bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Patterns of Comorbidities in Patients with Cardiovascular Disease and Type 2 Diabetes
Authors: IGLAY KRISTY , HANNACHI HAKIMA , ENGEL SAMUEL S. , LI XUEYING , O'CONNELL DAVID J. , MOORE LORI M. , RAJPATHAK SWAPNIL
Published: June 2018

Significant differences have been demonstrated in the risk of incident type 2 diabetes (T2D) and T2D-related complications by patient race. Because the presence of comorbidities can directly impact a physician’s selection of antidiabetic therapy, the current study sought to quantify differences in prevalence of diabetes-related comorbidities by race and cardiovascular disease (CVD) status in a large U.S. cohort. We conducted a retrospective study of T2D patients ≥18 years who had ≥1 encounter in the Quintiles Electronic Medical Record database from October 2014 to September 2015, as well as ≥1 year of medical history available. Of the 1,522,526 eligible patients, 54% were female, median age was 65 years, and median HbA1c was 6.7%. The cohort representation by race, and prevalence of comorbidities by CVD status, are shown in the table. Overall, 25% of patients had CVD, but this varied by race from 18.6% to 30.5%. The most prevalent comorbidities for all races included hypertension, hyperlipidemia, overweight/obesity, chronic kidney disease, neuropathy and heart failure, with rates generally higher among patients with CVD. Foot infections were also common for those with CVD across subgroups, but especially for Asian patients with CVD (36.9%).

In conclusion, patients with T2D and CVD had higher rates of common comorbidities vs. those without CVD, but rates varied by racial subgroups.

Disclosure

K. Iglay: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. H. Hannachi: Employee; Self; Merck & Co., Inc. S.S. Engel: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. X. Li: None. D.J. O'Connell: None. L.M. Moore: None. S. Rajpathak: Employee; Self; Merck & Co., Inc..
The Adiponectin-Mortality Paradox—A Systematic Review and Meta-analysis
Authors: SCARALE MARIA GIOVANNA , FONTANA ANDREA , TRISCHITTA VINCENZO , COPETTI MASSIMILIANO , MENZAGHI CLAUDIA
Published: June 2018

Surprisingly, several, though not all, studies have shown a positive relationship between serum adiponectin (ADPN) and mortality rate. In order to deeply address direction and strength of this paradoxical association, we carried out a systematic review and meta-analysis (MA) of prospective studies present in MEDLINE, Cochrane Library and Scopus by December, 1st 2017, with ADPN being the exposure and all-cause (AC) and cardiovascular (CV) mortality the outcomes. We performed random effect MA to pool individual hazard ratios (HRs; 95% CIs). To address the role of Natriuretic Peptides (NPs), known to increase both ADPN expression and mortality rate, a MA focused only on studies reporting HRs before and after NPs adjustment was also carried out. We assessed study heterogeneity by Q statistic and then performed meta-regressions considering male percentage, age, BMI, eGFR and clinical setting (general population, type 2 diabetes, CV disease, dialysis) as study level covariates. We identified 56 (n=64,775 subjects) and 30 (n=48,439) studies for AC and CV mortality, respectively. Heterogeneity across studies was observed for both outcomes (Q-test p<0.01). HRs, expressed as 1 SD increment of total ADPN, were 1.24 (1.17-1.30) and 1.28 (1.20-1.37) for AC and CV mortality, respectively. MA restricted to the 12 studies (n=19,010) reporting NPs data showed HRs for AC mortality equal to 1.24 (1.16-1.34) and 1.13 (1.06-1.21) without and with NPs adjustment, respectively (p<0.between HRs, when their correlation was >0.1). For CV mortality (6 studies, n=15,252), HRs were 1.21 (1.10-1.33) and 1.15 (1.06-1.24) without and with NPs adjustment, respectively (p<0.between HRs, when their correlation was >0.8). Male percentage, age, BMI, eGFR and clinical setting did not explain the observed heterogeneity among studies. Our results confirm the existence of a paradoxical association between high ADPN levels and increased mortality rate. Such paradox seems to be only partly explained by NPs levels.

Disclosure

M. Scarale: None. A. Fontana: None. V. Trischitta: None. M. Copetti: None. C. Menzaghi: None.
Fasting Plasma Mannose Level Is Associated with Insulin Sensitivity Independent of BMI in Japanese Individuals with Diabetes
Authors: AMANO ERI , FUNAKOSHI SHOGO , YOSHIMURA KUMIKO , HIRANO SEIKI , OHMI SATOKO , TERADA YOSHIO , FUJIMOTO SHIMPEI
Published: June 2018

Recently, integrated network analysis has revealed dysregulation in the metabolism of mannose, an epimer of glucose, in individuals with severe obesity who do not have significant diabetes. It was also found that fasting plasma mannose levels (M0) are associated with insulin resistance independent of BMI. Since the association between mannose and insulin sensitivity (IS) in those with impaired glucose tolerance remains unknown, we aimed to investigate the association in individuals with varying degrees of glucose tolerance. Based on data of 75g OGTT in Japanese individuals without diabetic medication, individuals were classified as normal (NGT), impaired glucose tolerance (IGT), and diabetes (DM). In each group, 25 subjects were consecutively recruited [total 75 individuals, age: 65±11 (mean±SD); BMI: 24.9±3.8]. Matsuda index (MI) was calculated as an index of IS. M0 was assayed using HPLC. Normally-distributed loge-transformed (ln-) values were used for MI and leptin. Although fasting plasma glucose (G0), HbA1c, and ln-MI were significantly different among 3 groups, age, sex, BMI, and M0 were not different. In simple regression analysis, ln-MI was negatively correlated with BMI (NGT: r=-0.639, IGT: r=-0.466, DM: r=-0.613) and ln-leptin (NGT: r=-0.480, IGT: r=-0.447, DM: r=-0.593) in all 3 groups. Interestingly, although ln-MI was not significantly correlated with M0 in NGT (r=0.241, P=0.245) and IGT (r=-0.296, P=0.152), it was moderately and negatively correlated in DM (r=-0.626, P<0.001). In DM, ln-MI was slightly correlated with G0 (r=-0.484, P=0.014). In multiple regression analysis in DM, ln-MI was independently predicted by BMI (β=-0.400) and M0 (β=-0.426), accounting for 51.2% (P<0.001) of the variability, which was larger than that in the prediction by BMI alone (37.6%).

