100ng) or PBS was injected subcutaneously to normal newborn rat pups on postnatal days 1-6. IL-4 had no adverse effects on newborn rat pups and weights did not differ between the IL-4 and PBS injected pups (n=15). IL-4 injection had no effect on insulin secretion as measured by both static incubation experiments and perifusion square wave studies (n=6). Surprisingly, at P14, animals treated with IL-4 in the newborn period had decreased body fat content (p=0.0173) compared to controls (n=6). Further, at 7 weeks of age IL-4 injected rats weighed less than controls (n=7; p=0.00017) and the weight difference increased with age. At 10 weeks, IL-4 injected rats had decreased fasting blood glucose levels (n=6-7; p=0.0055) and improved glucose tolerance and the area under the curve (AUC) was less than controls (n=3; p=0.0513). These results suggest that IL-4 is not sufficient to recapitulate the IUGR metabolic phenotype. However, IL-4 administered transiently during the neonatal period has lasting effects in adulthood, decreasing fat content and improving glucose tolerance.

Disclosure

T. Ying: None. R.A. Simmons: None.

Funding

National Institutes of Health
2025-P: Protective Effects of Orlistat against High-Fat Diet-Induced Metabolic Disorders in Mice
Authors: KE JING , AN YAXIN , CAO BIN , ZHAO DONG
Published: June 2019

Background: Accumulating evidence indicates that alterations of gut microbiota and metabolites have been involved in obesity and diabetes. Orlistat, a reversible inhibitor of pancreatic and gastric lipase, has beneficial effects on metabolism. However, the mechanism of its action is less understood.

Methods: Metabolic indices, including weight, glucose tolerance and plasma lipids were determined in WT (C57BL/6J mice), HFD and HFD + ORL group. The effects of orlistat on gut microbiota and circulating metabolites in mice were assessed by 16S rRNA gene sequencing from fecal samples and LC-MS/MS from plasma samples.

Results: Compared to HFD group, HFD + ORL group showed improvements in glucose tolerance and plasma cholesterol, and a distinct microbiota composition with a dominance of Rhodococcus and Pseudomonas on genus level, positively associated with ether lipid metabolism, fatty acid metabolism, α-linolenic acid metabolism and GnRH signaling pathway etc. Furthermore, metabolic perturbations caused by HFD were improved in the HFD + ORL group and were presented in PLS-DA analysis. The discrepant metabolites were involved in several metabolic pathways, such as alanine, aspartate and glutamate metabolism, as well as histidine metabolism etc. Intriguingly, fecal microbiome and metabolome results share two common metabolic pathways, linoleic acid metabolism and arachidonic acid metabolism.

Conclusion: Our study suggests that orlistat may exert protective effects against metabolic disorders through modulating gut microbiota, which was involved in some common metabolic pathways with metabolome.

Disclosure

J. Ke: None. Y. An: None. B. Cao: None. D. Zhao: None.
2026-P: Myeloid Sirtuin 6 Is a Molecular Switch of White Adipose Tissue Browning
Authors: LEE YOUNGYI
Published: June 2019

Emerging evidence reveals that cold exposure enhances alternative activation of macrophages. We recently reported that myeloid sirtuin 6 (Sirt6) drives macrophage phenotypes into M2 type. However, its role in adaptive thermogenesis has not been explored. In this study, we demonstrate that myeloid Sirt6 ablation attenuates thermogenic responses in subcutaneous adipose tissue (scWAT) during cold exposure. Compared with wild type mice, myeloid Sirt6 KO (mS6KO) mice displayed a lower core body temperature and were glucose intolerant in response to cold exposure. Accordingly, expression levels of thermogenic proteins and number of multilocular lipid droplets were decreased in scWAT of mS6KO mice. Mechanistically, the infiltration of M2 macrophages in scWAT was impaired in mS6KO mice, which contributed to the suppression of lipolysis in adipocytes. Together, these results establish myeloid Sirt6 as a critical determinant of beige cell formation in scWAT.

Disclosure

Y. Lee: None.
2032-P: The Effects of Liraglutide on Ameliorating Diabetic Kidney Disease Is via SIRT1/TXNIP Pathway
Authors: LIANG RIYING , WANG MEIJUN , FU CHANG , XU FEN , CAI MENGYIN
Published: June 2019

GLP-1 receptor agonist is one of the most effective drugs to treat type 2 diabetes. LEADER Clinical Trials revealed that liraglutide exerted its renoprotective effect by reducing microalbumin-urine and slowing down the decline of eGFR. However, the underlying mechanism remains elusive. High glucose exposure upregulates the expression of TXNIP, a pro-oxidative stress and pro-apoptotic protein, by regulating histone acetylation. SIRT1, a deacetylase, also plays an important role in protecting renal function. We investigated the role of SIRT1/TXNIP pathway in the beneficial effect of liraglutide on improving renal function. In our study, eight-week old male C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. Then, mice were divided into groups as follows: NC, HFD, HFD+ Liraglutide (HL) group for 8 weeks. The results revealed that the body weight, fasting blood glucose, glucose tolerance and insulin sensitivity were statistically improved in HL group when compared with HFD group. Significant reduction of kidney lipid deposition and Bowman’s capsule space were observed in HL group based on the histology results. Besides, urine albumin-to-creatinine ratio and apoptosis in the kidney were ameliorated in the HL group. Western blotting results revealed the expression of genes involved in apoptosis was notably downregulated after liraglutide treatment. In addition, the protein expression of SIRT1 was upregulated, whereas TXNIP was downregulated in the HL group. Collectively, the data indicated that the effect of liraglutide on renoprotection is via SIRT1/TXNIP pathway.

