bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptability of Closed-Loop during Labor, Delivery, and Postpartum—A Secondary Analysis of Data From Two Randomized Crossover Trials in Type 1 Diabetes Pregnancy
Authors: YAMAMOTO JENNIFER M. , STEWART ZOE A. , WILINSKA MALGORZATA E. , HARTNELL SARA , HOVORKA ROMAN , MURPHY HELEN R.
Published: June 2018

Our aim was to evaluate the efficacy of closed-loop insulin delivery for maintaining glucose control in women with type 1 diabetes during labor, delivery and the immediate postpartum period. We report on data collected from two randomized crossover trials examining closed-loop in pregnancy. This is an observational study of women who chose to continue closed-loop during labor, delivery and 48-hour postpartum period. Of the 32 women in these trials, 27 (84.4%) continued closed-loop during this time. Women who used closed-loop during labor and delivery spent 82.0% (IQR 49.3, 93.0) of time in the target range, with a mean glucose level of 124.2±25.4 mg/dl. Closed-loop performed well throughout all modes of delivery (Table 1). In the 48-hour postpartum period, the mean glucose was 130±25.0 mg/dl. During this time women spent 83.3% (IQR 75.2, 94.6) time-in-target range. There was no difference in mean glucose in mothers of infants with neonatal hypoglycemia vs. those without (mean maternal glucose of 124.2±28.8 and 122.4±19.8 mg/dL respectively; p=0.84). This study demonstrates that closed-loop insulin delivery is safe and effective in labor, delivery and the immediate postpartum period. Future research is needed to compare the biomedical efficacy of closed-loop with intensive insulin therapy and intrapartum sliding scale approaches.Table 1: Glucose control during labor and delivery by mode of deliveryVaginal Delivery n=4Emergency Caesarean Section n=12Elective Caesarian Section n=11Mean glucose (mg/dl)113.1±2.7126.1±27.0126.2±28.7Median time-in-target in %84.3 (74.7, 88.8)84.4 (48.5, 93.7)76.5 (48.2, 93.0Median time below target in %0 (0, 3.4)0.8 (0, 2.0)0 (0, 2.2)Median time above target in %15.7 (11.2, 22.0)11.4 (6.3, 50.4)16.5 (7.1, 51.8)Median number of hypoglycemic events0 (0, 1.0)0 (0, 1.0)0 (0, 1.0)Number of women with a hypoglycemic event133

Disclosure

J.M. Yamamoto: None. Z.A. Stewart: None. M.E. Wilinska: None. S. Hartnell: Speaker's Bureau; Self; Medtronic, Roche Pharma. R. Hovorka: Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, AstraZeneca. Other Relationship; Self; B. Braun Medical Inc.. Research Support; Self; Medtronic. Other Relationship; Self; Medtronic. Research Support; Self; Abbott, JDRF, Diabetes UK, National Institute of Diabetes and Digestive and Kidney Diseases. H.R. Murphy: Advisory Panel; Self; Medtronic MiniMed, Inc.. Research Support; Self; Abbott.
How Important Is Early Diagnosis and Intense Insulin Therapy in In Vitro Fertilization Pregnancies Complicated by Gestational Diabetes Mellitus?
Authors: THOMAKOS PETROS , KEPAPTSOGLOU OLGA , TROUVA ANASTASIA , BARETTO CAROL , TROUVAS DIMITRIS , TARAOUNE IBRAHIM , KORANTZIS ASTERIS , ZOUPAS CHRISTOS
Published: June 2018

GDM is increased in IVF pregnancies. There is limited literature on GDM screening and management of IVF pregnancies. The aim was to investigate the impact of GDM management on the outcome of IVF pregnancies. The study was conducted with 102 singleton IVF (a), 102 GDM spontaneous conceptions (b) vs. 102 normal pregnancies (c). The group characteristics: [age: 38.2±4 vs. 34.1±3 vs. 37.4±5 years, p<0.001 (a vs. b), NS (a vs. c), <0.001 (b vs. c); BMI: 25.8±5 vs. 23±4 vs. 22.7±4 kg/m2, p<0.001 (a vs. b), <0.001 (a vs. c), NS (b vs. c); HbA1c: 5.2±0.5 vs. 5.2±0.7 vs. 4.7±0.3%, p=NS (a vs. b), <0.001 (a vs. c), <0.001 (b vs. c); FBG: 84.1±8.4 vs. 84.2±7.1 vs. 78.2±5.2 mg/dl, p=NS (a vs. b), <0.001 (a vs. c), <0.001 (b vs. c); 1-hour postprandial BG: 103.6±11 vs. 106.5±10 mg/dl, p=NS (a vs. b); week of diagnosis GDM: 21.8±5.2 vs. 23.8±6.2, p=0.03 (a vs. b); week of starting insulin: 22.8±5 vs. 24.8±5, p=0.03 (a vs. b)].The obstetric and neonatal history are: Maternal weight gain: 10.4±4 vs. 11.9±3 vs. 10.5±2kg, p=0.035 (a vs. b), p=NS (a vs. c), p=0.03 (b vs. c); week. of delivery: 36.9±2 vs. 37.4±0.7 vs. 38.1±0.8, p=0.04 (a vs. b), p<0.001 (a vs. c), p<0.001 (b vs. c); neonatal birth wt.: 2857±517 vs. 2891±341 vs. 3117±347g, p=NS (a vs. b), p<0.001 (a vs. c), p<0.001 (b vs. c); preeclampsia rate: 4.9 vs. 3.9 vs. 1.9%; Respiratory Distress Syndrome: 14.7 vs. 12 vs. 5.8%; Neonatal hypoglycemia: 17.6 vs. 14.7 vs. 3.9%, NICU admits: 14.7 vs. 15.6 vs. 5.8%, C-Section: 86.3 vs. 56.9 vs. 41.1%. Associations between characteristics and adverse outcomes were tested among the IVF group. 1-hour Postprandial BG, but not FBG nor HbA1c, was associated with maternal-fetal complications (r=0.504, p<0.001). Maternal hypoglycemia did not affect fetal outcome. Age and BMI were not correlated with the week of GDM diagnosis. The data emphasizes the importance of strict postprandial metabolic control reached by intense early insulin therapy limiting the incidence of adverse pregnancy outcomes. IVF pregnancies must be screened for GDM much earlier than 24-28 weeks.