In conclusion, in our study, fasting plasma mannose was associated with insulin sensitivity independent of BMI in Japanese individuals with diabetes.

Disclosure

E. Amano: None. S. Funakoshi: None. K. Yoshimura: None. S. Hirano: None. S. Ohmi: None. Y. Terada: None. S. Fujimoto: None.
Sleep Disturbances Are Associated with Poorer Glycemia and Increased Obesity in Youth at Risk for or with Early Type 2 Diabetes (T2D)
Authors: MOKHLESI BABAK , TEMPLE KARLA A. , HOGAN ASHLEY N. , EDELSTEIN SHARON , NADEAU KRISTEN J. , SAM SUSAN , HANNON TAMARA , UTZSCHNEIDER KRISTINA , BARENGOLTS ELENA , MANCHANDA SHALINI , EHRMANN DAVID A. , CAUTER EVE VAN , CONSORTIUM RISE
Published: June 2018

Poor sleep may be associated with an increased risk of obesity and T2D in youth. We explored whether subjective sleep duration, sleep quality or risk factors for obstructive sleep apnea (OSA) are associated with BMI, glycemia or blood pressure (BP) in youth. Between 2013 and 2016, 236 overweight and obese youth (10-19 years old) at risk for or with recently diagnosed T2D were screened for the Restoring Insulin Secretion (RISE) Study. Data from a 2 hour OGTT and validated Sleep Disturbances Scale and Cleveland Adolescent Sleepiness questionnaires were available for 214 youth. Regression models explored the independent association between sleep variables and outcomes of fasting glucose, 2-h glucose, HbA1c, BMI and BP. The cohort consisted of 67% females, 33% males; 26% white, 26% black, 33% hispanic; age 14.1±2.1 years and BMI 35.9±6.5 kg/m2 (mean±SD). Based on the ADA criteria, 20% had normal glucose tolerance, 60% had prediabetes and 20% had T2D. Sleep duration <8 h and <7 h was reported in 74% and 43% respectively; 51% reported daytime sleepiness; 26% reported poor sleep quality, and 30% high risk for OSA. 28% of the cohort was on metformin. After adjusting for age, sex, race/ethnicity, BMI and metformin use, the presence of daytime sleepiness was associated with 0.19% higher HbA1c (p=0.018) and higher 2-h glucose (13.3 mg/dl, p=0.05), but sleep duration, quality, and OSA risk were not associated with any of the outcomes. After adjusting for age, sex, race/ethnicity and metformin use, poor sleep quality was associated with 2.95 kg/m2 higher BMI (p=0.003), and high OSA risk with 2.81 kg/m2 higher BMI (p<0.003). In these overweight and obese youth with or at risk for T2D, daytime sleepiness was associated with poorer glycemia, while poor sleep quality and high OSA risk were associated with higher BMI. These findings suggest that intervention studies aimed at improving sleep in youth are required to determine potential benefits on glycemia and weight.

Disclosure

B. Mokhlesi: None. K.A. Temple: None. A.N. Hogan: None. S. Edelstein: None. K.J. Nadeau: None. S. Sam: None. T. Hannon: Consultant; Self; Eli Lilly and Company. K. Utzschneider: Consultant; Self; Novo Nordisk Inc.. E. Barengolts: None. S. Manchanda: None. D.A. Ehrmann: None. E. Van Cauter: Research Support; Self; AstraZeneca. R. Consortium: None.
Self-Reported Sleep and Circadian Measures Are Not Associated with Glycemia in Adults with Prediabetes or Early Untreated Type 2 Diabetes (T2D)
Authors: MOKHLESI BABAK , TEMPLE KARLA A. , HOGAN ASHLEY N. , EDELSTEIN SHARON , UTZSCHNEIDER KRISTINA , NADEAU KRISTEN J. , HANNON TAMARA , SAM SUSAN , BARENGOLTS ELENA , MANCHANDA SHALINI , EHRMANN DAVID A. , CAUTER EVE VAN , CONSORTIUM RISE
Published: June 2018

Abnormal sleep and circadian misalignment (e.g., social jetlag, late chronotype, or shift work) have been associated with abnormal glucose metabolism. These associations have not been well established in adults who meet the ADA criteria for prediabetes. We hypothesized that self-reported short sleep, poor sleep quality or circadian misalignment are associated with worse glycemia, BP and BMI in adults with prediabetes or early untreated T2D. We screened 1,355 overweight/obese men and women age 20-65 y for the Restoring Insulin Secretion (RISE) Study. Completed data from a 2-h OGTT, HbA1c and sleep questionnaires were available for 704 adults with prediabetes and 258 with early untreated T2D. We used a modified Pittsburgh Sleep Quality Index to assess usual bedtime, wake time, and sleep duration on workdays and days off, and the Berlin questionnaire to assess the risk of obstructive sleep apnea (OSA). Regression models explored the independent associations of sleep variables with glycemic variables, BMI and BP. The cohort was 55% men, 45% women; 42% white, 36% black, 16% Hispanic; age 52.2±9.5 years and BMI 34.7±5.5 kg/m2 (mean±SD). Sleep duration was 6.6±1.3 h, poor sleep quality was reported by 54%, high risk for OSA in 64% and 20% did shift work. After adjusting for age, sex, and race/ethnicity, shift work was associated with 1.32 kg/m2 higher BMI (p=0.0043). After adjusting for age, sex, race/ethnicity and BMI, no sleep or circadian variables (sleep duration, sleep quality, OSA risk, shift work, social jetlag and chronotype) were associated with HbA1c, fasting or 2-h glucose, or BP. In this cohort with prediabetes or early untreated T2D, subjective measures of sleep duration, quality and circadian misalignment were not associated with measures of glycemia or BP. Shift workers were more obese. Further research using objective measures of sleep is needed to better delineate the relationship between sleep and glycemia.