Disclosure

R. Liang: None. M. Wang: None. C. Fu: None. F. Xu: None. M. Cai: None.
2047-P: UK First National Health Service (NHS) Endobarrier (EB) Service: Maintenance of Improvement One Year after Device Removal
Authors: RYDER ROBERT E.J. , GUPTA PIYA SEN , YADAGIRI MAHENDER , IRWIN SUSAN P. , BURBRIDGE WYN , BASHIR TAHIRA , WYRES MELANIE C. , ALLDEN RACHAEL , BLEASDALE JOHN , FOGDEN EDWARD , ANDERSON MARK
Published: June 2019

EB, a 60cm endoscopically inserted proximal intestinal liner, reduces weight and HbA1c over 1-year. In the 1st NHS EB service, we provided EB to patients with sub optimally controlled diabesity and monitored outcomes in a registry. 32/46 (70%) completing 1-year post EB removal (age 51.1±7.5 years, 56% male, diabetes duration 14 (8-21) years, BMI 41.7±7.8 kg/m2) attended follow-up. During EB treatment, mean ± SD HbA1c fell by 2.1±1.9%, from 9.5±1.9 to 7.4±1.1% (p<0.001), weight by 17.0±8.9 kg from 121.1 ± 28.4 to 104.1±29.1 kg (<0.001), systolic BP from 140.0±15.3 to 126.4±15.9 mmHg (<0.001), serum alanine aminotransferase (marker of liver fat) from 29.1±17.7 to 18.2±9.7 U/L (p<0.001). Median (IQR) total daily insulin dose reduced from 104 (60-140) to 20 (0-59) units (n=21, p<0.001); 7/21 (33%) insulin treated patients discontinued insulin. 1-year post EB removal 13/32 (41%) demonstrated sustained improvement with 12/32 (37%) partially sustaining improvement and 7/32 (22%) reverting to baseline (Figure). Of those deteriorating, 6/7 (86%) had depression and/or bereavement. 41/46 (89%) achieved the planned full year of EB treatment but 5/46 (11%) had early EB removal (4 GI bleed, 1 liver abscess) with all 5 fully recovering after removal. Our data demonstrates EB as highly effective in patients with refractory diabesity, with maintenance of significant improvement 1-year after removal in 78%.

Disclosure

R.E.J. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. P. Sen Gupta: None. M. Yadagiri: None. S.P. Irwin: Speaker's Bureau; Self; AstraZeneca. W. Burbridge: None. T. Bashir: None. M.C. Wyres: None. R. Allden: None. J. Bleasdale: None. E. Fogden: None. M. Anderson: None.
2050-P: A Multifactorial Telemedical Care Model for Long-Term Treatment of Obesity—A Randomized Controlled Trial
Authors: MARTIN RÖHLING , MARTIN KATHARINA , ELLINGER SABINE , MARTIN STEPHAN , KEMPF KERSTIN
Published: June 2019

Lifestyle interventions are indicated as first-line therapy to fight obesity focusing on various aspects of a healthy lifestyle. However, as most of these lifestyle programs only include single components, we designed a multifactorial, telemedical and group-based seminar program to improve weight loss in overweight individuals.

Overweight volunteers (BMI ≥25 kg/m2) were randomized into a starting intervention group (SI, n=15) or a waiting list control group (WL, n=15). The multicomponent intervention consisted of a (1) group-based seminar program addressing low-carbohydrate nutrition, physical activity, and the carbohydrate-blood glucose-insulin relationship. Further components used were (2) low-carbohydrate formula diet, (3) flash-glucose-monitoring devices and (4) telemedical supervision. Both groups received telemedical devices at baseline. After the 12-weeks intervention phase of SI, WL started with the same intervention. Participants received monthly calls by coaches until week 26. Data were recorded before and after 12, 26 and 52 weeks of follow-up.

After 12 weeks of intervention, SI demonstrated a stronger reduction in weight compared to WL (-7.8 kg vs. -1.5 kg; P<0.001). The estimated treatment difference between both groups was -6.3 kg with 95% confidence interval (95% CI) [-7.4; -4.5] (P<0.001). Compared to WL, fat mass and eating behavior improved in SI as well (all P<0.01). Furthermore, SI improved fasting blood glucose, HbA1c, quality of life (all P<0.05), fasting insulin, blood pressure (both P<0.01), and eating behavior (P<0.001) in the within-group analysis, while WL did not show any changes. After 26 and 52 weeks of follow-up, weight reduction could be maintained in the SI-group by -9.7 kg [95% CI: -16.1; -3.2] (P<0.001) and -7.8 kg [95% CI: -15.4; -0.9] (P<0.05), respectively.