Disclosure

P. Thomakos: None. O. Kepaptsoglou: None. A. Trouva: None. C. Baretto: None. D. Trouvas: None. I. Taraoune: None. A. Korantzis: None. C. Zoupas: None.
Software Price Modeling of Semaglutide
Authors: EILERMAN BRADLEY , TESTA LEONARD J.
Published: June 2018

GlucosePATH is a clinically validated decision support system which creates drug regimens for patients with type 2 diabetes. Regimens are optimized for HbA1c, weight, side effect and benefit impact, adherence and cost using a composite score from 0 to 100. Used on a population level, GlucosePATH can model drug distribution for sets of clinical values, showing drug prescription frequency to that population. As new agents such as semaglutide become available, projected distribution of these options can be described at various prices. Among other things, this shows the maximum and optimal price for a new agent, given the cost and performance of existing agents.

A data set of 191 patients with HbA1c >7 was drawn from a distribution of patients cared for by PCPs in a large health system. Total monthly cost of care was computed based on the mean retail cost drawn from the GoodRX API. Using scores drawn from GlucosePATH, drugs were redistributed to find the lowest total cost at which the population’s score was >70 out of 100. Total retail cost of care averaged $475.03 per month per patient for the 191 patients. Redistributed medication at this price generated a mean composite score of 71.5 at a projected mean HbA1c of 6.9.

Two price points were established for semaglutide. The “maximal price” (MP) is the highest price at which use of the agent in the population does not exceed the control group’s retail cost of care and the composite score threshold is met. (That is, introducing the new agent does not increase cost or worsen results for the population.) The “maximal revenue” (MR) is the price at which the agent’s manufacturer maximizes their gross revenue for the agent in the population.

Price optimization for semaglutide showed a MP between $800 and $825 (retail price: $808). At its MP, semaglutide would be prescribed to approximately 17% of the population with mean composite score of 76.1 and mean HbA1c of 6.9. At semaglutide’s MR of $450 per month, it would be prescribed to approximately 49% of the population and generate a mean composite score of 77.8 with a mean HbA1c of 6.9.

Disclosure

B. Eilerman: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Novo Nordisk Inc., Orexigen Therapeutics, Inc., Corcept Therapeutics, Eli Lilly and Company, Merck & Co., Inc., Janssen Pharmaceuticals, Inc.. Other Relationship; Self; PATH Decision Support Software LLC. L.J. Testa: Stock/Shareholder; Self; PATH Decision Support Software LLC.
Insulin Secretory Response Is Enhanced in Early Pregnancy
Authors: POWE CAMILLE E. , TANGREN JESSICA S. , LEONG AARON , PERCY SHANANSSA , KRINSKY SCOTT , ARENAS JULIANA , CAYFORD MELODY , FLOREZ JOSE C. , HIVERT MARIE-FRANCE , THADHANI RAVI
Published: June 2018

Background: Emerging evidence links early pregnancy (EP) abnormalities in glucose tolerance to adverse outcomes, but glycemic physiology changes in EP are not well characterized. We hypothesized that EP insulin secretory response would be enhanced compared to postpartum (PP), independent of insulin sensitivity.

Methods: To date, 14 women without pre-existing diabetes have undergone 75-gram oral glucose tests with timed measurements of insulin and glucose at 10-15 weeks gestation (EP) and 5-15 weeks after delivery (PP). We tested for a difference in insulin secretory response (Stumvoll 1st phase estimate) in EP compared to PP with adjustment for insulin sensitivity (Matsuda index) using a linear mixed effects model. We explored associations between participant characteristics and the change in insulin secretion between EP and PP using simple linear regression.

Results: Participants had a mean (standard deviation) age of 32.3 (5.0) years and BMI of 27 (4.9) kg/m2; 43% were nulliparous and 43% were racial/ethnic minorities. In EP vs. PP, insulin secretory response (Stumvoll 1st phase estimate) was 1474 (706) vs. 1221 (398) pmol/L, while insulin sensitivity (Matsuda index) was 9.4 (7.2) vs. 9.7 (6.8). Insulin secretory response was significantly enhanced in EP as compared to PP before and after adjustment for insulin sensitivity (β=236, standard error=115, P=0.04 in adjusted model). Lower insulin sensitivity in EP was associated with a greater change in insulin secretory response between EP and PP (β=-42.2, standard error=14.0, P=0.01). There was no association between age, BMI in EP, or the change in BMI between EP and PP and the change in insulin secretory response.

Conclusion: We found evidence of enhancement of insulin secretory response early in pregnancy, in the absence of a change in insulin sensitivity. In light of evidence that identification and treatment of mild glucose intolerance early in pregnancy may be beneficial, larger studies of glycemic physiology in the 1st trimester are warranted.

Disclosure

C.E. Powe: None. J.S. Tangren: None. A. Leong: None. S. Percy: None. S. Krinsky: None. J. Arenas: None. M. Cayford: None. J.C. Florez: Consultant; Self; Intarcia Therapeutics, Inc.. Consultant; Spouse/Partner; Santen. M. Hivert: None. R. Thadhani: None.
Failure of Maternal Glucose-Insulin Adjustments in Pregnancy Might Contribute to Poor Fetal Growth in India
Authors: DESHMUKH MADHURA KISHOR , DAMLE HEMANT , BHAT DATTATRAY , MEMANE NILAM S. , RAUT DEEPA A. , BHALERAO ABOLI A. , BONDARDE SOMNATH J. , YAJNIK CHITTARANJAN S.
Published: June 2018

Background: In the well-nourished Western populations maternal insulin concentrations (and insulin resistance) progressively increase during gestation to support fetal growth. Information in undernourished women from LMICs is scarce. We investigated serial glucose-insulin and lipid concentrations from early to late pregnancy in rural and urban Indian women, and studied their association with offspring birth weight.

