bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Risk Factor Profile between Carotid Intimal Medial Thickness and Pulse Wave Velocity in African-Americans with Type 2 Diabetes
Authors: ELUWOLE AYOBAMI , ADEDAYO AJIBOLA M. , TEDLA FASIKA , KREMER ARYE , MASTROGIOVANNI NICOLE , ROSENBERG CARL , DREIZEN PAUL , LAROSA JOHN , SALCICCIOLI LOUIS , BOUTJDIR MOHAMED , BANERJI MARY ANN , BROWN CLINTON , SALIFU MORO , BAKILLAH AHMED , LAZAR JASON
Published: June 2018

Background: Diabetes is a robust risk factor for cardiovascular events which is marked in African Americans for reasons that may be attributed to socioeconomic and biologic vulnerabilities. Both structural (arterial thickening) and functional (arterial stiffness) abnormalities of the vasculature are predictive of incidental clinical events. Study objective was to determine the risk factors and relationship between large artery stiffness and carotid intimal thickness in African Americans with type II diabetes.

Methods: 125 patients with diabetes were recruited from medical clinics. Medical information was obtained via interview and electronic medical record review. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Carotid Intimal Medial Thickness (CIMT) was obtained using B-mode ultrasound image analysis of the common carotid artery. Statistical analysis was done using SPSS version 23.

Results: Mean age 60±8 years, 64% female. 82% hypertension, dyslipidemia 83%, diabetes duration 10.2±7.6 years, Mean HbA1C= 8.1±2.2%. Mean CIMT=0.68±0.15, PWV= 8.6±2.9. There was no significant association between PWV and CIMT. CIMT positively correlated with gender (r=0.302, p=0.001), smoking (r=0.278, p=0.002), creatinine (r=0.260, p=0.006), triglycerides (r=0.279, p=0.002), pooled cohort score (r=0.353, p=0.001), and negatively with HDL (r= -0.196, p=0.031). PWV positively correlated with creatinine (r=0.300, p=0.001), duration of diabetes (r=0.195, p=0.037) and age (β=0.359, p<0.0001) and pooled cohort score (r=0.248, p=0.003). After adjusting for cardiovascular risk factors, gender (β=-2.000, p=0.019), and age (β=0.119, p=0.018) independently predict PWV but not CIMT.

Conclusion: Our findings indicate that PWV and CIMT differ in risk factor profile in African Americans with type II diabetes mellitus. Further studies are needed to clarify mediating factors.

Disclosure

A. Eluwole: None. A.M. Adedayo: None. F. Tedla: None. A. Kremer: None. N. Mastrogiovanni: None. C. Rosenberg: None. P. Dreizen: None. J. LaRosa: None. L. Salciccioli: None. M. Boutjdir: None. M. Banerji: Speaker's Bureau; Self; Merck & Co., Inc.. C. Brown: None. M. Salifu: None. A. Bakillah: None. J. Lazar: None.
Development of an Inflammatory Food Index and Association with Inflammatory Markers and Diabetes—Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: RIBOLDI BARBARA P. , LUFT VIVIAN C. , SCHMIDT MARIA I. , DUNCAN BRUCE B.
Published: June 2018

Introduction: Diet plays a central role in the regulation of inflammation and is closely related to the development of chronic diseases. Dietary patterns portray eating habits more comprehensively than nutrients or foods alone, and provide better understanding and predictive power in relation to causal processes. The objective was to develop an Index of Food Inflammation (IFI) derived from Reduced Rank Regression (RRR) based on its relation with inflammatory markers in the ELSA-Brasil population, and to evaluate its association with weight gain and incidence of diabetes.

Methods: Food consumption data were obtained from a food frequency questionnaire of 9778 participants, after exclusions. The RRR methodology initially involved 42 food groups. Spearman’s correlation coefficients were used to evaluate the associations between quantitative variables, and, for the IFI, linear regression to evaluate its association with weight gain, logistic regression with large gains, and Cox regression with incident diabetes.

Results: The inflammatory dietary pattern was composed of 17 pro-inflammatory food groups, including processed or red meat, pork, sugary soft drinks, and hotdogs, and seven anti-inflammatory groups, notably fruits, nuts and wine. The IFI was associated with weight gain, risk of a large weight gain (quartile 4 vs. 1: adjusted OR=1.42; 95% CI 1.15-1.76) and risk of developing diabetes (quartile 4 vs. 1: adjusted HR=1.29; 95% CI 1.01-1.65).

Conclusion: The associations, although small, suggest that subclinical inflammation could be one of the ways by which diet causes certain chronic diseases. Ultra-processing of foods could be an important determinant in the pro-inflammatory aspect of some current dietary patterns.

Disclosure

B.P. Riboldi: None. V.C. Luft: None. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
The Effect of Liraglutide on 24-Hour Ambulatory Blood Pressure in Patients with T2DM—A Pilot Study
Authors: LOVRE DRAGANA , KATALENICH BONNIE , OLMEDA CARLY CARRION , CAMITTA SARAH B. , KHAN AMNA N. , FONSECA VIVIAN , THETHI TINA K.
Published: June 2018

