bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial Differences in the Correlation of HbA1c to Early and Late Postprandial Glycemic Responses in Adults with Prediabetes
Authors: HSIA DANIEL S. , MARLATT KARA , PETERSON COURTNEY M. , RAVUSSIN ERIC 
Published: June 2018

Fasting plasma glucose (FPG), 2-hour oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1c) are used to screen for prediabetes and diabetes. While HbA1c testing offers the convenience of a single blood draw without fasting, it is known to have confounders such as age, race, and red blood cell turnover rate to name a few. Furthermore, dynamic tests such as the OGTT and mixed-meal tolerance test (MMTT) are usually better at detecting β-cell dysfunction and insulin resistance when insulin is measured. We sought to determine how well HbA1c values correlated with glucose levels during a MMTT and whether the correlation varied by race. Baseline data from a clinical trial of 59 adults [27 white and 32 African American (AA)] with prediabetes defined as either FPG of 100-125 mg/dL and/or HbA1c of 5.7-6.4% were used. In this cohort, we correlated HbA1c to glucose levels at 30 and 120 mins after ingesting a standardized meal (smoothie) of 400 kcal (20% protein, 40% fat, and 40% carbohydrate). Mean FPG was higher in white participants (108±10 mg/dL) compared to AA participants (102±10 mg/dL) (p&lt;0.05), while HbA1c was marginally higher in AA participants (5.7±0.2%) compared to white participants (5.6±0.3%) (p&lt;0.01). In the white participants, HbA1c correlated with glucose 30-mins post-meal (r=0.46, p&lt;0.03) but did not in AA participants (r=0.11, p&gt;0.53). In AA participants, HbA1c correlated with glucose 120-mins post-meal (r=0.48, p&lt;0.01) but did not in white participants (r=0.22, p=0.28). Thus, in this cohort, white adults with prediabetes showed greater impairment of fasting glucose than AA adults, despite lower HbA1c levels. Moreover, a higher HbA1c correlated with an impaired early glycemic response in white adults; whereas, a higher HbA1c correlated with impaired glucose tolerance in AA adults. These results may suggest racial differences in early vs. late postprandial responses that should be accounted for when screening for prediabetes and diabetes.

Disclosure
D.S. Hsia: None. K. Marlatt: None. C.M. Peterson: None. E. Ravussin: Board Member; Self; Amway. Consultant; Self; Amway, Janssen Research & Development. Research Support; Self; Amway, Novartis Pharmaceuticals Corporation, Sanofi-Aventis, Weight Watchers International, Inc., Ethicon US, LLC..
Cardiometabolic Disease Risk Assessment Predicts Incident Diabetes in a Large and Diverse Population
Authors: WILKINSON LUA , MEHTA TAPAN , GARVEY W. TIMOTHY 
Published: June 2018

Background: Risk scores for predicting type-2 diabetes mellitus (T2DM) have been developed, but few have included adequate African-Americans.
Objective: To derive and validate scoring systems to predict future diabetes in populations including caucasian- and African-Americans, weighted by sex and race.
Design, Setting, and Participants: We estimated 9.5-year risk of T2DM in participants with valid follow-up data taken from 12,1321 people in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, and externally validated it in 9,712 participants from the Atherosclerosis Risk in Communities study.
Methods: Cardiometabolic disease scores were calculated for each sex-race pair using quantitative clinical data. Incidence diabetes was defined as fasting glucose ≥ 126 mg/dL, non-fasting glucose ≥ 200mg/dL, currently on medication for T2DM, or self-report. Covariates included: sex, race, and age; waist circumference; blood pressure; HDL cholesterol; fasting triglycerides or on lipid-lowering medication. We assigned a simple integer score for each risk factor component using logistic regression coefficients for each sex-race pair. Discrimination was assessed with area under the receiver operating characteristic curves (AROCs).
Results: Diabetes incidence rates at a median follow-up of 9.5 years were 18.3% and 18.7% in African-American men and women, and 12.3% and 9.2% in caucasian-American men and women. Weighted covariates differed more by race than sex (p = 0.001). The AROCs ranged from 0.72 for black men to 0.78 for white women. Externally validated models performed well; AROC was 0.75 (black men) to 0.83 (white women).
Conclusion: The weighted CMDS score has high model discrimination using readily available clinical data, and can be used to quantify T2DM risk based on race- and sex- specific data; thus, diabetes prevention can be targeted to high risk individuals in a manner that optimizes outcomes, benefit/risk ratio, and cost-effectiveness.