Methods: Women from antenatal clinics were enrolled in early pregnancy. Fasting glucose, insulin, cholesterol and triglyceride concentrations were measured at 16, 28 and 33 weeks gestation and a75gm OGTT was performed at 28 weeks gestation. GDM was diagnosed using the prevalent WHO 1999/ IADPSG 2011 criteria. Demographic and anthropometric measurements were obtained, and babies were measured at birth.

Results: A total of 256 (161 rural, 95 urban) women were enrolled: they were 23 y old, 153 cm tall, and had a BMI 20.7 kg/m2at ∼16 weeks gestation. Thirty nine GDM women (22 rural) were excluded from further analysis. In 217 normal glucose tolerant women, fasting plasma glucose progressively fell with increasing gestation, insulin concentrations and HOMA-IR remained similar (51% showed a fall); total and HDL cholesterol and triglyceride concentrations increased. Urban women were older, taller and heavier, and had significantly higher glucose, insulin and HOMA-IR compared to rural women; they gained 7kg and rural women 6kg between early and late visits. Mean birth weight was 2.8kg, 39% babies were SGA and 1% LGA (INTERGROWTH). Birth weight was positively associated with maternal size (height, weight, BMI) and fasting plasma glucose concentrations. HOMA-IR was not independently associated.

Conclusion: The short and undernourished women from India failed to increase their insulin resistance with increasing gestation. This may be a novel explanation for fetal growth restriction in India and for its short term and long term sequele, including risk of diabetes.

Disclosure

M. Deshmukh: None. H. Damle: None. D. Bhat: None. N.S. Memane: None. D.A. Raut: None. A.A. Bhalerao: None. S.J. Bondarde: None. C.S. Yajnik: None.
Association between Glyburide Dose and Adverse Neonatal Outcomes in Women with Gestational Diabetes
Authors: FEGHALI MAISA N. , CARITIS STEVE , CATOV JANET M. , SCIFRES CHRISTINA M.
Published: June 2018

Glyburide is used to treat women with gestational diabetes (GDM). However, recent data has demonstrated that it crosses the placenta, and concerns about the neonatal effects of glyburide treatment including fetal overgrowth and neonatal hypoglycemia persist.

We sought to assess if there are subsets of women treated with glyburide who are at increased risk for adverse neonatal outcomes compared to women treated with medical nutritional therapy (MNT) alone using a retrospective cohort of 1,012 women with GDM. We collected characteristics including glucose values and pregnancy outcomes. We used bivariate and multivariable logistic regression analyses to assess the association between GDM treatment and pregnancy outcomes.

Treatment was divided into categories of MNT (n=343), glyburide <7.5 mg (n=495), and glyburide ≥7.5 mg/day (n=173). When compared to women treated with MNT or glyburide <7.5 mg, those treated with glyburide ≥7.5 mg/day were more likely to be obese (28.5 vs. 48.3 vs. 63.2%, p<0.001), gain excessive weight (35.2 vs. 42.9 vs. 56.4%, p<0.0001), and had higher mean glucose (106.4 vs. 114.3 vs. 121.9, p<0.001). Higher glyburide doses were associated with an increased risk for large for gestational age (LGA) and neonatal hypoglycemia. After adjusting for covariates including nulliparity, prepregnancy BMI, gestational weight gain, prematurity, and maternal glucose, women treated with ≥7.5 mg/day were 2.6-fold more likely to deliver an LGA infant, but there was no increased risk for hypoglycemia.

Our findings suggest that neonatal outcomes in women on lower glyburide doses are similar to those treated with MNT, but higher doses are associated with fetal overgrowth. Further studies are needed to determine optimal management of women receiving glyburide, specifically the maximal dose for use in pregnancy and identification of women who respond well to lower doses.

Disclosure

M.N. Feghali: None. S. Caritis: None. J.M. Catov: None. C.M. Scifres: None.
Effect of Preconceptional Care on Maternal and Fetal Outcomes in Type 1 Diabetes
Authors: DALAMA BELEN , DE URBINA ANA ORTIZ , GOYA MARIA , ARÉVALO SILVIA , RODÓ CARLOTA , MESA JORDI
Published: June 2018

Introduction: Pregnancy in women with type 1 diabetes (T1D) is associated with increased risk of maternal complications and neonatal morbidity. Our aim is to describe and compare maternal metabolic control and maternal-fetal outcomes (MFO) among pregnant T1D patients optimized preconceptionally (OP) as compared to those with unplanned pregnancies (UP).

Design and methods: We carried out a retrospective study of 92 singleton pregnancies in 79 T1D Caucasian patients, 59 of them were OP and 33 UP who attended our Diabetes and Pregnancy Unit since 2013 to 2017. In each of the groups were evaluated the pre-pregnancy characteristics, in each trimester and the MFO. Preconception A1C goal was <6% without exceeding 6.5% with a glycemic target of a fasting glucose between 70-95mg/dl and 1 hour postprandial 90 -140 mg/dl.

Results: Both groups did not differ by age: 34 (36-43) vs. 31 (21-42) years, T1D duration: 17 (2-35) vs. 14 (1-31) years and pregestational BMI. Pre-pregnancy A1C in OP vs. UP was 5.9% (5.1-6.0) vs. 7.4% (6.8-10.1) p< 0.001. During the first trimester: 5.7% (5.2-6.5) vs. 6.6% (5.7-7.8) p< 0.01, in the 2th: 5.8% (4.8-6.4) vs. 6.3% (5.3-7.0) and in the 3th: 5.9% (5.0-6.5) vs. 6.2% (5.2-6.9) without differences in weight gain and preeclampsia development. OP vs. UP patients had a 27.1% of cesarean delivery vs. 33.3% (p<0.05) with no differences in preterm and instrumental delivery. Regarding fetal outcomes the neonatal birth weight was 3270 gr (2198-4280) vs. 3370 gr (1200-4870) with a higher percentage in the UP of larger for gestational age newborns (15.2% vs. 3.3% p<0.05), malformations (1.6% vs. 15.1% p<0.05) and hypoglycemia (6.7% vs. 27.2% p<0.05). No differences in macrosomía, small for gestational age, shoulder dystocia, jaundice or respiratory distress.