A multifactorial program leads to long-term clinically relevant weight reductions and improvements in cardiovascular risk factors in overweight individuals.

Disclosure

M. Röhling: None. K. Martin: None. S. Ellinger: None. S. Martin: Consultant; Self; Almased Wellness GmbH, AstraZeneca, Lilly Diabetes. K. Kempf: Speaker's Bureau; Self; cognomed, Kirchheim Verlag.
2061-P: Inflammation Status Is Independent Risk Factor for the Development of Metabolic Syndrome in Both Metabolically Healthy Obese and Nonobese Adults
Authors: HUR KYU YEON , CHOI MIN SUN , PARK SUNG WOON , LEE SEUNG-EUN , AHN JIYEON , PARK JUN , PARK HYUNJU , KIM GYURI , JIN SANG-MAN , KIM JAE HYEON , LEE MOON-KYU
Published: June 2019

Objectives: The fact that metabolic syndrome is accompanied by a low-grade inflammation suggests inflammation may play an important role in the etiology. The aim of our study was to assess the association between heterogeneity of inflammation status and the incidence of metabolic syndrome (MetS) in the metabolically healthy persons who are either obese or nonobese.

Methods: This longitudinal study included all metabolically healthy persons who underwent four or more follow-up comprehensive health examinations either annually or biennially from August 2006 through August 2013 at the Health Promotion Center at Samsung Medical Center, Seoul, Republic of Korea. Metabolic health was defined as absence of any component of the MetS except obesity. We defined obesity using the BMI, which is classified into categories of normal (18.0-22.9 kg/m2), overweight (23-24.9 kg/m2), and obesity (25 kg/m2). Hematological indices such as WBC count or its subtypes (neutrophils, lymphocytes, monocytes) and hsCRP were measured. The outcome was the 7-year cumulative incidence of MetS.

Results: The person-years follow-up were 17,786 in normal weight, 10,376 in overweight, and 7,391 in obesity group. Baseline age, sex, physical activity, smoking, exercise, fasting plasma glucose, HbA1c, blood pressure, lipid profile, hematologic parameters, hsCRP were adjusted. Cox regression multivariate analysis resulted in neutrophil count (> 2,750/mm3) was associated with increased incidence of MetS in normal weight (HR 1.7; CI 1.29-2.35; p <0.001), overweight (HR 1.59; CI 1.29-1.95; p <0.001), and obesity (HR 1.26; CI 1.10-1.45; p<0.001).

Conclusion: This longitudinal analysis showed the neutrophil count is associated with the incidence of MetS in the metabolically heathy persons who are either obese or nonobese. Therefore, inflammatory status could be an independent risk factor for the development of metabolic syndrome irrespective of obesity.

Disclosure

K. Hur: None. M. Choi: None. S. Park: None. S. Lee: None. J. Ahn: None. J. Park: None. H. Park: None. G. Kim: None. S. Jin: None. J. Kim: None. M. Lee: None.
2066-P: Improvement of Hepatic Steatosis Index in Patients with Type 1 Diabetes and Obesity after Intensive Lifestyle Intervention: A One-Year Matched-Cohort Observational Study
Authors: TOMAH SHAHEEN , TASABEHJI MHD WAEL , GHAZI FAYEZ , SALAH TAREQ , ZHANG HONGXIA , ASHRAFZADEH SAHAR , HAMDY OSAMA
Published: June 2019

Prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing among patients with type 1 diabetes (T1D). Little is known about the impact of weight reduction on NAFLD in this population. We utilized the Hepatic Steatosis Index (HSI), a noninvasive surrogate predictor of NAFLD, to evaluate the effect of intensive lifestyle intervention (ILI) on hepatic steatosis in patients with T1D and obesity after one year.

We evaluated 88 adult patients with T1D and obesity who participated in a 12-week ILI program in real-world clinical practice within the past 13 years. We excluded 11 patients per the International Associations for Diagnosis of NAFLD guidelines. A total of 77 patients were included in the analysis (mean age 43±12 years, 65% female, diabetes duration 22±12 years, HSI 46.2±6.1, A1C 8.2±1%, body weight 102.5±17 kg, BMI 35.7±5 kg/m2). We matched them in 1:1 ratio with a cohort of similar T1D patients who received standard diabetes care at the same practice during the same period (mean age 43±12 years, 65% female, diabetes duration 22±9 years, HSI 45±5.7, A1C 8.2±0.9%, body weight 100±17 kg, BMI 35.3±5 kg/m2). HSI was calculated as 8*ALT/AST+BMI (+2 if female). There were no differences in HSI between the 2 cohorts at baseline.