Disclosure
L. Wilkinson: None. T. Mehta: Employee; Spouse/Partner; Becton, Dickinson and Company. Consultant; Self; NuTech Medical. W. Garvey: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc.. Research Support; Self; Sanofi, Pfizer Inc., Novo Nordisk Inc., AstraZeneca, Merck & Co., Inc., Elcelyx Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Eisai Inc..
Depression Screening in Adolescents with Type 1 Diabetes Mellitus
Authors: KIM GRACE K. , RELAN SHILPI , TOSUR MUSTAFA , AGARWAL SWASHTI , JINDAL ISHITA , MOORJANI TRACY PATEL , FEGAN-BOHM KELLY , GALLAGHER KATHERINE A. , HENDRIX KRISTEN 
Published: June 2018

Background: Adolescents with type 1 diabetes mellitus (T1D) are at increased risk for depressive symptoms relative to youth without diabetes, which is associated with poor diabetes outcomes (Hood et al, 2014). As part of ongoing Quality Improvement initiatives at Texas Children’s Hospital (TCH), we evaluated two validated depression screening measures, the PHQ-2 and PHQ-9: Modified for Teens, to standardize our depression screening process.
Objectives: We sought to (1) review screening outcomes from youth with T1D who completed both the PHQ-2 and PHQ-9, (2) determine which measure provided the greatest sensitivity to identifying depressive symptoms, and (3) create a standardized process for implementation of the more sensitive screen.
Methods: Data was collected by a chart review of PHQ-2 and PHQ-9 scores for all patients with T1D age 12-17 seen at TCH Endocrine clinic sites between January 1 –December 31, 2017. A positive screen was defined as PHQ-2 score ≥ 3 and PHQ-9 score ≥ 5. We then created an algorithm based on the more sensitive screen for referrals to mental health services.
Results: Of 961 eligible patients, 84% were screened using PHQ-2 and 15% using both the PHQ-2 and PHQ-9. Of the patients who completed both measures, the positive screening rate was 20% in PHQ-9 vs. 4% in PHQ-2. None of the patients with “moderate” PHQ-9 (≥5-9) screened positive on the PHQ-2, and only 1 patient with “severe” PHQ-9 (≥10) score screened positive on PHQ-2. Of the 3 patients who endorsed suicidality on the PHQ-9, none had a positive PHQ-2. 80% of patients who received both screens completed the screens within 2 months of each other.
Discussion: PHQ-2 depression screen may be less sensitive than PHQ-9 for capturing depressive symptoms in youth with T1D. We have created a standardized algorithm implementing PHQ-9 into the clinic flow and looking at optimizing mental health referrals.
Hood KK, Lawrence JM, Anderson A, Bell R, et al. Metabolic and inflammatory links to depression in youth with diabetes. Diabetes Care 2012;35:2443-2446.

Disclosure
G.K. Kim: None. S. Relan: None. M. Tosur: None. S. Agarwal: None. I. Jindal: None. T. Patel Moorjani: None. K. Fegan-Bohm: None. K.A. Gallagher: None. K. Hendrix: None.
Long-Term Incidence of Liver Disease in the Diabetes Population in Israel
Authors: GOLDSHTEIN INBAL , FERNANDES GAIL , KARASIK AVRAHAM , RAJPATHAK SWAPNIL , CHODICK GABRIEL 
Published: June 2018