Conclusion: In women with preexisting T1D preconceptional counseling and glycemic optimization represent a fundamental step towards improved pregnancy outcomes. Pre-pregnancy A1C <6% and during the 1th trimester seems to decrease the risk of adverse outcomes.

Disclosure

B. Dalama: None. A. Ortiz de Urbina: None. M. Goya: None. S. Arévalo: None. C. Rodó: None. J. Mesa: None.
Should We Perform an OGTT in All Latino Pregnant Women? The Negative Predictive Value of a Fasting Blood Glucose
Authors: MANCILLAS-ADAME LEONARDO G. , GONZALEZ CAMILO D. , VILLARREAL JOSE A. , SALDIVAR-RODRIGUEZ DONATO , LAVALLE-GONZALEZ FERNANDO J. , RODRIGUEZ-GUTIERREZ RENE , GONZALEZ-GONZALEZ JOSE G.
Published: June 2018

Background: Latino women are considered a high-risk group, prone to develop GDM. Currently, according to the ADA Standard of Care Recommendations, these subjects should undergo screening with an OGTT, which is a time and resource consuming procedure. A better selection of the individual would favor a cost-effective diagnostic approach. Our hypothesis is that we could find a fasting blood glucose threshold able to predict a normal OGTT response.

Methods: We analyzed the results of 363 one-step, 75-g OGTT performed in our clinic during 2017. Patients with a previously known glucose tolerance abnormality were excluded from the study.

Results: The fasting glucose value was diagnostic of GDM in 83/363 cases. After selecting only those cases with fasting value lower than 92 mg/dL, 22 additional subjects were diagnosed with GDM. The one-hour post-load value criteria was met in 16/280 (5.71%) whilst the 2 hour value diagnosed 6 additional subjects (2.86%). Two patients had both one and two hour positive criteria. The area under the curve was 0.75, for fasting blood glucose as a predictor of an abnormal glucose response.

Conclusions: In our population from a Mexican University Hospital, the fasting blood glucose detected fourfold the cases of GDM vs. the OGTT. It might be cost effective to perform a fasting glucose prior to prescribe an OGTT in pregnant subjects.

Disclosure

L.G. Mancillas-Adame: None. C.D. Gonzalez: None. J.A. Villarreal: None. D. Saldivar-Rodriguez: None. F.J. Lavalle-Gonzalez: None. R. Rodriguez-Gutierrez: None. J.G. Gonzalez-Gonzalez: None.
Maternal Diabetes during Pregnancy and Early Childhood Obesity—A Population-Level Analysis
Authors: BOWKER SAMANTHA L. , SAVU ANAMARIA , YEUNG ROSEANNE O. , RYAN EDMOND A. , KAUL PADMA
Published: June 2018

We examined the association between maternal diabetes status (preexisting diabetes mellitus (pre-DM), gestational diabetes mellitus (GDM), and no DM) during pregnancy and overweight or obesity status of the offspring in early childhood (4-6 years). Immunization records, containing height and weight at the time of preschool vaccination for children born between Jan 2005-Aug 2013 in Alberta, Canada were linked with the following: 1) maternal hospitalization and outpatient records prior to delivery; and 2) registry data containing birth weight, parity, and gestational age. World Health Organization (WHO) criteria were used to categorize children as overweight or obese. Our cohort had 91,382 live births from 68,457 mothers. Rates of pre-DM, GDM and no-DM were 0.8%, 6.2%, and 93.0%, respectively (Table). Childhood overweight/obesity rates were significantly higher among women with pre-DM or GDM, than with no-DM. After adjustment, both GDM and pre-DM were associated with a higher likelihood of having an overweight/obese child. Breast feeding data were available for 63,374 children. A higher proportion of GDM and pre-DM babies were not breast fed, which was also associated with a higher risk of childhood obesity. The impact of maternal diabetes on offspring weight continues beyond birth to early childhood. This association may be further exacerbated by breast feeding challenges in women with diabetes.

Disclosure

S.L. Bowker: None. A. Savu: None. R.O. Yeung: Consultant; Self; Sanofi. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. E.A. Ryan: None. P. Kaul: None.
History of Falls in the Previous Year Predicts Frailty among Community-Dwelling Older Patients with Diabetes Mellitus
Authors: VALENCIA WILLY MARCOS , MOGHADAM NIMA , BALDA-CANIZARES JAVIER , MINTZER MICHAEL J. , DANG STUTI , RUIZ JORGE G.
Published: June 2018

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization in older adults. Diabetes mellitus is considered a risk factor for both frailty and falls in older adults. The aim of this study was to determine in a community cohort of older patients (65 years and older) with type 2 diabetes mellitus (T2DM) whether a history of falls is associated with frailty. Community dwelling older Veterans with T2DM underwent frailty assessment with the validated 5-item FRAIL Scale (frail ≥ 3; pre-frail 1-2; robust 0 points) between January 2016 and December 2017. We aggregated data on patients with a least one fall in the previous year. Binomial logistic regression was used to examine the association between a history of falls in the previous year and frailty. Among 868 patients (mean age 74 ± 7 years, 98% men), 31% were robust, 36% prefrail, and 33% frail. Over the previous year, 164 falls occurred among 1older patients. The number of older individuals with at least one fall in the previous year was significantly higher in the frail as compared with prefrail and robust groups: 20%, 9%, and 9% respectively (p<.0005). A history of falls in the previous year was associated with an increased risk for frailty (odds ratio: 2.54 95% CI: 1.60-4.03). The population-attributable risk associated with a history of falls was 44% for frailty.

In conclusion, a history of falls in the previous year is a strong predictor of frailty in older patients with T2DM. Falls should be a key component of the clinical evaluation of older patients with T2DM.

Disclosure

W. Valencia: None. N. Moghadam: None. J. Balda-Canizares: None. M.J. Mintzer: None. S. Dang: None. J.G. Ruiz: None.
Cost-Related Barriers to New Diabetes Medications—A National Physician Survey
Authors: HAM SANDRA A. , NATHAN AVIVA , LAITEERAPONG NEDA , SARGIS ROBERT M. , QUINN MICHAEL T. , HUANG ELBERT
Published: June 2018

Background: In recent clinical trials, some SGLT2is and GLP-1 receptor agonists have been shown to reduce cardiovascular events, leading to their prioritization for patients with cardiovascular disease in diabetes care guidelines. However, because these medications are costly, oftentimes medication access is limited by insurance companies.