At 1 year, the ILI group lost an average of 5.6±2.7 kg (5.8%, p<0.05) and the control group maintained their baseline body weight (p<0.001 between groups). HSI decreased significantly from baseline in the ILI group (-2.7±1.05, p=0.01) but did not change in the control group (0.6±0.9, p=0.53, p<0.001 between groups). A greater proportion of patients in the ILI group achieved HSI <36 (NAFLD cut-off) (11.7% compared to 1.3% in the control group, p<0.01).

We conclude that an ILI program in real-world clinical practice may improve HSI in patients with T1D and obesity compared to standard care after 1 year. A greater proportion of patients enrolled in ILI achieved HSI indicative of lower likelihood of NAFLD diagnosis.

Disclosure

S. Tomah: Stock/Shareholder; Self; Amarin Corporation. M. Tasabehji: None. F. Ghazi: None. T. Salah: None. H. Zhang: None. S. Ashrafzadeh: None. O. Hamdy: Advisory Panel; Self; AstraZeneca, Sanofi-Aventis. Consultant; Self; Abbott, Merck & Co., Inc. Research Support; Self; National Dairy Council. Stock/Shareholder; Self; Healthimation, LLC.
2069-P: Energy Expenditure during Sleep Is an Independent Marker of Prediabetes—A Cross-Sectional Study of Overweight/Obese Subjects
Authors: TUCCINARDI DARIO , ROSSINI GIOVANNI , MADDALONI ERNESTO , MAGGI DARIA , MONTE LAVINIA , FIORITI ELVIRA , KYANVASH SHADI , POZZILLI PAOLO , MANFRINI SILVIA
Published: June 2019

Normal sleep is characterized by increased glycogen stores and reduced glucose turnover by metabolically active tissues, thus it is a state of decreased metabolism. It has been reported that reduced sleep quality is associated with disrupted glucose metabolism. However, the relationship between Sleep Metabolic Rate (SMR) and prediabetes defined by the presence of IFG and/or IGT, during 75-g OGTT, has not been clarified.

The aim of this study was to investigate the role of SMR in the association between sleep quality and prediabetes.

A total of 226 individuals [women 72.1%; mean (DS) age 50.46 (±13.1) years; BMI 33.4 (±8.41) Kg/m2] undergoing the OGTT, were also asked to wear a metabolic holter (Armband) for 3-days, to assess their daily energy expenditure (DEE). The Armband was also capable of measuring the SMR, the Total Sleep Time (TST) and Sleep Efficiency (SE). The SMR has been adjusted for Free Fat Mass (FFM) to reduce the overweight/obesity influence on energy expenditure (SMR/FFM).

A total of 78 subjects were identified as prediabetic. No difference in TST, SE, and DEE was observed between NGT and prediabetics. The SMR/FFM was significantly higher in patients with prediabetes (p<.004). Using multivariate logistic regression, with prediabetes status as dependent variable and sleep efficiency, age, fat mass, gender and SMR/FFM as independent variables, the latter resulted an independent marker of prediabetes (OR 1.52, 95% CI 1.03-2.24) p .034, Nagelkerke’s r2: 0.12.

The SMR/FFM increase in prediabetic overweight/obese subjects may be explained through several mechanisms such as the increased nocturnal gluconeogenesis and the possible shift towards other substrates utilization (e.g., cori and glucose-alanine cycle).

Disclosure

D. Tuccinardi: None. G. Rossini: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. D. Maggi: None. L. Monte: None. E. Fioriti: None. S. Kyanvash: None. P. Pozzilli: None. S. Manfrini: None.
2074-P: Significant Reduction of Visceral Adiposity in Type 2 Diabetics with Doctor-Supervised Weight Loss Program
Authors: DEMBROWSKI GERALD , BARNES JESSICA
Published: June 2019

Metabolic syndrome (MS), which affects ∼23% of the U.S. population, dramatically increases the risk of cardiovascular disease (CVD) and type 2 diabetes. While pharmacotherapies are available to treat diabetes (DIA), few strategies exist that target visceral adiposity (VA) as a means to reduce risk of current and future morbidity and mortality. Commercial weight loss programs target body weight but provide minimal effect on actual components of MS including VA. The 20Lighter Program (T20LP), employs change in VA as a primary outcome measure and clinical indicator of CVD and metabolic disease risk reduction. A retrospective review, via an IRB-approved protocol, of the first 2200 participants completing T20LP found 270 reported taking at least one prescription DIA medication (oral and/or injectable) at the time of enrollment. From baseline to 60 days, each group (diabetes, DIA; and nondiabetes, non-DIA) showed statistically significant and clinically meaningful reductions in body weight (13.8±1.1%; 14.0±0.32%), Body Mass Index (BMI) (13.2±0.14%; 13.4±0.06%), body fat (15.4±0.30%; 15.5±0.15%), and VA (25.2±0.18%; 25.8±0.09%). When the two groups were compared, a small numerical divergence in mean change was found in some outcomes favoring the DIA group, but none held statistical significance. Data reported as: (DIA; non-DIA) and shown as mean±SEM. Our data show participants on prescription medications for DIA attain significant and clinically relevant reductions in body weight, BMI, body fat, and VA. Diabetics participating in T20LP are capable of achieving body composition and metabolic improvements on par with nondiabetics, and nondiabetics showed no advantage in any physiologic or metabolic outcome in our study. T20LP is a comprehensive lifestyle program complementing existing strategies to provide overweight and obese adults and teens diagnosed with and at risk of MS with safe and effective weight loss and VA reduction.

