bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Parathyroid Hormone Is Associated with an Increased Mortality Risk in Type 2 Diabetes
Authors: MUENDLEIN AXEL , LEIHERER ANDREAS , SAELY CHRISTOPH H. , GEIGER KATHRIN , BRANDTNER EVA-MARIA , LARCHER BARBARA , MADER ARTHUR , FRAUNBERGER PETER , KLEBER MARCUS , DRESSEL ALEXANDER , MAERZ WINFRIED , DREXEL HEINZ
Published: June 2018

Parathyroid hormone (PTH) is one of the main regulators of calcium homeostasis. PTH levels are elevated in primary hyperparathyroidism as well as with vitamin D deficiency or chronic kidney disease. The association of increased PTH levels with all-cause mortality in high-risk patients is unclear. We therefore investigated the impact of serum PTH on mortality risk in a large series of 939 patients undergoing coronary angiography for the evaluation of established or suspected coronary artery disease (CAD), including 244 patients with type 2 diabetes (T2DM). Prospectively, deaths were recorded over a mean follow-up period of 6.2 years. PTH at baseline was inversely associated with eGFR (rho=-0.228; p<0.001) and 25-hydroxy-vitamin D (rho=-0.243; p<0.001) and was positively associated with age (rho=0.122; p<0.001) and BMI (rho=0.099, p=0.002). Prospectively, elevated PTH was not significantly associated with an increased mortality risk in the total study cohort (standardized HR 1.30 [0.96-1.76]; p=0.092). However, subgroup analysis with respect to T2DM showed a highly significant association of PTH with mortality in patients with T2DM (HR 2.32 [1.37-3.95]; p=0.002), but no association of PTH with mortality in nondiabetic subjects (HR 1.04 [0.82-1.32]; p=0.766). An interaction term T2DM x PTH was significant (p=0.006), indicating a significantly stronger influence of PTH on mortality risk in patients with diabetes than in individuals without T2DM. The impact of PTH on mortality risk in patients with T2DM remained significant after adjustment for age, gender, and BMI (HR 2.30 [1.34-3.93]; p=0.002) as well as after additional adjustment for, smoking, kidney function, baseline vitamin D and angiographically determined baseline CAD (HR 1.91 [1.07-3.40]; p=0.029). We conclude that elevated PTH levels are a strong and independent predictor of all-cause mortality in patients with T2DM.

Disclosure

A. Muendlein: None. A. Leiherer: None. C.H. Saely: None. K. Geiger: None. E. Brandtner: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. M. Kleber: None. A. Dressel: None. W. Maerz: None. H. Drexel: None.
The Relationship between Immigration Status and Cardiovascular Disease Risk Factors in United States Adults with Diabetes—A 14-Year Study
Authors: DAWSON APRILL , GARACCI EMMA , OZIEH MUKOSO N. , WALKER REBEKAH J. , EGEDE LEONARD E.
Published: June 2018

Introduction: Chronic diseases such as heart disease, stroke, and type 2 diabetes are common health issues in the U.S. About 9.4% of the U.S. population has diabetes. Research shows there is a relationship between immigration status and prevalence of chronic disease. The aim of this study is to understand the relationship between immigration status and CVD risk factors such as LDL, blood pressure, hemoglobin A1c (HbA1C), and body mass index (BMI).

Methods: The study included seven waves of data from the National Health and Nutrition Examination Survey (NHANES) for individuals with diabetes, aged 20 and older between 2001-2014. Survey participants were categorized as foreign-born and U.S. born based on self-report responses. Outcome measures included BMI, blood pressure, LDL, and HbA1C, measured as part of the NHANES procedures. Survey general linear regression methods were used to model each outcome and results were weighted to calculate nationally representative estimates.

Results: Approximately, 5,414 individuals (representing 22,788,949 U.S. adults) were included in the study. Twenty-seven percent of the sample were foreign-born representing about 18% of the U.S. population. After controlling for demographics, NHANES waves, access to health care, and years of residence in the U.S. foreign-born individuals had significantly lower BMI (-3.05; p<0.0001) and systolic blood pressure (-2.55; p=0.023). There was no significant difference in diastolic blood pressure, LDL, or HbA1C among foreign-born and U.S.-born.

Conclusions: Foreign-born individuals with diabetes have lower BMI and systolic blood pressure compared to U.S.-born individuals. Prior to adjusting for access to care, foreign-born had higher LDL suggesting the importance of improving access to care and ensuring that CVD risk factors are under control. Interventions focused on lowering LDL among foreign-born individuals will be critical in lowering their cardiovascular disease risk.

Disclosure

A. Dawson: None. E. Garacci: None. M.N. Ozieh: None. R.J. Walker: None. L.E. Egede: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Self; Novo Nordisk Inc..
A Real-World Evaluation of the Association between Cardiovascular Outcomes and T2D Therapy
Authors: THIEL ELLEN , MARDER WILLIAM D. , CEFALU WILLIAM T. , DARSOW TAMARA , PETERSEN MATT , LATTS LISA
Published: June 2018

Data from placebo controlled, randomized clinical trials (RCTs) have demonstrated cardio-protective effects of certain diabetes therapy classes, including sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon receptor agonists (GLP-1RA). However, the majority of these trials made comparisons to placebo and there is limited data on head to head comparisons between specific classes.

We performed an observational cohort study using the Truven Health MarketScan® Research Databases (2013-2016) to compare the risk of cardiovascular events between patients initiating treatment with SGLT2is, dipeptidyl peptidase-4 inhibitors (DPP-4is) and GLP-1-RAs vs. sulfonylureas (SUs) in a real-world setting. Propensity score weighting and doubly robust methods (boosting and Poisson regression) were used to control for differences in baseline characteristics. The primary study outcomes were hospitalization for congestive heart failure, acute myocardial infarction, stroke and a composite of all three. Lower extremity amputations were also examined. The relative risks of events in the 12 months before and after treatment initiation were compared to generate relative risk ratios.