Objectives: To determine the frequency that physicians encounter cost-related barriers to prescribing new diabetes medications.

Methods: We mailed a survey to a national sample of 720 primary care physicians (PCPs) and 480 endocrinologists in 2016 (adjusted response rate, 41%). Physicians were asked how often their patients were unable to start a new diabetes medication in general, and, specifically, an SGLT2i, because it was too expensive. Physicians also reported the frequency of completing a prior authorization (PA) for a new diabetes medication.

Results: In 2016, 28% (N=101) and 37% (N=129) of physicians reported that their patients were unable to start medications in general, and specifically, SGLT2is, due to costs “most of the time”/“always.” More PCPs (45%, N=86) than endocrinologists (26%, N=43) were unable to start SGLT2is due to costs. Daily PA were reported by 43% of physicians (N=151); 62% (N=101) endocrinologists completed PAs daily. Adjusting for specialty and panel size, physicians with >50% of patients age >65 were more likely to report that patients were unable to start a new medication or SGLT2i due to costs (OR=2.25, 95% CI=1.38-3.67; p=0.001 and OR=1.63, CI=1.02-2.60, p=0.04). Endocrinologists (OR=5.03, CI=3.09-8.18; p<0.001) and physicians with >1000 patients in their panel (OR=2.69, CI=1.61-4.49; p<0.001) were more likely to complete PAs daily.

Conclusions: U.S. physicians experience significant cost-related barriers to prescribing new diabetes medication classes. Pharmacy benefit management strategies will need to be updated to facilitate access to glucose-lowering medications with clear cardiovascular benefit.

Disclosure

S.A. Ham: None. A. Nathan: None. N. Laiteerapong: None. R.M. Sargis: Advisory Panel; Self; CVS/Caremark. M.T. Quinn: None. E. Huang: None.
Understanding the Relationship between Primary Care Provider (PCP) Encounter Cadence, Medication Adherence, and Diabetes Control
Authors: WIXSON SARAH E. , DOBBINS JESSICA , CORDIER TRISTAN A. , HAUGH GIL , RENDA ANDREW , HAPPE LAURA E. , TURCHIN ALEXANDER
Published: June 2018

Introduction: Regular PCP encounters are associated with wellbeing; there is limited evidence to support the ideal PCP encounter cadence to optimize patient outcomes. The aim of this study was to measure the association between PCP encounter cadence and medication adherence and diabetes control, among those newly diagnosed with T2DM.

Methods: A cohort of 7,106 persons enrolled in a Medicare Advantage health plan and newly diagnosed with T2DM between 7/1/12-6/30/13, was identified and followed for 36 months. Two methods measured PCP encounter cadence: total PCP encounters (frequency) and quarters with PCP encounter (regularity). Proportion of days covered (PDC) assessed noninsulin diabetes medication (NIDM) adherence (PDC ≥80.0%). Diabetes control was defined as A1c ≤ 8.0%. Logistic regression was used to measure the relationship between PCP encounter cadence and outcomes (NIDM adherence, diabetes control). Covariates included patient demographics, Charlson Comorbidity Index score, chronic conditions, healthcare utilization, insulin use, and prior NIDM adherence and diabetes control.

Results: Overall, 5,212 and 326 people met inclusion criteria for the NIDM adherence and diabetes control analyses, respectively. Adjusted models indicated that each additional PCP encounter was associated with a 12.3% increase in the likelihood of NIDM adherence (95% CI 1.10, 1.15), and each additional quarter with a PCP encounter was associated with a 27.4% increase in the likelihood of NIDM adherence (95% CI 1.22, 1.33). PCP encounters (OR 1.06; 95% CI 1.00, 1.12) and quarters with a PCP encounter (OR 1.13; 95% CI 0.98, 1.30) were directionally associated with diabetes control.

Conclusion: Our findings suggest that frequency and regularity of PCP encounters were associated with medication adherence. This study contributes to the data needed to establish evidence-based guidelines for PCP encounter cadence, for those newly diagnosed with T2DM.

Disclosure

S.E. Wixson: None. J. Dobbins: Employee; Self; Humana Inc. T.A. Cordier: Employee; Self; Humana Inc.. Stock/Shareholder; Self; Humana Inc.. G. Haugh: None. A. Renda: None. L.E. Happe: Employee; Self; Humana. Other Relationship; Self; Journal of Managed Care Pharmacy. A. Turchin: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Merck Sharp & Dohme Corp., Monarch Medical Technologies. Stock/Shareholder; Self; Brio Systems. Research Support; Self; Eli Lilly and Company.
Higher HbA1c Levels Should Be Used to Diagnose Diabetes and Prediabetes in Blacks
Authors: STAIMEZ LISA R. , FORD CHRISTOPHER N. , DANIELS LAUREN , GONZALEZ ADRIANA , KHAN FARAH N. , RHEE MARY , WILSON PETER W. , PHILLIPS LAWRENCE S.
Published: June 2018

Blacks have higher HbA1c levels than whites with similar glucose levels, suggesting that universal diagnostic criteria could lead to overdiagnosis of diabetes and prediabetes in blacks. We hypothesized alternative HbA1c diagnostic criteria could reduce misclassification in blacks. Data from 3,603 non-Hispanic (NH) white (67.6%) and 1,721 NH black (32.4%), nonpregnant adults (18-70 year) were included from 5 cycles (2005-2014) of the National Health and Nutrition Examination Survey with HbA1c and plasma glucose measures (i.e., fasting and 2 hour from oral glucose tolerance test, OGTT). Diabetes and prediabetes by HbA1c was compared with ’true’ OGTT classification to identify alternative HbA1c values with the lowest misclassification (false positives + false negatives). Survey-weighted rates were computed across a series of HbA1c cutpoints for diabetes (HbA1c ≥5.7 to ≥7.3%) and HbA1c ranges for prediabetes (4.9-5.6% to 6.8-7.5%) in 0.1% increments. By ADA OGTT criteria, the prevalence of diabetes and prediabetes in whites was 4.6% and 42.1%, respectively, and in blacks, 4.2% and 36.9%. Under ADA criteria for diabetes, misclassification was similar in whites (3.7%) and blacks (3.5%), but blacks had 6.3 times the rate of false positives (1.1% blacks vs. 0.2%; p<0.001) and 0.76 times false negatives (57.3 vs. 75.1%, p=0.016). Diabetes misclassification was lowest in whites at HbA1c ≥6.3% (3.4% misclassified) and in blacks at ≥6.9% (3.2%). Prediabetes misclassification was similar in whites (35.8%) and blacks (33.9%), but blacks had 2.8 times the rate of false positives (24.5% vs. 8.6%; p<0.001) and 0.68 times that of whites (50.0 vs. 73.2%, p<0.001). Misclassification was lowest in whites at HbA1c 5.6-6.3% (34.3% misclassified) and in blacks at 5.9-6.6% (31.3%).

