bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between Mean Glucose and A1C by Pubertal Stage in Youth with Type 1 Diabetes (T1D)
Authors: ZHU JIA , VOLKENING LISA , KATZ MICHELLE , LAFFEL LORI M.
Published: June 2018

Background: Correlations between mean glucose and A1c vary among persons with T1D, with weaker associations in youth vs. adults. We investigated the relationships between mean glucose assessed by continuous glucose monitoring (CGM) and A1c according to pubertal stage in youth with T1D.

Methods: Mean glucose and percent of time in various glucose ranges (<70, 70-180, >250 mg/dL) were calculated using CGM data from the 4 weeks before A1c measurement in 107 youth, ages 8-17, with T1D. Glucose data were compared by pubertal stage (pre-pubertal: Tanner (T) 1, pubertal: T2-4, post-pubertal: T5) and A1c categories (<7.5%, 7.5-8.4%, ≥8.5%).

Results: Mean (±SD) ages for the pre-pubertal (64% male), pubertal (56% male), and post-pubertal (32% male) groups were 10.1±1.3, 12.9±1.4, and 15.9±1.6 years, respectively. For the entire sample, CGM glucose (196±29 mg/dL) and A1c (7.8±0.8%) were highly correlated (r=.71, p<.001). Overall and among youth with A1c ≥7.5% vs. A1c <7.5%, there were no differences in mean glucose, A1c, or % time in various glucose ranges according to pubertal stage (Table).

Conclusions: Pre-pubertal youth appear to have higher mean glucose than reflected by their A1c, particularly for those achieving A1c <7.5%, suggesting greater glycemic excursions in young children. Ideally, A1c should be interpreted in association with CGM data, particularly in young children, in efforts to optimize glycemia.

Disclosure

J. Zhu: None. L. Volkening: None. M. Katz: None. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
Olive Oil Supplementation Reduces Proinflammatory Markers in the Placenta in a GDM Rat Model Induced by Intrauterine Programming
Authors: GOMEZ RIBOT DALMIRO L. , CAPOBIANCO EVANGELINA , LEVIEUX CECILIA P. , FORNES DAIANA , JAWERBAUM ALICIA
Published: June 2018

Gestational diabetes (GDM) is associated with an increased proinflammatory state in the placenta, which affects fetal development and offspring´s health. We have previously found that pregestational mild diabetes in Wistar rats (F0) programs GDM in the adult female offspring (F1). Our aim was to treat this F1 with a diet enriched in olive oil to address the ability of this treatment to prevent both excessive matrix metalloproteinase 2 (MMP2) and connective tissue growth factor (CTGF) levels and reduced PPARgamma levels in the placenta, associated to the proinflammatory state.

Methods: Mild pregestational diabetes was induced by neonatal streptozotocin administration (90mg/kg). Pregestational diabetic female rats and controls (F0) were mated with control males, and their adult female offspring (F1) mated with control males. F1 rats were fed a standard diet or a diet supplemented with 6% olive oil during pregnancy. On day 21 of pregnancy, maternal plasma and the placenta were evaluated.

Results: The olive oil treatment in the F1 pregnancy did not prevent maternal or fetal hyperglycemia in the pregnant offspring of pregestational diabetic rats. Maternal supplementation with olive oil reduced maternal triglyceridemia in GDM rats (21%, p<0.05) compared to GDM rats fed the standard diet. The placenta from GDM rats showed increased MMP2 and CTGF levels compared to controls (26%, p<0.and 37%, p<0.001, respectively), alterations prevented by the maternal treatment with olive oil. PPARgamma levels were reduced in GDM placentas treated and untreated with the olive-oil diet compared to controls (32% and 35% respectively, p<0.05).

Conclusions: Although the maternal diet enriched in olive oil was not able to prevent GDM induction or reduced PARgamma placental levels, it prevented maternal hypertriglyceridemia and exerted anti-inflammatory effects in the placenta from GDM rats, thus likely benefiting the fetal development.

Disclosure

D.L. Gomez Ribot: None. E. Capobianco: None. C.P. Levieux: None. D. Fornes: None. A. Jawerbaum: None.
Regulation and Role of Human Resistin in Diabetes during Pregnancy
Authors: JIANG SHAONING , TEAGUE APRIL M. , TRYGGESTAD JEANIE B. , LYONS TIMOTHY , CHERNAUSEK STEVEN
Published: June 2018

Diabetes during pregnancy affects placental function, which impacts fetal development and the long-term health of offspring. Resistin is a peptide hormone originally discovered in mice as an adipocyte-derived factor that induced insulin resistance. Unlike rodent, human resistin is primarily secreted by monocytes or macrophages. Resistin may act differently in humans, which remains unclear. The present study examined the effects of maternal diabetes on fetal resistin levels and the actions of human resistin in placenta mitochondrial biogenesis pathway. Concentrations of human resistin in cord sera were higher in diabetic pregnancies (67 ng/ml, n=42) compared to healthy controls (50 ng/ml, n=81, P< 0.05), and correlated (r=0.4, P=0.002) with a measure of maternal glycemia (glucose concentration 2 h post challenge). Resistin mRNA was abundant in cord blood mononuclear cells (CBMCs). Secretion of resistin from cultured CBMCs was increased in response to high glucose (25 mM) treatment. Exposing placental trophoblastic cells (BeWo cells) or human placental explant to resistin decreased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as the abundance of mitochondria transcription factor A (TFAM). In human term placentae, the levels of PGC-1α promotor methylation were positively correlated with cord blood resistin concentrations (r= 0.45, p=0.04, n=16).