Protective effects of SGLT2is compared to SUs were observed (Table). Interestingly, there was also a protective effect of DPP-4is on individual outcomes compared to SUs in contrast to DPP-4i vs. placebo in RCTs.

Disclosure

E. Thiel: None. W.D. Marder: Employee; Self; IBM. W.T. Cefalu: None. T. Darsow: None. M. Petersen: None. L. Latts: Other Relationship; Self; Medtronic, Novo Nordisk Inc., Sanofi.
Pericardial Adipose Tissue and Coronary Calcium in Type 1 Diabetes—The CACTI Study
Authors: KESHAWARZ AMENA , PYLE LAURA , ALMAN AMY C. , SASSANO CAPRICE , WESTFELDT ELIZABETH , SIPPL RACHEL M. , SNELL-BERGEON JANET K.
Published: June 2018

Type 1 diabetes (T1D) and menopause are associated with higher risk of coronary artery calcium (CAC). Accumulation of pericardial adipose tissue (PAT), a pro-inflammatory visceral fat higher in post-menopausal women and associated with increased CAC, may be a mechanism by which T1D is associated with higher CAC risk. We examined the effect of PAT on the relationship between T1D and CAC in women over time.

PAT and CAC volume data were collected from CT heart scans over 4 study visits from 725 women enrolled in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (mean baseline age ± SD, 37 ± 9 years). We used repeated measures modeling to examine changes in square root-transformed CAC volume over time by T1D, menopausal status, and quartile of PAT volume after adjusting for age, central obesity, and study visit.

PAT levels did not differ by T1D status (33.5 vs. 33.7, p=0.8), but there was a significant interaction between PAT, menopause, and T1D (p=0.02) in relation to CAC volume (Figure 1). In T1D women, higher PAT was associated with higher CAC volume regardless of menopause status, but the effect was greater in post-menopausal women. There was no difference in CAC in nondiabetic (non-DM) women across PAT quartiles or by menopause status. CAC was higher in T1D than non-DM women regardless of menopause status and PAT quartile.

PAT has a greater effect on CAC in women with T1D than non-DM women, despite similar PAT volumes.

Disclosure

A. Keshawarz: None. L. Pyle: None. A.C. Alman: None. C. Sassano: None. E. Westfeldt: None. R.M. Sippl: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.
Derivation of an EMR-Based Dysglycemia Risk Score
Authors: BOWEN MICHAEL E. , SANDERS JOANNE , ZHANG SONG , SANTINI NOEL O. , LINGVAY ILDIKO , HALM ETHAN
Published: June 2018

Few diabetes risk scores are derived from and designed for use in the electronic medical record (EMR). We developed an EMR-derived random blood glucose (RBG) diabetes risk score to detect dysglycemia (diabetes+prediabetes) and improve case identification. A RBG-risk score to detect prevalent dysglycemia (A1C≥5.7%) was derived from EMR data in an integrated safety-net health system. Primary care patients (age 18-64; resulted A1C in 2011-2014; ≥1 RBG 24 months prior to the A1C) were eligible. We excluded patients with diagnosed dysglycemia using ICD codes and lab results. Most recent RBG and EMR-extracted demographics, comorbidities, and diabetes risk factors on the date of the A1C were used to build logistic regression models predicting dysglycemia using backwards selection. Predictors retained in the final regression model were converted to a points-based risk score (Age 0-6; race 0-3, BMI 0-5; hypertension 0-1; RBG 0-13). We report dysglycemia risk, sensitivity, specificity, and PPV for clinically relevant cutpoints. The cohort included 11,387 patients (mean age 48, 65% female, 42% Hispanic, 36% black, mean BMI 32, 29% with hypertension), of whom 42% had dysglycemia. Screening criteria were met by 86% (ADA), 65% (USPSTF), and 40-60% of patients at clinically relevant Risk Scores (9-11). The Risk Score c-statistic was significantly better than both ADA (0.75 vs. 0.56; p<0.001) and USPSTF (0.75 vs. 0.60; p<0.001) guidelines. An example patient with a Risk Score of 9 would be: age 50, BMI 29, white, has hypertension and RBG 112. A score of 9 identified 61% of the sample as high risk (35%) for undiagnosed dysglycemia and yielded 80% sensitivity, 53% specificity, PPV 56%, and NPV 78%. Using a cutpoint of 9, if the Risk Score were run on 1000 patients, 610 would undergo screening, 335 new cases of dysglycemia would be detected, and 85 cases would be missed. An EMR-derived RBG-risk score capable of automation in the EMR outperforms screening guidelines to detect dysglycemia. Further validation studies are needed to determine clinical usefulness.

Disclosure

M.E. Bowen: None. J. Sanders: None. S. Zhang: None. N.O. Santini: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S. E. Halm: None.
Incidence and Risk of Celiac Disease in Individuals with Type 1 Diabetes over the Lifespan—A Population-Based Cohort Study Using the Health Improvement Network Database
Authors: VAJRAVELU MARY ELLEN , LEON DIVA DE , WEBER DAVID R. , KEREN RON , DENBURG MICHELLE R. , VERMA RITU
Published: June 2018

Objective: Individuals with type 1 diabetes (T1D) are at increased risk for celiac disease (CD), though the incidence for those diagnosed with T1D beyond childhood is unknown. We used survival analysis to investigate the incidence and risk factors for diagnosis of CD over time in a population-based cohort of children and adults with T1D.

Methods: Retrospective cohort study using The Health Improvement Network (THIN), a primary care electronic medical records database of >13 million people in the United Kingdom. Subjects were 1-35 years old at T1D diagnosis; subjects with type 2 diabetes or prevalent CD were excluded. We used Cox proportional hazards regression to identify factors associated with diagnosis of CD during follow-up. Risk factors assessed included age at T1D, sex, year of T1D diagnosis, and time-varying covariates of thyroid disease and adrenal insufficiency.