The GLP-1 receptor agonists have been shown to decrease blood pressure (BP) in clinical trials using office BP measurements. However, the effect of GLP-1 agonist liraglutide on 24-hour ambulatory blood pressure and on the nocturnal BP decrease (dipping) have not been adequately assessed in large trials. To better characterize the effect of GLP-1 agonists on 24-hour ambulatory BP in subjects with T2DM we conducted a randomized controlled trial comparing the effects of liraglutide to placebo. Eleven subjects with T2DM (mean age 58.6±7.4 years, female 63.7%, African-American 72.7%) were randomized to 8 weeks of treatment with liraglutide (n=6) or placebo (n=5). ABPM and EndoPAT (Peripheral Arterial Tone) for assessment of endothelial dysfunction were done at baseline, 4 weeks and 8 weeks of therapy. Mixed models with repeated measures was used to estimate the treatment effect over time. Treatment with liraglutide was found to increase the nighttime SBP (LSM±SE): 135.3±4.3 vs. 102.1±4.5 (mmHg), p=0.0015), diastolic BP (DBP) (74.7±6.1 vs. 57.5±5.6 (mmHg), p=0.047) and increase daytime heart rate (109.5±9.2 vs. 77.1±7.9 (mmHg), p=0.021) after adjusting for age, race, history of hypertension, current use of ACE-I/ARBs and Reactive Hyperemia Index (RHI). There was no significant change in BMI between baseline and 8 weeks (1.5±2.4 vs. 1.0±2.5 (kg/m2), p=0.65). After adjustment for treatment and other covariates, abnormal RHI (≤ 1.67) was associated with decreased nighttime SBP (110.6±3.4 vs. 126.8±3.4 (mmHg), p=0.0003), and increased nighttime DBP (69.1±5.0 vs. 63.2±5.1 (mmHg), p=0.16) although lack of power to detect the statistical significance.

In conclusion, our study showed that treatment with liraglutide over 8 weeks was unable to correct the abnormal elevation in nocturnal BP known to occur in patients with T2DM. ABPM also confirmed the known side effect of increase in heart rate previously seen in other liraglutide trials. Abnormal RHI tended to be associated with all patients with high DBP.

Disclosure

D. Lovre: None. B. Katalenich: None. C. Carrion Olmeda: None. S.B. Camitta: None. A.N. Khan: 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. T.K. Thethi: None.
Real-World Assessment of Sugar.IQ with Watson—A Cognitive Computing-Based Diabetes Management Solution
Authors: ZHONG YUXIANG , ARUNACHALAM SIDDHARTH , AGRAWAL PRATIK , NEEMUCHWALA HUZEFA , CORDERO TONI L. , KAUFMAN FRANCINE R.
Published: June 2018

Background: Cognitive computing technology providing personalized insights based on correlations between behavior patterns and glycemic outcomes was leveraged to create an interactive mobile assistant for T1D patients.

Method: Medtronic MiniMed™ Connect users (N=256) were invited to take part in a 90-day Sugar.IQ app pilot program that began April 11, 2017. The percentage of time in target range (TIR, 70-180 mg/dL), <70mg/dL, >180mg/dL, and excursions (periods >20 minutes and <70mg/dL or >180mg/dL) were collected 30 days before Sugar.IQ onboarding, and compared to those 90 days later (August 2017). Insights delivered to users and user feedback were also analyzed.

Results: There were 11,356 sensor-wear days; 10,761 unique Sugar.IQ usage sessions collected; and 4,688 insights delivered (1 every 3 days). Insights included 655 and 699 identifying behaviors associated with more time <70mg/dL and >180mg/dL, respectively. The Sugar.IQ app was used 2.1 times/day. Compared to baseline, TIR was 33 minutes longer per day (P<0.15) and hypoglycemia events reduced by 1.0 per month (P<0.001). A week after receiving insights associated with hypoglycemia, 55% and 54% of users had fewer hypoglycemia and hyperglycemia events, respectively. Hyperglycemia events >2 hours reduced by 1.3 per month (P<0.001). After receiving insights about low glucose associated with boluses delivered at rapid rates of change, users tended to take smaller boluses and consume less carb in the following 7 days. Among insights that included user feedback, 86% of users rated them as “Helpful” vs. “Not helpful.”

Conclusion: Timely and personalized insights, such as those provided during the Sugar.IQ pilot, may advance patient understanding of glucose trends, aid in behavioral change that improves therapy adherence, and lead to better outcomes.

Disclosure

Y. Zhong: None. S. Arunachalam: None. P. Agrawal: None. H. Neemuchwala: None. T.L. Cordero: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.
HERV-W-Env Involvement in Human T1D Pathogenesis—New Insights from Two Mouse Models
Authors: LEVET SANDRINE , JOANOU JULIE , QUERUEL NELLY , PIERQUIN JUSTINE , PERRON HERVE J.F.
Published: June 2018

Human endogenous retroviruses (HERVs), known to represent 8% of the human genome, have been associated with several autoimmune diseases. In particular, the envelope protein of HERV-W family (HERV-W-Env), which has been involved in the pathogenesis of Multiple Sclerosis (MS), displays pro-inflammatory and autoimmune properties. This has initially been demonstrated in an MS context, but it subsequently turned out to be relevant for type 1 diabetes (T1D). We recently observed that HERV-W-Env protein and RNA are detected respectively in sera and PBMC of more than 50% of T1D patients. We demonstrated that this pathogenic protein is expressed by acinar cells in human T1D pancreas, and is associated with the recruitment of macrophages within the pancreas of these patients. HERV-W-Env also displays direct pathogenic properties, as it inhibits insulin secretion by human Langerhans islets. In this new report, we present data from two transgenic mouse models in which HERV-W-Env is expressed under the control of HERV-LTR and CAG promoter. In a first model, transgenic mice, generated in a C57Bl6/J background, were challenged by repeated STZ injections. We observed that transgenic mice are more susceptible to pancreatic damage than wild type mice, as they developed more severe insulitis (P<0.0001) and hyperglycemia (P<0.01). In a second model, transgenic mice are currently backcrossed in a NOD/ShiLtJ background. Preliminary results revealed that NOD transgenic males start to develop a hyperglycemia as soon as 4 weeks old compared to their controls littermates. Early results from these transgenic mice support a role for HERV-W-Env in human T1D pathogenesis, particularly in patients expressing this pathogenic protein. They provide additional justification for the ongoing phase IIa clinical trial which is designed to neutralize HERV-W-Env in T1D patients using a monoclonal antibody named GNbAC1 (NCT03179423). Six months interim results of this new therapeutic approach will be available 3rd quarter 2018.