In summary, we have shown that resistin is increased in the fetal circulation during diabetic pregnancy and that this potentially reflects the response of monocytes/macrophages to hyperglycemia and metabolic stresses associated with diabetic pregnancy. In addition, human resistin has the capacity to decrease mitochondrial biogenesis by affecting the epigenetic regulation of PGC-1α expression. Thus, increased exposure to resistin may contribute to mitochondrial dysfunction and long-term aberrant energy metabolism characteristic of the offspring of diabetic pregnancies.

Disclosure

S. Jiang: None. A.M. Teague: None. J.B. Tryggestad: None. T. Lyons: None. S. Chernausek: Advisory Panel; Self; Novo Nordisk Inc..
Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women with Type 1 Diabetes
Authors: KELLY CLARE B. , YU JEREMY , JENKINS ALICIA , NANKERVIS ALISON J. , HANSSEN KRISTIAN F. , GARG SATISH K. , ASTON CHRISTOPHER E. , LYONS TIMOTHY
Published: June 2018

Preeclampsia (PE) occurs more frequently in pregnant diabetic than nondiabetic women (∼20% vs. ∼5%). Early identification of high risk women is needed. Dyslipidemia is implicated: we previously showed that early in pregnancy, increased cholesterol-rich lipoproteins are associated with subsequent PE in type 1 diabetes (T1D). Haptoglobin (Hp) is a plasma protein that binds free hemoglobin, and has two allelic forms, Hp-1, Hp-2, hence three phenotypes. Among people with diabetes, Hp 2-2 phenotype (present in ≈50%) has been associated with oxidative stress, cardiovascular risk and renal decline.

We investigated whether maternal Hp phenotype is associated with PE in T1D, and/or modulates lipoprotein-related risks for PE. A prospective study of pregnancy included 23 T1DM women (cases) who developed PE, and 24 T1DM (controls) who remained normotensive. All were free of microalbuminuria and hypertension at enrolment. Hp phenotype was determined by ELISA (Savyon Diagnostics Ltd.). Lipid profiles were measured at three study visits (V1-V3), all preceding PE onset: (mean ± SD) 12.4 ± 1.8, 21.7 ± 1.4, and 31.3 ± 1.4 weeks gestation.

Results: Hp phenotype did not differ between women with and without PE, and lipid profiles did not differ by Hp phenotype. In PE cases vs. controls, by univariate analysis, HDL-C was lower at V1 (1.9±0.4 vs. 2.2±0.5 mmol/l (mean ± SD)), while LDL-C was higher at V2 (3.1± 1.0 vs. 2.6± 0.8 mmol/l), as were triacylglycerols (1.6± 0.4 vs. 1.3± 0.4 mmol/l) (p<0.05). In Hp 2-2 women, these associations were stronger: in 2-2 cases (n=11) vs. 2-2 controls (n=9), HDL-C was lower at all visits (V1: p<0.05; V2, V3: p<0.01) and LDL-C was higher at V1 (p<0.01) and V2 (p<0.05). In contrast, in women with one or two Hp-1 alleles, no associations between lipids and PE were observed.

Conclusion: In T1D women, lipoprotein-related risks for PE may be limited to those with Hp 2-2 phenotype. The data provide further evidence of a role for Hp phenotype as a modulator of vascular risk in diabetes.

Disclosure

C.B. Kelly: None. J. Yu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. A.J. Nankervis: None. K.F. Hanssen: None. S.K. Garg: Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Sanofi US. Advisory Panel; Self; Sanofi US. Research Support; Self; MannKind Corporation, Diasome Pharmaceuticals, Inc., Labstyle Innovations, Lexicon Pharmaceuticals, Inc., Medtronic. Advisory Panel; Self; Novo Nordisk A/S. C.E. Aston: None. T. Lyons: None.
Enhanced Recipient Cardiovascular Health Pretransplant Predicts Better Clinical Outcomes following Islet Cell Transplant for Type 1 Diabetes
Authors: DANIELSON KIRSTIE K. , MONSON REBECCA S. , LI YI , RYDZON BRETT
Published: June 2018

Increased cardiovascular disease (CVD) risk is a clinically significant feature of type I diabetes (T1D). Several CVD markers were shown to regress or stabilize after functionally curing T1D via islet cell transplant (ICT), yet the inverse is unknown: does recipients’ CVD health at first ICT predict clinical outcomes following ICT. In 30 patients receiving 1-3 ICTs, CVD markers and basic labs were measured at first ICT (e.g., lipids, blood pressure, blood counts/chemistries, and carotid intima-media thickness [CIMT]), along with clinical outcomes (e.g., C-peptide/insulin from four distinct metabolic tests) measured serially after first ICT (mean [range] 2.1 [0.3-8.7] years). Multivariable regression of repeated measures determined longitudinal associations, adjusting for recipient demographics, BMI, ICT number, and islet equivalents transplanted. Mean (SD) age, T1D duration, and BMI at first ICT were 47.3 (11.5) and 29.4 (12.0) years, and 22.9 (1.9), respectively; 80% female. Lower LDL/HDL pre-ICT predicted greater fasting C-peptide (n=759 observations, p=0.01) and multiple measures of stimulated C-peptide and insulin (n=68-76, all p≤0.04); lower triglycerides pre-ICT (n=811, p=0.003) and systolic blood pressure day of first ICT (n=1142, p=0.007) predicted greater fasting C-peptide. Low (normal) hemoglobin and percent eosinophils the day of first ICT also predicted greater fasting C-peptide (n=1142, all p=0.002) and stimulated C-peptide and insulin (n=73-107, all p≤0.048). Lower recipient CIMT pre-ICT predicted greater acute insulin response post-ICT (n=42, p=0.04). Multiple traditional CVD protective factors, along with lower hemoglobin and eosinophils (both recently shown to be CVD protective factors), at first ICT predicted better outcomes. These results may be clinically significant as improving CVD health pre-ICT (e.g., with diet, exercise, and/or medications) may further support its success.