Results: Subjects (n=11,537; 43% female) had a median follow-up time of 6.8 years (IQR 2.5-14.1). CD was diagnosed in 234 (2%), with median time to diagnosis of 2.9 years (IQR 1.2-7.8); 37% were diagnosed > 5 years after T1D. Incidence (per 10,000 person-years) was greater in females than males (26.9 [95% CI 22.4-31.9] vs. 16.4 [95% CI 13.4-19.9]) and in subjects <10 years at T1D diagnosis (50.1 [95% CI 41.4-60.2] vs. 13.3 [95% CI 11.0-15.9]). In multivariable Cox regression, the hazard of CD was higher with younger age (HR 0.88 per year of age at T1D diagnosis, 95% CI 0.80-0.96, p=0.006), in females (HR 1.50, 95% CI 1.16-1.94, p=0.002), and with more recent year of diagnosis (HR 1.09, 95% CI 1.07-1.12, p < 0.001).

Conclusions: A significant proportion of CD cases were diagnosed more than 5 years after T1D diagnosis, the time frame currently recommended for screening. A more personalized approach to CD screening, accounting for the greater risk for younger-onset and female patients with T1D, may be warranted to minimize over-testing while limiting missed diagnoses.

Disclosure

M. Vajravelu: None. D. De Leon: Employee; Spouse/Partner; Merck & Co., Inc.. Research Support; Self; Zealand Pharma A/S. Consultant; Self; XOMA Corporation, ProSciento. Research Support; Self; Biomarin Corporation. D.R. Weber: None. R. Keren: None. M.R. Denburg: Research Support; Self; Mallinckrodt Pharmaceuticals. R. Verma: None.
Efficacy of a Novel Interim Intervention Technique (IIT) with Retrospective Flash Glucose Monitoring to Improve Glycemic Control
Authors: JAIN AKSHAY B.
Published: June 2018

Aim: Retrospective blinded flash glucose monitoring system (FGMS) is typically used for 14 days, prior to modification of therapy. We sought to assess the efficacy of a novel approach wherein an interim analysis was done within a week of starting FGMS and utilized to implement therapeutic modifications. The same sensor was reassessed within the following week to see the changes in glycemic control, thereby maximizing utility of a single sensor.

Methods: This is a retrospective analysis of 1consecutive adults with T2DM and HbA1c >7% on pharmacotherapy (oral agents and/or insulin) at a single centre. Patients started on blinded FGMS (Freestyle Libre Pro) were assessed within 1 week to get baseline estimate of glycemic trends. Glucose target range was set at 70-180 mg/dL. Patients kept a food log while on FGMS. Based on the glucose profile reports, dietary and pharmacotherapy changes were made and patients were re-evaluated in the next 7 days to assess the changes due to IIT, while wearing the same sensor. Analysis of pre and post: daily average glucose (DAG), time in target range (TITR), time above target range (TATR) and time below target range (TBTR) was performed.

Results: At baseline, patients had a DAG of 191.3 mg/dL. Average time for interim analysis was 5 days after FGMS initiation. After IIT, the DAG dropped to 137.4 mg/dL, within 14 days (p <0.001). The TATR dropped from 52.1% to 18.3% (p<0.001), with a concurrent decrease in TBTR from 5.7% to 1.5% (p<0.001). Recurrent hypoglycemias were detected in 27 (25%) patients, with average TBTR being 21.1% and TITR being 65.7% on interim analysis. Following IIT, the TBTR reduced to 1.9% (p<0.001) and TITR changed to 86.8% (p<0.001), without increase in TATR in these patients.

Conclusion: Using IIT, changes to patient’s lifestyle and/or pharmacotherapy can be made within a few days of FGMS, with the ability to gauge subsequent changes while still utilizing the same sensor. Significant improvement in glycemic control was achieved using this technique.

Disclosure

A.B. Jain: Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi.
Early Effects of Sleeve Gastrectomy (SG) on Systemic and Organ-Specific Dietary Fatty Acid Uptake, Postprandial Free Fatty Acids (FFA), and Glucose Metabolism in Type 2 Diabetes (T2D)
Authors: CARREAU ANNE-MARIE , NOLL CHRISTOPHE , GUERIN BRIGITTE , BIERTHO LAURENT , TURCOTTE ERIC E. , TCHERNOF ANDRE , CARPENTIER ANDRÉ
Published: June 2018

Postprandial dietary fatty acid (FA) biodistribution is impaired in subjects with glucose intolerance, with decreased FA storage in adipose tissues (AT) and increased FA uptake by the myocardium. These abnormalities are improved after 1 year of lifestyle-induced weight loss. Bariatric surgery leads to early metabolic improvements before weight loss, but the early effects on dietary FA metabolism and biodistribution have never been studied. 9 subjects with T2D underwent a 6-hour postprandial metabolic protocol before and 12 days after SG. A liquid meal containing [U-13C]-palmitate and [2H]-glucose was ingested at time 0, with an IV perfusion of [3H]-glucose and [7,7,8,8-2H]-palmitate, allowing quantification of glucose absorption, endogenous glucose production (EGP), lipolysis and dietary FA spillover. A capsule containing a positron-emitting long-chain FA analog (18FTHA) was taken with the meal for the quantification of organ-specific dietary FA uptake using PET/CT (n=6). Twelve days after SG, whole body and hepatic insulin sensitivity increased significantly whereas fasting and postprandial EGP decreased. Postprandial GLP-1, GIP, PYY and glucagon were higher after vs. before SG. Postprandial AUC of FFA (175 vs. 228 mmol/Lx min; p< 0.05) and total FA oxidation were higher (p< 0.02 from 180 min to 360 min), but dietary FA oxidation was reduced after SG (p< 0.002 from 180 min to 360 min). After SG, uptake of dietary FA 6 hours after the meal was reduced in the myocardium (mean SUV 2.07± 0.66 vs. 1.36± 0.44; p=0.06) and was increased in visceral AT (mean SUV 0.24± 0.2 vs. 0.42± 0.2; p=0.03), without changes in other organs.