Disclosure

S. Levet: Employee; Self; Geneuro Innovation. J. Joanou: Employee; Self; Geneuro Innovation. N. Queruel: Employee; Self; Geneuro Innovation. J. Pierquin: Employee; Self; Geneuro Innovation. H.J.F. Perron: Employee; Self; GeNeuro SA.
Dietary Fiber Intake and Glycemic Control—Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study
Authors: BASU ARPITA , ALMAN AMY C. , SNELL-BERGEON JANET K.
Published: June 2018

Background: Intake of sufficient dietary fiber has been recommended for glucose control, and typically low fiber intake is observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D).

Methods: We conducted a cross-sectional analysis of data from the CACTI study [n=1257; T1D: n=568; nondiabetic controls: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast) at screening visit. We used linear regression models to examine associations of total dietary fiber with HbA1c as a continuous variable. Models were stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of fiber with HbA1c.

Results: Baseline dietary fiber intake and HbA1c in the T1D group were 16g [median (IQ): 11-22g) and 7.9±1.3% mean (SD), respectively, and in the nondiabetic controls were 15g [median (IQ): 11-21g) and 5.4±0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r= -0.07, p=0.01). In adjusted linear regression models, total dietary fiber was significantly and inversely associated with HbA1c in the T1D group [estimate (beta±SE)= -0.32±0.15, p=0.034], as well as in the nondiabetic controls [-0.10±0.04, p=0.009]. Thus, at observed levels of intake, total dietary fiber reveals a protective association against poor glycemic control in T1D adults and in nondiabetic controls.

Disclosure

A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.
Text Message Responsiveness to BG Monitoring (BGM) Reminders Improves A1c in Teens with Type 1 Diabetes (T1D)
Authors: MCGILL DAYNA E. , VOLKENING LISA , BUTLER DEBORAH A. , LEVY WENDY , WASSERMAN RACHEL M. , ANDERSON BARBARA , LAFFEL LORI M.
Published: June 2018

Background: As teens with T1D become increasingly independent in self-care, adherence and glycemic control deteriorate. Teens need innovative ways to improve self-care and protect against glycemic decline. We evaluated a text messaging intervention in teens with T1D and assessed factors associated with text responsiveness and glycemic benefit over 18 months.

Methods: Teens with T1D (N=147), ages 13-17 years, received 2-way text reminders at self-selected times to check BG levels and reply by text with BG results. Teens received increasing numbers of text reminders, beginning with 1 and increasing to a maximum of 4/day.

Results: At baseline, teens (48% male, 78% white, 63% pump-treated) had mean±SD age 14.9±1.3 years, T1D duration 7.1±3.9 years, and A1c 8.5±1.1%. The mean proportion of days with 1+ BG response declined over time (months 0-6: 60±26% of days, months 6-12: 53±32%, months 12-18: 43±33%). Over the 18 month study, 50% of teens responded with 1+ BG result on ≥50% of days (“High Responders”). High Responders compared with “Low Responders” (<50% of days with 1+ BG response) were similar regarding age, T1D duration, and sex distribution but High Responders had lower baseline A1c (8.2±1.0 vs. 8.7±1.1%, p=.005) and higher daily BGM frequency (5.2±2.3 vs. 4.3±1.6, p=.01). Regression analysis controlling for baseline A1c revealed no significant change in A1c from baseline to 18 months in High Responders (p=.42) compared with a significant A1c increase in Low Responders (+0.3%, p=.009). In teens with baseline A1c ≥8%, High Responders (n=39) were 2.6 (95% CI 1.03, 6.6) times more likely than Low Responders (n=52) to improve A1c by ≥0.5% from baseline to 18 months (p=.04).

Conclusions: Responding to text reminders on ≥50% of days over 18 months provided clinically significant glycemic benefit to teens with T1D, especially in those with high baseline A1c. There remains a need to tailor interventions for teens over time to maintain their engagement and optimize improvements.

Disclosure

D.E. McGill: None. L. Volkening: None. D.A. Butler: None. W. Levy: None. R.M. Wasserman: None. B. Anderson: Advisory Panel; Self; Sanofi-Aventis. 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..
Hemodialysis (HD)-Mediated Improvements in Insulin Resistance Are Correlated with Nutritional Status in Patients with Type 2 Diabetes
Authors: FUNAKOSHI SATOSHI , HASHIGUCHI JYUNICHIRO , HAYASHIDA MASATOSHI , ETOH RICA , SAWASE KENJI , MORI YUTAKA , UTSUNOMIYA KAZUNORI , HARADA TAKASHI
Published: June 2018

Objective: Changes in C-peptide index (CPI) before and after hemodialysis (HD) were compared to explore factors associated with insulin resistance in diabetic patients receiving HD.

Methods: Fasting blood samples were drawn from type 2 diabetic patients receiving maintenance HD but not insulin therapy at our clinic before HD on the first day of the week they went on HD (pre-HD) as well as on the next day (post-HD) and CPI was calculated.

Results: The mean post-HD CPI was significantly lower than the mean pre-HD CPI (6.7 ± 2.7 ng/mL vs. 8.1 ± 3.3 ng/mL) in the 19 type 2 diabetic patients (men/women, 12/7) included in the study. The rate of decrease in CPI was strongly positively correlated with geriatric nutritional risk index (GNRI) (R2 = 0.692) in these patients, while it was not correlated with their glycoalbumin (GA) or fasting glucose values.

Conclusions: Despite reports that HD leads to resolution of uremia and excessive fluid overload resulting in improvements in insulin resistance, to date, very few reports compared insulin resistance before and after HD. This study showed that the rate of decrease in CPI was not increased in patients with favorable glycemic control but significantly increased in those with favorable nutritional status, suggesting that the patient’s overall status may have a role to play in HD-mediated improvements in insulin resistance in the short term.