Disclosure

K.K. Danielson: None. R.S. Monson: None. Y. Li: None. B. Rydzon: None.
Adipose Tissue Health Associates with the Development of Gestational Diabetes Mellitus in Nonobese Women
Authors: TUVDENDORJ DEMIDMAA R. , TUMURBAATAR BATBAYAR , POOLE AARON , THUKUNTLA SHWETHA , KOUTROUVELIS GAYLE O. , ABATE NICOLA
Published: June 2018

Background: Gestational diabetes mellitus (GDM) associates with health complications in both mother and child. Obesity and impaired adipose tissue (AT) health associate with the development of GDM. However, recent studies have shown that impaired AT health may occur in the absence of obesity. In this study we studied if AT health associates with the development of GDM in non-obese women. Method: Pregnant women diagnosed with GDM were studied. Age- and body mass index (BMI)-matched non-GDM women were enrolled as Controls (n=6 per group). Fasting blood and AT samples were obtained before and during cesarian section, respectively. The serum levels of adiponectin were measured using Bioplex assay. The expression of phosphorylated p38 (p-p38) in AT was measured using Western blotting, and the average values of adipocyte sizes were estimated. The differences in variables between the groups were determined using two-tailed unequal variance Student t test; p < 0.was considered as statistically significant.

Results: There were no difference in age (Control vs. GDM: 31±1 vs. 31±2, p = 0.973) and pre-pregnancy BMI (Control vs. GDM: 26±1 vs. 25±1, p = 0.852). In the GDM group, the serum concentration of adiponectin was significantly lower (Control vs. GDM: 16±3 vs. 7±1, p = 0.021); while the AT expression of p-p38 was significantly higher (Control vs. GDM: 0.55±0.14 vs. 1.42±0.23, p = 0.013). The adipocyte size was 11% lower in the GDM group, although the difference did not reach statistical significance (Control vs. GDM: 100±6 vs. 89±5, p = 0.173).

Conclusion: Our data demonstrate that AT health may play a significant role in the development of GDM in non-obese women. Future studies to determine the mechanisms whereby AT health leads to the development GDM in the absence of obesity are warranted.

Disclosure

D.R. Tuvdendorj: None. B. Tumurbaatar: None. A. Poole: None. S. Thukuntla: None. G.O. Koutrouvelis: None. N. Abate: None.
Metformin and Dietary Advice for Pregnant Women Who Are Overweight or Obese to Promote Gestational Restriction of Weight—The GROW Randomized Trial
Authors: DODD JODIE M. , LOUISE JENNIE , DEUSSEN ANDREA R. ,   THE GROW RANDOMIZED TRIAL GROUP
Published: June 2018

Background: Maternal obesity and gestational diabetes are characterised by insulin resistance, hyperglycemia, and low-grade chronic inflammation, contributing to excess availability of nutrients and fetal growth. Metformin is used increasingly in treatment of gestational diabetes.

Aim: To evaluate the effects of prenatal metformin among overweight and obese pregnant women on maternal and infant outcomes.

Methods: We conducted a randomized, placebo controlled trial. Women were recruited from public maternity hospitals in Adelaide, with a singleton, pregnancy between 10+0 and 20+0 weeks, and BMI ≥25.0 kg/m2 at their first prenatal visit. We used a computer randomization service, with stratification for parity, BMI (overweight vs. obese) and center of birth. Women were randomized to either Metformin or Placebo. Women used Metformin tablets (up to 2g daily) or identical appearing placebo. All women received a dietary and lifestyle intervention, consisting of three face-to-face sessions and three telephone calls over their pregnancy. Outcomes included infant birth weight >4kg, gestational weight gain, gestational diabetes and other pregnancy and birth outcomes.

Results: We randomized 524 pregnant women. Baseline characteristics at randomization were comparable. Women who received prenatal metformin in addition to the dietary intervention gained significantly less weight during pregnancy compared with women who received the dietary intervention and placebo (7.7 + 5.9kg vs. 8.9 +5.7kg; mean difference -1.16 (95% CI -2.3 to -0.05; p=0.04). There were no statistically significant differences with regards other clinical outcomes, including diagnosis of gestational diabetes.

Conclusions: The combination of prenatal metformin and a dietary intervention reduced gestational weight gain during pregnancy, but did not impact clinical pregnancy and birth outcomes.

Disclosure

J.M. Dodd: None. J. Louise: None. A.R. Deussen: None.
Associations of a Preconception Biomarker Risk Score with Future Gestational Diabetes
Authors: BADON SYLVIA E. , FERRARA ASSIAMIRA , ZHU YEYI , SRIDHAR SNEHA B. , LEE CATHERINE , EHRLICH SAMANTHA , QUESENBERRY CHARLES , HEDDERSON MONIQUE
Published: June 2018