In conclusion, there is reduced myocardial and increased visceral AT uptake of dietary FA associated with reduced dietary FA oxidation and increased FFA mobilization and oxidation, concomitant with reduced EGP and insulin sensitization in patients with T2D early after SG.

Disclosure

A. Carreau: None. C. Noll: None. B. Guerin: None. L. Biertho: Advisory Panel; Self; Novo Nordisk Inc.. Consultant; Self; Johnson & Johnson Services, Inc., Valeant Pharmaceuticals International, Inc.. E.E. Turcotte: None. A. Tchernof: Research Support; Self; Johnson & Johnson Services, Inc., Medtronic. A. Carpentier: Consultant; Self; UniQure, Janssen Pharmaceuticals, Inc., Siemens. Research Support; Self; Caprion, Merck Sharp & Dohme Corp., GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, AstraZeneca, Bristol-Myers Squibb Company, Sanofi-Aventis, Pfizer Inc., Novo Nordisk Inc., Exelixis, Amgen Inc..
Combining A1C with Glycated Albumin Improves Detection of Abnormal Glucose Tolerance in Nonobese Africans—The Africans in America Study
Authors: KABAKAMBIRA JEAN DAMASCENE , BRIKER SARA M. , BAKER RAFEAL L. , DUBOSE CHRISTOPHER , MABUNDO LILIAN , CHUNG STEPHANIE T. , SACKS DAVID B. , SUMNER ANNE E.
Published: June 2018

As diabetes prevalence rises in Africa, tests to detect abnormal glucose tolerance (abnl-GT) must be optimized. Recent reports suggest A1C performs well as a diagnostic test for abnl-GT in the OB. In contrast, glycated albumin (GA) contributes to the detection of abnl-GT in the nonobese. To determine if BMI affects sensitivity of A1C and GA in Africans, we evaluated the sensitivity of A1C and GA separately and combined to detect abnl-GT in 88 OB blacks (age 42±10y, BMI 33.4±2.9, range 30.0-42.4) and 232 nonobese blacks (age 38±10y, BMI 25.5±2.6, range 18.2-29.8) who were born in Africa and live in the U.S.A. Abnl-GT was determined by glucose criteria for the OGTT. Thresholds for A1C and GA were defined by the cut-off at their upper quartile (A1C≥5.7%; GA ≥13.97%). Prevalence of abnl-GT in OB and nonobese Africans were: 43% v 35%, P=0.20, resp. In the OB, sensitivities of A1C, GA and the combined tests were: 67%, 29% and 79% resp (Figure A). In the OB, sensitivity of A1C + GA was similar to A1C alone (P=0.13). For the nonobese, sensitivities of A1C, GA and the combined tests were: 35%, 38% and 62% resp (Figure B). Sensitivity increased when the tests were combined because abnl-GT was detected in 22 nonobese Africans not identified by A1C. Patterns were similar by sex and region of Africa. Data from Africans living in the U.S.A suggest detection of abnl-GT in the nonobese is improved by combining A1C with GA.

Disclosure

J. Kabakambira: None. S.M. Briker: None. R.L. Baker: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. D.B. Sacks: Other Relationship; Self; Sebia, Trinity Biotech. A.E. Sumner: None.
Serum Total Adiponectin Level Is Associated with Incident Prediabetes in Japanese Workers
Authors: HATA AKIKO , MIYOSHI MASASHI , NAKAO TAKAYUKI , ICHIHARA TAKAKO , TAMURA AYAKO , MINAGAWA TAKAKO , KUWAMURA YUMI , FUNAKI MAKOTO
Published: June 2018

Emerging evidence suggests that adiponectin secreted into the serum by adipocytes may be involved in the development of type 2 diabetes. In addition, some cross-sectional studies have suggested that adiponectin may be related to PreD (prediabetes). Thus, it is reasonable to expect that adiponectin may play a role in PreD development. However, there are still few prospective cohort studies, which could successfully demonstrate a causative relationship between adiponectin and PreD. The aim of this study was to establish the significance of Adipo (serum total adiponectin level) as a biomarker for PreD in Japanese workers. To this end, we analyzed data in our prospective occupational-based cohort study, which has been conducted since 2008. A total of 551 workers without PreD aged 20-60 years were followed-up (mean follow-up period 4.2 years). The subjects were divided into four categories based on the quartiles of baseline Adipo for each sex (male: < 4.9, 4.9-6.6, 6.7-8.9 and > 8.9 µg/ml, female: < 8.2, 8.2-11.1, 11.2-13.9 and > 13.9 µg/ml). The age- and sex-adjusted incidence of PreD significantly increased with decreasing quartile of Adipo at baseline (P for trend <0.001). In multivariate analyses after adjusting for age, sex, BMI, smoking habit, alcohol intake, regular exercise, HDL cholesterol, triglycerides, family history of diabetes, and hypertension, the hazard ratio of PreD was 1.64 [95% confidence interval: 1.to 2.51, P=0.02] in the second quartile and 1.33 [95% confidence interval: 0.83 to 2.11, P=0.24] in the lowest quartile, when compared with the highest quartile. Furthermore, the risk of PreD was 5% higher (P=0.04) with a per 1 µg/ml decrement of Adipo in the multivariate-adjusted model. These results suggest that decreased Adipo is a risk factor for the incidence of PreD in Japanese workers, which could assign a new role to Adipo as a biomarker for the early stage of glucose homeostasis disorders, besides being a biomarker for the development of diabetes and cardiovascular events.

Disclosure

A. Hata: None. M. Miyoshi: None. T. Nakao: None. T. Ichihara: None. A. Tamura: None. T. Minagawa: None. Y. Kuwamura: None. M. Funaki: Research Support; Self; Otsuka Holdings Co., Ltd., The Knowledge Cluster from the Ministry of Education, Science, and Culture of Japan. Board Member; Self; Mechanogenic C.C..
The Prevalence of Undiagnosed Diabetes Has Not Decreased in Spite of Increased Screening in an Australian Rural Area
Authors: SIMMONS DAVID , GLENISTER KRISTEN , MAGLIANO DIANNA J. , WRIGHT SIAN J. , BOURKE LISA
Published: June 2018

In the mid-2000s in Australia, national guidelines were introduced to promote diabetes screening in people aged 40+ years. We have tested whether diabetes screening has increased, and the prevalence of undiagnosed diabetes has decreased since the introduction of these guidelines. ’Crossroads’ is a repeat cross-sectional study conducted between 2000-2003 (Crossroads-I) and then 2016-2018 (Crossroads-II) in rural Australia (the Goulburn Valley, Victoria). Households visited were randomly selected, and the same households were then revisited in Crossroads-II, alongside proportionately randomly selected new houses. All adult residents are interviewed face to face by trained research assistants. Questions enquire about diabetes status, occurrence of diabetes screening in last 2 years and primary care utilisation. Randomly selected participants are invited to attend a ’clinic’ including a glucose tolerance test. The Crossroads-I cohort (n=3787) was younger and had a higher proportion of male participants than the Crossroads-II cohort (n=1733) (44 ± 17 vs. 53 ± 19 years p<0.0001, 46% vs. 42% male, p<0.0001). The age standardised prevalence of self-reported diabetes (7.0% vs. 5.4%, p<0.05), and age standardised screening rates (56.5% vs. 49.7%, p<0.05) were higher in Crossroads-II than Crossroads-I. Crude undiagnosed diabetes prevalence was also higher in Crossroads-II than Crossroads-I (17/430 (3.9%) vs. 15/814 (1.8%) p<0.05). Primary care utilisation was higher in Crossroads-II than I (6.4 vs. 4.7 visits in past 12 months, p<0.0001) and waiting times were shorter (3.0 vs. 3.9 days, p<0.0001). We conclude that diabetes screening has increased in this area in association with improved access to primary care, and guideline changes. Despite this, rates of undiagnosed diabetes have also increased in line with the overall prevalence of diabetes. Additional strategies are required to reduce undiagnosed diabetes rates further.

Disclosure

D. Simmons: Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, AstraZeneca, Novo Nordisk Inc., Medtronic. K. Glenister: None. D.J. Magliano: None. S.J. Wright: None. L. Bourke: None.
To Evaluate Patient Characteristics in Those with Elevated NT-proBNP in Type 2 DM Patients Optimized for Conventional CV Risk Factors on Standard Care for Two Years
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2018

Methodology: Two hundred T2DM patients on standard glucose lowering agents and who may be on lipid and blood pressure lowering agents were followed up for 2 years for improvement in CV risk markers like BMI, HbA1c, systolic blood pressure(S-BP), diastolic BP(D-BP), total cholesterol(TC), HDL, non-HDL, LDL, triglycerides(TG), cholesterol remnant(CR), highly-sensitive CRP(hsCRP), serum creatinine(Cr) and eGFR. T2DM patients with recent history of re-vascularisation or any major surgery were excluded. At the end of 2 years, NT-proBNP was measured as an assessment tool for residual CV risk. Those with higher NT-proBNP(>=125) were identified and patient level characteristics as described above were analysed and compared to patients with NT-proBNP <125. Data was analysed using SPSS version 20, represented as Mean + 2(SD) with 95% CI, descriptive statistics and independent t test was used and p-value of less than 0.was considered statically-significant (Si)>.

Results: Baseline characteristics of patients with elevated NT-pro-BNP were: 40(54.05%) males and 34 (45.9%) females, mean age 63.54 ± 10.61 years, mean age since diagnosis 13.5 ± 7.3 years and mean BMI 29.41 ± 5.32 kg/m2. The mean values at the end of 2 years in patients with elevated NT-proBNP were: HbA1c 6.7 ± 1.13, S-BP 132.24 ± 27.5, D-BP 72.93 ± 17.14, TC 140.22 ± 48.98, LDL 70.57 ± 32.95, TG 131.13 ± 91.37, HDL 38.8 ± 13.02, non-HDL 90.18 ± 37.44, CR 23.11 ± 17.7, Cr 1.01 ± 0.29, eGFR 79.29 ± 25.2, hsCRP 4.09 ± 0.51,. There was Si difference seen with regard to Age(p-0.039), weight(p-0.015), D-BP(p-0.016), non-HDL(p-0.05), Cr(p-0.001), eGFR(0.001) at 2 years in patients with elevated NT proBNP compared to those with normal levels.

Conclusion: Patients with elevated NT-proBNP were older, had greater D-BP, TC, LDL, TG, non HDL, CR, Cr and weight and lower HDL and eGFR compared to patients without elevated NT pro BNP at 2 year.

Disclosure

V. Gupta: None. V. Teli: None.
Activation of Cardiac Mitochondrial Akt Signaling Improved Diabetic Cardiomyopathy and Induced Liver Metabolic Remodeling
Authors: TA ALBERT , CHEN YU-HAN , CHEN YUMAY , LEE HYE-JIN , LIN HUGO YOU-HSIEN , WANG PING H.
Published: June 2018

Insulin stimulates Akt translocation to cardiac mitochondria, and we have recently shown that inhibition of cardiac mitochondrial Akt led to mitochondria dysfunction and cardiomyopathy. However, it is unknown whether activation of mitochondrial Akt in cardiac muscle can protect against the development of diabetic cardiomyopathy. To this end, we have generated an inducible, heart-specific, transgenic mice harboring a mitochondria-targeting constitutively active Akt (CAMAAKT). After 5 months of high fat-high fructose diet (HFF), the control mice developed myocardial fibrosis and cardiomegaly. In contrast, myocardial fibrosis and cardiomegaly were attenuated in the CAMAAKT mice on HFF. Compared to the control mice, the expression of myocardial BNPa, BNPb, and Myh7 (heart failure genes) were significantly suppressed in the CAMAAKT mice by 80%, 90%, and 80%, respectively (all p<0.01). Col1a1 and Col3a1 expression were reduced in the HFF-CAMAAKT mice, corroborating the reduction of myocardial fibrosis. These data indicated that activation of mitochondrial Akt protected against cardiomyopathy in diet-induced diabetes. In OGTT, fasting glucose level was unchanged but postprandial glucose levels were lower in the CAMAAKT mice. In another heart-specific transgenic mice harboring a mitochondria-targeting dominant negative Akt (CAMDAKT), the glucose curve in OGTT was significantly higher than the control mice. Therefore, mitochondrial Akt signaling in the heart could modulate whole body glucose homeostasis. Interestingly, the diet-induced fatty liver in the CAMAAKT mice was significantly less than the controls, suggesting that cardiac mitochondrial Akt signaling may remotely modulate fat metabolism in the liver.