Disclosure

B. Mokhlesi: None. K.A. Temple: None. A.N. Hogan: None. S. Edelstein: None. K. Utzschneider: Consultant; Self; Novo Nordisk Inc.. K.J. Nadeau: None. T. Hannon: Consultant; Self; Eli Lilly and Company. S. Sam: None. E. Barengolts: None. S. Manchanda: None. D.A. Ehrmann: None. E. Van Cauter: Research Support; Self; AstraZeneca. R. Consortium: None.
The Impact of Diabetes and Hyperglycemia in Patients Hospitalized for Dengue
Authors: BUENO COLMAN ELVIO D. , POZZO YESSIKA A. , UMPIERREZ GUILLERMO E. , MEDINA URSULA B. , BENITEZ ALDO , MARIN SUSANA N.
Published: June 2018

Dengue is a potentially letal mosquito-borne flavivirus disease with about 390 million worldwide infections per year. We have experienced recurrent dengue epidemics in Brazil and Paraguay. We aimed to determine the impact and clinical outcome of diabetes (DM) and hyperglycemia during hospital admission in hospitalized patients for dengue. A total of 294 patients were admitted to a single medical center. Of them,47 (16%) patients had the previous diagnosis of DM (age: 62±12 years, blood glucose [BG]: 238±116 mg/dl), 44 (14.9%) patients had hyperglycemia (BG ≥180 mg/dl) without a prior diagnosis of DM (49±18 years, BG; 165±34 mg/dl) and 214 (73%) had normoglycemia (49±19 years, BG: 110±18 mg/dl). Patients with diabetes and hyperglycemia were older and were more likely to present with severe or hemorrhagic dengue, hemodynamic shock, acute kidney injury (AKI) requiring admission to the ICU and blood transfusion, and longer length of stay. There was a single death in a non-DM patient. Compared to patients with normoglycemia, non-DM patients with hyperglycemia (≥180 mg/dl) had more severe form of dengue with AKI (9.1% vs. 20.7%, OR: 2.61), hemodynamic shock (3.4% vs. 33.3%, OR: 2.61), ICU admission (4.4% vs. 33%, p=0.03) and longer length of hospital stay (4.7 days and 7.1 days, p=0.01).

Conclusion: Patients with DM and hyperglycemia were more likely to develop a more severe and hemorrhagic dengue compared to patients with normoglycemia. Because there is no specific dengue therapeutics, prevention is currently limited to vector control measures. A dengue vaccine program could represent a major advance in the control of the disease in patients with diabetes.

Disclosure

E.D. Bueno Colman: None. Y.A. Pozzo: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc.. U.B. Medina: None. A. Benitez: None. S.N. Marin: None.
Multiple Chronic Comorbidities in a T2DM Mediterranean Population
Authors: FRANCH-NADAL JOSEP , MATA-CASES MANEL , REAL JORDI , DE CAMPOS KARINE FERREIRA , CEDENILLA MARTA , GÓMEZ ANTÓN , MAURICIO DIDAC
Published: June 2018

Objective: T2DM patients often have multiple comorbidities which may impact patients’ management approach and treatment selection. This is the first study examining the co-prevalence of comorbidities such as CVD and CKD (GFR <60 ml/min and/or UACR ≥ 30 mg/g) across T2DM patients in Spain using a well-validated local database (DB).

Methods: Retrospective cross-sectional study using the Spanish local electronic records DB “Information System for the Development of Research in Primary Care”, SIDIAP. Adult patients with T2DM were included and comorbid conditions were assessed using all medical records available from full years 2015-2016. Patient characteristics, laboratory measures and comorbidities were summarized via descriptive analyses, overall and by subgroups of age, gender and HbA1c levels.

Results: From 373,185 T2DM identified patients (overall population, OP), 55% were men, their mean age was 70 years, the mean T2DM duration was 9 years and the mean HbA1c value was 7.12% (SD 1.32). The most common comorbid conditions were hypertension (HTN): 72% of patients; hyperlipidemia (HL): 60%; obesity: 39%, CKD: 33% and CVD: 23%. The highest co-prevalence was the combination of HTN/HL (45.2%), followed by HTN/CKD (28.3%), HTN/CVD (18.8%) and CVD/HL (15.1%). CVD was more frequent in older groups (32.3% in patients ³75 years-old) and in men (27.8% vs. 17.6%), while heart failure was more frequent in women (8.0% vs. 6.1%). CKD was found to increase with age, reaching 51.9% in patients ≥75 years. The coexistence of CKD and CVD in the whole population was 11.1%. Among T2DM patients with CVD and available GFR data (79,158, 91% of CVD patients), 57.6% had a GFR ≥ 60 ml/min (around 12% of OP), whereas 20.7% had GFR from 45 to <60, 14.2% had GFR from 30 to <45; 6.2% had GFR from 15 to <30ml/min; and 1.3% had GFR < 15ml/min.

Conclusion: The frequency of comorbidities in T2DM patients from a Mediterranean area is high, and both age and gender play a role in overall comorbidity burden. CKD and CVD are frequent comorbid conditions among T2DM patients.