Individual preconception biomarkers have been associated with future gestational diabetes mellitus (GDM) risk. Creating a biomarker risk score incorporating several biomarkers may enhance identification of women at high risk for GDM before pregnancy. The objective of this study was to develop a preconception biomarker risk score and assess its association with subsequent GDM. We conducted a nested case-control study within a cohort of 4,098 women with serum and questionnaire data collected as part of a health checkup (1984-1996) and a subsequent pregnancy (1984-2009) in northern California. Two controls were matched to each GDM case (N=256 cases) on year and age at serum collection, age at pregnancy, and number of pregnancies between serum collection and index pregnancy. Biomarkers associated with GDM in univariable models were dichotomized into high/low risk using quartiles. A biomarker risk score was created by summing the number of high risk biomarkers that were significantly associated with GDM in a multivariable model. Receiver-operating-characteristic curve analyses were used to assess the incremental predictive value of the biomarker risk score beyond conventional GDM risk factors obtained from medical records (age, race/ethnicity, BMI, family history, previous GDM). Compared to low risk, high risk levels of total adiponectin (<7.2 μg/mL), SHBG (<44.2 nmol/L), and HOMA-IR (>3.9) were each independently associated with 2.03 (95% CI: 1.37, 3.02), 2.78 (95% CI: 1.87, 4.13), and 2.07 (95% CI: 1.40, 3.06) times the odds of GDM and thus included in the biomarker risk score. For each one unit increase in the biomarker risk score, odds of GDM were 2.04 times greater (95% CI: 1.62, 2.56). The biomarker risk score had relative incremental predictive value beyond conventional GDM risk factors (AUC= 0.73 vs. 0.67, P<0.0001). Our results suggest the biomarker risk score has potential clinical utility in preconception risk assessment for GDM beyond conventional clinical risk factors.

Disclosure

S.E. Badon: None. A. Ferrara: None. Y. Zhu: None. S.B. Sridhar: None. C. Lee: None. S. Ehrlich: None. C. Quesenberry: None. M. Hedderson: None.
Gestational Diabetes Mellitus (GDM) Predicts Future Risk of Serious Liver Disease
Authors: RETNAKARAN RAVI , LUO JIN , SHAH BAIJU R.
Published: June 2018

Like type 2 diabetes (T2DM), GDM has recently been associated with enhanced hepatic fat deposition. We thus hypothesized that GDM may predict future lifetime risk of serious liver disease, such as cirrhosis, liver failure and transplantation. Using population-based administrative databases, we identified all women in Ontario, Canada, with a live-birth pregnancy between April 1994 and March 2002 (n=698,078). The women were stratified into those who had GDM (n=17,932) and those who did not (n=680,146), and followed for median 17.1 years for the development of serious liver disease (defined by hospitalization for cirrhosis, liver failure or transplantation). Compared to their peers, women with GDM had an elevated risk of this outcome (HR=1.40, 95% CI 1.01-1.94). Since GDM also predicts future risk of T2DM, the women were further stratified based on incident T2DM in the years after delivery (Figure). Women with GDM who developed T2DM (n=8,567) had an elevated risk of serious liver disease (adjusted HR=1.56, 95% CI 1.02-2.39), as did those who did not have GDM but developed T2DM (n=44,148) (adjusted HR=2.48, 95% CI 2.10-2.93). However, there was no increased risk in women with GDM who did not develop T2DM (n=9,365) (adjusted HR=1.15, 95% CI 0.69-1.91). Thus, despite being a diagnosis of young women of childbearing age, GDM predicts future risk of serious liver disease, the development of which may be dependent upon progression to T2DM.

Disclosure

R. Retnakaran: Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Sanofi, Eli Lilly and Company. J. Luo: None. B.R. Shah: None.
Implementation of an Electronic Screening Tool to Detect Early GDM Uncovers Deficiencies
Authors: RODEL RACHEL , REEVES SHANE A. , BARBOUR LINDA A.
Published: June 2018

Intro: Given little consensus on screening/diagnosis for early GDM despite rapidly evolving expert opinion, providers are legitimately confused about who, how and when to screen. In 2017, the ADA modified their risk-based screening guidelines which were adopted by ACOG but implementation of these guidelines is largely unstudied. We compared rates of documented risk assessment before and after ACOG expanded screening criteria to determine rates of early testing and evaluate if an electronic screening form could increase documentation.

Methods: This QI study assessed provider screening practices before and after implementation of a new screening tool. Our academic center includes midwives, residents and OB/MFM faculty. In Oct 2017, in-person education and email surveys informed providers of a new electronic screening tool to promote GDM risk assessment. We reviewed initial visits at <20 weeks gestation. We examined rates of documentation, screening, risk factors and tests ordered.

Results: A random number sequence was used to identify 50 qualifying subjects by coding Nov 2016 and 2017 for a total of 100 patients. Prior to the screening tool 15/50 (30%) had documented risk assessment and 2/3 of these had testing ordered compared to 17/50 (34%) after the screening tool in which 1/2 were tested. A 1 hour, 50g test was ordered in 80% (2016) and in 88% (2017) and an A1c was ordered for the remaining. Of the 100 patients reviewed, 29 would have qualified for early testing based on race, ethnicity and BMI alone, but only 12 were tested.

Discussion: Unexpectedly, we found that early DM/GDM risk assessment is inadequately documented at our academic center and providing an electronic screening tool did little to increase documentation or adherence. Low rates of testing (<50% of high risk patients) are consistent with other data and suggest current strategies may be ineffective. Determining whether this reflects ambiguity over expert consensus or merely provider time constraints warrant active investigation.

Disclosure

R. Rodel: None. S.A. Reeves: None. L.A. Barbour: None.
Breastfeeding at Night Is Rarely Followed by Hypoglycemia in Puerperal Women with Type 1 Diabetes Using Carbohydrate Counting and Modern Insulin Treatment
Authors: RINGHOLM LENE , ROSKJÆR ANN B. , ENGBERG SUSANNE , ANDERSEN HENRIK U. , HOMMEL EVA , SECHER ANNA L. , DAMM PETER , MATHIESEN ELISABETH R.
Published: June 2018

Aim: Hypoglycemia in association with breastfeeding is a feared condition in women with type 1 diabetes. Thus, routine carbohydrate intake at each night-time breastfeeding is often recommended despite lack of evidence. We evaluated glucose levels during breastfeeding with focus on whether night-time breastfeeding induced hypoglycemia in women with type 1 diabetes.