In summary, activating cardiac mitochondrial Akt protected against diabetic cardiomyopathy, improved glucose tolerance, and attenuated fatty liver in HFF-induced diabetes.

Disclosure

A. Ta: None. Y. Chen: None. Y. Chen: None. H. Lee: None. H. Lin: None. P.H. Wang: None.
Impact of Patient-Centered Factors on Comparative Effectiveness of Initial Therapies in Treatment-Naïve T2D
Authors: TESTA MARCIA A. , TURCHIN ALEXANDER , SU MAXWELL , SIMONSON DONALD C.
Published: June 2018

The 2017 ADA and AACE consensus statements recommend individualizing A1C targets based on patient-centered demographic, clinical and socio-economic factors, and also starting initial therapy with metformin. We used benchmarking algorithms to predict personalized A1C outcomes and estimate treatment comparative effectiveness among diabetes therapies using electronic health records (EHR) collected from 233,627 primary care adult diabetes patients between 2000 and 2014, with 14,019 qualifying as treatment-naïve prior to or at the first EHR observation. EHR analyses were conducted at Partners HealthCare, an integrated healthcare delivery network in eastern Massachusetts. Initial monotherapy regimens were metformin (MET) 63.5%, sulfonylurea (SU) 12.5%, insulin 7.7%, thiazolidinediones (TZD) 1.5% and all other agents < 1%; combination therapies were 14%. The monotherapy MET and SU subgroup (n=10,466) was 53% female; 64% white, 15% black, 8.5% Hispanic; mean± SD age = 59 ± 13 yrs; A1C = 8.6 ± 1.8%; BMI = 33.2 ± 6.5 kg/m2; and median income = $67,119. Of these, 14.8% failed to reach A1C < 7%, and 9.0% did not reach A1C < 8%, prior to a first change in regimen. Logistic regression and survival models for achieving target A1C adjusting for baseline sex, age, race/ethnicity, income, BMI, hypertension, A1C and eGFR were predictive (p < 0.001). SU had lower odds of reaching A1C < 7% vs. MET [OR (95% CI) = 0.69 (0.59, 0.86); HR = 0.60 (0.57, 0.62)], p < 0.001. In the full sample (n = 14,019), all other regimens also had lower odds of A1C < 7% compared to MET [OR (95% CI): Insulin 0.28 (0.24, 0.33); Combinations 0.32 (0.29, 0.36); DPP-4i 0.35 (0.18, 0.67); Other 0.41 (0.22, 0.75); TZD 0.57 (0.39, 0.82); SU 0.72 (0.62, 0.84)]. Patient-centered factors contributed substantially to the heterogeneity of A1C treatment response as benchmarked against metformin; however, even after adjustment, metformin was more effective as initial therapy in T2D treatment naïve patients compared to all other treatments.

Disclosure

M.A. Testa: Stock/Shareholder; Spouse/Partner; GI Windows, Inc.. Stock/Shareholder; Self; Phase V Technologies, Inc. A. Turchin: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Merck Sharp & Dohme Corp., Monarch Medical Technologies. Stock/Shareholder; Self; Brio Systems. Research Support; Self; Eli Lilly and Company. M. Su: None. D.C. Simonson: Advisory Panel; Self; GI Windows, Inc.. Stock/Shareholder; Self; GI Windows, Inc.. Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc.
Continuous Glucose Monitoring in Youth with Pre-Type 1 Obesity/Pre-Type 2 Diabetes and Cystic Fibrosis
Authors: CHAN CHRISTINE L. , STECK ANDREA , VIGERS TIM B. , PYLE LAURA , DONG FRAN , THURSTON JESSICA , REWERS MARIAN , ZEITLER PHIL , NADEAU KRISTEN J.
Published: June 2018

Continuous glucose monitoring abnormalities are present in the prediabetic state, but how these abnormalities compare among individuals at risk for different types of diabetes (type 1, type 2, vs. cystic fibrosis related diabetes) is unknown. We compared CGM patterns of three distinct groups of youth at risk for diabetes, all with A1c <6.5%: pre-T1D (multiple islet antibody positive), obese/pre-T2D (BMI ≥85th%Ile), and cystic fibrosis (CF). None were on insulin or other medications affecting glucose metabolism. CGM was obtained for 3-7 days in our observational studies. Pre-T1D youth (A1c range 5.0-6.3%) were randomly matched 1:3 on A1c to the obese/pre-T2D and CF youth. Groups were compared using random effects models for continuous variables. Age, Sex distribution and HbA1c were not different between the groups after matching. The results are shown in the table. Of interest, youth with CF and pre-T1D had greater standard deviation, higher maximum and lower minimum glucoses than obese/pre-T2D youth.

In conclusion, CGM patterns are significantly different in pre-T1D and CF compared to obese/pre-T2D, reflecting differences in pathophysiology among these disease states. Early insulin deficiency appears to manifest as greater glycemic variability—higher SD, greater peaks and lows—in pre-T1D and CF, while insulin resistance leads to increased, but less variable, glucoses in obese/preT2D youth.