Disclosure

S. Funakoshi: None. J. Hashiguchi: None. M. Hayashida: None. R. Etoh: None. K. Sawase: None. Y. Mori: None. K. Utsunomiya: None. T. Harada: None.
The Impact of Obesity on Incidence of Type 2 Diabetes Mellitus (T2DM) among Women with Polycystic Ovary Syndrome (PCOS)
Authors: KAKOLY NADIRA SULTANA , EARNEST ARUL , TEEDE HELENA , MORAN LISA , LOXTON DEBORAH , JOHAM ANJU E.
Published: June 2018

There is controversy surrounding the impact of obesity on the development of type 2 diabetes mellitus (T2DM) among women with polycystic ovary syndrome (PCOS). We aimed to clarify the role of PCOS per se in the development of T2DM by identifying the population-based incidence rate of T2DM among women with PCOS according to risk factors including body-mass index (BMI), ethnicity, and family history of T2DM.

We undertook a historical population-based cohort study of women aged 18-23 years followed-up over 15 years (between years 2000 and 2015) using the Australian Longitudinal Study on Women’s Health (ALSWH) database. The study cohort consisted of women with self-reported PCOS and women without a diagnosis of PCOS (controls). We undertook survival analysis to identify potential predictors of T2DM using Cox Proportional Hazard Model and person-time analysis to calculate incidence rates of T2DM per 1000 person-years (PY).

During a follow-up of 1,919 years of person-time, 186 women developed T2DM. The incidence rate of T2DM was 4.22 per1000 (PY) in PCOS vs. 1.02 per 1000 PY in controls (p<0.001). The Kaplan-Meier survival probability estimates at 15 years were: 0.952 and 0.988 for women with and without PCOS respectively. On sub-group analyses, BMI categories across lean, overweight, and obese women with PCOS [IRR (incidence rate ratio): 4.68, 3.52 and 2.36)respectively] showed a higher risk for T2DM compared to controls. In the multivariate Cox analysis, PCOS, BMI, education, and family history of T2DM all independently increased the risk for T2DM in all women. PCOS was the strongest predictor [HR: 3.38 (95% CI: 2.21, 5.18), p<0.001] adjusting for BMI, education, and family history of T2DM.

PCOS is independently associated with an increased incidence of T2DM among young adult women and this increased risk varies by BMI. Screening of young women for T2DM should be considered, based on their overall diabetes risk taking into account PCOS status, BMI, and other risk factors.

Disclosure

N. Kakoly: None. A. Earnest: None. H. Teede: None. L. Moran: None. D. Loxton: None. A.E. Joham: None.
Association of Visceral Fat and Liver Fat, Not Thigh Muscle Area nor Attenuation, with the Incidence of Type 2 Diabetes
Authors: SATO KYOKO , UEHARA SHINICHIRO , SHIBATA MIKIKO , HIKITA YONEZO , FUJIMOTO WILFRED Y. , BOYKO EDWARD J. , HAYASHI TOMOSHIGE
Published: June 2018

Visceral fat, liver, and skeletal muscle are all major target organs of insulin and play key roles in the pathophysiology of type 2 diabetes. Not known is whether visceral fat, liver fat, and thigh skeletal muscle area or fat directly measured by computed tomography (CT) are independently associated with the incidence of type 2 diabetes. In a prospective cohort study, 1228 nondiabetic Japanese men and women were included. Intra-abdominal fat area (IAFA), liver-to-spleen (L/S) attenuation ratio to assess liver fat, and mid-thigh muscle area and attenuation were measured by CT. Low CT attenuation of liver and muscle reflects greater liver and intramuscular lipid content. Insulin resistance was assessed by HOMA-IR. Type 2 diabetes was diagnosed as fasting plasma glucose level ≥126 mg/dL, HbA1c ≥6.5%, or taking oral hypoglycemic medications or insulin. Discrete-time logistic hazard model was used. During the 7686 person-years of follow-up (median follow-up period, 7 years), 95 subjects developed type 2 diabetes. IAFA and L/S ratio, not thigh muscle area, were independently associated with the risk of type 2 diabetes. In multiple-adjusted models that included IAFA, L/S ratio, thigh muscle area, age, gender, family history of diabetes, HOMA-IR, smoking habit, daily alcohol consumption, and regular physical activity, odds ratios of type 2 diabetes for tertile 2 and 3 of IAFA were 2.23 (95% CI, 0.94-5.31) and 3.16 (1.33-7.52), respectively, compared to tertile 1, and those for tertile 1 and 2 of L/S ratio were 2.01 (1.01-3.97) and 2.(1.04-4.08), respectively, compared to tertile 3. However, those of tertile 2 and 3 of thigh muscle area were 0.76 (0.32-1.78) and 0.64 (0.24-1.69), respectively, compared to tertile 1. When thigh muscle attenuation was substituted for its area, results was identical to the above model.

In conclusion, both greater amounts of visceral and liver fat, not thigh muscle area nor attenuation, were independently associated with the risk of type 2 diabetes.

