bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Long-Term Cost-Effectiveness of Sitagliptin and SGLT2i Combination Therapy for the Treatment of Type 2 Diabetes
Authors: PAWASKAR MANJIRI , PINAR BILIR S. , GRABER-NAIDICH ANNA , GONZALEZ CLAUDIO D. , RAJPATHAK SWAPNIL , DAVIES GLENN M.
Published: June 2018

Clinical benefits of dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) combination therapy have been demonstrated through clinical trials; however, there is limited understanding of economic benefits of sequential use of these therapies. This study evaluated the long-term cost-effectiveness of a treatment strategy involving intensification with SGLT2is (pathway 1) compared to NPH insulin (pathway 2) in type 2 diabetes (T2D) patients not at goal on metformin and sitagliptin therapy in the UK. The QuintilesIMS CORE Diabetes Model was used to perform cost-effectiveness analysis over a patient’s lifetime. Treatment effect data were obtained from randomized clinical trials, and economic data were obtained from multiple published sources. Several scenario analyses were performed to assess the robustness of base case results. Pathway 1 increased total life years (13.49 vs. 13.37, respectively) and quality-adjusted life years (QALY) (9.40 and 9.22, respectively) compared to pathway 2. Although drug costs in pathway 1 were higher than pathway 2, they were offset by decreases in diabetes-related complications and body mass index, leading to lower total direct medical costs for pathway 1 (£25,747 vs. £26,095). Thus, pathway 1 dominates pathway 2, as it is both more effective and less costly. Results from scenario analyses assessing changes in treatment effect, hypoglycemia rate, body mass index, cardiovascular protective effect of SGLT2i consistently showed that pathway 1 was either dominant (incremental cost effectiveness ratio (ICER) <$0/QALY) or cost-effective [(ICER < £3,000/QALY for patients with lower baseline HbA1c (7%) or older age (65+years)]. Among patients not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2i is likely to be cost effective compared to intensification with NPH insulin as 3rd line therapy in T2D in the UK.

Disclosure

M. Pawaskar: Employee; Self; Merck & Co., Inc. S. Bilir: Consultant; Self; Merck & Co., Inc.. A. Graber-Naidich: None. C.D. Gonzalez: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Merck & Co., Inc. G.M. Davies: Employee; Self; Merck & Co., Inc..
Assessing the Value of Canagliflozin (CANA) vs. Sitagliptin (SITA) as Second-Line Therapy in the U.S.—The Importance of Considering Evidence from the CANVAS Program
Authors: WILLIS MICHAEL , NESLUSAN CHERYL , NILSSON ANDREAS , ASSEBURG CHRISTIAN
Published: June 2018

Efficient allocation of health care resources requires choosing treatments that provide good “value for money”, which for chronic and progressive diseases like diabetes requires long-term modeling. For patients not controlled on metformin (MET), the ADA’s Standards of Medical Care recommend that “drug-specific effects and patient factors” guide the choice of next agent and that those with atherosclerotic CVD receive treatment with agents with evidence of CV risk reduction. The SGLT2 inhibitors CANA and empagliflozin have shown such a benefit, unlike the DPP-4s. The objective of this analysis was to estimate the cost-effectiveness of CANA vs. SITA as add-on to MET from the U.S. 3rd party payer perspective. A comprehensive health economics model (ECHO-T2DM) was used to estimate health and cost consequences over 30 years. Baseline patient characteristics and biomarker changes were sourced from a previously reported head-to-head study of CANA vs. SITA as add-on to MET. Hazard ratios from the CANVAS Program for myocardial infarction (MI), stroke, heart failure hospitalization, and CV mortality were used to capture effects not mediated by changes in biomarkers (i.e., HbA1c, SBP, weight). Progression of DKD incorporated eGFR findings from the CANVAS program. In addition, adverse events associated with CANA were included in the simulations. Costs of health events and associated impacts on Quality-Adjusted Life Years (QALYs) were sourced from the literature. In the base case, use of CANA vs. SITA resulted in cost savings ($7,401), as well as increased longevity (0.48 years) and QALYs (0.46). The largest contributors to savings were antihyperglycemic drug costs (given less therapy intensification to maintain glucose control) and treatment costs associated with delayed DKD progression and MIs. These results suggest that the use of CANA vs. SITA as 2nd line therapy will improve health outcomes at a reduced cost.