Disclosure

J. Franch-Nadal: None. M. Mata-Cases: None. J. Real: None. K. Ferreira de Campos: Employee; Self; Merck Sharp & Dohme Corp. M. Cedenilla: Employee; Self; Merck Sharp & Dohme Corp. A. Gómez: Employee; Self; Merck Sharp & Dohme Corp. D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi.
Rate of Diabetes in Maricopa County, AZ
Authors: JAYCOX SHARON H. , PAGLIALUNGA SABINA
Published: June 2018

The prevalence of type 2 diabetes mellitus (T2DM) is well documented at the national, state, and even county level. Results are captured in the Behavior Risk Factor Surveillance System (BRFSS), a U.S. survey that collects data on disease rates and health-related risk behavior. The 2015 BRFSS audit revealed Arizona has an overall adult T2DM prevalence of 9.1%. Further, in Maricopa County, the region which includes the greater Phoenix area, the T2DM prevalence is higher at 10.8%. Conversely, there is limited data available on prediabetes rates in Maricopa County; therefore, we examined the rate of diabetes and prediabetes during community-partnered events as part of an educational “A1C initiative.” Basic demographic data as well as a fingerstick blood sample were obtained. HbA1c was measured with a hand-held monitor. 794 participants (272 men) were screened at 15 events from April 2016 to Sept 2017. The majority of participants were of Hispanic descent (54%). HbA1c results were categorized according to the ADA guidelines; normal (< 5.7%), prediabetes (5.7-6.4%) and diabetes (≥6.5%) ranges. Mean HbA1c for all participants was 6.0% +1.2%, with 16% and 35% falling in the diabetes and prediabetes ranges respectively. Diabetes and prediabetes rates for males and females were similar. By ethnicity, prediabetes was highest among African Americans (AA) (41%), followed by white non-Hispanics (35%) then Hispanics (33%). Despite AA having a higher diabetes rate at 21%, HbA1c was significantly higher in Hispanics vs. AA diabetes only subjects (8.6% +2.0 vs. 7.4% +1.4, p<0.001), suggesting worse glycemic control for the Hispanic group. In line with the national average of prediabetes prevalence at 33.9%, the overall rate we observed was similar, yet higher in certain groups. Notably, the diabetes rate was nearly double than that of the BRFSS report. The initiative provided vital (pre)diabetes awareness to Maricopa County residents. These findings were shared with our community partners, to aid in developing strategies to best assist those at risk of developing T2DM.

Disclosure

S.H. Jaycox: None. S. Paglialunga: Employee; Self; Celerion.
High-Risk Medication Use to Achieve Tight Glycemic Control among U.S. Adults with Serious Chronic Conditions
Authors: MCCOY ROZALINA G. , HOUTEN HOLLY VAN , LIPSKA KASIA J. , SHAH NILAY
Published: June 2018

For patients with serious comorbidities, diabetes management guidelines recommend more relaxed glycemic targets (glycosylated hemoglobin [HbA1c] <8-8.5% rather than <7%) and cautious use of agents known to cause hypoglycemia. We examined glycemic control and use of insulin and/or sulfonylureas among commercially insured and Medicare Advantage beneficiaries with serious comorbidities. Using OptumLabs Data Warehouse, we identified adults ≥18 years with diabetes and ≥1 of the following conditions (all identified by the guidelines) in 2014: dementia, end stage renal disease (ESRD), stages 3-4 chronic kidney disease (CKD), myocardial infarction (MI), heart failure (HF), cerebrovascular disease (CVD), chronic obstructive pulmonary disease (COPD), cancer, arthritis, urinary incontinence, falls, depression, hypertension, cirrhosis, proliferative retinopathy, peripheral neuropathy, and recent emergency department or hospital visit for hypoglycemia. We then identified their last available HbA1c in 2015 and the medications filled within 100 days of this HbA1c. There were 216,839 adults (mean age 65.5 years, 50.5% women, 58.6% white) with diabetes included in the study. The proportion of patients with HbA1c <7% was lowest among patients with retinopathy (28.9%), hypoglycemia (33.4%), and neuropathy (48.4%); it was highest among patients with dementia (59.1%). The majority (between 51.5% and 58.6%) of patients with the remaining conditions also had HbA1c <7%. The plurality of patients in each disease cohort was treated insulin and/or sulfonylurea, including 66.9% of patients with hypoglycemia, 54.4% with ESRD, 51.9% with CKD, 51.1% with cirrhosis, 46.8% with MI, 48% with HF, and 43% with dementia. Sulfonylureas were used in combination with insulin by nearly 6% of patients with ESRD, CKD, and cirrhosis. Thus, despite efforts to individualize therapy, the majority of patients with chronic conditions achieve HbA1c <7% and the plurality do so using high risk drugs.

Disclosure

R.G. McCoy: None. H. Van Houten: None. K.J. Lipska: Other Relationship; Self; Centers for Medicare and Medicaid Services. Research Support; Self; National Institutes of Health. N. Shah: None.
Effects of Lifestyle Intervention on Metabolism Profile in People with Impaired Glucose Tolerance—The China Da Qing Diabetes Prevention Study
Authors: QIAN XIN , CHEN YANYAN , JIA HONG-MEI , ZOU ZHONG-MEI , GONG QIUHONG , AN YALI , WANG JINPING , LI HUI , SHI NA , LI GUANGWEI
Published: June 2018

Aims: To investigate the effects of lifestyle intervention on metabolism profile in people with impaired glucose tolerance (IGT), and potential biomarkers for prevention of diabetes.

Methods: The study participants were identified as IGT by OGTT in 1986 and followed in 2006. Sixty participants were selected in the intervention group (I_Group) and 57 in control group (C_Group). UPLC-MS/MS analysis was performed by using the plasma samples. Principal component analysis and orthogonal partial least squares discriminant analysis were used for the data analysis.

Results: In 20-year follow-up study, I_Group had lower fasting plasma glucose, triglycerides and urine albumin/creatinine ratio comparing with C_Group. The metabolism profile was significant different between I_Group and C_Group, a total of 65 altered variables were obtained, and 9 metabolic pathways were changed, 4 pathways were considered as the most pertinent in the process of intervention: glycerophospholipid, arachidonic acid (AA) metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and vitamin B6 metabolism. In I_Group, after 6-year lifestyle intervention, 26 were still in IGT status and 34 change to diabetes after 20-year follow-up. The metabolism profile was significant difference between development of diabetes and still in IGT subjects, a total of 53 altered metabolites were obtained. Compared with the 65 metabolites, 7 metabolites decreased after intervention but increased when they change to diabetes, 1 metabolite had opposite change tendency. The above 8 metabolites involved in 5 metabolic pathways: glycerophospholipid metabolism, GPI-anchor biosynthesis, linoleic acid, α-Linolenic acid, and AA metabolism.