In light of the high variability in the literature on the burden of liver disease in relation to diabetes (DM), this study compared the incidence and risk of liver disease between patients with and without DM in a large population-based cohort. The study utilized the computerized database of a nationally representative payer-provider health fund in Israel. All members without cirrhosis, cancer, viral hepatitis or excess alcohol intake were followed from 2000 to 2017. Liver disease: Cirrhosis, liver transplant and hepatocellular carcinoma (HCC), were detected by coded diagnoses, procedures, and the national cancer registry. DM was defined by a previously validated registry. Age specific incidence density rates were calculated based on person years under observation. Risks of liver transplant, HCC and all-cause mortality in the cirrhotic diabetes patients were described using cox proportional hazards multivariate regression. The cohort included 1,083,4subjects with a mean follow-up of 15.1 years (SD=4.2), 2% with DM at index. A total of 2,511 incident cases of liver complications were observed. Higher incidence rates of cirrhosis were observed in patients with DM at index as compared with DM-free with rate ratios of 7.5 (95% CI: 6.5-8.7), 4.1 (3.8-4.4) and 2.3 (2.2-2.5) among patients aged &lt;40, 40-60 and &gt;60 years old respectively. DM was also associated with higher incidence of HCC (rate ratio 3.6 (95% CI: 3.2-4.1) and 1.7 (1.6-1.8) among ages 40-60 and &gt;60 years old respectively) and liver transplant (rate ratio of 4.5 (3.3-6.2) and 1.6 (1.1-2.2) among ages 40-60 and &gt;60 years old respectively). Among cirrhotic patients (n=1,527), those with DM had an adjusted HR=2.3 (95% CI: 1.2-4.5) for developing HCC, a HR=2.2 (0.9-5.3) for undergoing a liver transplant and a HR of 1.8 (1.5-2.3) for all-cause mortality as compared with DM-free, after controlling for age, BMI, sex and smoking. Diabetes is associated with higher incidence rates and higher risk of liver complications compared to those without diabetes.

Disclosure
I. Goldshtein: None. G. Fernandes: Employee; Self; Merck & Co., Inc.. Employee; Spouse/Partner; Janssen Research & Development. Stock/Shareholder; Self; Merck & Co., Inc.. Stock/Shareholder; Spouse/Partner; Janssen Research & Development. A. Karasik: Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Merck & Co., Inc., GlucoMe. S. Rajpathak: Employee; Self; Merck & Co., Inc.. G. Chodick: None.
Meta-analysis of Serum Uric Acid (SUA) and Cardiovascular Events in Diabetes Population
Authors: SHAO YIXUE , SHAO HUI , SHI LIZHENG 
Published: June 2018

Background: Recent studies found elevated serum uric acid (SUA) level were associated with type 2 diabetes mellitus (T2DM) progression. However, whether SUA level was relevant to the development of cardiovascular events was inconclusive.
Objective: To explore the association between SUA level and risk of cardiovascular events and all-cause mortality among patients with T2DM.
Method: A systematic literature search was conducted using the Web of Science and PubMed database (1980-2017). Search terms and strategies for PubMed were as follows: using [Title/Abstract] or [MeSH Terms] to search “diabetes”, “serum uric acid”, “cardiovascular disease”, and “all-cause mortality.” Studies that reported associations between SUA and cardiovascular events (i.e., coronary heart disease (CHD) and stroke), and all-cause mortality in patients with T2DM were identified, and these associations were extracted and converted into hazard ratio (HR) of cardiovascular events per 59μmol/l SUA increase. Meta-analysis was conducted to synthesize the associations between SUA level and risk of cardiovascular events, using random effect model to account for possible study heterogeneity. Heterogeneity was assessed using I2, and the meta-analysis was performed using Stata 12.0. This study was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.
Results: 6 (n=11,750 patients), 4 (n=3034 patients) and 2 studies (n=7792 patients) were identified reporting associations between SUA level and all-cause mortality, CHD and stroke respectively. HR for all-cause mortality, CHD, and stroke per 59 μmol/l increase was 1.150 (95% CI: 1.134, 1.165), 1.002 (95% CI: 0.983, 1.021) and 1.177 (95% CI: 1.070, 1.284), respectively. Heterogeneity bias was found in the analyses.
Conclusion: Overall, SUA were associated with higher risk of all-cause mortality and stroke. However, we found no significant association between SUA level and CHD among T2DM population.

