bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivational Stage at CGM Initiation Is Less Important than Timing of CGM Initiation in Predicting CGM Adherence
Authors: VERBEETEN KATE , CHAN JASON , SOURIAL NADIA , LAWSON MARGARET L. ,   CGM TIME TRIAL STUDY GROUP,   JDRF CANADIAN CLINICAL TRIALS NETWORK
Published: June 2018

Background: Readiness for making behavioral changes is a key factor determining success in the adoption of technologies like CGM in type 1 diabetes (T1D). SOCRATES (Stages of Change Readiness and Treatment Eagerness Scale-Diabetes Version) can classify individuals into 1 of 5 motivational stages: Precontemplation, Contemplation, Determination, Action and Maintenance. It was used in the CGM TIME Trial, a multicenter pediatric RCT comparing simultaneous pump and CGM (“SIM” group) to initiation of CGM 6 months later (“DEL” group) (MiniMed Veo™ System).

Aim: To examine the association of SOCRATES scores with 1) A1C at trial entry and 2) CGM adherence and change in A1C 6 months after CGM initiation.

Methods: 97/99 eligible children aged 10-18 years and 136/141 eligible parents completed SOCRATES at trial entry and 6 months. Multivariable linear regression tested the association between motivational stage and 1) child’s A1C at trial entry, and 2) change in A1C and CGM adherence 6 months after CGM initiation, adjusted for randomization group, gender, age, and diabetes duration.

Results: At trial entry, mean adjusted A1C was 1.02% lower for children in Precontemplation than those in Action (p<0.0001). The A1C of children whose parents were in Precontemplation was 0.83% lower than those in Maintenance (p=0.02) and 0.35% lower than those in Action (p=0.048). Motivational stage of children and parents at CGM initiation was not associated with CGM adherence or change in A1C 6 months later whereas there was an intervention effect with the SIM group using CGM an additional 3.4 hours per day (p=0.03) compared to the DEL group.

Conclusions: SOCRATES scores were associated with A1C at trial entry, but did not predict future CGM adherence or change in A1C. SOCRATES was a poor measure of readiness for change in children with T1D and their parents who were participating in a clinical trial. CGM adherence was related more to timing of CGM initiation than motivational stage.

Disclosure

K. Verbeeten: None. J. Chan: None. N. Sourial: None. M.L. Lawson: None.
Early and Later C-Peptide Responses during Oral Glucose Tolerance Testing (OGTT) Are Independently and Oppositely Predictive of Type 1 Diabetes (T1D) in Autoantibody-Positive (Ab+) Individuals
Authors: ISMAIL HEBA M. , BECKER DOROTHY J. , GEYER SUSAN , XU PING , LIBMAN INGRID , HEROLD KEVAN C. , ATKINSON MARK A. , REDONDO MARIA J. , PALMER JERRY P. , SOSENKO JAY
Published: June 2018

A longitudinal study showed that early C-peptide (C-P) responsiveness during OGTTs declined during progression to T1D, whereas later C-P responsiveness increased until the diagnosis was imminent. Here we exmaine: 1) whether the baseline C-P response pattern predicts T1D as suggested by the findings from that longitudinal study, and 2) the basis for the higher later C-peptide response during progression. Baseline 2-hour OGTTs from 670 Diabetes Prevention Trial-type 1 participants (age: 13.8±9.6 years; BMI-z: 0.3±1.1; 56% male) were analyzed. In univariate regression models, the early C-P response (30-0 min) was inversely predictive of T1D (X2=28.8, p<0.001), whereas the later C-P response (120-60 min) was positively predictive (X2= 23.3, p<0.001). Each was at least as predictive as the AUC C-peptide (inverse association; X2 = 20.4; p<0.001), a standard prediction measure. In a model including both early and late C-P responses, both remained oppositely predictive of T1D with a stronger overall association (X2=41.1; p<0.001 for both). To explain the positive association of greater T1D risk with a high later C-P, we examined the association between the sum of glucose levels from 60 to 120 min and the 120-60 min C-P; there was a strong positive association (r=0.44, p<0.001). All associations persisted after age and BMI-z adjustments.

In conclusion, the findings show that lower early and higher later C-P responses are both indicators of risk for progression to T1D. Moreover, the findings suggest that the increasing later C-P response reflects an attempt by the β-cell to compensate for higher glucose levels due to a deficient early C-P response. These findings are similar to the evolution of C-P responses during type 2 diabetes development. Partitioning C-peptide into early and later responses appears beneficial for T1D prediction and for studying β-cell deterioration during progression.

Disclosure

H.M. Ismail: None. D.J. Becker: None. S. Geyer: None. P. Xu: None. I. Libman: Consultant; Self; Novo Nordisk A/S. K.C. Herold: None. M.A. Atkinson: Other Relationship; Self; Patent Issued. M.J. Redondo: None. J.P. Palmer: None. J. Sosenko: None.
Nasal Glucagon Budget-Impact Model Shows Reduced Health Care Payer Costs for Severe Hypoglycemia Due to Emergency Services Costs Savings
Authors: MITCHELL BETH , POEHLMANN JOHANNES , OSUMILI BEATRICE , BAJPAI SANJAY K. , VALENTINE WILLIAM J.
Published: June 2018

Background: Nasal glucagon [NG] is a compact, portable, ready-to-use nasal spray for the treatment of severe hypoglycemic events [SHE] via intranasal absorption. Current treatment with intramuscular glucagon [IMG] requires multiple steps to administer, including reconstitution, and is difficult to administer for caregivers or passersby. Due to its mode of administration, NG has been demonstrated to result more often in successful (full-dose) administration of glucagon than IMG. The advantage of NG is expected to reduce payer costs due to less use of emergency services, including more treat and release, fewer ambulance trips and fewer emergency department visits.

Objective: Model 2-year budget impact of different scenarios of current (IMG, no kit) vs. future intervention mix (NG, IMG, no kit).