*pre-T1D and CF significantly different from pre-T2DCGM measure (sensor glucose) Mean (SE) (mg/dl)Pre-T1D (N=14)Pre-T2D (n=42)CF (n=42)P-valueAverage glucose117 (3)114 (2)111 (2)0.17Standard deviation (SD)26 (2)16 (1)22 (1)<0.0001*Maximum223 (14)162 (5)209 (7)<0.0001*Minimum62 (4)77 (2)62 (2)<0.0001*% time >12037 (5)31 (4)27 (2)0.24% time 14017 (4)12 (3)9 (1)0.23% time >2001.3 (0.7)0.4 (0.2)0.8 (0.2)0.11

Disclosure

C.L. Chan: None. A. Steck: None. T.B. Vigers: None. L. Pyle: None. F. Dong: None. J. Thurston: None. M. Rewers: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH. K.J. Nadeau: None.
Study on the Screening and Influence Factors for Prediabetes or Diabetes in Primary Health Care Centers of Shanghai
Authors: YINGLING CHENG
Published: June 2018

Background: Many studies have reported that diabetes mellitus show the low age tendency. Undiagnosed diabetes patients account for about 25-30% of diabetic patients.

Objective: This study aimed to analyze the epidemiological status and influence factors of prediabetes and diabetes, in order to build screening and intervention system for high-risk population in the primary health care centers.

Methods: A cross-sectional study was conducted. Residents over 35 years old were randomly enrolled from Jun 2016 to Aug 2017 in Electric Health Record (EHR) of Shanghai Minhang District. Data were collected by using questionnaire and physical examination and blood glucose test. Logistic regression was applied to analyze the risk factors for prediabetes and diabetic patients.

Results: A total of 12136 subjects were participated in this screening. Results indicated that 14.54% (n=1765) were diagnosed with diabetes and the prevalence rate in males (17.32%) was significantly higher than in females (12.97%) in each age groups (P< 0.001). Furthermore, 20.69% (n=2511) were diagnosed with prediabetes and males were (23.40%) higher than females (19.16%) (P<0.001). Obesity (BMI≥28)(OR=2.35), family history (OR=1.71), history of cardiovascular disease (OR =1.42), hypertension (OR=1.17), central obesity (OR=1.22), age (OR=1.03), gender (OR=1.31) and sedentary (OR=1.02) were the risk factor for prediabetes or diabetes (p<0.001). In addition, we also found that 54.29% (n= 6589) had over 3 risk factors.

Conclusions: It is concluded that we should pay more attention to population with family history and obesity in the screening of diabetes. Grading management and screening should be carried out in different stages of diabetes. Comprehensive prevention and control should be taken to slow progress in diabetes.

Disclosure

C. Yingling: None.
Are Diabetes Risk Scores the Best Way to Identify Those Who Will Benefit Most from Lifestyle Prevention?
Authors: SARI CAROLINA I. , MAGLIANO DIANNA J. , ZIMMET PAUL Z. , TUOMILEHTO JAAKKO , SUDHIRSEN KOWLESSUR , SÖDERBERG STEFAN , SHAW JONATHAN E.
Published: June 2018

Rationale: Lifestyle intervention programs are effective for preventing diabetes among those with impaired glucose tolerance (IGT), with little evidence of benefit in other high-risk states. The selection of those who are eligible for lifestyle intervention is often made via diabetes prediction tools which identity those at high risk of diabetes. Unless such scores preferentially identify IGT, this will lead to poor performance of diabetes prevention programs. We developed an IGT-specific risk model and a diabetes-specific risk model, and compare their abilities to identify those with IGT.

Methods: Data from population-based surveys conducted in Mauritius in 1987, 1992 and 1998 were used to develop prediction models for IGT and DM. A cross-sectional sample in 1987 was used to develop the IGT model. A cohort sample from 1987 to 1992 was used to develop the DM model. Logistic regression was used to develop the scores. The performances were investigated by calculating area under the receiver operator curve (aROC). The Youden index was used to find a cutpoint in probability. Both scores were tested on independent samples.

Results: The aROC for IGT and DM models were 0.68 and 0.69 respectively. The sensitivity of the IGT model (derived on 1987 data) in identifying IGT individuals on independent samples from 1992 was 66%. Among those above the Youden index cutpoint, 23%, 9% and 68% had IGT, IFG and NGT, respectively. In the DM model, sensitivity for IGT was 60%. Among those above the cutpoint 24%, 8% and 67% had IGT, IFG and NGT, respectively. Increasing the cutpoints to levels at which 40% of those above the cutpoint had IGT resulted in sensitivities for IGT of 15% and 5% in the IGT and DM models, respectively.

Conclusion: Our results show that risk scores perform poorly in identifying people with IGT, and that without screening identified populations with an oral glucose tolerance test, a high proportion of people entering DM prevention programs will not have IGT-the only state shown to respond to lifestyle.

Disclosure

C.I. Sari: None. D.J. Magliano: None. P.Z. Zimmet: None. J. Tuomilehto: None. K. Sudhirsen: None. S. Söderberg: Other Relationship; Self; GlaxoSmithKline plc.. Speaker's Bureau; Self; Actelion Pharmaceuticals US, Inc.. Other Relationship; Self; Swedish Heart-Lung Foundation. Advisory Panel; Self; Merck Sharp & Dohme Corp. J.E. Shaw: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Mylan. Advisory Panel; Self; Novo Nordisk Inc..
One-Hour Post-OGTT Glucose Improves the Early Prediction of Type 2 Diabetes beyond Metabolic Markers
Authors: PEDDINTI GOPAL , TUOMI TIINAMAIJA , BERGMAN MICHAEL , GROOP LEIF
Published: June 2018

Background: We previously evaluated metabolic markers (alpha-hydroxybutyrate, bradykinin hydroxyproline, mannose, alpha-tocopherol, 10:1 carnitine, and X-12063) for the early prediction of type 2 diabetes (T2D). The present study compared glucose measurements at different time points during an oral glucose tolerance test (OGTT) with the metabolites for predicting future T2D.

