bluuebunny/crossref_metadata_2025 huggingface dataset:
1257-P: Impact of Parental Smoking on Adipokine Profiles and Cardiometabolic Risk Factors in Chinese Children: The Beijing Child and Adolescent Metabolic Syndrome Cohort Study
Authors: LI MING , ZHANG QIAN , GAO SHAN , WILLI STEVEN M. , GROUP BCAMS
Published: June 2020

Exposure to secondhand smoke has relatively recently been recognized to be an important modifiable risk factor for obesity and cardiovascular disease, along with unhealthy diet, sedentary lifestyle and insufficient sleep. The mechanism(s) by which passive smoking imparts this risk and the tissues involved still require elucidation. We aimed to evaluate the association between parental smoking exposure (PSE), secretion of adipokines and cardiometabolic risk in Chinese children. A total of 3150 children (6-18ys) from the Beijing Child and Adolescent Metabolic Syndrome (MetS) study with data on PSE and potential confounders (pubertal stage, physical activity, diet and socioeconomic factors plus family history) were included. Six adipokines related to insulin resistance and MetS (leptin, adiponectin, retinol binding protein 4 (RBP4), fibroblast growth factor 21 (FGF-21), resistin and osteonectin) were measured. Of those children studied, nearly 65% reported PSE, defined as smoking in either parent. After adjusting for covariates, including pubertal stage, lifestyle factors, and family history, PSE was independently associated with increases of 39.2% in leptin and 3.9% in RBP-4 and decreases of 11.4% in FGF-21 and 4.6% in adiponectin levels (P < 0.05 for all). The risks of central obesity (OR 1.59, 95% CI 1.33-1.90, P < 0.001), hyperglycemia (OR 1.30, 95%CI 1.02-1.66, P<0.05), hypertension (1.22, 1.02-1.46, P = 0.001) and MetS (1.43, 1.11-1.85, P < 0.001) were all increased with PSE. However, the associations of PSE with hypertension and MetS were abolished after adjusting for adiposity parameters or the above-mentioned adipokines. In contrast, PSE was still associated with increased risk of hyperglycemia after adjusting for BMI in boys (OR 1.42, 95%CI: 1.01-2.00, P<0.05). Our findings suggest that PSE was associated with dysregulation of adipokine levels, which may mediate the development of MetS in early life.

Disclosure

M. Li: None. Q. Zhang: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Tolerion, Inc. Other Relationship; Self; Caladrius Biosciences, Inc.

Funding

National Natural Science Foundation of China (81970732); National Key Research and Development Program of China (2016YFC1304801); Key Program of Beijing Municipal Science and Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science and Technology Star Program (2004A027); Novo Nordisk Union Diabetes Research Talent Fund (2011A002); National Key Program of Clinical Science (WBYZ2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)
1261-P: OGTT Model–Derived ß-Cell Function Reveals Differential Loss in Youth vs. Adults during and following Treatment Withdrawal in the Restoring Insulin Secretion (RISE) Study
Authors: UTZSCHNEIDER KRISTINA , TRIPPUTI MARK , CREE-GREEN MELANIE , HANNON TAMARA S. , NADEAU KRISTEN J. , BARENGOLTS ELENA , PALMER JERRY P. , MATHER KIEREN J. , CAPRIO SONIA , EDELSTEIN SHARON , MARI ANDREA ,   THE RISE CONSORTIUM
Published: June 2020

Loss of β-cell function is critical in the pathogenesis of T2D and may progress more rapidly in youth. We compared 3-hr OGTT model-derived measures of β-cell function in youth and adults with IGT or T2D in RISE treated for 12 mo with metformin (MET), or glargine followed by metformin (G/M) and 9 mo after treatment withdrawal. Model parameters included insulin sensitivity (OGIS), insulin secretion rate (ISR) at glucose 6.5 mM (ISR-6.5), total ISR (tISR), glucose sensitivity (GS: slope ISR vs. glucose concentration) and rate sensitivity (RS: ISR relative to glucose rate of change). Linear mixed models tested for differences by time (0-12 and 0-21 mo), age (youth vs. adults) and treatment (MET vs. G/M). Key observations included the following. Insulin sensitivity (OGIS) increased transiently in all but adults on G/M. In youth, insulin secretion (ISR-6.5 and tISR) and RS decreased relative to baseline, with GS also decreased in the G/M arm. In contrast, in adults there were no significant changes in modeled parameters at 21 mo. Insulin secretion and β-cell function parameters decreased more in youth vs. adults in the G/M arm. By treatment, GS decreased more in the G/M vs. MET arm in youth, but there were no differences in adults.

In conclusion, only youth exhibited worsening of features of β-cell function that can only be derived with mathematical modeling.

Disclosure

K. Utzschneider: Other Relationship; Self; Medtronic. M. Tripputi: None. M. Cree-Green: Advisory Panel; Self; Novo Nordisk Inc. T.S. Hannon: None. K.J. Nadeau: None. E. Barengolts: None. J.P. Palmer: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. S. Edelstein: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. T. Consortium: None.

Funding

American Diabetes Association (1-14-RISE-01); National Institute of Diabetes and Digestive and Kidney Diseases
1275-P: Higher Branched-Chain Amino Acids in Youth with Type 2 Diabetes Paradoxically Increased by Short-Term Metformin
Authors: MEYERS ABBY , CRAVALHO CELESTE K. , VILLALOBOS-PEREZ ALFREDO , MATTA SAMANTHA , MABUNDO LILIAN , COURVILLE AMBER B. , SAMPSON MAUREEN L. , OTVOS JAMES D. , CHUNG STEPHANIE T.
Published: June 2020