Disclosure

M. Willis: Other Relationship; Self; Janssen Global Services, LLC. C. Neslusan: Employee; Self; Janssen Global Services, LLC. A. Nilsson: Other Relationship; Self; Janssen Global Services, LLC. C. Asseburg: Other Relationship; Self; Janssen Global Services, LLC..
Evaluation of Liraglutide Usage for Treatment of Type 2 Diabetes at a Veterans Affairs Medical Center
Authors: RYCHEL RIKKI L. , LOW MARY BETH , WATTS SHARON A. , FALCK-YTTER CORINNA , PASCUZZI KRISTINA M. , LYMAN ALESSANDRA
Published: June 2018

Approximately 25% of Veterans have diabetes. Both the American Diabetes Association (ADA) and Department of Veterans Affairs/Department of Defense (VA/DoD) guidelines recommend treatment with glucagon-like peptide-1 (GLP-1) agonists, such as liraglutide, as second line options after metformin. In May 2016, the Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives updated criteria for use of GLP-1 agonists, increasing prescribing of this drug class. This coincided with recent data demonstrating cardiovascular benefit of liraglutide and led to increased usage at the Louis Stokes Cleveland Veterans Affairs Medical Center (LSCVAMC). A medication use evaluation was conducted to assess adherence to the criteria for use and to describe the characteristics of liraglutide usage at LSCVAMC. Sixty-two patients with T2DM and a prescription for liraglutide initiated between July 1, 2016 and January 30, 2017 were included. Patients were predominantly male (97%), had a baseline hemoglobin A1c (HgbA1c) of 9.2% and were prescribed metformin (82%). Adherence to the criteria for use was 90%. Follow-up HgbA1c after three to six months was obtained in 87% of patients. Average HgbA1c reduction of 0.76% was achieved in 72% of patients, while 28% were without improvement. Given the less than expected reduction in HgbA1c seen with liraglutide and the pharmacoeconomic impact of this medication, facility changes were implemented to ensure more appropriate prescribing of liraglutide at the LSCVAMC.

Disclosure

R.L. Rychel: None. M. Low: None. S.A. Watts: None. C. Falck-Ytter: None. K.M. Pascuzzi: None. A. Lyman: None.
Physician-Targeted Education for Management of Chinese T2DM Patients Receiving Basal Insulin—BEYOND II Study Results
Authors: WENG JIANPING , ZHAO JIAJUN , ZHOU ZHIGUANG , GUO XIAOHUI , ZHENG XUEYING , LUO SIHUI ,   THE BEYOND II STUDY GROUP
Published: June 2018

BEYOND II was a multicenter, single-arm, observational study in which physicians received education based on T2DM treatment guidelines and effective patient education, reinforced by self-audit and peer-to-peer review over a 6-month period. The primary outcome measure was the proportion of study centers meeting individual improvement goals set by the Study Committee, based on HbA1c <7.0%. Two cohorts of ∼100 patients (baseline and post-education) with T2DM who had received basal-insulin (BI)-based treatment for ≥3 months were enrolled at each center. Of 71 centers that completed the study, 35 (49.3%) achieved improvement targets. Patients in the post-education cohort had improved glycemic control vs. the baseline cohort (Table). At centers meeting improvement targets, a higher proportion of physicians (n=356) self-rated as ’confident in most cases’ about insulin initiation (89.9% vs. 78.9%), titration (87.4% vs. 80.9%), and hypoglycemia management (89.0% vs. 80.6%) post education vs. baseline, but there was no change at centers not meeting improvement targets. In a multivariate regression, completion of education (yes vs. no) had the strongest positive association with achievement of HbA1c <7% (OR=1.55, p<0.001). Physician-targeted education was effective at around 50% of study centers for improving glycemic control in patients with T2DM receiving BI-based treatment.

TableVariableBaseline cohort (N=6386)Post-education cohort (N=6353)P-valueProportion of centers meeting individual improvement targets, n/n (%; 95% CI)--35/71 (49.3%; 37.2 to 61.4%)--Mean HbA1c, % (SD)8.10 (1.732)7.72 (1.579)<0.001Mean FPG, mmol/L (SD)9.10 (3.580)8.44 (3.172)<0.001HbA1c <7%, % (n/N)27.2 (1740/6386)36.5 (2322/6353)<0.001FPG <6.1 mmol/L, % (n/N)15.6 (994/6386)19.6 (1247/6353)<0.001Hypoglycemia (blood glucose ≤3.9 mmol/L or symptomatic hypoglycemia without confirmation), % (n/N)4.4 (282/6386)3.8 (241/6353)0.077

Disclosure

J. Weng: None. J. Zhao: None. Z. Zhou: None. X. Guo: None. X. Zheng: None. S. Luo: None.
An Innovative Cost-Effective Model of Using Advanced Care Practitioners (ACPs) in Improving Glycemic Control and LOS in a Large Hospital System
Authors: JOSHI RENU , HELMUTH AMY
Published: June 2018

In 2001 healthcare systems identified issues related to increased length of stay and suboptimal outcomes associated with poor inpatient glycemic control. Diabetes clinical initiative (DCI) team was created and the physician champion developed protocols and restructured the delivery of diabetic care across the healthcare system. However it was difficult to provide uninterrupted service due to shortage of Endocrinologists.

An innovative care model was designed in 2009 using specialty trained Endocrinology ACPs’ to improve Glycemic control across system and to provide uninterrupted service including weekends. The ACP’s were trained by the physician champion both with didactic teachings and ongoing case discussions. Automatic consults to ACPS’ were initiated for specific criteria identified by lead physicians .These criteria included HbA1C more than 8.5,Blood Glucose (BG) greater than 200 X4 in 24 hours, BG greater than 300 x2 in 24 hours and Hypoglycemia less than 40x2 in 24 hours .The ACPs’ were always supported by the endocrinology team .

For the last 8 years the glycemic control across the hospital has further improved from average blood glucose of 160-153mg/dl. The rate of mild hypoglycemia remains low at 2% and severe hypoglycemia at < 0.4% . This has resulted in continuation of improved LOS and patient satisfaction as well. Much improved results in Coronary artery bypass surgery (CABG) population have been shown with no deep sternal wound infections in last 6 years. The model remains cost effective for the whole system.

Summary: Innovative model of Glycemic control using specialty trained ACPS’ is cost effective and improves glycemic control and LOS. The ongoing education and support is critical to the success of the program.

Disclosure

R. Joshi: None. A. Helmuth: None.
Feasibility of Shared Telemedicine Appointments for Low SES Adolescents and Young Adults with T1D
Authors: FLORES GARCIA JAQUELIN J. , REID MARK W. , RAYMOND JENNIFER
Published: June 2018

Background: Shared medical appointments (SMA) via home telemedicine may improve clinic attendance and adherence to care recommendations in adolescent and young adult patients (AYA) with type 1 diabetes (T1D). Participation in home telemedicine requires basic health literacy, reliable access to high-speed Internet on a compatible device, and a private location for attending appointments. AYA from households with lower socioeconomic status (SES) may encounter barriers to participation in home telemedicine due to limited resources.

Objective: Evaluate the feasibility of conducting SMA via home telemedicine for low SES AYA with T1D.

Methods: We conducted baseline patient and family assessments as part of a prospective study on the use of SMA and telemedicine for AYA with T1D who attend a pediatric outpatient endocrinology clinic. We calculated SES for each family using a modified version of the Hollingshead index, and dichotomized patients into low and high SES groups.

Results: AYA reported nearly equal interest in attending SMA (Low: 76%; High: 66%), and in completing appointments online (Low: 41%; High: 45%), regardless of SES. Patients reported having access to high-speed Internet (100%), favored home appointments (Low: 35%; High: 42%), and reported having private space (Low: 83%; High: 88%). Low SES patients were younger than high SES patients (15 vs. 17 years, p = 0.01), and reported shorter disease duration (6 vs. 9 years, p < 0.01). Low SES patients reported needing help reading medical information at least sometimes more frequently (76%) than high SES patients (56%, p = 0.05). However, this effect was attenuated in multiple regression analysis, where variations in patients’ health literacy were associated with age (p < 0.05) instead of SES.

Conclusions: Low SES AYA with T1D are equally equipped and interested in utilizing shared telemedicine as high SES patients. Home telemedicine may be a feasible format for diabetes care and psychosocial support for all patients, regardless of SES.

Disclosure

J.J. Flores Garcia: None. M.W. Reid: None. J. Raymond: None.
Impact of Family-Centered Tailoring of Pediatric T1D Self-Management Resources
Authors: FIALLO-SCHARER ROSANNA V. , RAJAMANICKAM VICTORIA P. , CHEWNING BETTY A. , PALTA MARI , WETTERNECK TOSHA B. , WYSOCKI TIM , COX ELIZABETH D.
Published: June 2018

Background: Experts recommend family-centered self-management approaches that address specific T1D self-management barriers for each child and family. However, no system-level method currently exists to identify and address these barriers.

Objectives: To assess the impact on glycemic control and QoL for the child and parent of a family-centered approach to the delivery of diabetes self-management resources.

Methods: Children 8-16 years old with T1D and their parent(s) were randomized to receive either tailored self-management resources (intervention) or usual care. Our intervention 1) identified families’ self-management barriers with a validated survey, 2) tailored self-management resources to identified barriers, and 3) delivered these resources as group sessions coordinated with diabetes visits to optimize convenience, efficiency, and sustainability. Mixed effects models with repeated measures were used to examine the intervention’s impact on A1c and parent and child QoL during the 9-month intervention period and for a year thereafter.

Results: Among 363 potentially eligible families, 267 (74%) consented to participate. Randomization allocated 1families to usual care and 1to the intervention. Participants were children (8-12 years, 44%) and teens (13-16 years, 56%). Mean diabetes duration was 5.4 years (sd 3.3) and 14% had an A1c <7.5%. Most families (69%) attended at least 3 of the 4 intervention sessions. No overall intervention effect on A1c or QoL for the child or parent was shown. However, at one site, mean A1c in the year post-intervention declined by 0.059% more per month for intervention group teens than for those receiving usual care (p=0.02). At this same site, mean parent QoL increased by 0.61 points per month more during the intervention for parents of intervention group children than parents of those receiving usual care (p=0.03).

Conclusions: Findings can inform healthcare organizations’ decisions about ways to best deliver diabetes self-management resources.

Disclosure

R.V. Fiallo-Scharer: None. V.P. Rajamanickam: None. B.A. Chewning: None. M. Palta: None. T.B. Wetterneck: None. T. Wysocki: None. E.D. Cox: None.
Longitudinal Changes in Amino Acid (AA) Turnover in Pregnancy in Women with Normal Glucose Tolerance (NGT) and GDM—Relationship to Fetal Growth
Authors: CATALANO PATRICK , PRESLEY LARRAINE , DE MOUZON SYLVIE HAUGUEL , KALHAN SATISH
Published: June 2018

GDM have decreased glucose insulin sensitivity vs. NGT. However, there are less data on the impact of GDM on AA metabolism or relationship to fetal growth. Ten NGT and 8 GDM (≥ 1 abnormal value, 3 hour OGTT) were evaluated at 18-22 and 32-36 weeks for 2 potent amino acid secretogogues, Phenylalanine (PHE) and Leucine (LEU). PHE and LEU turnover was estimated (D5 PHE and 13C LEU) under basal and euglycemic hyperinsulinemic clamp conditions. Neonatal body composition was estimated using anthropometrics. There were no significant difference in maternal age, race, education, tobacco use, weight or body composition between GDM and NGT at 18-22 weeks. The was a higher family hx of diabetes in GDM (p=0.05). Basal LEU but not PHE turnover increased over time and was greater in GDM, Table. Glucose disposal decreased over time and was lower in GDM. During the clamp LEU but not PHE turnover increased over time and was greater in GDM. Clamp PHE turnover (µmol/kg/hour) at 18-22 weeks correlated with neonatal lean mass (r=0.48, p=0.048) and there was a trend for fat mass (r=0.47, p=0.058). Omitting 1 outlier there remained a trend for PHE turnover and neonatal lean mass (r=0.43, p=0.09). Leu turnover increased over time and was greater in GDM vs. NGT. In contrast, there were no significant changes in PHE turnover over time or between groups but PHE turnover in early pregnancy was related to fetal lean mass.Metabolic ResultsNGT (n=10)GDM (n=8)ANOVABasal Leucine turnover (umol/kg*ffm/hr)12-16 weeks129.8 ± 19.8155.6 ± 20.1p=0.00532-36 weeks134.1 ± 20.8157.0 ± 22.9pgroup = 0.001Leucine turnover (umol/kg*ffm/hr)12-16 weeks108.5 ± 18.5126.8 ± 20.8p=0.0232-36 weeks123.0 ± 19.8136.2 ± 21.8pgroup = 0.03mean ± SDpgroup difference between NGT & GDM

Disclosure

P. Catalano: None. L. Presley: None. S. Hauguel de Mouzon: None. S. Kalhan: None.
Are Changes in Whole-Body Insulin Sensitivity during Pregnancy Related to Changes in Ectopic Fat Stores?
Authors: VESCO KIMBERLY , MARSHALL NICOLE E. , ROONEY WILLIAM , LEO MICHAEL C. , BAETSCHER ERIC , FRANCISCO MELANIE , PURNELL JONATHAN Q.
Published: June 2018

Background: Our study is one of the first to assess relationships between changes in ectopic lipid stores [intrahepatic (IHL), intramyocellular (IMCL), and extramyocellular (EMCL)] from early to late pregnancy and changes in whole-body insulin sensitivity.

Methods: We evaluated 31 women without diabetes and enrollment BMI’s 18.5-38 kg/m2 in early (mean [min-max] 15.6 [12.9-17.3] weeks) and late (34.2 [32.3-37.3] weeks) gestation. Women with pregestational diabetes or multifetal pregnancies were excluded. Participants underwent insulin clamps to assess whole-body insulin sensitivity (M-value), 1H magnetic resonance spectroscopy to assess IHL, IMCL, and EMCL content, and BODPOD to assess % body fat, fat mass, and lean mass.

Results: Women were primarily white (90%) with mean (min-max) age of 30.5 (19 -39) years. M-value declined 27% between early and late visits (p<.001) and IHL, IMCL, and EMCL increased (p<.05). M-value was not significantly correlated with any total or ectopic fat in late pregnancy. Changes in these body composition variables from early to late pregnancy were not significantly associated with changes in M-value.

Conclusion: Whole-body insulin sensitivity declines from early to late pregnancy but was unrelated to changes in ectopic and total fat. Non-body composition factors appear to be the primary determinant of gestation-related insulin resistance.Table. Means, standard deviations, and Pearson’s correlation coefficients for insulin sensitivity (M-value), weight, and total and ectopic fat measures at late pregnancy and from early to late pregnancy.MeasureMean (SD) Late pregnancyCorrelation with M-valueMean (SD) change from early to late pregnancyCorrelation of change in measure with change in M-ValueM Value275.7 (69.8)--100.3 (112.6)*--Weight (kg)82.9 (12.3).3210.5 (3.3)-.01BMI (kg/m2)28.7 (3.8).153.6 (1.1)-.01Body fat (%)33.3 (6.4).18-0.8 (3.6).00Fat mass (kg)28.2 (8.7).253.0 (3.2).05Lean mass (kg)54.7 (5.9).297.5 (2.6)-.08IHL (% water peak)0.6 (0.3).120.1 (0.2)*-.18IMCL (% water peak)1.2 (0.6).010.3 (0.6)*-.02EMCL (% water peak)2.3 (1.4).290.5 (1.2)*-.06*p<.05

Disclosure

K. Vesco: None. N.E. Marshall: None. W. Rooney: None. M.C. Leo: None. E. Baetscher: None. M. Francisco: None. J.Q. Purnell: Advisory Panel; Self; Novo Nordisk Inc..
A Reduction in Sedentary Behavior in Obese Women Reduces Neonatal Adiposity—The DALI Randomized Controlled Trial
Authors: POPPEL MIREILLE VAN , SIMMONS DAVID , DESOYE GERNOT ,   DALI CORE INVESTIGATOR GROUP
Published: June 2018

Background: Maternal obesity and gestational weight gain are implicated in the development of childhood obesity tracking from neonatal adiposity. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity.

Methods: In the Vitamin D And Lifestyle Intervention (DALI) Lifestyle trial, 436 women with a body mass index ≥ 29 kg/m2 were randomly assigned to counseling on Healthy Eating (HE), Physical Activity (PA), HE&PA, or to usual care (UC). Neonatal outcomes were head, abdominal, arm and leg circumference, skin folds, estimated fat mass, fat percentage, fat free mass, and cord blood leptin. Intervention effects on neonatal outcomes were assessed in multilevel analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed.

Results: Outcomes were available from 334 neonates. A reduction in sum of skin folds (-1.8 mm; 95% CI, −3.5 to -0.2; p=0.03), fat mass (-63 g; 95% CI, -124 to -2; p=0.04), fat percentage (−1.2%; 95% CI -2.4 to -0.04; p=0.04), and cord blood leptin (-3.80 µg/l; 95% CI -7.15 to -0.45; p=0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (-5.79 µg/l; 95% CI, -11.43 to -0.14; p=0.05) compared to UC. Reduced sedentary behavior, but not gestational weight gain, mediated intervention effects on leptin in the HE&PA and PA group.

Conclusion: The HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary behavior seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity of the offspring need to be elucidated.

Disclosure

M. van Poppel: None. D. Simmons: Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, AstraZeneca, Novo Nordisk Inc., Medtronic. G. Desoye: None.
Management of GCK-MODY in Pregnancy—Does Clinical Practice Follow Current Recommendations?
Authors: DICKENS LAURA T. , LETOURNEAU LISA R. , PHILIPSON LOUIS H. , GREELEY SIRI ATMA W. , NAYLOR ROCHELLE N.
Published: June 2018

Recommendations for management of GCK-MODY during pregnancy are based on fetal genotype. Women with GCK-MODY should not be treated with insulin prior to conception and insulin should not be given if normal fetal growth is observed. Women should be treated with insulin if fetal ultrasound monitoring starting at 26 weeks shows macrosomia, suggesting the fetus is wild type for the GCK gene. There is limited data about management of GCK-MODY in pregnancy.

The aim of this study was to examine clinical management and pregnancy outcomes amongst women with a known diagnosis of GCK-MODY. A survey was distributed via Redcap to 94 women >/= 18 years enrolled in the University of Chicago Monogenic Diabetes Registry. All or part of the survey was completed by 59% of women.

GCK-MODY diagnosis was known at the time of pregnancy for 14 women with a total of 18 pregnancies, including 2 women who were currently pregnant. There were 13 term births and 3 premature births. Glucose-lowering therapy was used preconceptually in 33% of cases, including insulin use in 3 women. Insulin was started in 7 pregnancies; in 4 cases the fetus measured normal for dates and in 3 cases measured large. Insulin was started between 5-32 weeks (average 16.4 weeks). Insulin treatment was not started in 1 pregnancy where the baby measured large for dates and early induction was required. This offspring was WT for GCK.

In our study, contrary to current recommendations, one-third of pregnancies were treated with glucose-lowering medication prior to pregnancy, including insulin. Insulin initiation occurred early in gestation (average 16.4 weeks), rather than being based on fetal size on ultrasound monitoring. These observations suggest that for many pregnancies affected by GCK-MODY, management does not reflect current guidelines. Further studies to confirm the safety and efficacy of the current recommendations may improve provider confidence in deferring insulin treatment in cases where ultrasound monitoring shows normal fetal growth.

Disclosure

L.T. Dickens: None. L.R. Letourneau: Other Relationship; Self; Novo Nordisk Inc. L.H. Philipson: Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; JAEB Center For Health Research, JDRF, Janssen Pharmaceuticals, Inc., Medtronic MiniMed, Inc. S.W. Greeley: Research Support; Self; Novo Nordisk Inc.. R.N. Naylor: None.
Is Gestational Weight Gain below That Recommended by IOM for Obese Women with Insulin Treated Gestational Diabetes Safe?
Authors: BOGDANET DELIA , O'SHEA PAULA M. , DUNNE FIDELMA P.
Published: June 2018

The Institute of Medicine (IOM) recommends gestational weight gain (GWG) of 5-9 kg in women with a body mass index of >/=30. Debate continues as to whether GWG less than that recommended is safe. Concern relates to whether this would result in an increase in small for gestational age (SGA) infants, or an increase in rates of prematurity. We examined pregnancy outcomes for mothers with a BMI >/=30 and their offspring in 473 women. All women recorded on our Atlantic DIP database with a singleton pregnancy treated with insulin and a BMI>/=30 were included. Women were categorised into 3 groups as follows (1) those with weight loss, N = 97 (2) weight gain 0-5kg, N = 49 (3) weight gain >5kg N = 327, from first antenatal visit to delivery. Rates of maternal outcomes (pregnancy induced hypertension (PIH), preeclampsia (PET), antepartum (APH) and postpartum haemorrhage (PPH), week of delivery, caesarean section (CS) delivery) and neonatal outcomes (birth weight, large for gestational age (LGA), SGA, macrosomia, prematurity, neonatal morbidities) were compared. Mean maternal booking BMI was 38, 37.6 and 36 kg/m2 (p<0.01) and mean maternal age was 34.7, 34.1 and 33.3 years in groups 1,2 and 3 respectively (p=0.04). Rates of PIH PET APH PPH and CS were similar between groups. Glycaemic control prior to delivery was better in women in group 1 compared to groups 2 and 3 (HbA1C 37.2 vs. 38.4 vs. 39 mmol/mol; p = 0.02). Infant birth weight was lower in group 1 compared to groups 2 and 3 (3545g vs. 3645g vs. 3703g; p<0.01) Rates of LGA, macrosomia. SGA and prematurity (<37 gestational weeks) were similar between groups. Rates of neonatal hypoglycaemia were less in group 1 compared to groups 2 and 3; (2.1% vs. 14.3% vs. 4%; p<0.01), while all other morbidities were similar between groups. Gestational weight change for GDM women treated with insulin below that recommended by the IOM appears safe. In addition, it is associated with better maternal glycaemic control and lower infant birth weight.

Disclosure

D. Bogdanet: None. P.M. O'Shea: None. F.P. Dunne: None.
Chronic Sleep Disturbances Are Predictive of Incident Diabetes in Older AdultsߞVariations by Gender and Race/Ethnicity
Authors: GUYER HEIDI
Published: June 2018

Study Objectives: The current study was conducted to determine whether self-reported chronic sleep disturbances are predictive of incident diabetes in older adults, as well as to determine variations by gender and race/ethnicity.

Methods: 7446 participants from the Health and Retirement Study, a nationally-representative longitudinal cohort study of U.S. adults, were followed for eight years, between 20and 2014. Chronic sleep disturbance was defined as self-reported trouble falling asleep or staying asleep “most of the time.” Diabetes was based on self-reported doctor’s diagnosis or a Hemoglobin A1C value >=6.5mg/dl. Hazard ratios were calculated for baseline and on-going sleep disturbances.

Results: The average age of participants was 63.5 years. Close to 30% of men and 40% of women reported having a chronic sleep disturbance at baseline. The cumulative incidence of diabetes was 17.7% among men and 15.2% among women. Both men and women who developed diabetes were more likely to report chronic sleep disturbances at baseline than those who did not develop diabetes (men: 32.2% vs. 27.3%; women: 44.2% vs. 36.0%). Women were more likely to develop diabetes within eight years than men after adjustment for demographic covariates (women: HR 1.40 95% CI 1.19-1.63; men HR 1.27 95% CI 0.98-1.66). Black and Hispanic men and women with chronic sleep disturbances had a greater likelihood of developing diabetes within eight years than white men and women.

Conclusions: Self-reported chronic sleep disturbance is an independent predictor of incident diabetes in women. The likelihood of developing diabetes among those with chronic sleep disturbances is greater for women than men and greater for blacks and Hispanics than non-black/Hispanic older adults. This finding has both public health and clinical relevance in an aging society.

Disclosure

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

Mutations in the gene encoding glucokinase (GCK) cause maturity-onset diabetes of the young (MODY) 2, characterized by impaired prandial insulin secretion and hepatic glycogen storage. Recently diagnosed patients with type 1 diabetes (T1D) exhibit impairment of both beta cell function and hepatic energy metabolism. Thus, this study aimed at examining the effect of MODY 2 on hepatic insulin sensitivity and energy metabolism. Carriers of one recently described GCK mutation (D124N; c.370, GAC>AAC in exon 4) were compared to controls (CON) with similar sex, age and body mass index (BMI) (female/male: 1/2 vs. 3/6; 36±4 vs. 35±2 years; 20.1±1.6 vs. 25.7±1.5 kg/m2) from the German Diabetes Study (Registration_Clinicaltrials.gov NCT01409330). Whole body and hepatic insulin sensitivity (IS) were assessed by Botnia-clamp tests with [6,6-2H2]glucose. Beta cell function was determined from incremental AUC(C-peptide)0-60min/δAUC(glucose)0-60min during intravenous glucose tolerance test. Hepatocellular lipid content (HCL), γATP and inorganic phosphate (Pi) were measured with by 1H/31P magnetic resonance spectroscopy. MODY 2 patients had higher hemoglobin A1c (6.1±0.1 vs. 5.2±0.1%, p<0.001) along with approximately 62% lower glucose-stimulated C-peptide secretion than CON (p<0.05). They also had lower hepatic IS (1.8±0.1 vs. 2.3±0.1 mg/(kg*min), p<0.05), but similar whole body IS (12.6±1.9 vs. 13.1±1.5 mg/(kg*min), p=0.87) compared to CON. However, HCL (1.0±0.9 vs. 0.5±0.2%, p=0.46), γATP (3.5±0.3 vs. 3.5±0.6 mmol/l, p=0.99) and Pi (1.9±0.5 vs. 2.9±0.7 mmol/l, p=0.45) in the liver were comparable between both groups.

In conclusion, these data show that lower hepatic IS, but not abnormal hepatic energy metabolism, underlies the previously reported reduction in prandial hepatic glycogen synthesis. Moreover, impairment of hepatic IS is not necessarily associated with hepatic mitochondrial function.

Disclosure

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

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

Disclosure

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

Whether endogenous sex hormones are associated with chronic kidney disease (CKD) is not known. We conducted a secondary analysis of longitudinal data from the DPPOS, the follow-up study of the Diabetes Prevention Program (DPP), a randomized trial of diabetes prevention that assigned participants to placebo, metformin, or lifestyle intervention. This analysis included overweight and glucose-intolerant men (n=889) and women (n=1281) not using exogenous sex hormones who had urine albumin-to-creatinine ratio [ACR] < 30 mg/g and normal estimated glomerular filtration ratio [eGFR] ≥ 60 ml/min/1.73 m2.

Sex hormones (dehydroepiandrosterone [DHEAS], dihydrotestosterone, testosterone, estradiol, estrone, and sex hormone binding globulin [SHBG]) were measured at baseline. CKD was defined as incident low eGFR and/or albuminuria ACR ≥ 30 mg/g. eGFR and ACR were measured annually over 11 years of DPPOS follow-up. Multivariable Cox regression models adjusted for eGFR and log-ACR, age, race/ethnicity, body mass index, blood pressure, insulin resistance, high-density lipoprotein, C-reactive protein, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers at baseline.

At baseline, the mean (SD) of eGFR was 94 (15) ml/min/1.73 m2, and the median (IQR) of ACR was 4.5 (3.3-7.6) mg/g. During the follow-up period, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Fifty-four (7.1%) of men and 43 (3.9%) of women had both abnormalities. Among men, higher SHBG was associated with lower risk of low eGFR (pooled hazard ratio [HR] per SD, 95% confidence interval [CI]: 0.73 [0.57, 0.9], p=0.01) and lower risk for CKD (pooled HR per SD 95% CI: 0.78 [0.64, 0.95], p=0.01). No significant associations were observed among women.

We conclude that among overweight glucose-intolerant men, higher SHBG was associated with reduced risk of CKD.

Disclosure

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

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

Disclosure

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

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

Disclosure

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

Background: The metabolic syndrome is a cluster of risk factors which predicts future cardiovascular disease and type 2 diabetes. Evidences have showed that a disorder in serum Copper (Cu) level could have effects on human health. However, little data are available regarding how serum Cu affects metabolic syndrome in adults.

Method: Data from 3,375 subjects were examined from a nationally representative sample of the U.S. adults in the National Health and Nutrition Examination Survey 2011-2014. The metabolic syndrome was defined as satisfying three or more of the five criteria from the National Cholesterol Education Panel definition. Multivariate logistic and linear regression were applied to investigate the associations of serum Cu levels with metabolic syndrome prevalence and its component.

Results: In the logistic models, non-Hispanic black with the highest serum Cu levels demonstrated a greater increase in risk of metabolic syndrome (OR: 2.69, 95% CI: 1.08-6.70, P for trend= 0.001) when compared to those with the lowest serum Cu levels. Moreover, we identified a remarkable association between serum Cu levels and high fasting blood glucose condition in non-Hispanic black (OR: 2.44, 95% CI: 1.04-5.76, P for trend= 0.031). No significant associations between serum Cu level and other components of metabolic syndrome were observed, regardless of race. In the linear regressions, a strong positive association between serum Cu levels and fasting blood glucose was also observed (coefficient= 0.231, 95% CI: 0.053-0.409, P< 0.001) in non-Hispanic black.

Conclusion: Our results provide the first epidemiological evidence that serum Cu concentrations may be positively associated with the prevalence of metabolic syndrome and with fasting blood glucose in non-Hispanic black. Further clinical and animal studies are urgently needed to clarify the putative causal relationships.

Disclosure

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

Objective: To compare the impact of home-based care and education delivered by community health representatives (CHRs) as part of a clinical care team vs. usual clinic-based care on measures of patient activation and risk factors for diabetes in adult Zuni Indians.

Methods: We conducted a pilot randomized controlled trial of a home-based intervention vs. usual clinic care provided by the local Zuni Indian Health Service (IHS). The study’s primary outcome was patient activation, assessed by the Patient Activation Measure (PAM). We screened 315 Zuni adults and enrolled and randomized 125 Zuni adults into the study. We used linear and logistic regression with generalized estimating equations to compare changes in the outcomes of interest over time between the two study groups.

Results: Compared to those receiving usual care at IHS, Zuni adults in the intervention group experienced significantly greater improvement in the patient activation measure, quality of life, and in several clinical measures of risk factors for diabetes at 12 months. Participants in the intervention increased their PAM total scores, on average, by 8.6 points more than participants randomized to usual care (p=0.023). BMI in the intervention group decreased by 1.kg/m2 more than was observed in the control group (p=0.007). Hemoglobin A1C levels in the intervention group decreased by 8% more than in the control group (p=0.022). The hs-CRP levels in the intervention group decreased by 62% more than in the control group (p<0.001).

Discussion: Delivering culturally appropriate home-based care and education by CHRs is a promising approach for improving disease-specific knowledge, confidence, and self-management skills among rural minority populations at high risk for diabetes who experience barriers to accessing health care.

Disclosure

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

Objective: Colorectal cancer surgery is often followed by postoperative complications which may impact survival. Diabetes mellitus (DM) and DM related comorbidities may initiate difficulties during cancer specific treatment and may have an impact on cancer management and outcome. The aim of our study was to find out if DM in patients with advanced colorectal carcinoma is associated with cancer-specific and overall survival.

Material and Methods: This study included 200 consecutive patients (131 males, 69 females, mean age 63 years) with elective colorectal cancer surgery at the Institute of Oncology Ljubljana from September 2010 to March 2013. Even 64% of patients had Stage 3 or 4 disease, so neo-adjuvant chemotherapy and/or radiotherapy were carried out in 59% of cases. DM was found in 39 (19.5%) patients. Data about gender, age, body mass index, presence of DM, American Society of Anesthesiologists (ASA) physical status score, stage of disease and postoperative complications were collected prospectively. Univariate survival analysis was used to identify factors correlated with disease-specific and overall survival.

Results: Patients with DM had higher ASA score and BMI than those without DM. Rectum, colon and both of them were affected by cancer in 68%, 30% and 2% of cases, respectively. Stage 3 or 4 disease was found in patients with DM and without DM in 62% and 65%, respectively. Mean follow-up period was 4.75 years. Recurrence was diagnosed in 23% of patients with DM and in 25% of patients without DM. Altogether 41 patients died of cancer and 12 patients of other causes. Three-year cancer-specific survival in patients with DM and without DM was 85% and 89%, respectively (p=0.68). Three-year overall survival in patients with DM and without DM was 82% and 84%, respectively (p=0.63).

Conclusions: Presence of DM was not associated with tumor stage, disease-specific survival or overall survival in our group of patients with advanced colorectal carcinoma.

Disclosure

N. Satej: Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi, AstraZeneca. N. Besic: Speaker's Bureau; Spouse/Partner; Novo Nordisk Inc., AstraZeneca, Sanofi. A. Pavlic: None. M. Kerin Povsic: None.