Disclosure

G. Dembrowski: Stock/Shareholder; Self; 20Lighter Program. Stock/Shareholder; Spouse/Partner; 20Lighter Program. J. Barnes: Stock/Shareholder; Self; 20Lighter Program. Stock/Shareholder; Spouse/Partner; 20Lighter Program.
2078-P: Association of Dietary Intake of Phosphorus with Obesity in Japanese Patients with Type 2 Diabetes Mellitus (T2DM)
Authors: HATTA MARIKO , FUJIHARA KAZUYA , MATSUBAYASHI YASUHIRO , TAKEDA YASUNAGA , NEDACHI RINA , ISHII DAI , HORIKAWA CHIKA , KATO MITSUTOSHI , MAEGAWA HIROSHI , SONE HIROHITO , STUDY GROUP JDDM
Published: June 2019

Although serum phosphate concentrations have been consistently reported to have a negative correlation with BMI, there have been some conflicting reports of the relationship of dietary intake of phosphorus with BMI. Thus, we investigated the association between phosphorus intake and obesity in Japanese patients with diabetes mellitus. Analyzed were 1891 patients with T2DM (mean age, 62 y; men, 62%) in our nationwide registry who had completed a food frequency questionnaire. Obesity was defined according to BMI >25. The association between phosphorus intake and obesity was determined by multivariate regression as well as quintile analyses. Mean daily intake of phosphorus was 996 mg in men and 977 mg in women, values that were quite close to those of the general population in Japan. Intake of phosphorus was significantly associated with decreased risk of obesity with an odds ratio (OR) of 0.90 (0.87-0.94) per 50 mg increase in phosphorus intake. Quintile analysis revealed potent negative correlations in both men and women (Table). Food groups strongly associated with phosphorus among our patients were fish (0.58), dairy products (0.54) and beans (0.52). These results imply the clinical relevance of controlling phosphorus intake as part of medical nutrition therapy for patients with T2DM.

Disclosure

M. Hatta: None. K. Fujihara: None. Y. Matsubayashi: None. Y. Takeda: None. R. Nedachi: None. D. Ishii: None. C. Horikawa: None. M. Kato: None. H. Maegawa: Research Support; Self; Antares Pharma, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
2079-P: Association of Serum FAM19A5 with Metabolic and Vascular Risk Factors in Human Subjects With or Without Type 2 Diabetes
Authors: LEE YOU-BIN , KIM JUNG A. , ROH EUN , HONG SO-HYEON , CHOI KYUNG MOOK , BAIK SEI HYUN , YOO HYE JIN
Published: June 2019

Introduction: A recent in-vitro and in-vivo experimental study has revealed that family with sequence similarity 19 [chemokine (C-C motif)-like] member A5 (FAM19A5), a novel secreted adipokine has inhibitory effects on proliferation and migration of vascular smooth muscle cells, and neointima formation of injured arteries. However, the relationship between serum FAM19A5 level and cardio-metabolic risks has not been evaluated in humans. For the first time, we investigated the association between serum FAM19A5 concentration with various metabolic and vascular risk factors in human subjects with or without type 2 diabetes.

Methods: Circulating FAM19A5 concentration was measured in 223 individuals (45 without diabetes and 178 with type 2 diabetes), and the association of FAM19A5 level with cardio-metabolic risk factors including body composition, plasma glucose, glycated hemoglobin (HbA1c), and atherosclerosis was explored.

Results: Serum FAM19A5 (pg/ml) was higher in patients with type 2 diabetes [172.70 (116.19, 286.42)] compared with that in individuals without diabetes [92.09 (70.32, 147.24)] (p<0.001). Advance in serum FAM19A5 tertile was associated with a trend of increase in waist hip ratio (WHR), fasting plasma glucose (FPG), and mean brachial-ankle pulse wave velocity (baPWV) values. Serum FAM19A5 was positively correlated with waist circumference, WHR, alanine aminotransferase, FPG, HbA1c, and mean baPWV values. Multiple stepwise regression analysis identified WHR, low density lipoprotein cholesterol, and baPWV as determining factors for log-transformed serum FAM19A5 concentration (R2=0.0689).

Discussion: A novel adipokine FAM19A5 was closely related to various metabolic and vascular risk factors in human subjects, suggesting its potential as a biomarker of cardio-metabolic disease in humans.