Disclosure

K. Sato: None. S. Uehara: None. M. Shibata: None. Y. Hikita: None. W.Y. Fujimoto: None. E.J. Boyko: None. T. Hayashi: None.
The Association between Lipid Profile Abnormalities and the Risk of Proteinuria in Japanese Men with Impaired Fasting Glucose or Type 2 Diabetes
Authors: UEHARA SHINICHIRO , SATO KYOKO , SHIBATA MIKIKO , OUE KEIKO , KAMBE HIROSHI , MORIMOTO MICHIO , HAYASHI TOMOSHIGE
Published: June 2018

Lipid profile abnormalities have been reported to be associated with cardiometabolic diseases, but it is not fully known whether lipid profile abnormalities are prospectively associated with the risk of proteinuria in subjects with impaired fasting glucose (IFG) or type 2 diabetes. Study subjects included 3801 Japanese men aged 40-55 years who had fasting plasma glucose ≥100 mg/dL, no proteinuria, eGFR ≥60 mL/min/1.73 m2, and no history of cancer and were not taking antihypertensive, lipid-lowering, and hypoglycemic medications at baseline. The incidence of proteinuria was defined as “consecutive proteinuria” if it was detected twice consecutively as 1+ or higher on urine dipstick during the follow-up periods to exclude chance proteinuria as much as possible. Triglycerides, HDL-cholesterol, non HDL-cholesterol, and LDL-cholesterol levels were obtained at baseline. During the 11-year follow-up period, we confirmed 221 cases of proteinuria. In Cox proportional-hazards analysis, higher level of triglycerides increased the risk of proteinuria and higher level of HDL-cholesterol decreased the risk of proteinuria. After adjustment for age, eGFR, fasting plasma glucose, hypertension status, alcohol consumption, regular physical activity, and smoking status, hazard ratios (HRs) for triglycerides levels of 100-149, 150-199, and ≥200 mg/dL were 1.07 (95% CI, 0.73-1.55), 1.22 (0.80-1.84), and 1.47 (1.01-2.13), respectively, compared with <100 mg/dL. The HRs for HDL-cholesterol levels of 40-59, 60-79, and ≥80 mg/dL were 0.52 (0.36-0.75), 0.52 (0.34-0.82), and 0.44 (0.22-0.92), respectively, compared with <40 mg/dL. However, neither non HDL-cholesterol nor LDL-cholesterol were associated with the risk of proteinuria.

In conclusion, higher level of triglycerides increased the risk of incident consecutive proteinuria and higher level of HDL-cholesterol decreased it in the middle-aged Japanese men with IFG or type 2 diabetes.

Disclosure

S. Uehara: None. K. Sato: None. M. Shibata: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None.
Effect of Gestational Diabetes and Maternal Obesity on Fetal Programming—Are miRNAs Key Epigenetic Modifiers or Biomarkers of an Altered Intrauterine Milieu?
Authors: JOSHI APOORVA , GOETZL LAURA , PINNEY SARA E.
Published: June 2018

Background: Pregnancies complicated by gestational diabetes (GDM) or maternal obesity (MOB) induce abnormal fetal development that can lead to diabetes and obesity later in life with sex specific manifestations. Alterations in miRNA expression in GDM and MOB exposed offspring and effects on development have not been fully described.

Hypothesis: Exposure to an aberrant intrauterine milieu complicated by GDM and MOB leads to changes in miRNA and target gene expression in human fetal liver.

Methods: Candidate miRNA expression was measured in second trimester AF from women diagnosed with GDM via multiplex miRNA assay (Firefly Bioworks, Abcam). Gene targets of differentially expressed miRNAs were determined from TargetScan and pathway enrichment determined via Ingenuity Pathway Analysis (IPA). MiRNA and target gene expression (mRNA and protein) were measured in a separate cohort of 2nd trimester primary human fetal hepatocytes (PHFH) exposed to MOB via QPCR and western blot. All studies were approved by UPENN and TEMPLE University IRBs.

Results: GDM exposed AF had significant increases in miRNAs 199a-3p, 503-5p, and 1268a (p<0.05) and sex specific analysis showed enrichment in miRNAs 378a-3p, 885-5p, and 7-1-3p in female offspring samples (p<0.05). IPA with gene targets of enriched miRNAs centered hepatic pathways. GDM exposed AF miRNA enrichment was confirmed in PHFH exposed to MOB for miRNAs 885-5p, 199-3p, 503-5p, and 7-1-3p (p<0.05). Female PHFH exposed to MOB were enriched for miRNAs 885-5p, 199-3p, 503-5p, and 7-1-3p (p<0.05) and corresponded to decreased expression of target genes ABCA1, PAK4. In male PHFHs, no miRNA expression changes were measured but there was increased expression of ABCA1 and PAK4 (p<0.05).

Conclusion: Our data suggest sex specific changes in miRNA and target gene expression in PHFH may be one mechanism responsible for sex specific metabolic changes in offspring exposed to GDM and obesity in utero.

Disclosure

A. Joshi: None. L. Goetzl: None. S.E. Pinney: None.
Prediabetes Is Associated with Increased Long-Term Mortality Regardless of Subsequent Glycemic Progression
Authors: WOO YU CHO , LEE CHI HO , FONG HO YI , YEUNG MAN YI , LAM KAREN S.L.
Published: June 2018

Objective: To study the mortality risk in a long-term population-based prospective study among subjects with prediabetes (PreDM) at baseline, compared to those with persistent normal glucose tolerance (NGT), taking into account whether they had had non-persistent PreDM, persistent PreDM, or converted to diabetes, during the follow-up period.

Methods: Subjects without history of diabetes had oral glucose tolerance test (OGTT) performed at each visit. Those who attended the baseline visit (1995-6) and returned for assessment at least once in 2000-4, 2005-8 and 2010-2 were included. PreDM was defined as impaired fasting glucose (≥ 5.6 mmol/L) or impaired glucose tolerance (2hour post-OGTT glucose ≥ 7.8 and <11.1 mmol/L). They were considered non-persistent PreDM if they reversed to NGT at least once, persistent if they remained PreDM throughout and converted if they progressed to diabetes. The NGT group included those attending at least 3 visits and had NGT persistently. Deaths from the Death Registry were adjudicated by record review. Mortality risk of PreDM subjects was compared to the NGT group.