Disclosure
Y. Shao: None. H. Shao: None. L. Shi: None.
Reduced Lower-Limb Muscle Strength in Type 2 Diabetes Patients with Arthritis Is Associated with Impaired Beta-Cell Function
Authors: ZAHARIA OANA P. , PESTA DOMINIK , BOBROV PAVEL , KUPRIYANOVA YULIYA , BÓDIS KÁLMÁN , BURKART VOLKER , HWANG JONG-HEE , MÜSSIG KARSTEN , RODEN MICHAEL , SZENDROEDI JULIA 
Published: June 2018

Insulin levels might affect the integrity of musculoskeletal structures. We hypothesized that in type 2 diabetes patients (T2D) with arthritis musculoskeletal impairment is associated with insulin secretion. This analysis of the German Diabetes Study comprised T2D with (T2D+A (n[m/f]=12[4/8], age 63±9 years, BMI 34.8±7.2 kg/m2) or without arthritis (T2D-A: 22[12/10], 59±13 years, 32.8±6.5 kg/m2) and healthy controls (CON: 18[10/8], 42±16 years, 25.3±4.1 kg/m2). Group comparison analyses were adjusted for age, sex and BMI. T2D duration was &lt;5 years. Beta-cell function was assessed from C-peptide levels during glucagon stimulation test (GST) and intravenous glucose tolerance tests (IVGTT), insulin sensitivity (IS) from hyperinsulinemic-euglycemic clamps. Isometric knee extension force (KEF) was assessed with a dynamometer and range of motion (ROM) was measured using a goniometer. IS was comparable in T2D+A and T2D-A (3.5±0.7 vs. 5.1±2.4 mg*kg-¹*min-¹), but lower than in CON (11.5±3.3 mg*kg-¹*min-¹, p&lt;0.05). Hemoglobin A1c (HbA1c) was similar in T2D+A and T2D-A (53±6 vs. 51±11 mmol/mol), but higher than in CON (33±3 mmol/mol, p&lt;0.05). In T2D+A, C-peptide secretion (IVGTT) was 43% and 63% lower (p&lt;0.05) than in T2D-A and in CON, respectively. C-peptide secretion (IVGTT) correlated inversely with HbA1c levels in T2D+A (r=-0.81, p&lt;0.05) and T2D-A (r=-0.60, p&lt;0.05). In T2D+A, KEF was 60% lower than in CON (19±11 kg vs. 47±12 kg, p&lt;0.05) and correlated negatively with C-peptide secretion (GST; r=-0.99, p&lt;0.05). ROM was 8% and 19% lower (p&lt;0.05) in T2D+A than in T2D-A and CON, respectively. Within T2D+A, ROM was negatively correlated with insulin secretion (IVGTT; r=-0.64, p&lt;0.05).
In conclusion, musculoskeletal impairment is associated with decreased beta-cell function in T2D patients suffering from arthritis, possibly mediated by chronic hyperglycemia.

Disclosure
O.P. Zaharia: None. D. Pesta: None. P. Bobrov: None. Y. Kupriyanova: None. K. Bódis: None. V. Burkart: None. J. Hwang: None. K. Müssig: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. J. Szendroedi: None.
The Natural Course and Risk Factors for Progression of Diabetic Retinopathy-KNDP Prospective Cohort Study
Authors: MOON HYUN UK , JEON JA YOUNG , LEE SOOJIN , HAN SEUNG JIN , KIM HAE JIN , CHUN KI HONG , KIM TAE HO , KIM YOUNG SEOL , WOO JEONG-TAEK , AHN KYU JEUNG , NAM MOONSUK , BAIK SEI HYUN , PARK YONGSOO , LEE KWANWOO 
Published: June 2018