Branched chain amino acids (BCAA) are important signaling molecules that are strongly related to type 2 diabetes (T2D), but the data linking BCAAs to reduced insulin sensitivity (IS) in youth is conflicting. This complex relationship of BCAAs with IS and glycemia may be further confounded by metformin that potentially alters BCAA synthesis and transport via gut mechanisms. Therefore, we compared: (1) BCAAs in 20 youth with T2D pre-metformin to 10 normal glucose tolerant (NGT) age/BMI-matched controls and (2) the change in BCAAs after 3 months of metformin in 8 youth with T2D. Fasting BCAAs were measured with nuclear magnetic resonance spectroscopy and IS and oral disposition index (oDI) calculated during a multi-sample 75g OGTT. Compared to NGT, youth with T2D had higher BCAAs and hemoglobin A1c (HbA1c) but lower IS and oDI (Table). Higher total BCAAs pre-metformin correlated with HbA1c (r=0.6, P<0.001,), inversely correlated with oDI (r= -0.5, P=0.02,), but not with IS or BMI (r=0.2, P>0.2). Metformin decreased HbA1c and increased leucine and isoleucine (Table), but there was no change in BMI, IS or valine (all P>0.05). In youth, higher BCAAs were related to lower β-cell function relative to IS and worse glycemia. Although metformin improved glycemia, BCAAs were paradoxically increased suggesting that BCAAs may not be a useful treatment biomarker or indicator of changes in metabolic status.

Disclosure

A. Meyers: None. C.K. Cravalho: None. A. Villalobos-Perez: None. S. Matta: None. L. Mabundo: None. A.B. Courville: None. M.L. Sampson: None. J.D. Otvos: Employee; Self; LabCorp. S.T. Chung: None.

Funding

National Institutes of Health (to S.T.C., L.M., A.B.C.)
128-LB: Effects of Glucagon Receptor Antagonism (GRA) on Ketone Body Formation during Insulinopenia in Type 1 Diabetes (T1D)
Authors: BOEDER SCHAFER C. , INES DANIEL G. , CARTER LESLIE , GIOVANNETTI ERIN R. , ARMSTRONG DEBRA , BURKE PAIVI , PETTUS JEREMY
Published: June 2020

Background: Diabetic ketoacidosis is a common and life-threatening complication of T1D. Glucagon stimulates ketogenesis via peripheral lipolysis and hepatic β-oxidation of free fatty acids (FFA). Blocking glucagon action may decrease ketone formation and reduce the risk of DKA.

Methods: In this pilot study, 4 participants with T1D underwent 6 hours of insulin withdrawal before and after 4 weeks of monoclonal GRA treatment (REMD-477, 70mg weekly). Serial measurements of plasma glucose, FFA, and β-hydroxybutyrate (BHB) were collected to determine the efficacy of GRA therapy in reducing ketone formation in the setting of insulinopenia.

Results: Pre- vs. post-treatment concentrations (mean ± SD; paired two-tailed t-test) after 6-hour insulin withdrawal were: Glucose (263 ± 63 vs. 235 ± 109 mg/dL; P = 0.53), FFA (1.37 ± 0.60 vs. 1.09 ± 0.77 mmol/L; P = 0.07), and BHB (1.30 ± 0.70 vs. 0.63 ± 0.54 mmol/L; P = 0.08). Glucagon concentrations increased (26.8 ± 9.9 vs. 454 ± 245 pg/mL; P = 0.04) with blockade of glucagon action. Frequent insulin draws confirmed insulinopenia.

Conclusions: These preliminary results suggest that GRA treatment may reduce ketogenesis in the clinical setting in which DKA occurs (insulinopenia). These trends will be tested in a larger, randomized study. If confirmed, this would represent a novel therapy to reduce the risk of life-threatening DKA in T1D.

Disclosure

S.C. Boeder: Consultant; Self; Cecelia Health, Science 37. Research Support; Self; Dexcom, Inc. D.G. Ines: None. L. Carter: None. E.R. Giovannetti: None. D. Armstrong: None. P. Burke: None. J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi.

Funding

National Institutes of Health (UL1TR001442, P30DK063491)
129-OR: Abnormal Mitochondrial Activity in Pain Processing Regions of the Brain in Painful Diabetic Peripheral Neuropathy
Authors: SLOAN GORDON P. , ANTON ADRIANA , SELVARAJAH DINESH , TESFAYE SOLOMON , WILKINSON IAIN D.
Published: June 2020

Aims: The management of painful diabetic peripheral neuropathy (pDPN) is inadequate because the disease mechanisms are not fully understood. We assessed cerebral cellular bioenergetics using phosphorus magnetic resonance spectroscopy (31P-MRS) to determine whether high energy phosphate metabolite levels are altered in the pain processing regions of the brain in pDPN.

Methods: A total of 66 subjects, 44 with type 2 diabetes (12 no-DPN, 13 painless-DPN and 19 pDPN) and 12 healthy volunteers (HV), underwent detailed clinical and neurophysiological assessments, and 31P-MRS brain imaging at 3-Tesla (Ingenia, Phillips Healthcare) with voxels placed over the right somatosensory cortex and the thalamus (TR 4s, TR 0.26ms, voxel size 21 x 21 x 40mm3). Measures reflecting cellular bioenergetics (mitochondrial function), ATP to phosphocreatine (PCr) and inorganic phosphate (Pi) ratios (ATP:PCr and ATP:Pi) were calculated.

Results: There was a significant group effect in the ATP:PCr ratio at the thalamus (p=0.016) and somatosensory cortex (p=0.025). The ATP:PCr at the thalamus was significantly higher in the pDPN group (0.50±0.06) compared to HV (0.44±0.04, p=0.024) and no-DPN (0.42±0.07, p=0.006). Moreover, the ATP:PCr ratio at the somatosensory cortex was significantly higher in pDPN (0.48 ±0.1) compared to HV (0.38 ±0.1, p=0.035). In addition, the ratio correlated with the numeric pain score ratings during the MRI scan at both brain regions.

Conclusions: This is the first study to use 31P-MRS to study cerebral energetics in human-DPN and peripheral painful neuropathies. We demonstrated significantly higher ATP:PCr ratios in patients with pDPN in the somatosensory cortex and thalamus, which correlated with pain severity. This is suggestive of increased cellular energy usage in pain processing regions of the brain, perhaps due to continuous nociceptive inputs. Altered cerebral phosphorus metabolite ratios may serve as a biomarker of neuropathic pain in diabetes.