Conclusions: The 65 metabolites and 4 metabolic pathways were changed after lifestyle intervention, 8 altered metabolites involved in 5 pathways were considered as the potential biomarkers related to diabetes outcome.

Disclosure

X. Qian: None. Y. Chen: None. H. Jia: None. Z. Zou: None. Q. Gong: None. Y. An: None. J. Wang: None. H. Li: None. N. Shi: None. G. Li: None.
Serum Fibroblast Growth Factor-21 Is Related to Atherosclerosis Independent of Nonalcoholic Fatty Liver Disease and Predicts Incident Atherosclerotic Cardiovascular Diseases
Authors: WU LIANG , QIAN LINGLING , LI HUATING , JIA WEIPING
Published: June 2018

Fibroblast growth factor 21 (FGF-21), a key hepatokine regulating lipid metabolism, is related to several atherosclerotic diseases. But whether this relationship is mediated by nonalcoholic fatty liver disease (NAFLD) is not clear. Here we assessed the association of serum FGF-21 with atherosclerosis in non-NAFLD subjects and further investigated prospectively whether baseline FGF-21 could predict incident atherosclerotic cardiovascular disease (ASCVD) in a 7-year community study.Serum FGF-21 were measured in a cross-sectional cohort of 371 type 2 diabetic patients without NAFLD as determined by hepatic magnetic resonance spectroscopy, and a population-based prospective cohort of 7subjects from the Shanghai Diabetes Study. In the cross-sectional study, serum FGF-21 was significantly higher in those with subclinical carotid atherosclerosis (268.8 [139.0-415.2] vs. 188.3 [100.2-376.4] pg/ml, P=0.005). Multiple logistic regression analysis showed that serum FGF-21 was independently associated with atherosclerosis. In the prospective study, baseline serum FGF-21 was significantly higher in those who developed ischemic heart disease (479.5 [302.4-627.0] pg/ml, P=0.004) or cerebral infarction (401.6 [238.3-616.4] pg/ml, P=0.021) than those who did not (325.2 [189.0-498.9] pg/ml) during the follow-up. In multivariable Cox regression analysis, baseline serum FGF-21 independently predicted incident ASCVD events and significantly improved discriminatory and reclassifying abilities of the prediction model after adjustment for established cardiovascular risk factors.This study provides the first evidence that FGF-21 is elevated, independent of NAFLD, in subjects with subclinical atherosclerosis. Baseline FGF-21 is an independent predictor of incident ASCVD and could be utilized as a novel biomarker for primary prevention in general population.

Disclosure

L. Wu: None. L. Qian: None. H. Li: None. W. Jia: None.
Plasma Strontium and Interactions between Calcium and Strontium for Type 2 Diabetes—A Hospital-Based Case-Control Study
Authors: CHEN LIANGKAI , WANG QIANG , HU XIAOLI , WANG XIAOQIAN , SUN TAOPING , BAO WEI , LIU LIEGANG
Published: June 2018

Objective: Strontium and calcium play an essential role in bone metabolism but a paucity of epidemiological or experimental studies referring the role of strontium in the development type 2 diabetes (T2D). Prior studies have reported conflicting results for the relationships between plasma strontium and T2D. We therefore investigated the association between plasma strontium as well as the ratio of calcium to strontium (Ca/Sr) and newly diagnosed T2D.

Methods: After propensity score matching for age and sex, 2,5newly-diagnosed T2D patients and 2,5controls with normal glucose tolerance were recruited in the case-control study. Plasma strontium and calcium levels were determined by inductively coupled plasma mass spectrometry (ICP-MS). Multivariate logistic regression analysis was used to evaluate the independent association of plasma strontium levels and Ca/Sr values with the likelihood of T2D.

Results: Compared with the middle quintile, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals of T2D associated with the lowest quintile and the highest quintile of plasma strontium were 2.01 (1.66, 2.44) and 2.01 (1.65, 2.44), of plasma Ca/Sr were 2.11 (1.75, 2.54) and 2.01 (1.66, 2.43), respectively. In spline analysis, the U-shaped associations were consistently indicated, with the lowest odds of T2D at the plasma strontium concentration of 42.52 μg/L, and Ca/Sr value of 1500 approximately. We also discovered the pattern of high plasma calcium and low strontium level was associated with the highest odds of T2D, while the pattern of high plasma calcium and moderate to high strontium level was associated with the lowest odds of T2D.

Conclusions: Our results suggested U-shaped associations between plasma strontium, Ca/Sr and T2D; both low and high levels of plasma strontium and Ca/Sr were associated with higher odds of newly diagnosed T2D. We should not only pay attention to calcium, but also to strontium and the homeostasis of the both.

Disclosure

L. Chen: None. Q. Wang: None. X. Hu: None. X. Wang: None. T. Sun: None. W. Bao: None. L. Liu: None.
Population-Level Burden of Diabetes by Leisure, Transportation, and Work-Based Physical Activity—NHANES, 2011–16
Authors: ECHEVERRIA SANDRA , DIVNEY ANNA A. , TSUI EMMA K. , MIRZAYI CHLOE
Published: June 2018

Introduction: An abundance of evidence has shown that leisure-time physical activity (PA) is associated with reduced risk of diabetes. Adults, however, engage in various forms of PA, with potentially differential health effects. We tested if specific modes of PA are differentially associated with diabetes prevalence in a population-based adult sample.

Methods: Among 16903 racially/ethnically diverse adults ≥20 years old participating in NHANES 2011-16, we fit separate log binomial models to test associations between mode of PA and diabetes, and whether associations differed by race/ethnicity. Participants completed none, some (1-149 min/week) or met national PA guidelines (150+ min/week) for leisure time, work, transportation and combined modes (’All’). Diabetes was based on laboratory-confirmed HbA1C ≥ 6.5% or ever being told by a health professional respondent had diabetes.