Findings: 1225 subjects, 529 with PreDM (non-persistent, 41.9%; persistent, 23.3%; converted, 34.8%), were included for analysis. Factors independently associated with PreDM at baseline were age, body mass index, dyslipidemia and physical inactivity, as analysed by logistic regression. After 21.8 (IQR: 21.4-22.3) years, there were 101 deaths. Age, smoking and PreDM were the independent predictors of death identified using backward multivariable Cox regression. The non-persistent, persistent and converted groups all had higher mortality risk compared to NGT (Hazard Ratio: 2.33, 2.47, 2.43, all p<0.05).

Conclusions: We concluded that PreDM increased long-term mortality, regardless of the subsequent mode of glycemic progression. Measures for smoking control and prevention of PreDM through promotion of healthy diet, regular exercise and weight control, are recommended.

Disclosure

Y. Woo: None. C. Lee: None. H. Fong: None. M. Yeung: None. K.S.L. Lam: None.
Study on the Correlation between Cholecystectomy and Nonalcoholic Fatty Liver Disease in Type 2 Diabetes
Authors: YE LU , CHEN HAIBING
Published: June 2018

Objective: To study the relationship between nonalcoholic fatty liver disease and cholecystectomy in patients with type 2 diabetes mellitus (DM).

Methods: From January 2011 to December 2014 3970 cases of hospitalized patients with type 2 diabetes, divided 2 groups, without cholecystectomy group (3435 cases) and cholecystectomy group (535 cases), clinical data and biochemical indexes of the two groups were compared including liver function, renal function, blood lipid, glycosylated hemoglobin, glycated albumin and blood routine, CRP data.

Results: The prevalence of NAFLD in the cholecystectomy group was higher than that in the without cholecystectomy group(60.9% vs. 46.1%), and the difference was significant (P<0.001). The levels of TG and BMI in the cholecystectomy group were higher than those in the without cholecystectomy group (P<0.05). The risk factors of NAFLD two classification logistic regression analysis of risk factors, there exists in the model of 5 variables, including history of cholecystectomy (P<0.001, OR=1.896), sex (P<0.001, OR=0.584), waist circumference (P <0.001, OR = 1.047), TG (P <0.001, OR= 2.058),BMI(P<0.05,OR=1.173) were independently correlated with NAFLD.

Conclusion: Cholecystectomy is an independent risk factor for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus.

Disclosure

L. Ye: None. H. Chen: None.
Diabetes Risk Behaviors Are Higher among Sexual Minority U.S. High School Students
Authors: BEACH LAUREN B. , TURNER BLAIR , MARRO RACHEL , PHILLIPS GREGORY
Published: June 2018

Low physical activity (PA) and high sedentary behavior (SB) are associated with increased type 2 diabetes risk among youth. We investigated PA and SB among Youth Risk Behavior Survey (YRBS) respondents to determine if sexual minority youth may be at increased diabetes risk compared to heterosexual youth. Weighted city and state YRBS data were pooled across 44 jurisdictions biennially from 2009-2015, resulting in a sample size of 97 jurisdiction-years (350,673 students). Respondents had a median age of 16 years, were 50.3% male, and 46.8% white. Overall, 88.4% identified as heterosexual, 2.1% as gay/lesbian, 5.7% as bisexual, and 3.7% as unsure; more female (15.3%) than male (7.7%) students reported a non-heterosexual identity. Among females, bisexual and unsure (but not lesbian) youth reported significantly more hours per day of SB compared to heterosexual peers. We found no significant differences in SB among males. Both female and male sexual minority youth reported significantly fewer days per week of PA compared to sex-matched heterosexual peers. All unadjusted PA and SB findings remained significant after adjusting for age, BMI, race/ethnicity, and survey year, except among lesbian youth. Studies of type 2 diabetes and risk factors among youth need to assess and account for sexual identity to ensure sexual minority populations are a priority target for prevention.

Table I. Bold text: Unadjusted p-value significant; *Adjusted p-value <0.001; hetero=referenceSB (95%CI) Hours/DayPA (95% CI) Days/WeekSexual IdentityMaleFemaleMaleFemaleHeterosexual3.7 (3.7-3.8)3.6 (3.6-3.7)4.4 (4.3-4.4)3.4 (3.4-3.6)Gay/Lesbian3.7 (3.4-4.0)3.9 (3.7-4.2)2.8* (2.6-3.1)3.1 (2.9-3.4)Bisexual4.0 (3.7-4.3)4.3* (4.1-4.4)3.1* (2.7-3.4)3.0* (2.8-3.1)Unsure4.0 (3.7-4.4)4.3* (4.0-4.6)3.0* (2.7-3.3)3.0* (2.7-3.4)

Disclosure

L.B. Beach: None. B. Turner: None. R. Marro: None. G. Phillips: None.
Conformance to Type 2 Diabetes (T2D) Guidelines in a Large U.S. Health Plan
Authors: MEHTA RAJESH , EDWARDS ALISON , RAJPATHAK SWAPNIL , SHARMA AJAY , SNOW KENNETH J. , IGLAY KRISTY
Published: June 2018

Almost half of U.S. T2D patients (pts) have suboptimal glycemic control (A1c ≥7%). One factor that may be associated with this is clinical inertia related to physician/patient actions or lack of “conformance” to guidelines. We characterized uncontrolled pts in terms of conformance in a large U.S. database (Aetna). This study included T2D pts with at least one A1c ≥7% from Jul 2014-Aug 2015 with ≥6 months pre-index data (Era 1), 12 months post-index data to assess conformance (Era 2), and ≥6 months data post-Era 2 to assess outcomes (Era 3; Figure). Conformance was defined as high (HC) or low (LC) based on provider actions (A1c test performed, T2D office visit, or medication changed/added) and patient goal attainment (A1c <7%). There were 21,171 eligible pts who had the following characteristics: median age 60 years, 55% male, and 80% HC. In a multivariate model, odds ratios (OR) for Era 1 factors associated with HC were: comorbidities (OR=1.09 [1.07, 1.12]), A1c test (OR=1.43 [1.28, 1.60]), PCP visit (OR=3.23 [3.01, 3.47]), nephropathy screening (OR=0.84 [0.79, 0.89]), oral T2D medication use (OR=0.83 [0.77, 0.90]), age (OR=0.99 [0.98, 0.99]), GLP-1 use (OR=1.20 [1.004, 1.44]), and episode risk group score (measure of healthcare utilization; OR=1.01 [1.001, 1.03]).