Disclosure

G.P. Sloan: None. A. Anton: None. D. Selvarajah: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. I.D. Wilkinson: None.
1309-P: Adolescent Preferences on the Use of Social Media by Diabetes Care Teams to Support Diabetes Management
Authors: MALIK FAISAL , MORENO MEGAN A. , MANGIONE-SMITH RITA , PIHOKER CATHERINE , ELLYSON ALICE M. , GILL HARSIMRAT , CHALMERS KRISTEN , CHRISTAKIS DIMITRI
Published: June 2020

Objective: To examine adolescent preferences related to the use of social media (SM) as a tool to manage their type 1 diabetes (T1D) with their diabetes care team.

Methods: Adolescents with T1D (13-18 years old) in the Seattle, WA area were surveyed from August-December 2019 about their SM use and interest in communicating with their diabetes care team over SM.

Results: 232 adolescents with T1D completed the survey (response rate = 53%); mean age 15.1 years, 94% used SM, 85% used SM at least once/day. Approximately 70% indicated that if given the option, they were very likely or somewhat likely to communicate with their diabetes provider on SM. Over 72% shared they were very likely or somewhat likely to use SM direct messaging to ask urgent questions and 64% would use it for non-urgent questions. A majority of participants agreed that they would want to receive educational material (62%) and insulin dose adjustment support over SM (58%); Figure. Most agreed that SM communication would facilitate increased independent communication (61%) and positively impact patient-care team relationships (63%). A minority of participants (38%) reported privacy concerns.

Conclusions: Adolescents with T1D expressed interest in using SM to support diabetes management and increase direct engagement with their diabetes care team. Healthcare teams should explore the use of SM to provide tailored support to adolescents with T1D.

Disclosure

F. Malik: None. M.A. Moreno: None. R. Mangione-Smith: None. C. Pihoker: None. A.M. Ellyson: None. H. Gill: None. K. Chalmers: None. D. Christakis: None.

Funding

National Institutes of Health (K23DK119465)
1312-P: Pancreas Volume in Individuals with MODY 1, 2, 3, and 5
Authors: WRIGHT JORDAN J. , WILLIAMS JONATHAN M. , VIROSTKO JOHN , HILMES MELISSA A. , DU LIPING , KANG HAKMOOK , GREELEY SIRI ATMA W. , RUSSELL WILLIAM E. , MOORE DANIEL J. , POWERS ALVIN C.
Published: June 2020

Individuals with new-onset type 1 diabetes (T1D) have a smaller pancreas volume, which declines further during the first years after diagnosis. Whether this reflects the insulin deficiency associated with T1D or the underlying process leading to T1D is not clear. Mutations in several genes that are active in the pancreas and/or pancreatic islet cells cause varying degrees of insulin deficiency, resulting in Maturity Onset Diabetes of Youth (MODY). To determine whether decreased pancreas volume is associated with these other forms of diabetes, we used a standardized MRI protocol that has been validated in over 500 scans to measure pancreas volume normalized to body weight (pancreas volume index, PVI). Individuals with mutations in HNF4A (MODY 1, ages 19-71, PVI 0.79 ± 0.07 mL/kg, N=4), GCK (MODY 2, ages 9-55, PVI 0.97 ± 0.10 mL/kg, N=5), or HNF1A (MODY 3, ages 16-60, PVI 0.80 ± 0.09 mL/kg, N=7) had pancreas volume similar to controls (ages 8-65, 0.96 ± 0.03 mL/kg, N=78, p>0.59). Pancreas volume was not different in individuals with MODY 1, 2, or 3 who required insulin replacement therapy compared with those not on insulin (PVI 0.82 ± 0.08 vs. 0.89 ± 0.09 mL/kg, N=9 and 7, p=0.56). Individuals with a mutation in HNF1B (MODY 5), a less common mutation that can be associated with pancreatic hypoplasia, had widely variable pancreas volume (PVI 0.90 ± 0.36 mL/kg, N=3). Further studies to assess pancreas size in other forms of MODY are needed and may provide insight into why the pancreas volume is reduced in T1D.

Disclosure

J.J. Wright: None. J.M. Williams: None. J. Virostko: None. M.A. Hilmes: None. L. Du: None. H. Kang: None. S.W. Greeley: None. W.E. Russell: None. D.J. Moore: None. A.C. Powers: None.

Funding

JDRF (3-SRA-2019-759-M-B, 3-SRA-2015-102-M-B)
134-OR: Effects of PCSK9 Inhibitors on Glucose Metabolism and ß-Cell Function in Humans
Authors: MOFFA SIMONA , MEZZA TERESA , ASSUNTA CEFALO CHIARA MARIA , CINTI FRANCESCA , SORICE GIAN PIO , IMPRONTA FLAVIA , CAPECE UMBERTO , MARI ANDREA , GIACCARI ANDREA
Published: June 2020

PCSK9 inhibitors are monoclonal antibodies effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. Since PCSK9 is also expressed in other organs, including pancreas, studies on PCSK9 KO mice, have shown impaired insulin secretion. Other murine models in which PCSK9 was silenced only in the liver (mimicking the action of PCSK9i) had normal glucose metabolism. The aim of our study was to evaluate the effect of PCSK9 inhibitors on glucose metabolism and beta cell function in humans. 11 nondiabetic subjects candidate for PCSK9i therapy were enrolled in the study. All subjects underwent an OGTT at baseline and after 6 months of therapy, at which point surrogate insulin sensitivity indices were obtained (Matsuda; OGIS). During OGTT, insulin secretion parameters were derived from C-peptide levels by deconvolution; we evaluated basal insulin secretion rate, total insulin secretion rate and β-cell glucose sensitivity, for 6 of the 11 enrolled subjects. All patients showed a 53.3% reduction in LDL cholesterol after 6 months of therapy; the mean LDL-C baseline level (B) was 202.5 ± 45 mg/dl, while mean LDL-C post therapy (PT) value was 94.6 ± 27 mg/dl. Glycemic and insulinemic curves showed no significant differences between baseline and follow-up. Matsuda index (B 4.1 ± 1, PT 3.4 ± 0.7 mL min-1kg-1) and OGIS (B 396.9 ± 32, PT 386.2 ± 28 ml min-1m-2), showed no differences between baseline and post-therapy evaluation. There were no significant differences in insulin secretion parameters: basal insulin secretion rate (B 63.7 ± 34, PT 66.4 ± 23 pmol min-1m-2), total insulin secretion rate (B 48.7 ± 17, PT 46.9 ± 16, nmol m-2) and β-cell glucose sensitivity (B 117.5 ± 69, PT 141.2 ± 47 pmol min-1m-2mM-1) obtained from c-peptide deconvolution. Our study, although preliminary and in a small sample of patients, suggests that PCSK9is does not cause alterations in glucose metabolism and beta cell function. Further studies and a longer follow-up may provide us with further data to confirm our observations.