Methods: Populations defined by diabetes type, age and treatment were assessed using population-specific SHE incidence and mortality data. Budget impact was calculated from the U.S. Medicare perspective, with cost data sourced from literature and fee schedules. For adults with type 1 diabetes, an incidence of 366 SHEs per 1,000 person-years and a kit ownership proportion of 60% were assumed. Of patients with kits, 20% and 30% were assumed to own NG kits in the first and second year, respectively. Both NG and IMG kits were modeled using current glucagon list price. All model inputs were varied in sensitivity analyses.

Results: Reduced spending on SHE with the new mix was observed in all modeled populations with higher cost-savings in populations at higher risk of SHE. For 10,000 adults with type 1 diabetes, Medicare pays USD 11.7 million with the current mix and would pay USD 10.6 million for the new mix over 2 years. Savings with NG resulted from reductions in emergency services due to a higher probability of successful SHE treatment by caregivers or passersby.

Conclusions: NG as a treatment option for SHE is associated with substantial cost savings for U.S. payers.

Disclosure

B. Mitchell: Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. J. Poehlmann: Consultant; Self; Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Pharma, UCB, Inc. B. Osumili: Employee; Self; Eli Lilly and Company. S.K. Bajpai: Employee; Self; Eli Lilly and Company. W.J. Valentine: Consultant; Self; Air Liquide, Astellas Pharma US, Inc., Edwards Lifesciences, Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Pharma, UCB, Inc..
Association of Age, Sex, and Weight with Moderate-to-Vigorous Physical Activity in a Pediatric Type 1 Diabetes Population
Authors: THOMPSON NELS E. , WATSON DAVID A. , BARNES TIMOTHY L. , GANDRUD LAURA M.
Published: June 2018

Current guidelines from the ADA recommend that children and adolescents with T1D engage in at least 60 minutes of moderate-to-vigorous physical activity (MVPA) every day. However, subjectivity of MVPA reporting methods and short study durations compromise the applicability of existing data; there is not a clear picture of MVPA in this population. Therefore, objective measures of MVPA in children and adolescents with T1D are necessary to better understand the importance of other factors related to MVPA like sex, age, and weight.

In a prospective cohort of 1children and adolescents with T1D, physical activity was objectively monitored for 6 months using commercially available activity monitors. Weekly MVPA was summarized as the average number of hours of MVPA for weeks with valid activity monitor use. Regular weekly MVPA in children and adolescents was described by age, sex, and weight. The Mann-Whitney U test was used to assess associations.

In the study population, we observed an average (SD) weekly MVPA of 2.4 (1.7) hours and median (Q1, Q3) weekly MVPA of 1.9 (0.9, 3.0) hours. Sex was significantly associated with MVPA (p<0.0001) with average (SD) weekly MVPA of 3.5 (2.4) hours for males and 1.4 (1.0) hours for females. There was no significant difference in weekly MVPA between children (8-12 years) and adolescents (13-17 years). Interestingly, overweight children (BMI z-score above 85th percentile) were more active than non-overweight children (average weekly MVPA of 3.0 and 2.1 hours respectively), however this difference was not statistically significant.

This study presents data on MVPA in children and adolescents with T1D over a long duration using objectively measured physical activity. Our results suggest that sex is an important factor associated with MVPA and that over 75% of children in this population do not regularly meet the ADA MVPA recommendations.

Disclosure

N.E. Thompson: None. D.A. Watson: None. T.L. Barnes: None. L.M. Gandrud: Consultant; Self; UnitedHealth Group.
Racial Disparities in Cost of Diabetes for U.S. Medicare Beneficiaries
Authors: GLANTZ NAMINO M. , DUNCAN IAN , AHMED TAMIM , FAN LUDI , REED BEVERLY , KALIRAI SAMANEH , KERR DAVID
Published: June 2018

Diabetes disproportionately impacts U.S. minority populations, with Hispanics almost twice as likely as non-Hispanic whites (nHW) to be diagnosed. We analyzed data from the Medicare 5% sample file by race/ethnicity for both type 1 (T1D) and type 2 diabetes (T2D). We identified 1,397,933 enrollees in fee-for-service without Medicare Advantage coverage during 2012-13.

Although nHW accounted for the majority of this population (81.3%), the prevalence of T1D and T2D was higher for Hispanics than nHW (3.4% vs. 1.8%, p=.0006 for T1D and 33.4% vs. 21.9%, p<.0001 for T2D). Hispanics also had more acute hospital admissions (p=.0235 for T1D and p=.0009 for T2D) and longer length of stay (7.5 vs. 6.9 days for T1D, p=.0105 and 6.7 vs. 6.2 for T2D, p<.0001). Allowed and paid costs per member per month adjusted for confounding were higher for nHW compared to Hispanics with T1D (both p<.0001), and higher for Hispanics compared to nHW for T2D (both p<.0001).

The burden of chronic disease was significantly higher in Hispanics than nHW (both T1D and T2D, p<.0001). Hispanics with T1D were also more likely to have A1c and lipid tests (p=.0014 and p=.0011 respectively), although retinopathy and nephropathy screening rates were similar. For T2D, Hispanics were more likely to have A1c and lipid testing as well as retinopathy and nephropathy screening (all p<.0001).

This highlights important racial disparities in the burden and cost of diabetes for Medicare recipients in the U.S.

Table: Adjusted costs per member per month by race and type of diabetesRace/Diabetes TypeAllowedPaidNon-diabetes Hispanic$626$548Non-diabetes nHW$572$490Hispanic T1D$2214$1933nHW T1D$2320*$2010*Hispanic T2D$1320$1158nHW T2D$1300**$1127***p<.0001 vs Hispanics with T1D, ** p<.0001 vs Hispanics with T2D

Disclosure

N.M. Glantz: Research Support; Self; Eli Lilly and Company. I. Duncan: Consultant; Self; Eli Lilly and Company. T. Ahmed: None. L. Fan: Employee; Self; Eli Lilly and Company. B. Reed: None. S. Kalirai: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. D. Kerr: Advisory Panel; Self; Glooko, Inc.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Sanofi-Aventis. Stock/Shareholder; Self; Cellnovo. Advisory Panel; Self; Novo Nordisk Inc..
Storage Conditions of Insulin in Domestic Refrigerators and Carried by Patients—Insulin Is Often Stored Outside Recommended Temperature Range
Authors: BRAUNE KATARINA , KRÄMER LAURA A. , ZAYANI AMIN , WEINSTEIN JEREMIAS , HEINEMANN LUTZ
Published: June 2018

Objective: Not much is known about how patients with diabetes store their insulin in daily life. Objective of our study was to monitor temperature of refrigerated and carried insulin in industrialized countries to investigate how often storage conditions do not meet the manufacturers’ recommendations.

Method: Patients (n=338; 46% in the U.S., 41% in the EU) put a total number of 400 temperature loggers (MedAngel ONE, NL) next to their insulin into their refrigerator or diabetes bag. Temperature was measured every 3 minutes (up to 480 times/day). Measurements were sent to an app and stored in a protected online database. Whenever temperature exceeded the recommended range (2-8°C for refrigerated insulin, 2-30°C when opened/carried), the user was notified by an alarm. Data was collected from November 2016 to February 2018 with an average protocol length of 49 days.

Results: Temperature logs from individual sensors were analyzed (230 for refrigerated, 170 for carried insulin). Deviations were found in 315 (78.8%) logs (230 (100%) refrigerated, 85 (50%) carried). For refrigerated insulin, temperature recorded by an average sensor was out of the 2-8°C range 11.31% of the time (10.10%-13.10%; 2 hours 43 minutes/day) with an average deviation of 3.68K (SD 5.02K). For carried insulin, temperatures were out of 2-30°C range 0.54% of the time (0.48%-0.64%; 8 minutes/day) with an average deviation of 1.11K (SD 1.24K). 17% of sensors measured temperatures <0°C (57 refrigerated, 9 carried).

Conclusion: Long-term storage conditions of insulin are known to have an impact on its blood-glucose lowering effect. These observational data showed that in a significant number of cases insulin was exposed to temperatures outside the recommended range, especially when refrigerated. Thus, domestic refrigerators may pose an underestimated risk for insulin quality. The extent of how temperature deviations in storage affect insulin efficacy and patient outcomes needs further systematic investigation.

Disclosure

K. Braune: None. L.A. Krämer: Employee; Self; Med Angel BV. A. Zayani: Stock/Shareholder; Self; Med Angel BV. Employee; Self; Med Angel BV. J. Weinstein: Employee; Self; Med Angel BV. L. Heinemann: Stock/Shareholder; Self; Profil Institute for Metabolic Research, ProSciento. Consultant; Self; Roche Diabetes Care Health and Digital Solutions.
IGFs and IGF-Binding Proteins in Pregnancy and Gestational Diabetes Mellitus
Authors: ANDERLOVÁ KATEřINA , SIMJAK PATRIK , CINKAJZLOVA ANNA , KLOUCKOVA JANA , KRATOCHVILOVA HELENA , LACINOVÁ ZDENA , KAVÁLKOVÁ PETRA , KREJCI HANA , MRAZ MILOS , HALUZIK MARTIN , KRSEK MICHAL
Published: June 2018

The insulin-like growth factor (IGF) axis is involved in the regulation of growth and metabolism; however, little is known about its role in the development of gestational diabetes mellitus (GDM). The aim of our study was to determine serum IGF-1, IGF-2 and selected IGF binding protein (IGFBP) levels and their mRNA expression in subcutaneous (SAT) and visceral adipose tissue (VAT) and placenta in the context of pregnancy and GDM. Thirty-seven pregnant females - 21 with GDM (GDM group) and 16 without GDM (P group) - and 15 age-matched non-pregnant control females (NP group) were included into the study. Blood samples were taken in 28th-32th and 36th-38th gestational week and 6-12 months after delivery (GDM and P group) or before diagnostic laparoscopy (NP group). SAT, VAT and placental samples were obtained during delivery or surgery, respectively. Compared with NP group serum IGF-1, IGFBP-1 and 3 were increased in both GDM and P subjects reaching maximum levels in 38th-39th gestational week. IGF-2 was elevated only in GDM group culminating 6 months after delivery (745.1±24.7 vs. 909.2±62.8 vs. 998.7±92.7 ng/ml, p=0.017 for GDM and 726.9±28.4 vs. 791.2±44.2 vs. 748.9±58.4 ng/ml, p=0.341 for P group, respectively). IGFBP-3 was higher and IGFBP-4 was decreased in GDM vs. P group during the whole study (IGFBP3: 631.0±22.9 vs. 536.9±15.4 ng/ml, p=0.003 for GDM vs. P group; IGFBP4: 14.79±2.71 vs. 22.78±2.94 ng/ml, p<0.001 for GDM vs. P group). mRNA expression of IGF-1, IGFBP-3, 4 and 5 was increased in SAT, while IGF-2 and IGFBP-4 mRNA was elevated in VAT in GDM and P relative to NP group. Placental mRNA expression of IGF-2, IGF-2 receptor, IGFBP-3 and 4 was higher in GDM compared with P group.

In conclusion, females with GDM had increased serum IGF-2, IGFBP-3 and reduced IGFBP-4 levels and elevated placental mRNA expression of several components of IGF axis compared with pregnant women without GDM. These changes might play a role in the development of GDM.

Disclosure

K. Anderlová: None. P. Simjak: None. A. Cinkajzlova: None. J. Klouckova: None. H. Kratochvilova: None. Z. Lacinová: None. P. Kaválková: None. H. Krejci: None. M. Mraz: None. M. Haluzik: None. M. Krsek: None.
The Association between Free Fatty Acid Level at Midpregnancy and Postpartum Glucose Intolerance in Women with Gestational Diabetes Mellitus
Authors: KIM KYUNG-SOO , KIM SOO-KYUNG , CHO YONG-WOOK , PARK SEOK WON
Published: June 2018

Free fatty acid (FFA) is correlated with fetal growth during pregnancy and with neonatal fat mass in women with gestational diabetes mellitus (GDM). However, there are few studies between FFA level and postpartum glucose metabolism in women with GDM. The aim of this study was to evaluate the association between FFA level at mid-pregnancy and postpartum glucose intolerance in women with GDM. We enrolled 769 pregnant women diagnosed with GDM from February 2009 to October 2016. FFA levels (fasting and postprandial 2-h) were measured during 24-32 gestational weeks and 75-g OGTT was performed at 6-12 weeks after delivery. High FFA was defined by more than the median level of FFA at mid-pregnancy. Postpartum glucose intolerance was defined as fasting plasma glucose (FPG) ≥ 100 mg/dL or 2-h plasma glucose (2-h PG) ≥ 140 mg/dL. Mean age was 33.1 years and mean pre-pregnancy BMI was 22.4 kg/m2. The prevalence of postpartum glucose intolerance was 48.0% (n = 369). Although postprandial 2-h FFA level and FFA difference (between fasting and postprandial 2-h FFA) were not significantly different between two groups, women with postpartum glucose intolerance had higher fasting FFA level at mid-pregnancy than those with normal glucose tolerance (733.7 μEq/L vs. 700.6 μEq/L, P = 0.049). Compared to women with low fasting FFA, women with high fasting FFA had higher postpartum glucose intolerance (51.8% vs. 44.1%, P = 0.033). After adjustment for maternal age, pre-pregnancy BMI, parity, family history of diabetes, FPG, and lipid measures (total cholesterol, triglyceride, HDL-cholesterol), women with high fasting FFA were 1.47 times (95% CI 1.07-2.01) more likely to have postpartum glucose intolerance than those with low fasting FFA. In women with GDM, high fasting FFA level at mid-pregnancy is associated with elevated risk of postpartum glucose intolerance.

Disclosure

K. Kim: None. S. Kim: None. Y. Cho: None. S. Park: None.
CGM Shows Islet Transplantation Prevents Hypoglycemia, Correcting Time in Range and Reducing Glycemic Variability, Despite Subnormal Beta-Cell Function
Authors: FORBES SHAREEN , OLATEJU TOLU OLUTOYIN , LAM ANNA , CASEY JOHN , CAMPBELL JOHN , REID LAURA , ORAM RICHARD A. , MALCOLM ANDREW J. , SHAPIRO A.M. JAMES , SENIOR PETER A.
Published: June 2018

The impact of clinical islet transplant (CIT) on glycemic variability compared with type 1 diabetes (T1D) subjects and nondiabetic controls has not been explored.

Aim: To evaluate the relationship between glycemic variability (by CGM) and islet graft function in CIT vs. T1D subjects on Continuous Subcutaneous Insulin Infusions (CSII), using healthy, nondiabetic subjects as reference.

Methods: CIT recipients n=39, (insulin independent vs. dependent: n=15 vs. n=24) and subjects on CSII therapy (n=10) all with T1D were assessed at 1 year post-intervention with CGM. Published data from nondiabetic controls were used for comparison. Fasting glucose, C-peptide and HbA1c concentrations and insulin dose were recorded (including in a control cohort, n=28) where applicable; BETA-2 scores were calculated in those with endogenous C-peptide.

Results: CIT recipients had decreased coefficient variation of glucose and lower time in hypoglycemia vs. those on CSII therapy; BETA-2 scores were ∼20% lower in CIT recipients vs. controls (p<0.05).

Conclusion: Islet transplant recipients have diminished glycemic variability with abrogation of hypoglycemia vs. CSII at 1 year. Normalisation of time in range and glycemic variability was observed in insulin independent CIT recipients despite beta cell function ∼20% lower than in nondiabetic subjects.

Disclosure

S. Forbes: None. T. Olateju: None. A. Lam: None. J. Casey: None. J. Campbell: None. L. Reid: None. R.A. Oram: Other Relationship; Self; Randox. A.J. Malcolm: None. A. Shapiro: Consultant; Self; Viacyte, Inc., Protokinetix. P.A. Senior: Consultant; Self; Abbott, AstraZeneca. Research Support; Self; AstraZeneca, Prometic Life Sciences Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; AstraZeneca, Merck & Co., Inc., Abbott. Research Support; Self; Viacyte, Inc..
Knowledge of Gestational Diabetes Mellitus among Women of Reproductive Age in Rivers State—Implications for Prevention and Control
Authors: OGU ROSEMARY , MADUKA OMOSIVIE , AGALA VETTY R. , PORBENI IBIMONYE ,   TE MEDICAL WOMEN'S ASSOCIATION OF NIGERIA, STA RIVERS
Published: June 2018

Background: Diabetes mellitus has attained the status of an epidemic in slow motion. Gestational diabetes mellitus (GDM) is a sub-type which occurs in pregnancy. As part of a baseline assessment, the researchers sought to determine knowledge of GDM among women of reproductive age in the state.

Methods: The study was a descriptive cross-sectional household survey involving 2595 women of reproductive age residing in five local government areas in the state. It employed a multi-stage sampling technique to collect data using an interviewer-administered questionnaire built using Open Data Kit (ODK) software uploaded on android mobile phones.

Results: The response rate was 100%. Mean age was 29.25 ± 7.11 years. The majority (2,351;90.6%) had heard about diabetes Mellitus but only 991 (38.2%) knew that diabetes can occur for the first time in pregnancy. Only 747 (28.8%), 929 (35.8%) and 790 (30.4%) respondents had good knowledge scores for GDM definition and risk factors, GDM screening diagnosis and treatment and GDM complications respectively. Only 681 (26.2%) had good overall knowledge of GDM. The major sources of knowledge of GDM were from friends (49.8%), health workers (34.6%) and mass media (10.4%). Residence in two urban LGAs (AdjO.R=1.79; 95% CI=1.36-2.34) and (AdjO.R=1.89; 95% CI =1.37-2.61), being married (AdjO.R=1.50; 95% CI=1.16-1.95) and having been pregnant (AdjO.R=2.69; 95% CI= 1.99-3.64) positively predicted good overall knowledge of GDM.

Conclusion: These results underscore the need for information, education and communication (IEC) activities on a large scale targeted at women of reproductive age and their partners for prevention and control of GDM.

Disclosure

R. Ogu: None. O. Maduka: None. V.R. Agala: None. I. Porbeni: None.
Intensive Metabolic Control of T1D Pregnant Women in CSII vs. MDI—A Retrospective Analysis
Authors: PARRETTINI SARA , GIARDINA IRENE , CARDINI FRANCESCA , TORLONE ELISABETTA
Published: June 2018

Diabetes-complicated pregnancy requires intensive gluco-metabolic monitoring. There is no clear evidence that insulin pump therapy (CSII) is superior to multiple daily injections with insulin analogs (MDI) in achieving tight glycemic control. We conducted a retrospective analysis on 72 (69 singles and 3 twins) T1D pregnant women, followed at the Diabetes and Pregnancy Unit (University Hospital, Perugia) since the first weeks of gestation or before conception. Maternal metabolic parameters (HbA1c, mean BG, weight gain, prandial and basal insulin needs and percentage increase in insulin requirement, I:CHO ratio) at conception, and each trimester, were assessed. Finally, neonatal outcomes (birth weight, newborn age, neonatal complications-malformations incidence) were analyzed. We compared the data with regard to applied regimens (CSII vs. MDI). 28 women were on CSII (38.8%) and 44 on MDI therapy, with mean HbA1c at conception of 7.1 ± 0.7% vs. 7.2 ± 1.2%, respecively (P> 0.05). Women who received pre-conceptional counseling (56% of CSII women vs. 13% of MDI), showed significantly lower HbA1c at conception (6.7 ± 0.6 vs. 7.3 ± 1.1, p <0.05). Disease duration, previous abortion rate and prevalence of chronic complications (class D-G, White classification) were significantly higher in CSII group. In single pregnancies, no significant differences were observed, in CSII vs. MDI, as far as HbA1c, insulin (U/Kg), percentage increase of insulin requirement, I:CHO ratio, weight increase, gestation term, birth weight, prevalence of maternal and neonatal complications were concerned (p> 0.05). CSII was not proved superior to MDI in the management of pregnancy, in terms of neither maternal insulin requirements nor of maternal-fetal outcomes. Intensive management of diabetic pregnancy ensures stringent glycemic control, regardless of treatment with CSII or MDI. The choice of treatment modality should be targeted on pre-gestational and individual parameters.

Disclosure

S. Parrettini: None. I. Giardina: None. F. Cardini: None. E. Torlone: Other Relationship; Self; Medtronic MiniMed, Inc., Novo Nordisk Inc., Eli Lilly and Company, Roche Diabetes Care Health and Digital Solutions, Sanofi-Aventis, Menarini Group.
Treatment of Gestational Diabetes and Offspring Early Childhood Growth
Authors: FEGHALI MAISA N. , ATLASS JACQUELINE , CARITIS STEVE , CATOV JANET M. , SCIFRES CHRISTINA M.
Published: June 2018

Gestational diabetes mellitus (GDM) is associated with childhood obesity and there is concern that glyburide is associated with macrosomia and perhaps childhood overgrowth.

We sought to examine if GDM treatment type is associated with differences in early childhood growth using a retrospective cohort of 952 women with GDM and their offspring. We collected pregnancy and breastfeeding data as well as height and weight through age 3. We used bivariate and multivariable regression analyses to compare early childhood growth among maternal GDM treatment.

Treatment was divided into medical nutritional therapy (MNT), glyburide, and insulin. LGA at birth was more common in offspring exposed to insulin and glyburide compared to those treated with MNT (11.7 vs. 9.2 vs. 5.7%, p=0.03). Weight or BMI at 6 months, 1, 2 and 3 years of age did not differ among children born to women with different GDM treatments. GDM treatment type was not predictive of weight or associated with a higher risk for BMI >85th percentile at age 2 or 3 years after adjusting for covariates including gender, age at recorded weight, birth weight category, pre-pregnancy BMI, gestational weight gain, and breastfeeding.

Our findings suggest that maternal pre-pregnancy BMI but not GDM treatment is associated with variations in early childhood growth. Further studies are needed to determine if these findings persist beyond 3 years of age and to explore differences in body composition.

Factors associated with offspring weight at 2 yearsFactors associated with offspring weight at 3 yearsBeta Coefficient (95% CI)PBeta Coefficient (95% CI)PMNT (n=344) Glyburide (n=490) Insulin (n=117)Ref -0.16 (-0.48-0.15) -0.27 (-0.74-0.21)n/a 0.30 0.27Ref -0.13 (-0.53-0.26) 0.35 (-0.22-0.93)n/a 0.50 0.23Female gender-0.48 (-0.75- -0.20)0.001-0.59 (-0.94- -0.25)0.001Prepregnancy BMI0.16 (0.06-0.27)0.0030.17 (0.02-0.31)0.026Pregnancy weight gain (lbs)0.0(-0.003-0.02)0.150.036 (0.011-0.061)0.004Any breastfeeding-0.30 (-0.06- -0.02)0.04-0.41 (-0.77- -0.04)0.03Birth weight category AGA SGA LGARef -1.16 (-1.6- -0.7) 0.88 (0.32-1.44)n/a <0.001 0.002Ref -1.40 (-1.99- -0.82) 1.53 (0.91-2.15)n/a <0.0 01 <0.001

Disclosure

M.N. Feghali: None. J. Atlass: None. S. Caritis: None. J.M. Catov: None. C.M. Scifres: None.
Serum Sclerostin, Body Composition, and Physical Function in Postmenopausal Women with Type 2 Diabetes
Authors: BANDEIRA FRANCISCO , CHAVES CONCEIÇAO D. , BANDEIRA FARIAS MARIA ELBA , PIMENTEL LARISSA B. , FARIAS LEONARDO
Published: June 2018

Backgound: Sclerostin (SCL), produced mainly by osteocytes, inhibits the Wnt pathway and bone formation, and may be influenced by skeletal muscle mass.

Objective: To evaluate serum sclerostin levels, body composition and physical function in postmenopausal women (PMW) with T2DM.

Methods: We studied 250 PMW (125 with T2DM and 125 PMW without diabetes) with HbA1c below 10%, estimated GFR above 60 ml/min/1.73m2, and compared body composition analysis by multifrequency-bioelectrical impedance, gait speed (GS) and serum sclerostin with metabolic parameters.

Results: Although there were no differences between cases and controls regarding age and years since menopause (62.9±8.3 vs. 61.8±7.5 years, p=0.11; 14.3 ± 12.1 vs. 12.1±8.2 years, p=0.12, respectively), high circulating SCL and sarcopenia (low GS and fat free mass index) were found in 76% / 89.6% of T2DM vs. 61.6% / 72.8% of controls; p=0.014 and p=0.001, respectively. T2DM had more adiposity than controls: BMI 31.0± 29.5 vs. 29.4±29 kg/m2, p=0.04; WC 102.2±12.8 vs. 95.5±11.6 cm, p<0.001; fat mass 29.3±7.6 vs. 26.7±7.1% body weight, p=0.008; and serum triglycerides 153.8±74 vs. 128.3±50.0 mg/dl, p=0.004.

Conclusion: Serum sclerostin is high in PMW with T2DM, as well as the presence of sarcopenia. Since SCL is also involved in vascular endothelial remodeling and inflammation, adiposopathy may also be related to high SCL in T2DM.

Disclosure

F. Bandeira: Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. C.D. Chaves: None. M. Bandeira Farias: None. L.B. Pimentel: None. L. Farias: None.
Long-Term Effects of Lifestyle Intervention and Metformin during DPP on Appendicular Lean Mass
Authors: SCHWARTZ ANN V. , PAN QING , HAZUDA HELEN P. , HORTON EDWARD , HOSKIN MARY A. , KALYANI RITA RASTOGI , KNOWLER WILLIAM C. , KRISKA ANDREA , SCHLÖGL MATHIAS , FLOREZ HERMES ,   DPP RESEARCH GROUP
Published: June 2018

Weight loss prevents progression to diabetes but long term effects on lean mass are unknown. We determined if intensive lifestyle modification (ILS), metformin (MET) or placebo (PLB) treatment in the Diabetes Prevention Program (DPP) had differential effects on appendicular lean mass (ALM) and sarcopenic-obesity (SO) ∼16 years after DPP randomization in the DPP Outcome Study (DPPOS). During DPP, 3234 participants at high risk for diabetes were randomized to ILS, MET or PLB; 2779 continued in DPPOS and were offered modified group ILS. During DPPOS, ILS was offered additional lifestyle reinforcement semi-annually and MET received unmasked metformin. This analysis includes 1374 DPPOS participants who had dual-energy X-ray absorptiometry scans at year 12 for ALM (sum of lean mass in arms and legs). Low ALM was defined as ALM/BMI <0.789 for men or <0.512 for women. SO was defined as low ALM with BMI>30. Prevalence of low ALM and SO was compared across the 3 groups using Pearson’s chi-squared test. Logistic regression models determined the associations between treatment and low ALM or SO and between weight loss and low ALM or SO. Mean age at Y12 was 66.5 (±9.5) years. Mean time since DPP baseline was 15.6 (±0.7) years. Weight loss (DPP baseline to DPPOS Y12) did not differ by group (-4.4 kg ILS; -3.5 kg MET; -3.1 kg PLB; p=0.114). Prevalence of low ALM differed by group in men (35.7% ILS, 28.3% MET, 22.5% PLB; p=0.049) but not women (20.9% ILS, 24.8% MET, 24.1% PLB; p=0.482). In men, low ALM prevalence was higher in ILS compared with PLB (P=0.024) but not in MET vs. PLB. Prevalence of SO did not differ across groups in men (23.1% ISL, 22.0% MET, 14.1% PLB; p=0.112) or women (17.3% ILS, 20.9% MET, 20.3% PLB; p=0.492). SO prevalence was not different in ILS vs. PLB or in MET vs. PLB in men or women. More weight loss was associated with higher risk of low ALM and SO in women and men (p<0.001) independent of group. In men but not women at high risk of diabetes, lifestyle intervention to prevent diabetes may contribute to lower ALM.

Disclosure

A.V. Schwartz: None. Q. Pan: None. H.P. Hazuda: None. E. Horton: Advisory Panel; Self; PTS Diagnostics, Merck & Co., Inc., Theracos, Inc.. M.A. Hoskin: None. R. Rastogi Kalyani: None. W.C. Knowler: None. A. Kriska: None. M. Schlögl: None. H. Florez: Advisory Panel; Self; Sanofi. D. Research Group: None.
Trajectories of Health-Related Quality of Life (HR-QoL) in Older Adults with Diabetes
Authors: PARK SUNHEE , LEE TAEWHA
Published: June 2018

Background: Health-related quality of life (HR-QoL)—a major outcome of diabetes management interventions—is a general self-rated concept regarding one’s biological functions, symptoms, and functional status. However, there is limited information on the longitudinal changes in HR-QoL of older adults over time.

Objective: To identify different patterns of HR-QoL changes in longitudinal data and reveal potential predictors of these trajectories among older adults with diabetes

Methods: Subjects were older adults over 65 years with diabetes (n = 440), who participated in the Korea Health Panel survey for five consecutive years (2009-2013). HR-QoL longitudinal data were measured using Euro-QoL 5-Dimension Questionnaire. Growth mixture modeling was used to estimate distinct patterns, and binary and logistic regressions were used to determine factors affecting different trajectories of HR-QoL patterns using STATA 14.0.

Results: Four distinct trajectories of HR-QoL were found to be the best based on the Bayesian information criterion. High decrease HR-QoL indicates older adults with diabetes (10.0%) whose HR-QoL remained stable in the high score and began decreasing four years post-estimation. High stable HR-QoL indicates constantly high HR-QoL of older adults with diabetes (52.8%). Medium stable HRQoL indicates constantly medium HR-QoL of older adults with diabetes (36.0%). Medium increase indicates (1.3% of subjects) an HR-QoL trajectory pattern, which decreased from a medium level and increased three years post-estimation. Distinct trajectories of HR-QoL significantly associated with decrease vs. stable were age, having a spouse, impaired vision, subjective health status, and medication compliance.

Conclusion: It is suggested that although most participants had stable HR-QoL, comprehensive assessment and individualized management programs are needed to improve HR-QoL of older adults with diabetes.

Disclosure

S. Park: None. T. Lee: None.
Targeting Ketohexokinase (KHK) with a Novel Antisense Oligonucleotide (ASO) Decreases De Novo Lipogenesis and Improves Insulin-Mediated Whole Body Glucose Metabolism
Authors: LIU DONGQING , STERPKA JOHN A. , VATNER DANIEL F. , BELL MELANIE , MURRAY SUE , BHANOT SANJAY , CLINE GARY , SAMUEL VARMAN
Published: June 2018

Increased sucrose consumption is associated with rising rates of obesity and related conditions [e.g., insulin resistance, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD)]. Ketohexokinase (KHK) catalyzes the first step of fructose metabolism and is highly expressed in liver, kidney and brain, though found in many tissues. Essential fructosuria (hepatic KHK deficiency) is a benign condition, suggesting that KHK is a viable drug target. Inhibition of hepatic KHK would block metabolism of fructose (50% of dietary sucrose) and improve numerous facets of metabolism. ASO’s potently decrease target expression in liver and WAT and we hypothesized that a novel KHK ASO would prevent NAFLD and insulin resistance in normal rats fed a low fat (12% calories from fat), sucrose containing diet (17% calories from fructose). KHK ASO decreased hepatic KHK mRNA and protein expression by 96 and 90%, respectively. KHK ASO decreased WAT mRNA expression by 65%. KHK ASO did not alter body mass. KHK ASO decreased fasting plasma glucose (102±2 vs. 94±2 mg/dL, P=0.01), fasting plasma triglyceride 60% (52±7 vs. 21±2 mg/dL P<0.01) and liver triglyceride by 30% (8.2±0.4 vs. 5.6±0.3 mg TG/g liver, P<0.001) but not plasma insulin or non-esterified fatty acids. Insulin sensitivity was assessed by a 4 mU kg-1 min-1 hyperinsulinemic-euglycemic clamp. Surprisingly, there were no differences in rates of EGP or suppression of EGP. Instead there was a 25% improvement in insulin stimulated whole body glucose metabolism (36.6±0.8 vs. 45.6±2.2, P<0.01). We attribute this to a 40% decrease in hepatic DNL (53±4 vs. 32±4%, P<0.01) and VLDL secretion rate (11.0± 0.8 vs. 5.5± 0.5 mg/dL-min P<0.01) independent of changes in SREBP1 or ChREBP mRNA expression. Thus, decreased DNL and VLDL export prevents fructose induced peripheral insulin resistance.

Conclusion: KHK ASO prevents NAFLD, decreases plasma triglyceride and improves insulin sensitivity.

Disclosure

D. Liu: None. J.A. Sterpka: None. D.F. Vatner: None. M. Bell: Employee; Self; Ionis Pharmaceuticals, Inc.. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. S. Murray: Employee; Self; Ionis Pharmaceuticals, Inc. S. Bhanot: Employee; Self; Ionis Pharmaceuticals, Inc.. G. Cline: None. V. Samuel: None.
Point-of-Care HbA1c—A Case for Diabetes Screening and Diagnosis
Authors: SZABLOWSKI CARRIE J. , SUSCHA EMILY , DAVIS KADDY , XIE CHARLES Z. , MOSKOWITZ KEITH , ANDERSON JAMES H. , MECHLEY AMY
Published: June 2018

Background: Hemoglobin A1C (A1C) is routinely used to screen, diagnose, and monitor diabetes. A1C is the desired tool to assess glycemic status as it reflects 90 days of glycemic control and does not require fasting. Point-of-care (POC) A1C offers rapid turnaround enabling direct patient engagement. POC A1C tests are indicated for monitoring, but not screening or diagnosis, due to perceived inaccuracy and imprecision. To counter this impression, we evaluated the performance of two POC A1C analyzers relative to the clinical laboratory (CL).

Method: Blood from 48 subjects was collected with A1C values from 4.8-12.0% A1C. Capillary blood was analyzed on the PTS Diagnostics A1CNow®+ system and Siemens DCA Vantage® while venous blood was tested at external labs on the Tosoh G8 and Roche Cobas® c513 as CL comparators. For reference, venous blood was analyzed on the Roche Cobas Integra® 400 plus. Regression analysis was used to evaluate accuracy and paired differences to measure bias. Clinical risk was calculated using A1C category cut points of < 5.7, 5.7-6.4, and ≥ 6.5% A1C. Chi-squared test was used to assess differences between methods. Precision was performed on the POC systems using 10 replicates at approx. 4.5, 7, and 10% A1C.

Results: Average paired biases were identical for the POC and CL analyzers (-0.04% A1C). Slopes were 0.97, 0.99, and 0.97 for the A1CNow+, DCA, and CL analyzers (p = 0.71) and intercepts were 0.15, 0.04, and 0.12 (p = 0.99). Regression values were 0.987, 0.996, and 0.998, respectively. Clinical risk agreement was 94% for A1CNow+, 100% for the DCA, and 98% for CL analyzers (p = 0.17). Pooled precision was 3.3% CV for A1CNow+ and 1.7% CV for DCA.

Conclusion: The A1CNow+ and DCA were shown to be as accurate as the clinical lab in measuring A1C values. Risk analysis showed no statistical differences between the CL and POC analyzers in classifying diabetes. The A1CNow+ and DCA are valuable tools in evaluating the diabetic state and provide physicians with real-time information to better care for patients.

Disclosure

C.J. Szablowski: Employee; Self; PTS Diagnostics. E. Suscha: Employee; Self; PTS Diagnostics. K. Davis: Employee; Self; PTS Diagnostics. C.Z. Xie: Employee; Self; PTS Diagnostics. K. Moskowitz: Employee; Self; PTS Diagnostics. Stock/Shareholder; Self; PTS Diagnostics. J.H. Anderson: Employee; Self; PTS Diagnostics. Board Member; Self; GENEREX Biotechnology. A. Mechley: Consultant; Self; PTS Diagnostics.
Estimation of Population Insulin Sensitivity (SI) from Sparsely Sampled Oral Glucose Tolerance Test (OGTT) Data
Authors: STEFANOVSKI DARKO , UMPIERREZ GUILLERMO E. , VELLANKI PRIYATHAMA
Published: June 2018

The oral glucose tolerance test (OGTT) minimal model analysis by Cobelli et al. obtains estimates of insulin sensitivity (SI) based on mathematical models that are highly concordant with the euglycemic clamp, the gold standard for estimation SI. This model requires a minimum of 7 blood samples during the 2-hour OGTT. However, in many OGTT studies, the number of samples is below the number that permits the estimation of SI. One way to address (overcome) this issue is by pooling sparsely sampled data (<7 samples) from a specific cohort to obtain population estimates of parameters of SI. Here we present a novel methodology of estimating population SI using sparsely-sampled OGTT protocol. A cohort of 6 African American subjects (3 Female/ 3 Male) without a known history of T2D underwent 75-gm OGTTs with 6 samples performed at 0, 15, 30, 60, 90 and 120 minutes. The population SI was estimated concurrently fitting the data from all subjects. We obtained population estimates of SI using from 3 to 6 samples per subject. SI estimates for each subject were also calculated. Sparse-sampling population estimated SI varied from SI=4.74±.75 10-4.(mu/l)-1.min-1 for 4 samples to SI= 6.40±2.40 10-4.(mu/l)-1.min-1 for 3 samples. The individual estimates of SI had a mean of SI= 4.72±2.43 10-4.(mu/l)-1.min-1. SI obtained with the sparse-sampling methodology did not differ from the mean individual estimates of SI. We conclude that Sparse-sampling estimation of SI (<7 samples) is a useful tool for estimation of population parameters of SI where there are not enough observations per subject to estimate individual insulin sensitivity. This methodology will provide better phenotyping of insulin sensitivity for studies where previously more crude measures were used.

Disclosure

D. Stefanovski: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca.
Maturity-Onset Diabetes of the Young (MODY) in a Racially Diverse Pediatric Population
Authors: RELAN SHILPI , HESSEL FRANCES C. , TIMMONS KELLY D. , SONABEND RONA , REDONDO MARIA J.
Published: June 2018

Current practice guidelines recommend considering a diagnosis of MODY in patients with a strong family history but without typical features of type 2 diabetes (T2D) (i.e., obesity, insulin resistance, high-risk ethnicity) or type 1 diabetes (T1D) (i.e., islet autoantibodies).

We aimed to test if these criteria apply to a racially diverse pediatric patient population.

Using EPIC Population Health, we retrospectively reviewed electronic medical records (IRB H-41512) of youth diagnosed with MODY between 2013-2017 in a large academic pediatric hospital in Southwestern U.S.

We found that, out of 46 patients with MODY, 50% (n=23) had MODY 2, 17.3% (n=8) MODY 3, 17.3% (n=8) MODY 5, 8.6% (n=4) MODY 1, 2.1% (n=1) MODY 4, and 8.6% of patients had a clinical diagnosis of MODY due to inability to perform molecular testing. The mean (SD, range) age of diabetes diagnosis was 10.1 years (4.4, 2-17); 52% of patients were females; 50% were non-Hispanic white, 32.5% Hispanic, 6.5% African American, 6.6% Lebanese, 2.2% Asian and 2.2% others/unknown. Notably, 15.2% (n=7, all with a molecular diagnosis of MODY) had positive islet antibodies, 8.6% (n=4) Hashimoto’s thyroiditis and 2.1% (n=1) vitiligo. Obesity/overweight was present in 23.8%, 15.2% had hypertension / prehypertension and 21.7% had dyslipidemia. Diabetes was absent in parents and siblings of 26% (n=12) of patients, although in 5 patients, the mother had gestational diabetes. Persistent microalbuminuria was found in 2 youth with MODY 2 and diabetic neuropathy in 1 patient with MODY 2. The mean (SD, range) time between the diagnoses of diabetes and MODY was 14.3 months (22.3, 1-120).

In conclusion, youth with MODY often were of ethnic minorities, lacked a family history of diabetes and had characteristics typical of T1D or T2D, suggesting that the current guidelines to consider a diagnosis of MODY may not apply to a racially diverse U.S. pediatric population. Furthermore, in contrast to previous studies, we identified microvascular complications in youth with MODY 2.

Disclosure

S. Relan: None. F.C. Hessel: None. K.D. Timmons: None. R. Sonabend: None. M.J. Redondo: None.
The Cuban Prospective Study-Diabetes and Cause-Specific Mortality in Cuba
Authors: CHARLES SHAQUILLE J.C.
Published: June 2018

Introduction: Large-scale prospective studies of diabetes and cause-specific mortality have been conducted mainly in high-income countries, where there is good access to healthcare. However, there is limited evidence on the effect of diabetes on mortality in low- and middle-income countries, such as Cuba.

Methods: From 1996-2002, we recruited 146,556 participants (aged ≥30) from the general population in Cuba into a prospective cohort study. We recorded the presence or absence of previously diagnosed diabetes, and monitored for deaths through December 31st, 2015. We estimated adjusted hazard ratios (HR) for cause-specific mortality at ages 30-84 years among participants who had diabetes at recruitment vs. those who did not have diabetes at recruitment; participants with prior chronic disease other than diabetes were excluded from the analyses.

Results: At recruitment, the overall prevalence of diabetes was 4% in men and 7% in women, and the mean age was 53 (SD13) years. Previously diagnosed diabetes was associated with about twice the risk of all-cause mortality (HR 1.89 [95% CI 1.79-1.99]; mean age at death 70 [SD12]). The association was stronger at younger ages, but did not differ by sex: HR 2.68 (2.29-3.14) at 30-59 years, 2.20 (2.03-2.38) at 60-74 years, and 1.56 (1.44-1.68) at 75-84 years. Diabetes was strongly associated with mortality from renal, cardiovascular and respiratory diseases, but not with cancer. The excess mortality associated with diabetes accounted for ∼10% of all premature deaths (<75 years) in Cuba for 2015; mostly from cardiovascular disease.

Conclusion: Despite limited resources in Cuba, the association of diabetes with all-cause mortality was similar to high-income countries and less extreme than in many other middle-income countries.

Disclosure

S.J.C. Charles: None.