Disclosure

Y. Lee: None. J.A. Kim: None. E. Roh: None. S. Hong: None. K. Choi: None. S. Baik: None. H. Yoo: None.
208-LB: Fatty Liver Disease Differentiates Subpopulations with Higher Risk of Incident Type 2 Diabetes Regardless of Their Metabolic Health and Obesity Status: A Nationwide Population-Based Cohort Study
Authors: MI KANG YU , KYUNG CHO YUN , HEE YOO JEE , LEE JIWOO , HAN CHOI JONG , PARK JOONG-YEOL , JE LEE WOO , HEE JUNG CHANG
Published: June 2019

Objective: We aimed to evaluate the risk of incident type 2 diabetes (T2D) in metabolically healthy, obese (MHO) individuals and the role of fatty liver disease (FLD) in this potentially causal relationship.

Methods: We enrolled 514,866 participants from the Korean National Health Insurance Service-National Health Screening Cohort in 2002-2015. Subjects were categorized into metabolically healthy, non-obese (MHNO), metabolically unhealthy, non-obese (MUNO), MHO, and metabolically unhealthy, obese (MUO) groups. Well-validated FLD indices were used in this study; Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Visceral Adiposity Index (VAI).

Results: Over 5.6 years, 67,807 (27.8%) of 244,301 subjects free of T2D and liver disease besides FLD developed T2D. The risk correlated with obesity (HR, 1.35; 95% CI 1.33-1.37) and the number of metabolic risk factors; HRs for 1, 2, 3, and 4 risk factors were 1.43 (95% CI, 1.39-1.47), 1.92 (95% CI, 1.87-1.97), 2.51 (95% CI, 2.44-2.58), and 3.14 (95% CI, 3.02-3.26), respectively. Compared with the MHNO group, the risk of T2D was significantly higher in MUO (multivariate HR, 1.95; 95% CI, 1.91-2.00), MUNO (HR, 1.63; 95% CI, 1.60-1.67), and MHO (HR, 1.28; 95% CI, 1.25-1.30) individuals. Higher FLD scores among MHO individuals also exhibited a strong correlation with the incident T2D, compared with both the MHNO group and the MHO counterpart with lower FLD scores (P < 0.05 for all comparisons). Survival trees analysis based on log-rank test revealed that the best cut-off points to predict incident T2D were 25.1, 33.4, and 1.7 for FLI, HSI, and VAI, respectively.

Conclusion: The number of metabolic risk factors, obesity, and FLD are significant predictors of incident T2D. Higher T2D risk in MHO individuals, with an excess risk related to higher FLD scores, necessitates more intensive monitoring and interventions in these individuals.

Disclosure

Y. Kang: None. Y. Cho: None. J. Yoo: None. J. Lee: None. J. Choi: None. J. Park: None. W. Lee: None. C. Jung: None.
2088-P: Soluble EGFR and Adipsin Are Independent Serum Biomarkers for Insulin Resistance in Mouse and Human
Authors: KYOHARA MAYU , SHIRAKAWA JUN , TERAUCHI YASUO
Published: June 2019

We identified soluble epidermal growth factor receptor (sEGFR), a hepatokine, and Adipsin, a adipokine, by serum quantitative proteomics as common factors, whose protein levels were significantly reduced across 4, 8, 12, and 24 weeks of ages in obese diabetic db/db mice and were restored by treatment with liraglutide. In this study, we investigated the properties of sEGFR and Adipsin as biomarkers in mouse and human. In mice, the expression of EGFR and Adipsin were abundant in the liver and adipose tissue, respectively, and significantly reduced in db/db mice. The sEGFR and Adipsin were significantly decreased in sera of high-fat diet-fed mice and ob/ob mice. Next, we measured the sEGFR and Adipsin levels in sera from 47 nondiabetes subjects and 106 patients with type 2 diabetes, and analyzed the correlation with clinical parameters by using multiple linear regression analysis. No correlations were observed between sEGFR and Adipsin levels. The sEGFR levels were positively correlated with HbA1c, fasting blood glucose, and HOMA-IR, and the association was remained after adjustment for age and sex (β = 0.357, p < 0.001; β = 0.299, p < 0.001; β = 0.259, p = 0.004). The sEGFR levels were also positively correlated with T-chol, TG, LDL-chol, and AST after adjustment for age and sex (β = 0.378, p < 0.001; β = 0.275, p < 0.001; β = 0.235, p = 0.004; β = 0.202, p = 0.014). The Adipsin levels were positively correlated with BMI, waist circumference, fasting serum insulin, and HOMA-IR, and remained correlation after adjustment for age and sex (β = 0.532, p < 0.001; β = 0.475, p < 0.001; β = 0.383, p < 0.001; β = 0.342, p = 0.003). The Adipsin levels were also positively correlated with FIB-4 index (liver fibrosis index), and negatively correlated with eGFR after adjustment for age and sex (β = 0.264, p = 0.013; β = -0.352, p < 0.001). These findings suggest that sEGFR and Adipsin are independent biomarkers that correlate with factors for insulin resistance, and might reflect liver and fat insulin resistance, respectively.