Disclosure

S. Moffa: None. T. Mezza: None. C. Cefalo: None. F. Cinti: None. G. Sorice: None. F. Impronta: None. U. Capece: None. A. Mari: Consultant; Self; Lilly Diabetes. Research Support; Self; Boehringer Ingelheim International GmbH. A. Giaccari: Speaker’s Bureau; Self; Amgen, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi-Aventis.
1370-P: Pregnant Dyslipidemia Affects Postpartum Metabolism in Gestational Diabetes Mellitus Patients
Authors: XIAO HUANGMENG , PEI LING , LI ZETING , HUANG XIAOYU , YUE SHUFAN , CAO XIAOPEI
Published: June 2020

Women with gestational diabetes mellitus (GDM) have higher rate of dyslipidemia during pregnancy than those without GDM. However, whether this higher level of blood lipid during pregnancy in GDM women has effects on postpartum metabolism is rarely reported. The purpose of this study is to assess the influence of dyslipidemia during pregnancy on postpartum metabolism in women with history of GDM . A total of 443 women with history of GDM were enrolled in this retrospective cohort study. All of them have completed revisit at 4-12 week postpartum. The demographic and pregnant medical records were collected. In the postpartum revisit, 75g-OGTT test and physical examination were performed. The serum lipid level and insulin concentration were measured. Pregnant dyslipidemia were categorized according to the criteria of Williams obstetrics in pregnancy. The relationship between pregnant dyslipidemia and postpartum metabolism was statistically analyzed. On the whole, postpartum blood lipid levels showed a downward trend comparing with those during pregnancy. However, 39.4% of those GDM women presented dyslipidemia at 4-12 week postpartum, including 61.2% of mixed hyperlipidemia, and 38.8% of single component dyslipidemia. Women with pregnant dyslipidemia had higher postpartum total cholesterol level, TG level as well as LDL-c level. The triglyceride (TG) level during pregnancy were positively correlated with postpartum fasting blood glucose level, fasting insulin level and insulin resistance index (HOMA-IR). On the other hand, the HDL-c level during pregnancy were negatively correlated with postpartum fasting blood glucose and HOMA-IR.

In conclusion, the abnormally increased blood lipid levels during pregnancy in GDM women are relative to the postpartum hyperglycemia and hyperlipidemia. Management of pregnant dyslipidemia may be beneficial to the postpartum metabolism in GDM women.

Disclosure

H. Xiao: None. L. Pei: None. Z. Li: None. X. Huang: None. S. Yue: None. X. Cao: None.

Funding

Sun Yat-sen University (2017001); Science and Technology Planning Project of Guangzhou (201803010101)
1373-P: Adherence to Healthy Lifestyle on Subsequent Risk of Type 2 Diabetes (T2D) among Women with a History of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study
Authors: QIAN FRANK , CHAVARRO JORGE E. , LEY SYLVIA H. , TOBIAS DEIRDRE , YEUNG EDWINA , LI MENGYING , LIU AIYI , MILLS JAMES , SUN QI , HU FRANK , ZHANG CUILIN
Published: June 2020

Background: Women with a history of GDM are at exceptionally high risk of T2D but adopting a healthy lifestyle may mitigate this risk.

Methods: We analyzed 4,287 women with a prior clinician diagnosis of GDM from the Nurses’ Health Study II cohort as part of the Diabetes and Women’s Health Study. Healthy lifestyle factors, which were assessed every 2-4 years, included no current smoking, normal body mass index (<25 kg/m2), regular moderate-to-vigorous physical activity (>500 MET-min/week), high-quality diet (above median for the Alternative Healthy Eating Index), and moderate alcohol consumption (>0-15 g/day). Self-reported incident T2D was confirmed via validated supplementary questionnaire (98% concordance with medical records). Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI), adjusting for demographic, reproductive, and clinical characteristics.

Results: We ascertained 835 incident T2D cases during a median 27.9 years of follow-up. Compared to women reporting no healthy lifestyle factors, HR (95% CI) for risk of T2D among those with 1, 2, 3, 4, or 5 factors were 0.91 (0.64, 1.30), 0.62 (0.44, 0.87), 0.45 (0.31, 0.64), 0.33 (0.22, 0.48), and 0.13 (0.06, 0.28), respectively (P<trend<0.001) (Table 1). When number of health lifestyle factors was modeled continuously, each additional factor was associated with a 29% lower risk of T2D, HR (95% CI): 0.71 (0.67, 0.76). In addition, >86% (population attributable risk [PAR]%: 86.3%; 95% CI: 70.6%, 93.7%) of T2D cases were theoretically preventable if participants had adherence to all 5 healthy lifestyle factors.

Conclusion: Adherence to healthy lifestyle factors was associated with a substantially lower likelihood of progressing to T2D in women with a history of GDM, and strategies to improve long-term adherence are warranted.