Conclusion: Overdiagnosis of diabetes and prediabetes is disproportionately high among NH blacks compared to NH whites. Increasing the HbA1c diagnostic thresholds by 0.3-0.6% for NH blacks could potentially avert 3.2 million false positives.

Disclosure

L.R. Staimez: None. C.N. Ford: None. L. Daniels: None. A. Gonzalez: None. F.N. Khan: None. M. Rhee: None. P.W. Wilson: None. L.S. Phillips: Other Relationship; Self; DIASYST Inc.. Research Support; Self; Amylin Pharmaceuticals, Eli Lilly and Company, Novo Nordisk Inc., Sanofi-Aventis, PhaseBio Pharmaceuticals, Inc., Roche Diabetes Care Health and Digital Solutions, AbbVie Inc., Vascular Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., GlaxoSmithKline plc., Pfizer Inc.. Other Relationship; Self; Novartis Pharmaceuticals Corporation, Merck & Co., Inc..
Duplicate Oral Glucose Tolerance Tests Provide Highly Reproducible Results for the Diagnosis of Diabetes in Africans—The Africans in America Study
Authors: BRIKER SARA M. , KABAKAMBIRA JEAN DAMASCENE , BAKER RAFEAL L. , DUBOSE CHRISTOPHER , MABUNDO LILIAN , CHUNG STEPHANIE T. , UTUMATWISHIMA JEAN N. , SUMNER ANNE E.
Published: June 2018

With the diabetes epidemic spreading across Africa, undiagnosed diabetes threatens health. As the reproducibility of the OGTT in Africans is not known, the value of using the OGTT to diagnose diabetes (DM) in Africans is uncertain. Therefore, the Africans in America study enrolled 62 blacks (71% male, age 40±11y (mean±SD), BMI 27.8±4.6 kg/m2) who were born in Africa, identified as healthy and currently live in the Washington, DC area. Two OGTT were performed with 11±9 days between tests. The OGTT was used to define normal glucose tolerance (NGT), prediabetes (preDM) and DM. For reproducibility, the κ statistic was used and interpreted by conventional standards (slight 0.00 to 0.20, fair 0.21 to 0.40; substantial 0.61 to 0.80, excellent 0.81 to 1.0). At the 1st OGTT, NGT, preDM and DM were diagnosed in 40%, 26% and 34% of Africans, resp. At the 2nd OGTT, NGT, preDM and DM were diagnosed in 40%, 32% and 27%, resp. When all 3 glucose tolerance categories were considered, the κ statistic was 0.76. Dividing the cohort into 2 groups (with and without DM), the κ statistic increased to 0.85. Furthermore, no one diagnosed with DM on the first 1st OGTT was diagnosed with NGT on the 2nd OGTT (Table). In addition, no one without DM on the 1st OGTT was diagnosed with DM on the 2nd OGTT (Table). Based on data from Africans living in America, the OGTT is highly reproducible for the detection of DM.

Disclosure

S.M. Briker: None. J. Kabakambira: None. R.L. Baker: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. J.N. Utumatwishima: None. A.E. Sumner: None.
Novel Nomogram for Screening the Risk of Developing Diabetes in a Korean Population
Authors: CHUNG SEUNG MIN , MOON JUN SUNG , YOON JI SUNG , WON KYU CHANG
Published: June 2018

Aims: We propose a novel nomogram, which graphically expresses the numerical relationship between type 2 diabetes (T2D) and disease-related risk factors.

Methods: Data of 8999 patients from the 2013-2014 Korean National Health and Nutrition Examination Survey were analyzed. Multiple logistic regression analysis was performed to assess risk factors for T2D and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot were created to evaluate the accuracy of the nomogram.

Results: The risk factor with the greatest impact on the incidence of T2D was age over 60 years (OR=9.458), followed by presence of dyslipidemia and cardiovascular disease (OR=8.981), family history of T2D (OR=2.916), abdominal obesity (OR=1.759), hypertension (OR=1.747), male gender (OR=1.549), current-smoking status (OR=1.523), lower education level (OR=1.417), and lower income (OR=1.300). The area under the ROC curve (AUC) showed statistically significant determination (AUC=0.826). The equation of the calibration plot was drawn along the ideal line; coefficient of determination was 0.864.

Conclusion: Our proposed nomogram could accurately predict the incidence risk of T2D from nationwide data. The novel nomogram can be a useful tool for screening patients with T2D incidence in a Korean population.

Disclosure

S. Chung: None. J. Moon: None. J. Yoon: None. K. Won: None.
Hypertension Is Associated with a Higher Progression Rate of Insulin Resistance and the Incidence of Diabetes
Authors: LIN CHIA-HUNG , LI HUNG-YUAN
Published: June 2018

Background: Hypertension is a risk factor of diabetes. However, the underlying mechanisms are not fully elucidated. Therefore, we investigated this issue in a prospective cohort in Taiwan.

Methods: A total of 1177 subjects without diabetes at baseline were enrolled from 20to 2016 at National Taiwan University Hospital Yun-Lin branch with a median follow-up period of 4.5 years. Diabetes was diagnosed by the results of OGTT and HbA1c, or if antidiabetic agents were used. Insulin resistance index by the Homeostatic model assessment 2 (HOMA2-IR) were used to estimate insulin resistance.