Introduction: We investigated the annual incidence rate and risk factors for progression of diabetic retinopathy in The Korea National Diabetes Program.
Method: The Korean national Diabetes Program (KNDP) is a prospective, multicenter, and observational cohort study performed on type 2 diabetic patients in Korea. The study started in May 20and continued to follow-up until March 2014. Of the 3,949 patients enrolled in the KNDP, we analyzed 2962 patients who had both eyes photographed and assessed at baseline and further follow-up. An ophthalmologist evaluated and graded the funduscopic findings. Diabetic reinopathy (DR) was classified as 4 stages which were no DR, NPDR, PDR and blindness. We calculated the annual incidence rate from stage to stage. We analyzed the risk factor for progression of diabetic retinopathy.
Results: The mean follow-up time (SD) was 4.1 (1.7) years. The mean age and DM duration were 54.6 (9.8) years and 6.7 (6.5) years, respectively. The mean level of fasting glucose and HbA1c was 144 (50) mg/dl and 7.7 (1.7), respectively. Of those, patients with diabetic retinopathy was 691 (23.4%). The annual progression rate from no retinopathy to NPDR was 3.28% (295/2271). Patients progressed directly from NPDR to PDR at a rate of 3.13% (85/871). Three of 200 patients with PDR progressed to blindness, at an annual rate of 0.57%. Patients who further progressed retinopathy had older age, longer DM duration, higher levels of HbA1c, higher systolic blood pressure, and more history of cerebrovascular disease than those who didn’t progress retinopathy.
Conclusion: We reported the results of larger scale on DR progression than previous study of Korea. When compared to previous studies, the disease progression has improved over the 2 decades in Korean patients with type 2 diabetes. Our findings are consistent with other recent small studies from Korea. This study also confirmed risk factors for DR progression.

Disclosure
H. Moon: None. J. Jeon: None. S. Lee: None. S. Han: None. H. Kim: None. K. Chun: None. T. Kim: None. Y. Kim: None. J. Woo: None. K. Ahn: None. M. Nam: None. S. Baik: None. Y. Park: None. K. Lee: None.
Applying 8-oxoGuo for Prediction of Mortality in Patients with Type 2 Diabetes and Microalbuminuria—A Post-Hoc Analysis of the Steno-2 Trial
Authors: KJAER LAURA K. , OELLGAARD JENS , HENRIKSEN TRINE , GÆDE PETER , PEDERSEN OLUF , POULSEN HENRIK E. 
Published: June 2018

RNA oxidation product, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), has been associated with mortality in two cohorts of patients with type 2 diabetes (T2D). However, the potential effect of registered treatments decreasing urine 8-oxoGuo level remains unraveled. In the Steno-2 study intensified multifactorial intervention compared with conventional multifactorial therapy cut by half mortality in T2D patients with microalbuminuria. We assessed association between total mortality and 8-oxoGuo from advanced baseline and for 19.9 years, and from end of 7.8 years of intervention for 12.1 years.
In 1993, 160 T2D patients with microalbuminuria were included in the trial. Urine samples were available from 155 patients in 1995 (advanced baseline) and from 125 patients in 2001 (end of intervention). Cox regression was used for log2-transformed 8-oxoGuo and dichotomized (cut-off at median; low vs. high RNA oxidation).
During a follow-up of 19.9 years after advanced baseline, 89 died. From the end of 7.8 years of intervention and during remaining 12.1 years of observation, 61 of 125 died. From advanced baseline and onwards, no association between 8-oxoGuo and mortality was found (p=0.40). From end of intervention and onwards, a doubling of 8-oxoGuo showed a hazard ratio (HR) of 3.(95% CI [1.86−5.12]; p&lt;0.001; z-score=4.36) after multiple adjustments. Patients with low 8-oxoGuo in the intensive-therapy group had the lowest risk of dying compared with high 8-oxoGuo in the conventional group from advanced baseline and onwards, HR 0.40 (95% CI [0.21−0.75]; p=0.004), and from end of intervention and onwards, HR 0.28 (95% CI [0.13−0.60]; p=0.001) adjusted for age and sex.
In T2D patients with microalbuminuria, urine 8-oxoGuo level after 7.8 years of multifactorial intervention was associated with total mortality during 12.1 years of post-trial follow-up. Patients with low 8-oxoGuo in the intensified multifactorial group had the lowest risk of dying.