In conclusion, factors associated with conformance to guidelines, as identified in this study, can help target interventions to improve clinical outcomes in these high risk subgroups.

Disclosure

R. Mehta: None. A. Edwards: None. S. Rajpathak: Employee; Self; Merck & Co., Inc.. A. Sharma: None. K.J. Snow: Employee; Self; Aetna Inc. K. Iglay: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc..
Circulating Exosomal miRNA Signature in Pregnancies with Gestational Diabetes Mellitus across Gestation
Authors: GUANZON DOMINIC , LAI ANDREW , SCHOLZ-ROMERO KATHERIN , ZUÑIGA FELIPE , DIAZ EMILIO , DAVID MCINTYRE H. , LAPPAS MARTHA , SALOMON CARLOS
Published: June 2018

Exosomes are small nanovesicles that carry bioactive molecules (e.g., miRNAs) which can be delivered to other cells and modify their phenotype. Recently, we have established that the number of circulating exosomes is higher in women with gestational diabetes mellitus (GDM); however, the exosomal miRNA profile in GDM across gestation has not been established yet. The aim of this study was to establish the circulating exosomal miRNA profile in women with normal glucose tolerance (NGT) and GDM women (BMI-matched) in a prospective cohort of patients at three time points during pregnancy. Exosomal RNA was sequenced using an Illumina NextSeq 500 platform. Linear mixed modelling was performed on the normalized miRNAs across gestation for normal and GDM pregnancies, using the lme4 package in R. Statistically significant differences in miRNA expression between NGT and GDM women was determined using likelihood ratio tests. In the first trimester of pregnancy, 92% (84 out of 92) of exosomal miRNAs were significantly elevated in plasma of women with GDM when compared to NGT women. Interestingly, in the second trimester of pregnancy the expression of these miRNA decreased in the GDM women with no significance difference observed in the exosomal miRNA profile between GDM and NGT women. Gene ontology analysis revealed that miRNAs which changed expression across gestation for GDM pregnancies are involved in the regulation of insulin.

In summary, we have identified a range of exosomal miRNAs which change expression across gestation for GDM and normal pregnancies. Gene ontology analysis revealed that these miRNAs are involved in the regulation of insulin, playing significant role in the pathophysiology of GDM.

Disclosure

D. Guanzon: None. A. Lai: None. K. Scholz-Romero: None. F. Zuñiga: None. E. Diaz: None. H. McIntyre: Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Danish Diabetes Academy. M. Lappas: None. C. Salomon: None.
Circulating Sphingolipids, Insulin, HOMA-IR, and HOMA-B—The Strong Heart Family Study
Authors: LEMAITRE ROZENN N. , YU CHAOYU , HOOFNAGLE ANDREW , NAIR HARI , JENSEN PAUL N. , FRETTS AMANDA M. , UMANS JASON G. , SITLANI COLLEEN , SISCOVICK DAVID , KING IRENA , SOTOODEHNIA NONA , MCKNIGHT BARBARA
Published: June 2018

High levels of fasting plasma insulin, reflecting insulin resistance, are an early event in the progression to type 2 diabetes. Experimental studies implicate ceramides in insulin resistance; however, whether circulating ceramides and related sphingolipids are associated with plasma insulin in humans is uncertain. We measured 15 ceramide and sphingomyelin species with different saturated fatty acids in baseline fasting plasma samples from the Strong Heart Family Study, a prospective cohort of American Indians. We examined associations of sphingolipids with plasma insulin, HOMA-IR and HOMA-B at baseline and follow-up (median 5 years later) using linear mixed models adjusted for family structure. Among 2086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0, 18:0, 20:0 or 22:0 were associated with higher plasma insulin and higher HOMA-IR at baseline and follow-up (Table). BMI modified associations of sphingomyelin species carrying 18:0, 20:0, 22:0 or 24:0 with insulin (p<0.003); higher sphingomyelin levels were associated with lower fasting insulin and HOMA indices only among those with normal BMI. Our study suggests lowering circulating ceramides might be a target in prediabetes, and targeting sphingomyelins should take into account BMI.

Table. Plasma Ceramides, Insulin and HOMAIR.SpeciesFold change in geometric mean with 2 fold higher ceramide (95% CI), p-valueBaseline insulinFollow-up insulinBaseline HOMAIRFollow-up HOMAIRCer-16:01.13 (1.07-1.20) 1.9x10-51.10 (1.01-1.21) 0.031.15 (1.08-1.22) 4.7x10-61.11 (1.01-1.22) 0.03Cer-18:01.11 (1.06-1.15) 1.0x10-61.12 (1.06-1.19) 1.0x10-51.12 (1.08-1.17) 6.3x10-81.13 (1.06-1.20) 2.0x10-4Cer-20:01.12 (1.07-1.17) 1.5x10-71.10 (1.03-1.18) 0.0031.13 (1.08-1.18) 1.3x10-71.11 (1.04-1.19) 0.002Cer-22:01.13 (1.08-1.19) 3.9x10-71.12 (1.04-1.20) 0.0041.15 (1.09-1.21) 1.0x10-71.13 (1.04-1.22) 0.004Cer-24:01.(0.99-1.11) 0.081.09 (1.01-1.19) 0.041.(1.00-1.13) 0.041.11 (1.01-1.21) 0.03Covariates: age, sex, site, education, smoking, log(BMI), waist, physical activity.