Disclosure

F. Qian: None. J.E. Chavarro: None. S.H. Ley: None. D. Tobias: None. E. Yeung: None. M. Li: None. A. Liu: None. J. Mills: None. Q. Sun: None. F. Hu: None. C. Zhang: None.
1382-P: Does Tight Gestational Diabetes Mellitus Control Have an Impact on the Maternal and Neonatal Outcome Compared with General Populations? Which Factors Predict the Adverse Pregnancy Outcomes?
Authors: THOMAKOS PETROS , KEPAPTSOGLOU OLGA , BARRETO CAROL , TROUVA ANASTASIA , TROUVAS DIMITRIS , ZOUPAS CHRISTOS S.P.
Published: June 2020

The prevalence of adverse outcomes in GDM pregnancies compared to the general population are still high in studies, which used ADA treatment criteria. Our goal was to compare outcomes of tight controlled GDM pregnancies achieving optimal glycemic patterns with normal pregnancies. A cross-sectional study of 280 singleton pregnancies: 140 GDM with a mean FBG ≤90 and 1h PP ≤ 120mg/dL vs. 140 normal pregnancies, age and BMI matched. FBG and 1h PP BG for each participant was determined by the average of their SMBG readings. Clinical characteristics - age: 35.7±5 vs. 35.4±5 years; BMI: 23.1±5 vs. 23.7±4 kg/m2; OGTT 0’: 94.1±14.4, 60’: 186.1±27.7, 120’: 161,2±20.4 mg/dL; HbA1c: 5.2±0.6 vs. 4.8±0.3 %, p<0.001; FBG: 83.7±8 mg/dl; 1h PP BG: 106.5±11 mg/dl; GDM diagnosis week: 25.8±4; starting insulin week: 26.8±5; insulin dose: 46.3±13 iu/day. Obstetric and neonatal history between groups: Weight gain: 11.8±4 vs. 10.4±2 kg, p=0.03; delivery week: 37.7±2 vs. 38.1±1, p=0.01; neonatal birth weight: 3050±327 vs. 3200±355 g, p<0.001; SGA: 5.7 vs. 4.3%; LGA: 5.7 vs. 3.6 %; women hypoglycemia episodes: 21.4 %; pre-eclampsia rate: 4.2 vs. 2.8 %; RDS: 10 vs. 7.1 %; Neonatal hypoglycemia: 6.4 vs. 5.7%, NICU admittance: 17.8 vs. 6.4%, p=0.02, Caesarean section: 60 vs. 23.6 %, p<0.001. No cases of severe maternal hypoglycemia and perinatal mortality. An association between: maternal-fetal complications and increased 1h PP BG (r=303), 1h (r=348), 2h (r=228) OGTT values. No association between adverse fetal outcome and maternal hypoglycemia. Tight metabolic control with early insulin therapy minimizes adverse pregnancy outcomes. Performing GDM screenings before 24-28 weeks in women >35 years of age is recommended. Outcome of the pregnancies was not adversely affected by maternal hypoglycemia. 1h PP BG and 1h and 2h OGTT values predicts outcome in GDM pregnancies. More research is needed to understand the optimal BG targets in GDM management.

Disclosure

P. Thomakos: None. O. Kepaptsoglou: None. C. Barreto: None. A. Trouva: None. D. Trouvas: None. C.S.P. Zoupas: None.
1385-P: Utility of Hemoglobin A1c for Predicting Adverse Pregnancy Outcomes in Women with Gestational Diabetes Mellitus
Authors: SIMMONS DAVID , IMMANUEL JINCY , EAGLETON CARL , BAKER JOHN
Published: June 2020

Aims: Despite current treatment strategies, gestational diabetes mellitus (GDM) remains a major risk factor for pregnancy complications. We examined whether the HbA1c measured at the time of oral glucose tolerance test (OGTT) predicts residual risk of adverse outcomes in women with treated GDM.

Methods: Women with GDM (defined using the New Zealand criteria) enrolled in the Diabetes in Pregnancy Registry in South Auckland, New Zealand at ≥ 20 weeks gestation were included. Glycaemic targets used were fasting ≤5.0 mmol/l and 2-hour post-meal ≤6.7 mmol/l.

Results: Of the 1403 women enrolled, 304 (21.7%) had an HbA1c 41-49 mmol/mol (5.9-6.6%). Women with higher HbA1c were significantly older, with higher BMI and fasting and 2-hour OGTT values. They were more likely to be multiparous, of Pacific ethnicity, and have a family history of diabetes. After adjusting for known risk factors, higher HbA1c was associated with increased risk of large for gestational age (LGA) babies (odds ratio (OR) 2.08 (1.47-2.93)) and preeclampsia (OR 2.09 (1.34-3.29)). The OGTT fasting glucose was predictive of LGA (OR 1.61 (1.17-2.21)), but not the 2-hour value (OR 1.12 (0.98-1.28)). The areas under the receiver operating characteristic curves for predicting LGA and preeclampsia by HbA1c, OGTT fasting, OGTT 2-hour, and 1-hour 50g polycose test were: LGA, 0.58 (0.51-0.65), 0.66 (0.59-0.73), 0.45 (0.37-0.52), and 0.59 (0.51-0.66) respectively; preeclampsia, 0.66 (0.57-0.75), 0.58(0.48-0.67), 0.46 (0.35-0.56), and 0.52 (0.42-0.62) respectively.

Conclusions: HbA1c, fasting, and 1-hour glucose at GDM diagnosis predict residual adverse outcomes in treated women with late GDM. Studies are needed to test whether earlier treatment, or targeting the 1-hour post-prandial glucose can reduce this residual risk.

Disclosure

D. Simmons: None. J. Immanuel: None. C. Eagleton: None. J. Baker: None.
1386-P: Long-Term Weight Change after Pregnancy and Type 2 Diabetes Risk in Women with a History of Gestational Diabetes
Authors: BADON SYLVIA E. , XU FEI , QUESENBERRY CHARLES , FERRARA ASSIAMIRA , HEDDERSON MONIQUE M.
Published: June 2020