Results: For each mode of PA and All modes combined, respondents completing 150+ minutes of PA were 33% to 39% less likely to have diabetes than respondents who completed no PA, even after controlling for covariates. There was a general gradient of decreasing prevalence with increasing PA. Effects varied by race/ethnicity for all PA modes except work-based PA (P<.01).

Conclusions: Meeting PA guidelines via any mode appears to confer protection from diabetes, but there are differential effects by mode and race/ethnicity.

Disclosure

S. Echeverria: None. A.A. Divney: None. E.K. Tsui: None. C. Mirzayi: None.
Impact of Childhood and Adult Socioeconomic Position (SEP) on Incidence of Type 2 Diabetes—The REGARDS Study, 2003–2016
Authors: BECKLES GLORIA L.A. , WU CHENGYI , MCCLURE LESLIE A. , CARSON APRIL P. , BULLARD KAI M. , IMPERATORE GIUSEPPINA , UNVERZAGT FREDERICK , HOWARD VIRGINIA J.
Published: June 2018

Exposure to socioeconomic stressors during early life may influence the incidence of type 2 diabetes (T2DM). We examined data from 1,207 African American (AA) and 4,149 white REGARDS participants aged ≥45 years with no evidence of T2DM at baseline (2003-2007), who completed the Childhood and Family Life Questionnaire (2011-2013) and the 2nd in-home visit (2013-2016). Incident T2DM cases were identified by self-reported physician diagnosis plus use of hypoglycemic drugs, fasting plasma glucose ≥126 mg/dL, or random plasma glucose ≥200 mg/dL. We estimated incidence rate as cases/1000 persons. Childhood SEP (CSEP) was derived from participants’ parental/caregiver education level and material assets. Adult SEP (ASEP) was derived from participants’ own education level and annual household income at baseline. SEP scores were categorized as low/medium/high. We fit multivariable logistic regression models to estimate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) for the separate and simultaneous effects of SEP measures on T2DM incidence, stratified by race. In 9.1 years of follow-up, 572 new cases of T2DM occurred; crude incidence rate=106.8/1000 (AA=168.2/1000; white= 88.9/1000). Controlled for age, sex, and percent life lived in Stroke Belt, low CSEP was associated with incident T2DM in AAs (aOR=1.65, 95% CI 1.05-2.52) but not in whites (aOR=1.01, 95% CI 0.703-1.46). Low ASEP was associated with incident DM in both racial groups: AA aOR=2.57 (95% CI 1.42-4.64); white aOR=2.42 (95% CI 1.69-3.45). With both SEP measures in the model, CSEP was no longer significant in AA but ASEP remained significant in both racial groups. Controlling for traditional T2DM risk factors the ASEP ORs remained significant in AA and whites. Low CSEP was associated with incident T2DM among AA but not whites; however, this may reflect indirect action through low ASEP. Low ASEP was associated with T2DM in both racial groups, partly explained by traditional T2DM risk factors.

Disclosure

G.L.A. Beckles: None. C. Wu: None. L.A. McClure: None. A.P. Carson: Research Support; Self; Amgen Inc.. K.M. Bullard: None. G. Imperatore: None. F. Unverzagt: None. V.J. Howard: None.
Risk of Islet and Celiac Autoimmunity in Cotwins of Probands with Type 1 Diabetes
Authors: TRIOLO TAYLOR M. , FOUTS ALEXANDRA R. , PYLE LAURA , YU LIPING , GOTTLIEB PETER , STECK ANDREA
Published: June 2018

Concordance for persistent islet autoimmunity (IA) and type 1 diabetes (T1D) in monozygotic twins (MZ) after one twin is diagnosed has been highly variable (30-70%), while risk for development of IA in dizygotic twins (DZ) is thought to be similar to non-twin siblings. Since 1995, the Twin Family Study at the Barbara Davis Center has followed 336 twins (168 twin probands diagnosed with T1D and 168 cotwins) with a median follow-up of 14 years (ICR:10-18 years). Zygosity testing confirmed a total of 80 MZ pairs and 88 DZ pairs. Cotwins were followed for the development of IA and celiac autoimmunity (CDA). In MZ cotwins, cumulative incidence for IA was 14% by age 20 and 63% by age 45, while development of CDA was 10% by 20 years. Development of IA and CDA by age 20 was 9.2% and 12.3% in DZ cotwins respectively, with development of IA reaching 70% by age 30 (Figure). In Cox proportional hazards models, only the proband’s age at diagnosis, but not sex, HLA-DR3 nor DR4 were associated with time to IA and CDA in cotwins. In MZ twins, younger age of the proband was associated with an increased hazard ratio (HR) for both IA and CDA, while younger age in DZ twins was associated with an increased HR for IA only.

In conclusion, CDA risk does not appear to increase after age 15. With long term follow-up, cumulative incidence for IA is high in DZ twins, similar to MZ twins, suggesting a role of possible early environmental factors shared by T1D-discordant cotwins.