Methods: Fasting (FPG), 30, 60, and 120 minute plasma glucose (PG) levels were measured in 543 individuals from the Botnia Prospective Study, 146 of whom progressed to T2D within a 10 year period. Machine learning based predictive models for the future risk of T2D were built based on (1) OGTT-derived glucose measurements, (2) clinical risk factors (age, sex, body mass index, and family history of T2D, (3) metabolites, (4) combinations of PG levels and metabolites, (5) combinations of PG levels and clinical risk factors, and (6) combinations of PG levels, clinical risk factors, and metabolites. The metabolites were also correlated with the PG levels.

Results: The 1-h PG predictive performance (area under the receiver operating characteristic curve, AUC = 0.76, sensitivity = 0.70, specificity = 0.69) was superior to FPG, 2-h PG, or individual metabolites, and was as good as the multivariate model with all six metabolites (AUC = 0.78, DeLong’s p = 0.24). The combined predictive model that included the 1-h PG, clinical risk factors, and six metabolites (AUC = 0.81, sensitivity = 0.74, specificity = 0.75) significantly improved the predictive performance beyond the 1-h PG alone (p = 0.02) and the combined model with clinical risk factors and six metabolites (p = 0.02).

Conclusion: The 1-h PG predicts risk for T2D better than FPG or the 2-h PG. Although several multivariate models containing the metabolites improved the prediction performance beyond the 1-h PG, the 1-h PG alone was on par, and is a more practical biomarker. Shortening the OGTT to 1 hour provides a better and simpler assessment of T2D risk than the current OGTT.

Disclosure

G. Peddinti: None. T. Tuomi: None. M. Bergman: None. L. Groop: None.
Self-Monitoring of Blood Glucose (SMBG) in Youth with Poorly Controlled Type 2 Diabetes (T2D) in the TODAY Study
Authors: WEINSTOCK RUTH S. , BRAFFETT BARBARA , CHAN CHRISTINE L. , CHANG NANCY T. , HAYMOND MOREY W. , SCHWARTZMAN BETH
Published: June 2018

Objective: Determine if SMBG increased after starting insulin in T2D youth with poor glycemic control in the TODAY study.

Methods: Youth with recent onset T2D (n=699) were randomized to receive metformin ± rosiglitazone (rosi) or intensive lifestyle. They were asked to perform SMBG daily (supplies provided). When they reached primary outcome (PO; A1c ≥8% over 6 mon or inability to wean from temporary insulin due to metabolic decompensation), metformin (not rosi) was continued, daily insulin glargine started; dosing was intensified as needed. A1c and SMBG data for 2 year before and after PO were analyzed. SMBG% was defined as percent of days between visits when the meter was used ≥1 time.

Results: Of 319 youth who reached PO, 298 started insulin and 282 had SMBG data. At PO, mean (SD) age was 15.8±2.3 year, 65.3% female, 38.3% non-Hispanic black, 16.3% Hispanic, 7.1% non-Hispanic white, BMI 35.5±7.9 kg/m2, and A1c 9.6±2.0%. Median SMBG% was 40% at PO which increased to 49% at 6 mo and fell to 41% at 1 year; 22% of youth tested ≥80% of days at PO, which increased to 25% at 6 mo and fell to 19% at 1 year. Compared with those who tested <80% at PO, youth who tested ≥80% were younger, with lower BMI and A1c. Use of SMBG was associated with ≥1% reduction in A1c at 6 and 1 year after insulin initiation (Figure).

Conclusion: Adherence to SMBG was poor but associated with lower A1c. Research is needed on interventions to help youth with T2D reach A1c goals.

Disclosure

R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases. B. Braffett: None. C.L. Chan: None. N.T. Chang: None. M.W. Haymond: Advisory Panel; Self; Zealand Pharma A/S. Other Relationship; Self; Xeris Pharmaceuticals, Inc.. B. Schwartzman: None.
Diagnostic Accuracy in LADA—Low Correlation between Primary Care Physicians (PCPs) and an Endocrinologist
Authors: FERRARI ALDO DE , OVALLE FERNANDO
Published: June 2018

Background: Patients with LADA benefit from different interventions than those with T2D. However, distinguishing one entity from the other may be challenging in individual patients. We hypothesized that LADA is being underdiagnosed by PCPs.

Methods: We retrospectively reviewed the medical charts of 1257 patients that consecutively presented to our diabetes clinic from 2001-10. Inclusion criteria were: age >18 years, having diabetes, and having been assessed by one of our investigators upon presentation. We collected demographic, clinical, and laboratorial data from their first visit to our clinic.

Findings: Of 1257 only 6 (0.5%) were referred to our clinic with a diagnosis of LADA. In contrast, we identified a total of 133 individuals with LADA (10.6%). There was good correlation between PCPs and an endocrinologist in the diagnosis of common diabetes subtypes like T1D and T2D, but it was poor for less common diabetes subtypes including LADA (Table). Most of the patients with LADA were originally classified as T2D (n=105). Seven percent of patients with LADA in our population had a history of DKA.

Interpretation: LADA is currently being underdiagnosed by PCPs. Strategies to raise awareness of the existence of this patient population as well as cost-effective strategies to identify them are largely needed.

Prevalence of diabetes subtypes in 1257 patients as diagnosed by PCPs and an endocrinologistPrevalence according to PCPsPrevalence according to an endocrinologistPearson’s correlationCystic-fibrosis related diabetes, % (n)0.8 (10)1.0 (12)0.91Type 1 diabetes, % (n)22.3 (280)24.3 (305)0.78Type 2 diabetes, % (n)70.5 (886)49.6 (624)0.62LADA, % (n)0.5 (6)10.6 (133)0.16Other subtypes, % (n)5.9 (75)14.5 (183)0.32

Disclosure

A. De Ferrari: None. F. Ovalle: Consultant; Self; Bayer AG, Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Consultant; Self; Sanofi. Research Support; Self; Sanofi.