Disclosure

M. Kyohara: None. J. Shirakawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.
2091-P: Relationship between Prediabetes (Pre-DM) and the Frequency of Periodontal Disease (PD) in Patients with Severe Obesity—A Retrospective Cohort Study in an Academic Center in Paraguay
Authors: JIMÉNEZ DE PANE VIOLETA M. , BENITEZ ALDO , PALACIOS MAFALDA , BUENO COLMAN ELVIO DARIO , JIMENEZ JORGE T.
Published: June 2019

Objectives: To determine the relationship between the Pre-DM and the PD frequency in patients with significant obesity and also between the Pre-DM as part of the metabolic syndrome (MS) and the PD in these patients.

Methods: Retrospective cohort study with patients with severe obesity from an unit of multidisciplinary management of obesity. They were distinguished in patients with Pre-DM or normoglycemia. The outcome was the presence and degree of PD with the Modified Periodontal Index of Russell (MPIR).

Results: There were evaluated 62 patients, half of them with Pre-DM. The Pre-DM vs. normoglycemia cohorts had: weight (in kg) 133,3±37,2 vs. 114,7±20,7 (p 0,01) and BMI 49,1±12,9 vs. 43,1±6,3 (p 0,02). According to the MPIR no patient was healthy. In the Pre-DM and normoglycemia cohorts the frequency of gingivitis and periodontitis was equal: 22,5 and 77,4% respectively. The frequency of severe periodontitis (SP) was 51,6% in patients with Pre-DM and 29,03% with normoglycemia (RR 1,77 - p 0,06). The SP was more frequent with higher fasting glucose levels: 29,4, 38,7 and 57,14% for each tertile respectively, as well as with greater BMI: 28,9, 50 and 75% for each tertile. Among patients with Pre-DM and BMI ≥ 45,9 kg/m2, 75% had SP vs. 26,7% of those with lower BMI (RR 2,81 - p 0, 01). Amidst patients with vs. without MS: 44,2 vs. 31,6% had SP (RR 1,39 - p 0,3). The frequency of SP had a fairly linear rise with the increase in the number of elements of the MS: 20, 36, 37, 53 and 43% in the presence of 1 to 5 elements of MS respectively (p > 0,05).

Conclusions: The PD was not more common in patients with Pre-DM. SP was more frequent in those patients with Pre-DM, with a greater and statistically significant difference in those with more severe degrees of obesity. These results show that in the context of severe obesity and MS, even mild hyperglycemia seems to be related to SP and the need to request an evaluation of oral health in this group of patients.

Disclosure

V.M. Jiménez de Pane: None. A. Benitez: None. M. Palacios: None. E. Bueno Colman: None. J.T. Jimenez: None.
2095-P: Association between Markers of Neuro and Systemic Inflammation and Cognitive Function in Obesity
Authors: KHAN ADAM , JOERS JAMES M. , LUCIANA MONICA , RUBIN NATHAN , SIDDIQUI YOUSUF , MANGIA SILVIA , EBERLY LYNN E. , IKRAMUDDIN SAYEED , SEAQUIST ELIZABETH R. , OZ GULIN , MOHEET AMIR
Published: June 2019

Obesity is associated with alterations in brain structure and cognitive impairment. The mechanisms underlying obesity related decline in cognitive function are not well understood. Obesity related chronic systemic inflammation is postulated to be one of the potential mechanisms leading to cognitive dysfunction. It is unknown whether inflammation impacts brain areas important for higher level cognition such as the anterior cingulate cortex (ACC). Elevated myo-inositol (Ins), as measured by magnetic resonance spectroscopy (MRS), may be a marker of neuroinflammation and reflects activated astrocytes and microglia. We hypothesized that obese subjects (OB) will have higher ACC Ins compared to normal weight controls (CON) and that higher Ins will be associated with elevated blood inflammatory markers and reduced cognitive performance. We examined neurochemical profile from a 24x24x12mm3 voxel over the ACC using 1H MRS at 3 and 7 Tesla (T), in 5 nondiabetic OB (age 33 ± 5 years, BMI 43 ± 6 kg/m2) and 4 CON (age 36 ± 3 years, BMI 23 ± 3 kg/m2). Subjects also underwent cognitive testing and measurement of blood inflammatory markers. MR spectra were quantified using LCModel and the concentrations are expressed as a ratio to total creatine (tCr). There was a strong trend of higher Ins/tCr in ACC in OB compared to CON both at 3T (0.96 ± 0.06 vs. 0.88 ± 0.05, p =0.07) and 7T (0.91 ± 0.07 vs. 0.83 ± 0.08, p =0.17). Pearson correlations were used to test the relationship between Ins/tCr and markers of inflammation among all subjects. Higher blood inflammatory markers were associated with higher Ins/tCr (3T) in ACC (CRP, r=.74, p= 0.04; TNF α, r=.89, p=0.003) and with low levels of crystallized ability as measured by the NIH Toolbox Cognition Battery (CRP, r=-.73, p=0.03). Higher ACC Ins/tCr was also associated with poorer performance on a measure of fine motor coordination (r=.93, p=0.001). These data support the hypothesis that inflammation may contribute to the pathogenesis of brain and cognitive alterations in obesity.