Disclosure

T.M. Triolo: None. A.R. Fouts: None. L. Pyle: None. L. Yu: None. P. Gottlieb: Advisory Panel; Self; Bristol-Myers Squibb Company. Research Support; Self; Caladrius Biosciences, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; ImmunoMolecular Therapeutics. Consultant; Self; Kamada. Research Support; Self; JDRF, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., MacroGenics, Inc., Pfizer Inc.. Advisory Panel; Self; Viacyte, Inc.. Research Support; Self; GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.. A. Steck: None.
Continuous Glucose Monitoring Predicts Progression to Diabetes in Autoantibody-Positive Children
Authors: STECK ANDREA , DONG FRAN , TAKI IMAN , HOFFMAN MICHELLE R. , SIMMONS KIMBER , FROHNERT BRIGITTE I. , REWERS MARIAN
Published: June 2018

Children with islet autoantibodies (Ab+) are at high risk for developing clinical type 1 diabetes (T1D) and need accurate surveillance for prediction and diagnosis of T1D. Monitoring typically utilizes repeated 2-hour oral glucose tolerance tests. The objective of this study was to explore whether continuous glucose monitoring (CGM) could be an alternative measure for T1D prediction. In the Diabetes Autoimmunity Study in the Young (DAISY), 23 Ab+ subjects with a baseline CGM were followed for development of T1D for a mean of 28 months (8 of these progressed to T1D at a mean age of 15.2 years). Compared to non-progressors, subjects who progressed to T1D had significantly increased glycemic variability (SD 29 vs. 21 mg/dl, p=0.047), daytime sensor average (122 vs. 1mg/dl, p=0.02), and daytime sensor AUC (p=0.047). They spent 24% of time above 140 mg/dl and 12% above 160 mg/dl compared to, respectively, 8% and 3% (both p=0.005) for non-progressors; time spent over 200 mg/dl was minimal and not different between groups. Performance of prediction by receiver operating curve (ROC) analyses showed AUC of 0.85 for both %time spent above 140 mg/dl and 160 mg/dl. The cutoff of 18% time spent above 140 mg/dl had 100% specificity and 100% PPV with good sensitivity for diabetes prediction (Table).

In conclusion, ≥18% CGM time spent above 140 mg/dl accurately predicts progression to clinical diabetes in islet Ab+ children.TableIndexCutoffPPVNPVSensitivitySpecificity% time > 12036%0.7140.8120.6250.867% time > 14018%1.0000.8830.7501.000% time > 1606%0.8330.8240.6250.933% time > 1802%0.7140.8130.6250.867% time > 2000.2%0.5460.8130.7500.667

Disclosure

A. Steck: None. F. Dong: None. I. Taki: None. M.R. Hoffman: None. K. Simmons: None. B.I. Frohnert: None. M. Rewers: None.
Teraspanin 7 Autoantibodies in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults
Authors: ZHOU ZHIGUANG , SHI XIAJIE , ZHENG PEILIN , HUANG GAN , WANG YANFEI , DENG CHAO
Published: June 2018

Objective: This study aimed to investigate the prevalence of the newly-identified islet autoantibody, tetraspanin 7 autoantibody (TSPAN7A) in Chinese type 1 diabetes (T1D) and Latent Autoimmune Diabetes in Adults (LADA), and the correlation between TSPAN7A and islet function in LADA patients.

Research Design and Methods: Patients with newly onset T1D (n=158), long-lasting T1D (n=157), LADA (n=175), type 2 diabetes (T2D; n=204) and healthy control subjects (n=170) were recruited for the cross sectional study. Another cohort including 46 LADA patients with 3-year follow-up was recruited forthe longitudinal study. TSPAN7A was assayed by luciferase immunoprecipitation system assay.

Results: The prevalence of TSPAN7A in newly onset T1D, non-newly onset T1D, T2D, LADA and healthy control subjects were 25.3% (40/158), 10.2% (16/157), 0.5% (1/204), 21.1 (37/175) and 1.2% (2/170), respectively. Out of the 23 patients with newly onset T1D but negative for GADA, IA2 and ZnT8A, 3 patients were positive for TSPAN7A (13.0%) improving the detection of autoantibodies from 81.6% to 83.5% in T1D. In LADA patients, analysis of logistic regression demonstrated that duration (OR=1.77, P=0.026), GADA titer (OR=2.79, P=0.006) and TSPAN7A (OR=2.86, P=0.034) were the risk factors to islet function while BMI was the protection factor (OR=0.35, P=0.001). In the follow-up study, LADA patients with TSPAN7A showed a worse islet function compared those negative for TSPAN7A after 3-year diagnosis.

Conclusion: TSPAN7A is a novel diagnostic tool for T1D and LADA. Combination of TSPAN7A with other autoantibodies can improve the diagnosis of T1D. TSPAN7A is negatively correlated with islet function in LADA.

Disclosure

Z. Zhou: None. X. Shi: None. P. Zheng: None. G. Huang: None. Y. Wang: None. C. Deng: None.
Initial Diastolic Blood Pressure and Risk of Pregnancy Hypertensive Disorders in Pregestational Diabetes—Can We Set a Number?
Authors: OPPERMANN MARIA LUCIA R. , HIRAKATA VÂNIA N. , ALESSI JANINE , WIEGAND DANIELA , REICHELT ANGELA J.
Published: June 2018

Background: In pregestational diabetes (PGD) pregnancies, blood pressure (BP) close to normal is warranted to prevent pregnancy hypertensive disorders (PHD); targets are not well defined. Diastolic BP (DBP) was recently described as a modifiable factor.

Aim: to evaluate distinct levels of DBP as risk factors to PHD in a retrospective cohort of PGD women.

Methods: Women were cared for at a specialized prenatal care facility. DBP measured at the first antenatal appointment was categorized. Poisson regression with robust estimates was used.

Results: Baseline characteristics of women are in Table 1, and multivariable analysis, in Table 2.

Conclusion: In this PGD cohort, a DBP >80 mmHg at booking was associated to increased risk of PHD, suggesting that levels above this value should be prevented.

Table 1. Characteristics of Pregestational WomenType 1 diabetes (n=84)Type 2 diabetes (n=129)PHD32 (38.1)No PHD52 (61.9)pPHD32 (24.8)No PHD97 (75.2)pAge (years)26.8 (5.5)27.7 (5.9)0.51534.1 (4.3)33.1 (5.8)0.385Self-declared white93.884.60.36496.970.10.004Years since diagnosis15.4 (7.3)11.9 (8.7)0.0586.8 (6.2)3.5 (4.2)0.008Previous PHD4 (12.5)3 (5.8)0.4986 (18.8)22 (22.7)0.826Chronic hypertension8 (25.0)4 (7.7)0.05016 (50.0)24 (24.7)0.014Systolic BP (mmHg)120 (14)116 (14)0.214128 (16)119 (14)0.003Diastolic BP (mmHg)77 (13)72 (10)0.04282 (13)76 (11)0.025DBP > 70 mmHg56.248.10.61562.161.5>0.999DBP > 75 mmHg56.246.20.50062.160.4>0.999DBP > 80 mmHg21.95.80.06237.923.10.182Mean (SD) or %

Table 2. Risk of Pregnancy Hypertensive Disorders (n=178)Risk factorRelative risk95% CIpType 1 diabetes1.911.20-3.020.006Self-declared white skin3.711.22-11.270.021Primigravid1.130.76-1.680.558Diastolic blood pressure > 80 mmHg1.641.05-2.560.031Initial A1c test ≥7.0%0.6780.44-1.050.083Excessive GWG1.551.04-2.300.030

Disclosure

M.R. Oppermann: None. V.N. Hirakata: None. J. Alessi: None. D. Wiegand: None. A.J. Reichelt: None.
Cost-Effectiveness of Structured Lifestyle Programs for Diabetes Prevention in the Medicaid Population
Authors: LAXY MICHAEL , ZHANG PING , SHAO HUI , PENG NG BOON , ALI MOHAMMED K. , GREGG EDWARD W.
Published: June 2018

Background: The Diabetes Prevention Program (DPP) showed that structured lifestyle interventions can delay or prevent onset of type 2 diabetes in high risk individuals. Despite disproportionate diabetes burdens in low-income individuals, there are no data regarding expected health and economic impacts of structured diabetes prevention in the Medicaid population.

Objective: To examine the net costs and health benefits of extending coverage for structured lifestyle programs to the Medicaid population.

Methods: We modelled a prevention strategy consisting of triannual screening for prediabetes (FPG?100 mg/dl or A1c?5.7%) followed by a DPP-like lifestyle program vs. routine care in non-disabled U.S. Medicaid beneficiaries aged 25-64 years. Medicaid population characteristics were extracted from 2006-2016 NHANES surveys. Costs of diabetes and its complications were estimated from Medicaid administrative claims data of 8 states comprising 52% of the U.S. adult Medicaid population. Based on DPP-like studies in Medicaid populations, we assumed the intervention will reduce diabetes incidence by 32% and will be delivered at costs defined in the Medicare Payment Scheme. We estimated incremental health benefits (in quality-adjusted life-years (QALYs)) gained and net costs (in 2016 U.S. dollars) of screening and delivering lifestyle programs and subtracted savings through prevention of diabetes from a Medicaid perspective over a 10 year time horizon.

Results: Given a 25% screening and intervention uptake in approximately 27 million non-disabled Medicaid beneficiaries across 50 states, extending coverage could prevent or delay 135,000 cases of diabetes, gain 243,000 QALYs, and cost $1.35 billion (incremental cost effectiveness ratio $55,000 per QALY gained).

Conclusions: Extending Medicaid coverage for life-style diabetes prevention programs might be a good use of health care resources and will potentially diminish the diabetes burden in low income individuals.

Disclosure

M. Laxy: None. P. Zhang: None. H. Shao: None. B. Ng: None. M.K. Ali: None. E.W. Gregg: None.
Cost-Effectiveness of Structured Lifestyle Intervention in Overweight and Obese Adults with Type 2 Diabetes—Results from the Action for Health in Diabetes (Look AHEAD) Study
Authors: ZHANG PING , CHEN HAIYING , ESPELAND MARK , WING RENA R. , MONTEZ MARIA G. , HUCKFELDT PETER J. , EVANS MARY , GREGG EDWARD W. , KNOWLER WILLIAM C.
Published: June 2018

Look AHEAD is a multicenter randomized clinical trial designed to examine the effects of an intensive lifestyle intervention (ILI), compared with diabetes support and education (DSE), for reducing cardiovascular events in 5,145 adults with overweight/obesity and type 2 diabetes. Here we reported the cost-effectiveness of the ILI, measured in costs per quality-adjusted life year (QALY), relative to DSE as implemented during the 10-year intervention period of the trial.

Health utility (HU) values were measured using HU Index-2, HU Index-3, SF-6D and Feeling Thermometer. Cost were measured in 2012 U.S. dollars. All data were collected prospectively. QALYs were calculated as the product of predicted survival probability and predicted health utility values. Cumulative total cost was calculated as a sum of intervention cost and health expenditures, each of which was calculated as the product of predicted survival probability and predicted intervention cost and health expenditures.

The estimated total and incremental QALYS and costs, and cost-effectiveness ratios (CER) are presented in the Table. ILI was likely to be not cost effective over the 10 year intervention period. Long term health benefits from the follow-up of the study participants can provide important information regarding the long-term cost-effectiveness of ILI.MeasurementsDSE (95% CI)ILI (95% CI)ILI-DSE (95%CI)CE Ratio (95% CI)HUI-2 (QALYs)6.08 (6.03, 6.13)6.10 (6.05, 6.15)0.03 (-0.04, 0.09)-----HUI-3 (QALYs)5.94 (5.88, 5.99)5.94 (5.87, 5.99)0 (-0.08, 0.07)-----SF-6D (QALYs)5.92 (5.88, 5.96)5.99 (5.95, 6.03)0.07 (0.02, 0.12)101,635 (42567, 320360)Feeling thermometer (QALYs)6.03 (5.98, 6.07)6.18 (6.67, 6.77)0.15 (0.10, 0.21)45,487 (23270, 81851)Total cost ($)78,466 (76324, 80708)85,490 (83341, 87666)7,024 (4121, 9932)-----

Disclosure

P. Zhang: None. H. Chen: None. M. Espeland: Consultant; Self; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Heart, Lung, and Blood Institute. R.R. Wing: None. M.G. Montez: None. P.J. Huckfeldt: None. M. Evans: None. E.W. Gregg: None. W.C. Knowler: None.