Women with a history of gestational diabetes (GDM) are at high risk for developing type 2 diabetes, which may be further increased with weight gain after pregnancy. Our objective was to determine associations of long-term weight changes after a GDM pregnancy and type 2 diabetes risk. We used data on a cohort of 139 women with a GDM pregnancy identified though the Kaiser Permanente Northern California (KPNC) GDM registry (1986-2009) who completed a follow-up study visit an average of 16 years later (2011-2013). Type 2 diabetes was identified through the KPNC diabetes registry, self-report during follow-up visit recruitment, or at least one abnormal value on a 75-gram, 2-hour oral glucose tolerance test (2015 ADA criteria) conducted at the follow-up visit. Clinically measured weights extracted from the electronic health record were used to calculate average BMI change per year between delivery and either type 2 diabetes identification date or follow-up visit date. We used modified Poisson regression to estimate relative risks of type 2 diabetes associated with BMI change categories. Twenty-six percent of women lost weight [mean -0.3 BMI units/year, equivalent to -0.8 kg/year for a woman of the average height in our cohort (1.6 m)], 24% maintained their weight (<0.17 BMI units/year, mean 0.10 BMI units/year [0.3 kg/year]), and 50% gained weight (≥0.17 BMI units/year, mean 0.5 BMI units/year [1.3 kg/year]). Overall, 50% of women developed type 2 diabetes. Each additional BMI unit gained was associated with 28% greater risk of type 2 diabetes (95% CI: 0.98, 1.67) adjusting for age at delivery, race/ethnicity, pre-pregnancy BMI, and years since delivery. Women who lost weight had 39% lower risk of developing type 2 diabetes (95% CI: 0.33, 1.12) compared to women who maintained their weight, though estimates were imprecise. Our findings suggest that long-term weight gain after a GDM pregnancy may increase risk of type 2 diabetes, supporting postpartum weight loss intervention efforts.

Disclosure

S.E. Badon: None. F. Xu: None. C. Quesenberry: None. A. Ferrara: None. M.M. Hedderson: None.

Funding

National Institutes of Health (R01HD065904)
1399-P: Overuse of Glucose-Lowering Therapy Predicts Higher One-Year Mortality in Geriatric Patients with Type 2 Diabetes
Authors: CHRISTIAENS ANTOINE , BOLAND BENOIT J. , HENRARD SÉVERINE
Published: June 2020

Background: The 2019 Endocrine Society guidelines for treatment of diabetes in older people define individualised HbA1c targets for glucose-lowering therapy (GLT) in older people with type 2 diabetes (T2D) according to their health status. Our study assessed the association between GLT appropriateness according to these guidelines (appropriate, overuse, underuse) and one-year mortality.

Methods: Retrospective study of all inpatients ≥75 years with T2D and GLT admitted to a geriatric ward of an academic hospital (Brussels) between 2008-2015. Factors associated with one-year mortality were tested in multivariable Cox proportional hazards regression.

Results: Among the 318 patients (84 years; 54% women), GLT overuse was detected in 57.2% and underuse in 17.9%. In multivariable analysis, one-year mortality was associated with poor health (HR: 1.59, p=0.033) and GLT overuse (HR: 1.73, p=0.023). One-year survival was the highest in patients in intermediate health with appropriate GLT and the lowest in those in poor health with GLT overuse (Figure 1; one-year survival [95%CI]: 0.87 [0.76-1.00] and 0.53 [0.45-0.62], respectively).

Conclusion: GLT overuse and poor health status are independent predictors of one-year mortality in geriatric patients with type 2 diabetes. As many of these patients met these two conditions, there is room to improve GLT individualisation and deprescribing.

Disclosure

A. Christiaens: None. B.J. Boland: None. S. Henrard: None.

Funding

Fund for Scientific Research (FC23595)
1407-P: Predictors of Glycemic Control among Older Adults with Type 2 Diabetes Stratified by Living Environment
Authors: DAWSON APRILL Z. , LU KAIWEI , WALKER REBEKAH J. , EGEDE LEONARD E.
Published: June 2020

About 50% of adults with diabetes are ages 50 and older. As individuals age, their living situation changes which may impact self-care and glycemic control (GC). We examined predictors of GC among older adults with diabetes stratified by living environment; defined as living independently, living at home with a caregiver, or living in a nursing home.

Data on 2370 adults ages 50 and older with diabetes from the Health and Retirement Study (2006 - 2014) was analyzed. Generalized estimating equations were used to assess the association between HbA1c and living environment. GC was the outcome and living environment was the primary independent variable. Covariates were socioeconomic factors, cognitive impairment, functional limitations, health status, lifestyle, and comorbidities. We also identified predictors of GC stratified by living environment.

Unadjusted models showed no difference in HbA1c for individuals living with a caregiver compared to those living independently. Living in a nursing home was associated with lower HbA1c (β -0.33; p=0.011), however after adjusting for covariates the relationship was not significant. Predictors of GC among older adults living independently were: age (β -0.018; p<0.001), being female (β -0.20; p=0.007), non-Hispanic Black (β 0.53; p<0.001), Hispanic/Other (β 0.47; p<0.001), no physical activity (β -0.20; p=0.032). Predictors of GC among older adults living at home with a caregiver were: having a GED/high school diploma (β -0.49; p=0.029), not being physically active (β -0.45; p=0.013), and ADLs (β 0.12; p=0.03). Predictors of GC among older adults living in a nursing home were being Hispanic/Other (β 0.94; p=0.048).

In this nationally representative sample, type of living environment does not have an effect on GC, however predictors of GC varied across living environment. Interventions need to be tailored to living environment of seniors.

Disclosure

A.Z. Dawson: None. K. Lu: None. R.J. Walker: None. L.E. Egede: None.

Funding

American Diabetes Association (1-19-JDF-075 to R.J.W.); National Institute of Diabetes and Digestive and Kidney Diseases (K24DK093699, R01DK118038, R01DK120861); National Institute on Minority Health and Health Disparities (R01MD013826)
1412-P: Change in Insulin Secretion Along with Aging in a General Japanese Population
Authors: FUJITA TOMOYUKI , DAIMON MAKOTO , MURAKAMI HIROSHI , NISHIYA YUKI , MURABAYASHI MASAYA , MIZUSHIRI SATORU , MATSUHASHI YUKI
Published: June 2020

Objective: Although increase in type 2 diabetes (DM) along with aging is well documented, change in insulin secretion along with aging and factors related to its change in general, nondiabetic, population has not been well examined so far. Therefore, we evaluated the relationships between insulin secretion and age, or aging, in a general population.