Methods: Prospective study of 25 consecutive breastfeeding women (mean age 30.8 (SD ±5.9) years, 64% nulliparous, singleton pregnancy) with type 1 diabetes for 18.8 (±10.5) years. All were experienced in carbohydrate counting with 44% on insulin pump and 56% on multiple daily injections. At 33 (±7.2) and 66 (±14.2) days postpartum blinded continuous glucose monitoring (CGM) was applied for six days and the women recorded breastfeedings and carbohydrate intake.

Results: At both CGM periods mean glucose levels were similar at night (11 pm to 7 am) (8.3 (±1.7) and 8.7 (±2.5) mmol/l, p=0.56) and over 24 hours (8.4 (±1.5) and 8.7 (±2.1) mmol/l, p=0.56). The percentage of time <4.0 mmol/l was similar at night (median 5.8% (range 0-20.8) and 3.1% (0-36.1), p=0.24) and over 24 hours (5.0% (0-19.8) and 3.9% (0-22.8), p=0.75). At 33 days postpartum maternal weight was close to the pre-pregnancy weight (79.1 (±15.0) vs. 75.6 (±14.2) kg, p=0.50) while insulin dose was 18% lower than before pregnancy (p=0.04). A total of 340 night-time breastfeedings were recorded with 2 (0-4) breastfeedings per night. Carbohydrate was ingested at 42 (12%) of the breastfeedings. CGM <4.0 mmol/l within three hours after night-time breastfeeding occurred after 5% of breastfeedings.

Conclusion: Despite almost 300 night-time breastfeedings without carbohydrate intake, hypoglycemia within 3 hours after breastfeeding was rare. The recommendation of routine carbohydrate intake at night-time breastfeeding in women with type 1 diabetes on modern insulin treatment who count carbohydrate may be obsolete.

Disclosure

L. Ringholm: None. A.B. Roskjær: None. S. Engberg: None. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Advisory Panel; Self; AstraZeneca. E. Hommel: None. A.L. Secher: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. E.R. Mathiesen: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S, Novo Nordisk Foundation, Novo Nordisk A/S.
Labor Induction and Cesarean Delivery Risk in Women with Gestational Diabetes Mellitus
Authors: HAMEL MAUREEN S. , KOLE MARTHA B. , ROUSE DWIGHT , WERNER ERIKA
Published: June 2018

Objective: Previous studies suggest that labor induction is associated with an increased risk of cesarean delivery (CD), but more modern studies question this finding. In particular, it is uncertain how induction affects CD risk among women with gestational diabetes mellitus (GDM), who are often induced. Therefore, we sought to assess the risk of CD among women with GDM who presented for induction compared to those who presented in spontaneous labor.

Methods: Secondary analysis of a prospective cohort study of singleton pregnancies complicated by GDM. Women planning an elective or repeat cesarean were excluded. All women were delivered at a single institution. The primary outcome for this analysis was mode of delivery (CD vs. vaginal delivery). Women who presented for an induction were compared to those who presented in spontaneous labor (including rupture of membranes at 34 weeks or greater). Covariates, including gestational age at delivery were investigated as confounders and adjusted for if the p<0.05. The study had 80% power to detect an 18% decrease in the absolute rate of vaginal deliveries in the induction group compared to the spontaneous labor group with an alpha of 0.05.

Results: Of the 222 women meeting study inclusion criteria, 80 (36%) presented in spontaneous labor and 142 (64%) underwent labor induction. The overall CD rate was 21.6% (n=48). When comparing labor induction to spontaneous labor to, there was no significant difference in the CD rate (21.8% vs. 21.3% p=0.41). Women who were induced compared to those who labored spontaneously differed only with regard to BMI at delivery (p=0.04), and hypertension (p<0.01). Even after adjusting for these covariates, the risk of CD did not differ between groups (aOR 1.01 95% CI 0.51, 2.02). Moreover, the risk remained non-signification even when gestational age was included in the model.

Conclusion: Induction of labor among women with GDM is not associated with an increased risk of CD and should not be avoided in an attempt to minimize CD risk.

Disclosure

M.S. Hamel: None. M.B. Kole: None. D. Rouse: None. E. Werner: None.
Sex Hormone–Binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes—A Longitudinal Pregnancy Cohort Study and a Meta-analysis
Authors: LI MENGYING , RAWAL SHRISTI , HINKLE STEFANIE , LIU SIMIN , TEKOLA-AYELE FASIL , ZHANG CUILIN
Published: June 2018

Background: Sex hormone-binding globulin (SHBG) has been implicated in glucose metabolism and the development of type 2 diabetes. However, its role in glucose metabolism during pregnancy is unclear.

Objectives: This study investigated the prospective associations of SHBG with cardiometabolic biomarkers during pregnancy and gestational diabetes (GDM) risk.

Methods: We conducted a nested case-control study of 107 GDM cases and 214 matched controls without GDM in the NICHD Fetal Growth Studies-Singleton Cohort. GDM was ascertained by medical record review. Blood samples were drawn at 10-14, 15-26, 23-31 and 33-39 gestational weeks (GW). Prospective associations of SHBG with cardiometabolic biomarkers were estimated using Spearman’s correlation coefficient adjusting for potential confounders. Difference in SHBG levels between GDM and non-GDM women was estimated in the present study cohort and a meta-analysis of existing prospective evidence. Odds ratios (OR) for GDM by SHBG quartiles were estimated using conditional logistic regression.