Results: Subjects with hypertension by the JNC7 criteria had higher HOMA-IR at baseline and was associated with increased incidence of diabetes, adjusted for HOMA2-%B, HOMA2-IR, BMI, HbA1c, plasma triglyceride, age, gender, family history of diabetes and plasma CRP (adjusted HR 1.51, 95% CI 1.04-2.20, p=0.030). Subjects with treated hypertension had the highest risk of diabetes, followed by subjects with newly-diagnosed hypertension, compared with subjects with pre-hypertension and normal subjects. The progression rate of HOMA2-IR every 5 years (δHOMA2-IR/5 year) was higher in subjects with hypertension than in subjects without hypertension (adjusted p=0.001). Subjects with treated hypertension had the highest δHOMA2-IR/5 year, followed by subjects with newly-diagnosed hypertension, compared with normal subjects (adjusted p for trend=0.05). However, hypertension by the 2017 ACC/AHA criteria was not significantly associated with incident diabetes in adjusted models. The δHOMA2-IR/5 year for hypertension by this criteria was lower than that by the JNC7 criteria.

Conclusion: Hypertension is associated with an accelerated progression of insulin resistance and an increased risk of diabetes. Application of 2017 ACC/AHA criteria for hypertension attenuates the associations.

Disclosure

C. Lin: None. H. Li: None.
Copeptin as a Novel Biomarker of Obesity-Induced Insulin Resistance and Metabolic Syndrome
Authors: ELTABAKH SOAD M.M. , ZEIDAN MOHAMED , MAGED HALA , ZIKRY MAGDY , KHEDR MARWA
Published: June 2018

The objective of the study was to evaluate whether circulating Copeptin could be used as a novel biomarker associated with measures of insulin resistance and presence of metabolic syndrome in obese individuals. The study was carried out on three groups: G1: Twenty obese individuals with metabolic syndrome, G2: Twenty age-matched obese adults without metabolic syndrome, and G3: control group: Twenty age-matched non obese healthy adult voluntrrers. Both group (1) and (2) were selected to be obese with Body Mass Index (BMI) is greater than 30kg/m2. All groups were subjected to: complete physical examination, assessment of metabolic syndrome criteria according to the National Heart, Lung and Blood Institute (NHLBI) and the American Heart Association (AHA), fasting plasma glucose (FPG), fasting insulin, lipid profile, assessment of insulin resistance by HOMA-IR and measurement of plasma Copeptin level using ELISA technique. The results of Plasma Copeptin levels were significantly increased in G1 than the other two groups (median 38.30 ng/ml for G1 vs. 25.and 23.00 in G2 and G3 respectively, P < 0.001). Evident Positive correlation were found between plasma Copeptin level and HOMA-IR, FBG, TG, WC and BMI, and Negative correlation with HDL level (P <0.for HOMA-IR and FPG; P < 0.01 for TG, WC, BMI, and HDL). The area under the receiver-operating characteristic curve (AUC) for Copeptin was 0.79 (95% confidence interval, CI:0.67 to 0.89).

Conclusion: Our results suggest that circulating Copeptin could be used as a possible biomarker of obesity-induced insulin resistance that provide diagnostic advantage to measures of metabolic syndrome. Further prospective multi center studies on a large scale of cases are needed.

Disclosure

S.M.M. Eltabakh: None. M. Zeidan: None. H. Maged: None. M. Zikry: None. M. Khedr: None.
Circulating Metabolites and the Risk of Type 2 Diabetes—A Prospective Study of 10,938 Young Adults from Four Finnish Cohorts
Authors: AHOLA-OLLI ARI V. , MUSTELIN LINDA , KALIMERI MARIA , KETTUNEN JOHANNES , JOKELAINEN JARI J. , AUVINEN JUHA , PUUKKA KATRI S. , HAVULINNA AKI S. , LEHTIMÄKI TERHO , KÄHÖNEN MIKA , SALOMAA VEIKKO , PEROLA MARKUS , JARVELIN MARJO-RIITTA , ALA-KORPELA MIKA , WURTZ PETER
Published: June 2018

Background: Advances in metabolomics have allowed high-throughput metabolic profiling of large population samples. We aimed to identify circulating lipids and metabolites predictive of the risk for type 2 diabetes in young adults.

Methods: Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 10,938 individuals from four Finnish cohorts (mean age 35 years, range 24-45). Associations between baseline metabolites and diabetes onset during 7-15 years of follow-up (330 incident cases) were assessed by logistic regression adjusted for sex, baseline age and glucose.

Findings: Out of 229 metabolic measures, 174 were associated with risk for incident diabetes in meta-analysis of the four cohorts (P<0.001; range of odds ratios (OR) per 1-SD: 0.41-1.85). Among the strongest biomarkers were increased concentrations of branched-chained and aromatic amino acids (OR: 1.54-1.74) and triglycerides in very-low-density lipoproteins (VLDL; OR 1.78), and lower levels of omega-6 fatty acids (OR 0.61) and free cholesterol within large high-density lipoprotein (HDL; OR 0.41). A biomarker score was derived in three of the cohorts, comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesterol esters to total lipids in large VLDL. When validated in the fourth cohort, those in the upper quartile of the biomarker score had considerably higher 15-year-risk for diabetes compared to those in the lowest quartile (OR 16.1).

Interpretation: Metabolic aberrations across multiple molecular pathways are predictive of the long-term risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may facilitate targeting preventive interventions at young asymptomatic individuals at increased risk for type 2 diabetes.