Methods: 1. cross sectional study: Among participants of the population-based Iwaki study of Japanese people held in 2014-2017, those without diabetes were enrolled (gender (M/F): 536/882; age: 53.0±16.0) 2. longitudinal study: Among participants described above, those attended the study consecutively in 2014 and 2017 were enrolled (gender (M/F): 257/401; age: 53.7±14.1). Insulin secretion was evaluated using homeostasis model assessment (HOMA-β).

Results: 1: Univariate regression analyses revealed that the relationship between HOMA-β and age appeared to be non-linear but L-shaped, with an inflection point at about 55 and 50 years for men and women, respectively. Under the ages, HOMA-β are correlated with age (β= -0.32, p<0.01, and β=-0.16, p<0.01, for men and women, respectively), while above the age, such correlation was not observed (p=0.06 and 0.42, respectively).2: Analyses to evaluate factors associated with such decreases in HOMA-β in the 3-year duration showed no significant factor for men but HDL-c (β= -0.30, p<0.01), FIB-4 index representing degree of fibrotic change of liver (β=0.25, p=0.01) and for women after adjustment for multiple factors such as BMI, serum lipid parameters, and, so on.

Conclusions: Insulin secretion seems to decrease along with aging till middle age, but after the age, it dose not decrease or stays similar throughout in a general Japanese population, indicating that aging per se may not be a major determinant for impaired insulin secretion in a general, or physiological condition. Further, factors related to abnormal liver function can be markers to predict decrease in insulin secretion, at least, in women.

Disclosure

T. Fujita: None. M. Daimon: None. H. Murakami: None. Y. Nishiya: None. M. Murabayashi: None. S. Mizushiri: None. Y. Matsuhashi: None.
1413-P: Uncovering the Disease Progression Profile of the Patients with Type 2 Diabetes Mellitus and Atrial Fibrillation
Authors: TANG ZEFANG , WANG JINGJING , ZHANG YUAN , HU PENGWEI , MEI JING , LI SHOACHUN
Published: June 2020

Background: Type 2 diabetes mellitus (T2DM) is a risk factor of Atrial Fibrillation (AF). However, few publications studied the, especially the profile changes due to aging. In this study, we created a statistical strategy to delineate the disease progression profile of the T2DM patients with AF across different age groups.

Method: From IBM Explorys database, 0.48M patients with T2DM and AF were extracted. Patients were separated into 45-60 (54,793), 60-75 (199,944) and 75-90 (227,402) age groups, respectively. The statistical model utilized bootstrap strategy to calculate odds ratio of new developed diseases in 2 years after T2DM and AF diagnose for each group. Diseases with OR > 3 were identified as the progressed diseases. For comparison, we filtered the progressed diseases calculated in T2DM patient cohort.

Result: We found 19 common progressed diseases such as the heart failure and coronary arteriosclerosis (Fig 1). Meanwhile, we also found 7, 17, 25 age-group specific progressed diseases, respectively. Patients in 45-60 tend to get moderate diseases such as syncope (OR = 3.3) and disorder of lung (OR = 3.7) after T2DM and AF diagnose while patients in 75-90 are more likely to get severe diseases such as chronic kidney disease stage 4 (OR = 10.6) and tricuspid valve disorder (OR = 9.5).

Conclusion: Overall, these 2-year progressed diseases could aid clinical decision making.

Disclosure

Z. Tang: None. J. Wang: None. Y. Zhang: None. P. Hu: None. J. Mei: None. S. Li: None.
1415-P: The Variation in Muscle Strength and Quality in Chinese Patients with Type 2 Diabetes
Authors: HE QINGHUA , GUO LIXIN
Published: June 2020

Objective: To examine the characteristics of muscle strength and quality in Chinese patients with T2DM.

Methods: T2DM patients aged 50 years or older (Diabetes group, n=670, 320/350 males/females) were recruited from nine hospitals in Beijing, China. Age-matched nondiabetes participants (Control group, n=214, 54/160 males/females) were recruited from a cohort for routine physical examination. Body composition was determined by a bioimpedance analyzer. Low muscle mass was determined as the appendicular skeletal muscle mass index (ASMI) below the lower quintile of the homogeneity, same sex and healthy young reference group and the cutoff point was 7.18 kg/m2 in men and 5.73 kg/m2 in women. Low muscle strength was defined as handgrip strength below the lower quintile of the same sex subjects in this study and the cutoff value were 29.5 kg and 21.2 kg for males and females. Muscle quality was measured by ratios of muscle strength to appendicular skeletal muscle mass. Multivariate Logistic Regression was used for Correlation Analysis.

Results: (1)There was no difference in age and BMI between two groups. (2) Diabetes group showed higher significantly in FPG level[(5.6±0.7)mmol/l vs. (8.3±2.6)mmol/l], Waist to hip ratio[0.85(0.80,0.90) vs. 0.92(0.87,0.95)], the proportion combined with hypertension and coronary heart disease than control group. (3) Compared with control group, grip strength [(36.6±8.5)kg vs. (31.3±6.4)kg] and muscle quality[(12.4±2.8) vs. (10.8±2.7)] decreased significantly in diabetes group in male but not in female. (4) In male, BMI (t=-5.567, 95%CI -0.375∼-0.179) and HbA1c(t=-2.322 95%CI -0.420∼-0.035) showed negative correlated with muscle quality. Aging (OR=1.062, 95% CI 1.023-1.103) and HbA1c (OR=1.353, 95%CI 1.150-1.591)were risk factors associated with low muscle strength.

Conclusion: Muscle strength and quality decreased significantly in male T2DM Chinese patients. Aged, HbA1c and BMI were risk factors associated with low muscle quality and low muscle strength.