Results: SHBG at GW 10-14 was significantly and inversely related to fasting glucose, fasting insulin, insulin resistance and HbA1c levels, and positively related to high-density lipoprotein and cholesterol levels at GW 15-26. Cases had lower SHBG levels compared to controls at GW 10-14 (mean ± SD: 204.0 ± 97.6 vs. 220.9 ± 102.5 nmol/L) and 15-26 (305.6 ± 124.3 vs. 322.7 ± 105.1 nmol/L), yet the differences were not significant. Meta-analysis of 11 prospective studies, including ours, estimated SHBG levels to be 0.50 SD (95% CI: 0.36-0.65) lower among women with than without GDM.

Conclusions: Higher SHBG levels in early pregnancy was associated with a favorable glucose metabolic profile among pregnant women. Synthesis of prospective studies supports an inverse association between SHBG levels and GDM risk.

Disclosure

M. Li: None. S. Rawal: None. S. Hinkle: None. S. Liu: None. F. Tekola-Ayele: None. C. Zhang: None.
Is Screening for Early Gestational Diabetes Mellitus Associated with a Better Prognosis? An Observational Study Including 8,713 Women
Authors: COSSON EMMANUEL , BANON DORIAN SANDRE , GARY FRANÇOISE , PHARISIEN ISABELLE , PORTAL JEAN-JACQUES , VALENSI PAUL , CARBILLON LIONEL
Published: June 2018

In addition to screening for gestational diabetes mellitus (GDM) after 24 gestational weeks (GW), the IADPSG proposed to screen in early pregnancy and to refer women with early GDM (eGDM) for immediate care. The usefulness of this strategy is still unknown. We included women with a singleton pregnancy, without personal history of diabetes or bariatric surgery, who delivered in our hospital between 2012 and 2016. We compared the incidence of preeclampsia or large for gestational age infant or shoulder dystocia in women with an early screening before 22 WG -leading to care for eGDM (FPG) 92-125 mg/dL) or diabetes in pregnancy (DIP: FPG≥126 mg/dL) if present- (screened group) or without (unscreened group). Compared with women in the unscreened group (n=4634, 53.3%), those in the screened group (n=4079) had different ethnicities (p<0.0001) and more risk factors for GDM: overweight (48.6 vs. 45.7, p<0.01), family history of diabetes (27.8 vs. 25.0%, p<0.01), personal history of GDM (6.4 vs. 4.3%, p<0.01) and macrosomic infant (3.6 vs. 2.7%, p<0.05). Early screening increased from year 2012 to 2016 (p<0.0001). In the early screened group, the prevalence of GDM and DIP was 22.8% (including 10.3% of eGDM) and 0.9%, respectively. In the unscreened group, the prevalence of GDM was 17.2% and DIP 1.2%. The rate of insulin therapy was 8.6% in the screened group and 5.6% in the unscreened group (p<0.001). The rate of the composite criterion was similar in the screened and unscreened groups (12.5 vs. 11.8%, p=0.3534), also when we only considered women with risk factors for GDM (14.0 vs. 14.9%, p=0.3137). The incidence of other outcomes was similar in both groups. To conclude, a strategy including early FPG measurement during pregnancy may not improve pregnancy prognosis but we still need to adjust the results for confounding factors (ongoing) because the women in the early-screened group had a similar prognosis as those only screened after 22 GW despite a higher risk of complications.

Disclosure

E. Cosson: Consultant; Self; Lilly France. Board Member; Self; Novartis France. Consultant; Self; Roche Diagnostics France. Board Member; Self; Ascensia Diabetes Care. Consultant; Self; Bezins France. Board Member; Self; MSD France. D. Sandre Banon: None. F. Gary: None. I. Pharisien: None. J. Portal: None. P. Valensi: None. L. Carbillon: None.
iPRO—Effects of Increased Dietary Protein with GDMA1
Authors: TROUT KIMBERLY K.
Published: June 2018

Purpose/Aim: Primary aim of this study was to evaluate outcomes of glucose and insulin responses to meals and snacks using a randomized crossover design of isocaloric diets comparing increased protein (30% protein, 35% carbohydrate, 35% fat) with a decreased protein (15% protein, 50% carbohydrate, 35% fat) diet.

Methods: Women diagnosed with GDMA1 between 28-35 weeks gestation were randomly allocated to receive one of 2 initial dietary treatments for an overnight admission to inpatient research unit where all meals and snacks were provided. After a 3-7 day washout period, participants were readmitted and received the opposite treatment. A continuous glucose monitoring system (CGMS) was inserted on admission and correlated with blood glucose/hormonal data.

Results: Preliminary results (n=6) with mixed model analysis revealed that the p-value for total glucose AUC shows no statistically significant difference between the two treatments (Table 1). However, at 60” after breakfast on day 2, mean BG was 136 mg/dl on lower protein diet (Tx B) and 117 mg/dl on higher protein diet (TxA, p<0.05).

Discussion: These preliminary results suggest that overall carbohydrate restrictions may be relaxed, as total glucose AUC was not significantly different between the 2 treatment groups. However, further analysis may reveal that increased protein and decreased carbohydrate at specific meals (e.g., breakfast) may prove beneficial in meeting blood glucose targets.Table 1TxVariableNMeanStd DevMedianMinMaxATotal Glu AUC63062.98418.623023.812562.043647.79BTotal Gl;u AUC62824.39579.312659.942319.713830.79

Disclosure

K.K. Trout: None.
Impact of Maternal Metabolic Parameters on Birth Weight and Cord Blood Insulin Concentration—Findings from the Born in Guangzhou Study
Authors: WANG JINGYA , KUANG YASHU , PRICE MALCOLM J. , LU JINHUA , HE JIANRONG , XIA HUIMIN , QIU XIU , CHENG KAR KEUNG , NIRANTHARAKUMAR KRISHNARAJAH
Published: June 2018

Objective: To investigate the relationship between maternal metabolic parameters with birth weight (BW) and cord blood insulin level(CBI).

Research Design and Methods: Participants were mother-baby pairs (n=1,522) from the Born in Guangzhou Cohort Study (delivered during January 2015 to June 2016). Data on maternal pre-pregnancy BMI, Gestational Weight Gain (GWG), mid-pregnancy fasting glucose and lipid levels were collected; and associations with new-born BW and CBI (z-score) were assessed using multivariable linear regression model, controlling for maternal age, ethnic group, parity and early pregnancy cigarettes exposure. The effect estimates (Regression Co-Efficient: RCE) were standardised to compare the strength of associations of the exposures on BW and CBI z-score.

Results: Z-scores for pre-pregnancy BMI (RCE: 0.20[95% CI: 0.15, 0.24]), early GWG (RCE: 0.18[95% CI: 0.13, 0.23]), glucose (RCE: 0.08[95% CI: 0.04, 0.12]) and triglycerides (RCE: 0.12[95% CI: 0.08, 0.16])) were positively associated with BW z-score. Similar associations were observed with CBI z-score (pre-pregnancy BMI (RCE: 0.11[95% CI: 0.06, 0.16]), early GWG (RCE: 0.07[95% CI: 0.00, 0.13]), glucose (RCE: 0.14[95% CI: 0.09, 0.19]) and triglycerides (RCE: 0.07[95% CI: 0.02, 0.12]). Maternal fasting high-density lipoprotein was negatively associated with BW z-score (RCE:-0.04[95% CI:-0.09, -0.00]) and CBI z-score (RCE: -0.04[95% CI:-0.09, 0.01]) but the 95% CI for the latter included the null.

Conclusions: Maternal pre-pregnancy BMI had the strongest association with BW and CBI, emphasising the importance of optimising preconception BMI. Our results also suggest potential under-recognised adverse effects of intrauterine exposure to gestational dyslipidaemia and that this may warrant clinical attention.

Disclosure

J. Wang: None. Y. Kuang: None. M.J. Price: None. J. Lu: None. J. He: None. H. Xia: None. X. Qiu: None. K. Cheng: None. K. Nirantharakumar: None.
Fatty Liver Disease among Adolescent Offspring Born to Women with Pregestational Type 1 Diabetes (The EPICOM Study)
Authors: KNORR SINE , BYTOFT BIRGITTE , LOHSE ZUZANA , CLAUSEN TINE D. , JENSEN RIKKE B. , DAMM PETER , BECK-NIELSEN HENNING , GRAVHOLT CLAUS H. , JENSEN DORTE M.
Published: June 2018

Intrauterine exposure to maternal type 1 diabetes (T1DM) is associated with a less favourable metabolic profile later in life. Fatty liver disease can be considered as the hepatic manifestation of the cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational T1DM on the offspring’s risk of fatty liver disease and any association between maternal glycemic control during pregnancy and later risk of fatty liver disease in the offspring.

The study is a prospective nationwide follow-up study including offspring (n=277) born to mothers with pregestational T1DM between 1993-1999 and matched un-exposed controls (n=303). Age at the time of follow-up was 16.7 years (range 13.0-20.4 years). We used the Fatty Liver Index (FLI) and Waist-to-Height ratio (WHtR) to evaluate risk of fatty liver disease among the offspring. A FLI>60 or a WHtR>0.469 were used as indicators of fatty liver disease. Results are displayed in Table 1. More diabetes exposed offspring had high FLI and WHtR indices compared to un-exposed controls. Adjustment for maternal prepregnancy BMI, gender, age, and pubertal stage did not change overall results. No association between maternal glycemic control during pregnancy and risk of fatty liver disease was found.Table 1: Comparison of indicators of fatty liver disease among offspring born to mothers with T1DM.nExposedControlsp-value(n=277)(n=303)FLI < 30495229 (46)266 (54)FLI>30 < 602518 (72)7 (28)FLI>60149 (64)5 (36)0.02*WHtR <0.469489213 (44)276 (56)WHtR >0.4699164 (70)27 (30)<0.001*Data are displayed as numbers and percent.* Pearsons chi-squared test. FLI<30 rules out and FLI>60 as well as well as a WHtR>0.469 rules in fatty liver disease.

Conclusion: Intrauterine exposure to maternal T1DM may predispose to fatty liver disease.

Disclosure

S. Knorr: None. B. Bytoft: None. Z. Lohse: None. T.D. Clausen: None. R.B. Jensen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. H. Beck-Nielsen: None. C.H. Gravholt: None. D.M. Jensen: None.
Software Price Modeling of Ertugliflozin
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 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 of 100. Total retail cost of care averaged $475 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 ertugliflozin. 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 manufacturer maximizes their gross revenue for the agent in the population.

Price optimization for ertugliflozin showed a MP of approximately $300 (retail price: $270). At its MP, ertugliflozin would be prescribed to approximately 10% of the population with mean composite score of 76.8 and mean HbA1c 6.9. At ertugliflozin’s MR of approximately $175 per month, it would be prescribed to approximately 39% of the population and generate a mean composite score of 77.6 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.
Risk Factors for Pregnancy Hypertensive Disorders in a Cohort of Women with Pregestational Diabetes
Authors: OPPERMANN MARIA LUCIA R. , ALESSI JANINE , HIRAKATA VÂNIA N. , WIEGAND DANIELA , REICHELT ANGELA J.
Published: June 2018

Background: Pregestational diabetes (PGD) is associated with increased incidence of pregnancy hypertensive disorders (PHD).

Aim: to describe incidence and risk factors for PHD in a retrospective cohort of PGD women.

Methods: Women were evaluated at a specialized prenatal care facility. PHD comprised preeclampsia and gestational hypertension. Gestational weight gain (GWG) was categorized as excessive/non-excessive (2009 IOM); A1C test was measured before the 28th gestational week; most women did not receive prepregnancy counseling.

Results: Of 220 women, 85 were type 1 and 135, type 2 diabetes. Main characteristics (type 1 x type 2) were: age 27.3 (5.7) x 33.5 (5.5) years, p<0.001; self-declared white skin: 88.2% x 76.3%, p=0.044; primigravid: 48.2% x 15.6%, p<0.001; previous PHD: 8.2% x 20.7%, p=0.023; CH: 14.1% x 29.6%, p=0.013; initial A1c test ≥7.0%: 84.3% x 64.3%, p=0.002; excessive GWG: 27.0% x 35.9%, p=0.264. PHD was diagnosed in 64 of 213 women (30%; 95% CI: 24.2-36.5%) and 52 (23.6%; 95% CI 18.4-29.7%) had CH. The Table lists adjusted RR for risk factors.

Conclusion: This PGD cohort showed an increased incidence of PHD, which supports early pregnancy preventive measures, as aspirin. Excessive GWG, a modifiable risk factor, may be prevented through focused prepregnancy and antenatal surveillance.

Table. Risk Factors for Pregnancy Hypertensive Disorders in 213 Women with Pregestational Diabetes.

Risk factorRelative risk95% CI pType 1 diabetes1.771.11-2.800.015Self-declared white skin3.711.18-11.680.025Primigravid1.230.79-1.920.365Chronic hypertension2.101.38-3.17< 0.001Initial A1c test ≥7.0%0.700.46-1.070.102Excessive GWG1.821.26-2.620.001

Disclosure

M.R. Oppermann: None. J. Alessi: None. V.N. Hirakata: None. D. Wiegand: None. A.J. Reichelt: None.
Progression of Coronary Artery Calcification Is Associated with Clinically Relevant Cognitive Impairment in Type 1 Diabetes
Authors: GUO JINGCHUAN , NUNLEY KAREN , ROSANO CATERINA , ORCHARD TREVOR J.
Published: June 2018

An increased risk of cognitive dysfunction has been identified in type 1 diabetes (T1D). The association between cardiovascular disease and dementia has been examined in the general population, but the relationship is not known in T1D. The study assessed the role of coronary artery calcification (CAC) on cognitive impairment in 148 mid-aged T1D patients from the Pittsburgh Epidemiology of Diabetes Complications Study cohort of childhood-onset T1D. Baseline CAC was measured in 1996-98 and repeated 4-8 years later (2000-06). Per extensive neuropsychological testing in 2010-13, 28% (41/148) of participants met the study definition of clinically relevant cognitive impairment (two or more of 7 select test scores ≥1.5SD worse than demographically appropriate published norms). Mean age and T1D duration at first CAC measure were 37 and 29 years, respectively. In logistic regression models with backward selection, allowing for previously established risk factors for cognitive impairment in this T1D cohort (sex, T1D duration, BMI, HbA1c, ApoE4 status, ankle-brachial index, statin use, proliferative retinopathy, distal symmetric polyneuropathy, and CAD), initial CAC volume was associated with cognitive impairment (OR: 1.08, 95% CI: 1.02-1.15). In those with an initial CAC>0 (n=68), including both CAC volume and density scores in the model along with other risk factors, both CAC volume (positively OR: 1.21 (1.07-1.37)) and CAC density (inversely OR: 0.41 (0.18-0.93)) were associated with cognitive impairment. In those with repeated CAC measures (n=116), the annual progression of CAC volume (determined by Hokanson method) doubled the odds of having cognitive impairment (OR: 1.96 (1.18-3.28)).

Progression of CAC volume was independently associated with clinically relevant cognitive impairment in mid-age adults with long lasting T1D. In those with prevalent CAC, CAC density appears to protect against cognitive impairment when controlling for CAC volume.

Disclosure

J. Guo: None. K. Nunley: None. C. Rosano: None. T.J. Orchard: None.
Life-Course Glucose Trajectory and Cognitive Function in Middle Age—Evidence from the Bogalusa Heart Study
Authors: STUCHLIK PATRICK , CARMICHAEL OWEN , HARVILLE EMILY , HE HUA , ROMERO MARYELLEN , GUSTAT JEANETTE , FONSECA VIVIAN , BAZZANO LYDIA A.
Published: June 2018

Although the adverse effects of elevated glucose on cognitive function have been well-documented, most cognitive evidence comes from older adults. In this study, we make use of repeated measurements across five decades of the Bogalusa Heart Study and latent class methodology to examine the association of glucose from childhood through early adulthood on cognitive function in middle age. From our cohort of n=1,298 adults, after adjustment for age, sex, race, BMI, diabetic status, smoking, physical activity, and depressive symptoms, we identified four trajectory classes of glucose over the life course: (1) “healthy and stable;” (2) “healthy but slightly increasing;” (3) “decreasing;” and (4) “sharply increasing” (Figure). The distributions of trajectory class membership were modeled with a relative cognitive z-score, computed from a battery of tests covering major neuropsychological domains. Mean z-scores, where higher indicates better relative cognitive function, for classes 1-4 were 1.04, 0.85, 0.19, and -6.69, respectively. Parameter estimates were positive for classes 1-3, and negative for class 4 (p<0.05). The “sharply increasing” class was inversely associated with each individual cognitive test except Logical Memory II-Recognition. Our findings suggest increasing glucose trajectories may adversely affect cognition earlier in adulthood than previously thought.

Disclosure

P. Stuchlik: None. O. Carmichael: None. E. Harville: None. H. He: None. M. Romero: None. J. Gustat: None. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. L.A. Bazzano: None.