Disclosure

R.N. Lemaitre: None. C. Yu: None. A. Hoofnagle: Research Support; Self; Waters Corporation. H. Nair: None. P.N. Jensen: None. A.M. Fretts: None. J.G. Umans: None. C. Sitlani: None. D. Siscovick: None. I. King: None. N. Sotoodehnia: None. B. McKnight: None.
Metformin Regresses Left Ventricular Hypertrophy in Normotensive Patients with Coronary Artery Disease without Type 2 Diabetes Mellitus—The MET-REMODEL Trial
Authors: MOHAN MOHAPRADEEP , AL-TALABANY SHAWEEN , MCKINNIE ANGELA M. , MORDI IFY , SINGH JAGDEEP S. , GANDY STEPHEN J. , CHOY ANNAMARIA , HOUSTON JOHN G. , GEORGE JACOB , STRUTHERS ALLAN D. , LANG CHIM C. ,   MET-REMODEL INVESTIGATORS
Published: June 2018

Background: Left ventricular hypertrophy (LVH) is highly prevalent in patients with coronary artery disease (CAD) and is an independent predictor of cardiovascular mortality. Metformin has been shown to regress LV mass (LVM) in animal models of LVH. We hypothesize that metformin may regress LVH in nondiabetic and normotensive CAD patients with prediabetes and/or insulin resistance.

Methods: In this randomized double-blind placebo controlled trial, 68 patients with prediabetes (HbA1c ?39 mmol/mol and less than 48 mmol/mol) and/or insulin resistance (fasting insulin resistance index ? 2.7) were assigned to receive either metformin (2g daily dose) or placebo for 12 months. An intention-to-treat (ITT) and per-protocol analysis was designed to determine the effect of metformin on the following study endpoints: Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging; other endpoints were changes in LVM, changes in body weight, office blood pressure (BP) and biomarkers.

Results: In the ITT analysis (n=61), metformin treatment significantly reduced: LVMI (metformin -2.7 ± 2.3 g/m1.7 vs. placebo -1.4 ± 2.7 g/m1.7; P=0.05), body weight (lowered by 3.6 kgs, p=0.002), office systolic BP (metformin -4.8 ± 15.6 mmHg vs. placebo 4.6 ± 15.7 mmHg; P=0.02) and reduced concentration of thiobarbituric acid reactive substances (TBARs), a biomarker for oxidative stress (p=0.04). In the on-per protocol analysis (n=56), metformin resulted in a greater reduction of LVMI (metformin -3.1 ± 1.9 g/m1.7 vs. placebo -1.2 ± 2.7 g/m1.7; P=0.005), and greater weight reduction of 4.2kgs (p=0.001).

Conclusions: Metformin treatment significantly reduced LVMI, office SBP, body weight and oxidative stress. These results reveal a novel mechanism for the cardioprotective effect of metformin and raise the possibility of using metformin in nondiabetic patients with CAD.

Disclosure

M. Mohan: None. S. Al-Talabany: None. A.M. McKinnie: None. I. Mordi: None. J.S. Singh: None. S.J. Gandy: None. A. Choy: None. J.G. Houston: None. J. George: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. C.C. Lang: None.
Nationwide Analysis of Excess Deaths Attributable to Diabetes in Brazil
Authors: BRACCO PAULA , GREGG EDWARD W. , ROLKA DEBORAH B. , SCHMIDT MARIA I. , BARRETO SANDHI MARIA , LOTUFO PAULO A. , MELO ENIRTES C. , DUNCAN BRUCE B.
Published: June 2018

Background: Little is known about the magnitude of excess mortality due to diabetes in low and middle income countries. Brazilian data to that end have been limited by reliance on death certificates and their subjective assignment of diabetes as a cause of death. We provide estimates of excess mortality due to diabetes by combining mortality risks from the ELSA-Brasil cohort with nationally representative surveys and databases.

Methods: We calculated the standardized mortality rate ratio for those with (vs. without) self-reported diabetes in ELSA-Brasil by Poisson regression adjusting for age, sex, race and education. We obtained similarly adjusted, self-reported diabetes prevalence from the 2013 National Health Survey. Mortality and population projections were from national statistics. We combined these data to model the excess deaths due to diabetes.

Results: In 2013, among adults with diabetes aged 35 to 74 (table), 73,092 deaths (13% of total) could have been avoided if the mortality rate in people with diabetes were the same as in those without diabetes. The percent ranged from 5.9% in persons aged 35-49 to more than 16% in those 60 or older. In the national mortality system, only 31,117 deaths had diabetes as a main cause.

Age GroupStandardized Mortality Rate Ratio Population NTotal Deaths NDeaths among People with Diabetes NExcess Deaths Associated with Self-Reported Diabetes  With diabetesWithout diabetes Assuming diabetes mortality rateAssuming non-diabetes mortality rateExcess deaths among people with diabetes N% of total deaths35-492.40 (1.13  - 5.08)746,790 (3.7 %)19,538,124 (96.3%)120,20011,7224,6777,0455.950-591.94 (1.24 - 3.04)992,878 (10.2%)8,781,526 (79.8%)140,57730,86012,91417,94612.860-691.93 (1.35 - 2.74)941,815 (16.3%)4,853,378 (83.7%)182,45055,78725,15930,62816.870-741.58 (0.94 - 2.66)338,769 (20.3%)1,333,776 (79.7%)106,63735,53518,06217,47316.4Total1.91 (1.51 - 2.41)3,020,252 (8.1%)34,506,804 (92.9%)549,864133,90460,81273,09213.3

Conclusion: This calculation of excess deaths related to known diabetes in Brazil suggests a major diabetes mortality burden, which is considerably underestimated by calculations based only on death certificates.

Disclosure

P. Bracco: None. E.W. Gregg: None. D.B. Rolka: None. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. S. Barreto: None. P.A. Lotufo: Consultant; Self; AbbVie Inc.. E.C. Melo: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.