Disclosure

Q. He: None. L. Guo: None.

Funding

Beijing Science and Technology Commission
1416-P: Blood Pressure Variability and Risk of Heart Failure Events in ACCORD and the VADT
Authors: NUYUJUKIAN DANIEL S. , KOSKA JURAJ , REAVEN PETER , ZHOU JIN
Published: June 2020

We examined the relationship between blood pressure variability and risk of heart failure (HF) in two cohorts of type 2 diabetes (T2D) participating in trials of glucose and/or other risk factor management. Data were drawn from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Veterans Affairs Diabetes Trial (VADT). Coefficient of variation (CV) and average real variability (ARV) were calculated for systolic (SBP) and diastolic blood pressure (DBP) along with maximum and cumulative mean SBP and DBP during both trials. In ACCORD (Table), CV and ARV of SBP and DBP were associated with increased risk of HF, even after adjusting for other risk factors and mean blood pressure (e.g., CV-SBP: HR=1.15, p = 0.01; CV-DBP: HR=1.18, p = 0.003). In the VADT, DBP variability was associated with increased risk of HF (ARV-DBP: HR=1.16, p = 0.001; CV-DBP: HR=1.09, p = 0.04). Further, in ACCORD, those with progressively lower baseline blood pressure demonstrated a stepwise increase in risk of HF with higher CV-SBP, ARV-SBP, and CV-DBP (e.g., for CV-SBP: those with baseline SBP ≥ 140, < 140, < 130 and < 120 mmHg, respectively had the following HRs; 1.03, 1.21, 1.50, and 1.69). Blood pressure variability is independently associated with HF risk and this relationship is most robust at low blood pressure in individuals with T2D. These results may have implications for optimizing blood pressure treatment strategies in those with T2D.

Disclosure

D.S. Nuyujukian: None. J. Koska: None. P. Reaven: Consultant; Self; Boston Heart Diagnostics, Intercept Pharmaceuticals, Inc. Research Support; Self; Bristol-Myers Squibb, Lysulin. J. Zhou: None.

Funding

National Institutes of Health (R01067690, R01094775)
146-LB: Increasing Insulin Pump Use across Five National Diabetes Centers: Results from the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: EBEKOZIEN OSAGIE , RIOLES NICOLE , INDYK JUSTIN A. , LYONS SARAH , MAJIDI SHIDEH , PROFFITT TAYLOR , LEE JOYCE M.
Published: June 2020

The T1DX-QI is a type 1 diabetes learning health system including over 10 diabetes centers across the U.S. The program is coordinated by the T1D Exchange in Boston, MA.

Several research studies have demonstrated the impact of insulin pump use and frequent insulin bolusing on diabetes-related clinical outcomes. Five centers in the T1DX-QI used QI methodology including Plan - Do- Study - Act (PDSA) cycles to test and expand insulin pump use initiatives among patients aged 12 - 26 years at their centers. Successful interventions include developing mobile technology classes, redesigning workflow, coaching patients to bolus for meals and corrections, and removing barriers to adoption.

The centers shared data monthly with the coordinating office. These data were used for ongoing QI coaching and to promote the cross-sharing of best practices. Statistical Process Control charts with the relevant rules for fundamental improvements were used to evaluate project effectiveness. Two examples appear in Figure 1.

Three of five participating centers had substantial improvement in this process, ranging from 6% - 17%. There was a 10% significant change among the collaborative cohort in 20 months. Successful QI interventions improved pump use. Further expansion is needed to increase the percentages of patients meeting bolusing goals.

Disclosure

O. Ebekozien: None. N. Rioles: None. J.A. Indyk: None. S. Lyons: Other Relationship; Self; Springer Publishing Company. S. Majidi: Advisory Panel; Self; Companion Medical. T. Proffitt: None. J.M. Lee: Advisory Panel; Self; Goodrx. Consultant; Self; T1D Exchange. Research Support; Self; Lenovo.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
146-OR: Specific Metabolomic Signatures Associate with Diabetes Remission after Weight Loss
Authors: KWEE LYDIA C. , ILKAYEVA OLGA , MUEHLBAUER MICHAEL , WOLFE BRUCE M. , PURNELL JONATHAN Q. , PI-SUNYER XAVIER , CHEN HAIYING , NEWGARD CHRISTOPHER B. , SHAH SVATI H. , LAFERRERE BLANDINE
Published: June 2020

The response to weight loss intervention is heterogeneous both in weight loss amount and improvement in metabolism. We seek to identify biomarkers predictive of long-term weight loss and type 2 diabetes (T2D) remission in the Longitudinal Assessment of Bariatric Surgery (LABS) and the Look AHEAD (Action for Health in Diabetes) studies.

Methods: LABS is a longitudinal observational study of 2458 consecutive cases (2006-2009) of bariatric surgery. Look AHEAD is an RCT comparing an intensive lifestyle intervention to T2D support and education in 5,145 U.S. adults with obesity and T2D enrolled between 2001-2004. Targeted mass spectrometry-based profiling of 135 metabolites was performed in pre-intervention blood samples from individuals selected based on sustained T2D remission (N=93 LABS, N=80 Look AHEAD) and extremes (top and bottom 13th percentile) of weight loss (N=151 LABS, 23 with T2D) at 4 or 5 years. We used PCA for dimensionality reduction of metabolites and logistic regression models to determine association between metabolic factors and phenotype. Improvement in model fit and net reclassification index analyses were performed to determine if metabolites improved a clinical model for predicting remission.

Results: One factor composed of branched chain amino acids (BCAA) and tyrosine (p=0.045), and one composed of betaine and choline (p=0.02) were associated with T2D remission. Inclusion of these factors in a clinical prediction model improved the fit (p=0.04). Only one factor, composed of C31:1-C37:1 sphingomyelins, associated with weight loss at 5 years (p=0.036).

Conclusions. Our findings define novel associations between metabolites in the BCAA and trimethylamine-N-oxide-microbiome-related pathways that are independently and incrementally associated with sustained T2D remission after weight loss. Future studies of these analytes could help in the discovery of metabolic regulatory mechanisms, and guide more personalized weight loss interventions in individuals with T2D.

Disclosure

L.C. Kwee: None. O. Ilkayeva: None. M. Muehlbauer: None. B.M. Wolfe: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk A/S. H. Chen: None. C.B. Newgard: None. S.H. Shah: Research Support; Self; AstraZeneca, Verily Life Sciences LLC.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK108580)