Disclosure

A.V. Ahola-Olli: None. L. Mustelin: Employee; Self; Nightingale Health Ltd. M. Kalimeri: Employee; Self; Nightingale Health Oy. J. Kettunen: Other Relationship; Self; Nightingale Ltd. J.J. Jokelainen: None. J. Auvinen: None. K.S. Puukka: None. A.S. Havulinna: None. T. Lehtimäki: None. M. Kähönen: None. V. Salomaa: Other Relationship; Self; Novo Nordisk Inc.. M. Perola: None. M. Jarvelin: None. M. Ala-Korpela: None. P. Wurtz: Employee; Self; Nightingale Health. Stock/Shareholder; Self; Nightingale Health.
Impact of “Mismatches” in HbA1c vs. Glucose on Diagnosis as Diabetes or Prediabetes
Authors: GONZALEZ ADRIANA , CUI XIANGQIN , STAIMEZ LISA R. , FORD CHRISTOPHER N. , KHAN FARAH N. , WILSON PETER W. , PHILLIPS LAWRENCE S. , RHEE MARY
Published: June 2018

HbA1c is widely used for diagnosis and management of diabetes and prediabetes, but HbA1c may be high or low relative to underlying glucose levels in different individuals-“mismatches.” We hypothesized that “high mismatches” could lead to overdiagnosis, and “low mismatches” to underdiagnosis of diabetes and prediabetes. We pooled 31generally healthy subjects without known diabetes from the Screening for Impaired Glucose Tolerance study (n=1571) and the VA Screening for Diabetes study (n=1535); each had a 75g OGTT and a 50g glucose challenge on separate days. Subjects were 66% male, 65% black, with mean age 52 year, BMI 30 kg/m2 and HbA1c 5.6%. By ADA OGTT criteria, 56% had normal glucose metabolism (NGM, FPG <100 and 2hPG <140), 37% had prediabetes (PreDM), and 7% had T2DM (FPG >125 or 2hPG >199). To approximate glucose levels during the day, we took the mean of each subject’s OGTT FPG and 2hPG, and 1 hPG after 50 g glucose. Linear regression was used to derive [predicted HbA1c = 0.0078*GLUC + 4.70], from which the HbA1c Glycation Index (HGI) for each subject was expressed as [observed-predicted HbA1c]. Subjects were divided into tertiles according to their HGI levels: “high mismatch” (high HGI), “no mismatch” (mod HGI), and “low mismatch” (low HGI). The “high mismatch” group was enriched in African-Americans (84%) and males (78%) but otherwise clinically comparable, all p<0.001. By ADA OGTT criteria, the distribution of NGM, PreDM, and T2DM (55%, 37%, 7%, resp) was comparable across HGI tertiles. However, by ADA HbA1c criteria, the “no mismatch” group had 67% NGM, 32% PreDM, and 1% T2DM, but “high mismatches” were 7% NGM, 80% PreDM, and 13% T2DM-mostly abnormal, and “low mismatches” were 96% NGM, 4% PreDM, and 0% T2DM-mostly normal.

Conclusion: “Mismatches” in HbA1c vs. glucose are common, and could lead to errors if the diagnosis is based only on HbA1c - overdiagnosis in “high mismatches”, and underdiagnosis in “low mismatches.” FPG and/or OGTT should be used to complement HbA1c in diagnosing diabetes and prediabetes.

Disclosure

A. Gonzalez: None. X. Cui: None. L.R. Staimez: None. C.N. Ford: None. F.N. Khan: None. P.W. Wilson: None. L.S. Phillips: Other Relationship; Self; DIASYST Inc.. Research Support; Self; Amylin Pharmaceuticals, Eli Lilly and Company, Novo Nordisk Inc., Sanofi-Aventis, PhaseBio Pharmaceuticals, Inc., Roche Diabetes Care Health and Digital Solutions, AbbVie Inc., Vascular Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., GlaxoSmithKline plc., Pfizer Inc.. Other Relationship; Self; Novartis Pharmaceuticals Corporation, Merck & Co., Inc.. M. Rhee: None.
Screening for Cystic Fibrosis–Related Diabetes and Prediabetes—Evaluating 1,5-Anhydroglucitol, Fructosamine, Glycated Albumin, and Hemoglobin A1c
Authors: TOMMERDAHL KALIE L. , BRINTON JOHN T. , VIGERS TIM B. , NADEAU KRISTEN J. , ZEITLER PHIL , CHAN CHRISTINE L.
Published: June 2018

Dysglycemia in the cystic fibrosis (CF) population is widespread and screening via oral glucose tolerance tests (OGTT) can be burdensome. Our primary aim was to investigate 1,5-anhydroglucitol (1,5AG), fructosamine (FA), glycated albumin (%GA), and hemoglobin A1c (HbA1c) as screening tests for cystic fibrosis-related prediabetes (CFPD) and cystic fibrosis-related diabetes (CFRD) in youth with CF as defined by the OGTT 2-hour glucose (2hG). Our secondary aim was to determine if alternate screening tests can identify those with better or worse lung function (forced expiratory volume in 1 second, FEV1%; forced vital capacity, FVC%). Youth 10-18 years with CF had 1,5AG, FA, %GA, HbA1c, and a 2 hour OGTT collected during a single study visit. Pearson’s correlation coefficient determined the correlation between all 4 glycemic estimates and 2hG. Receiver Operative Characteristic (ROC) curves were generated. The Youden Index determined optimal cut points for predicting CFPD (2hG≥140-200 mg/dL) and CFRD (2hG≥200 mg/dL). Lung function measures above and below these cutpoints were compared. Fifty-eight youth with CF participated (2hG<140, n=31; CFPD, n=17; CFRD, n=10; mean age 14±3.5 years, 43% male, BMI z-score 0.0±0.8, FEV1% 90±15.0, FVC% 99±14.1). FA, %GA, and HbA1c correlated with 2hG (p-<0.05). ROC area under the curves (ROC-AUCs) for all 4 alternate markers were low for both CFPD (0.53-0.67) and CFRD (0.56-0.66). HbA1c had the highest ROC-AUC of 0.66 (95% CI: 0.47-0.84) for identifying CFRD and 0.67 (95% CI: 0.53-0.8) for CFPD. When lung function was compared stratifying above and below the Youden cutpoint for CFRD, only HbA1c identified significant differences in FVC% (105% vs. 96%, p=0.02); FEV1% was not statistically significant (96% vs. 88%, p=0.06). All 4 alternate markers had poor diagnostic accuracy for identifying CFRD by 2hG, although HbA1c may be useful in detecting CFPD and in stratifying individuals with CF by lung function.

Disclosure

K.L. Tommerdahl: None. J.T. Brinton: None. T.B. Vigers: None. K.J. Nadeau: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH. C.L. Chan: None.