Disclosure

A. Khan: None. J.M. Joers: None. M. Luciana: None. N. Rubin: None. Y. Siddiqui: None. S. Mangia: None. L.E. Eberly: None. S. Ikramuddin: Research Support; Self; Medtronic. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD. G. Oz: None. A. Moheet: None.

Funding

National Institutes of Health
2098-P: The Accuracy of Meal Test to Diagnose Hypoglycemia after Gastric Bypass
Authors: HONKA HENRI , DEFRONZO RALPH A. , PATTI MARY E. , SALEHI MARZIEH
Published: June 2019

Gastric bypass (GB) alters postprandial glucose pattern with a higher peak of glucose and lower glucose nadir. Glycemic effects of GB is exaggerated in patients suffering from postprandial hyperinsulinemic hypoglycemia. Diagnosis is complex and requires documentation of concurrent symptoms with low glucose that are relieved by carbohydrate (CHO) intake (Whipple’s triad). Mixed meal tolerance test (MTT) is often used to provoke hypoglycemia but glucose threshold to fulfill Whipple’s triad remains unknown. Here we measured accuracy of 350-kcal MTT (Ensure Plus®, 51 g CHO) to diagnose hypoglycemia in 95 GB subject (43 with prior documented hypoglycemia [H] and 52 asymptomatic [A]). In addition, measured outcomes were compared with those during isovolemic 250-kcal liquid MTT (Ensure®, 40 g CHO) in a separate cohort of 49 GB subjects (31 H vs. 18 A). Time and weight loss since surgery, BMI, and A1c were similar between H and A. The H subjects had lower fasting glucose (80±1 vs. 84±1 mg/dL, P<0.05) and nadir glucose levels (51±2 vs. 67±2 mg/dL, P<0.001). Nadir glucose values were associated with fasting glucose (r=0.6, P<0.001). Plotting true positive rate (sensitivity) against false positive rates (1-specificity) for nadir glucose during MTT yielded an area under the Receiver Operating Characteristics (ROC) curve of 0.80±0.05. A nadir blood glucose cut-off of 53 mg/dL produced the highest sum of sensitivity (65%) and specificity (88%) for detecting hypoglycemia. Lower CHO ingestion (40 g) did not significantly affect the accuracy of MTT to diagnose hypoglycemia (AUC ROC: 0.69±0.08). Our findings indicates that mixed meals containing 40-50 g of CHO have good discriminatory value to diagnose hypoglycemia after GB using blood glucose threshold of <54mg/dL.

Disclosure

H. Honka: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. M.E. Patti: Consultant; Self; Eiger BioPharmaceuticals. Research Support; Self; Dexcom, Inc., Janssen Pharmaceuticals, Inc., MedImmune, Xeris Pharmaceuticals, Inc. M. Salehi: None.

Funding

National Institutes of Health (DK105379, DK083554 to M.S.); National Center for Advancing Translational Sciences (8UL1TR000077); Finnish Cultural Foundation (00180071)
2112-P: Weight Trajectory from Young Adulthood to Midlife and Mortality in U.S. Adults
Authors: CHEN CHEN , PAN XIONG-FEI , PAN AN
Published: June 2019

Excess adiposity mostly accrues from young adulthood to midlife, however the impact of weight change in early life on mortality risk in later life is unclear.

A total of 26724 individuals aged 40 years and older from the 1988-2010 U.S. National Health and Nutrition Examination Survey (NHANES) recalled their weight at young adulthood (at age of 25 years) and middle adulthood (at ten years before the NHANES survey cycle started). Based on these two weight status, they were categorized into four weight change groups: those who maintained as non-obese (stable non-obese of BMI <30 in both times), those who changed from non-obese to an obese body shape (gaining), those who moved from an obese BMI to a non-obese BMI (losing) and those who remained obese (stable obese). Mortality status was linked with death certificate records from National Death Index up to December 31, 2011. Cox proportional hazard models adjusting for covariates were used for calculating hazard ratios (HRs) and 95% confidence intervals (CI).

During a mean follow-up of 18.9 years, 6732 deaths occurred. Compared with stable non-obese category, those in the gaining group had a 27% (HR 1.27; 95% CI 1.16-1.39) and 40% (1.40; 1.17-1.66) increased risk of total mortality and cardiovascular mortality respectively; those in the stable obese group had significantly higher risk of total mortality (1.87; 1.62-2.15) and cardiovascular mortality (2.40; 1.79-3.22). Weight change was not significantly associated with cancer mortality. Although the weight loss category was associated with a non-significant modest increased risk of total mortality (1.36; 0.96-1.92), the association was mainly driven by non-cardiovascular and non-cancer causes (1.80; 1.13-2.87), rather than cardiovascular mortality (0.82; 0.50-1.33) or cancer mortality (1.18; 0.58-2.42). Analysis in never smokers, different sex and age groups showed similar results.

Maintaining a non-obese body shape from young adulthood to midlife is important for preventing premature death in later life.

Disclosure

C. Chen: None. X. Pan: None. A. Pan: None.

Funding

National Key Research and Development Program of China (2017YFC0907504)