Disclosure
L.K. Kjaer: None. J. Oellgaard: None. T. Henriksen: None. P. Gæde: None. O. Pedersen: None. H.E. Poulsen: None.
Cardiovascular Outcomes and Mortality in Type 2 Diabetes with Associated Cardio-Renal-Metabolic Comorbidities
Authors: ARNOLD SUZANNE V. , HUNT PHILLIP R. , CHEN HUNGTA , MACLACHLAN SHARON , REPETTO ENRICO , VORA JITEN , KOSIBOROD MIKHAIL 
Published: June 2018

Cardio-renal-metabolic comorbidities (CRMCs) associated with type 2 diabetes (T2DM) increase patient morbidity and mortality. We evaluated the incremental contribution of various CRMCs to the risk of myocardial infarction, stroke, or cardiovascular death (MACE), heart failure (HF), and all-cause mortality (ACM) in patients with newly diagnosed T2DM. Using ICD-9 codes, T2DM patients were identified in a U.S. EMR (Humedica/Optum) database along with other CRMCs (hypertension {HTN}, hyperlipidemia {HPLD}, chronic kidney disease {CKD}) at the time of T2DM diagnosis. Patients’ records were assessed for the occurrence of MACE, HF, and ACM. Between 1 Jan 2011 and 31 Mar 2015, 180722 incident T2DM patients were identified (age {mean [SD]}: 62.4 [13.5], 52.0% male) with/without CRMCs: T2DM only (n=25114; 13.9%), T2DM+HTN (n=20863; 11.5%), T2DM+HPLD (n=13274; 7.3%) T2DM+HTN+HPLD (n=52415; 29.0%), and T2DM+HTN+HPLD+CKD (9.9%). The risk of MACE, HF and ACM increased with a greater number of CRMCs (Table), CKD being associated with the highest incremental risk for ACM. In patients with new diagnosis of T2DM, the risk of MACE, HF, and death increased incrementally with a greater number of CRMCs; with CKD being the main driver of mortality. These results may have implications for risk factor management, and potentially selection of treatment strategies among T2DM patients with various CRMCs.
TableMACE, HF, and ACM rates in patients with incident T2DM and cardio-renal-metabolic diseasesOutcomesCRMCs at time of T2DM DiagnosisEvent rate (95% CI) events/100 PYIncremental % increase in relative riskMACET2DM only5.16 (5.00, 5.32)ReferenceT2DM + HTN + HPLD7.04 (6.91, 7.18)36T2DM + HTN + HPLD + CKD9.15 (8.87, 9.43)30HFT2DM only4.84 (4.69, 5.00)ReferenceT2DM + HTN + HPLD6.24 (6.12, 6.37)29T2DM + HTN + HPLD + CKD8.40 (8.14, 8.66)35ACMT2DM only2.26 (2.16, 2.37)ReferenceT2DM + HTN + HPLD2.57 (2.50, 2.64)14T2DM + HTN + HPLD + CKD5.19 (5.01, 5.38)102ACM, all-cause mortality; CI, confidence interval; CRMCs, cardio-renal-metabolic comorbidities; CKD, chronic kidney disease; HF, heart failure; HTN, hypertension; HPLD, hyperlipidemia; MACE, myocardial infarction, stroke, or cardiovascular death; PY, patient-years; T2DM, type 2 diabetes mellitus.

Disclosure
S.V. Arnold: None. P.R. Hunt: Consultant; Self; AstraZeneca, Sanofi US. H. Chen: Employee; Self; AstraZeneca. S. MacLachlan: Consultant; Self; AstraZeneca. E. Repetto: Employee; Self; AstraZeneca. J. Vora: Other Relationship; Self; AstraZeneca. M. Kosiborod: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Amgen Inc., Sanofi, Boehringer Ingelheim GmbH, GlaxoSmithKline plc., Glytec Systems, Merck & Co., Inc., Novo Nordisk A/S, Janssen Pharmaceuticals, Inc., ZS Pharma, Inc., Intarcia Therapeutics, Inc., Novartis AG. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH.