bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 &lt;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 &gt;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.
Impact of the Structured, Comprehensive Clinic-Led, Population-Targeted Diabetes Intervention Program as Compared with the Standard Care Approach
Authors: KUBERAN INDUMATHI , RAO SAMEER , WADHWA NAVNEET 
Published: June 2018

We implemented a structured comprehensive Diabetes Management Plan (DMP) which includes monthly diabetologist counselling, pharmacological interventions, dietician review and education, follow-up through face to face and mobile technology, exercise motivation and periodic investigations, at a onetime enrolment cost. ANOVA, Chi-Square test were used for the statistical analysis. We conducted a retrospective analysis of the glycemic measures of effectiveness in patients enrolled with DMP (n=47, males= 32, females = 15; mean age (years) 50.4 ± 9.4, min 27, max 72) compared to the group receiving the conventional Standard Of Care (SOC) over one year (n=47, males= 24, females = 23; mean age (years) 54.3 ± 13.9, min 24, max 78); (p=0.116) from Jan- Dec 2017. At end of one year of follow-up, DMP group (baseline HbA1c 9.1±1.57%) demonstrated higher HbA1c reductions of 1.86±1.10% as compared to the SOC group (baseline HbA1c 8.59±1.5%), which was statistically significant (p=0.046). DMP group (baseline Fasting Blood Glucose (FBG) 167.5±59.32 mg/dl) demonstrated higher FBG reductions of 34.89 ± 36.71 which was highly statistically significant from baseline (p=0.001). However, FBG was not statistically significant as compared to the baseline within the SOC group (baseline 147.25 ± 52.11 mg/dl, (p=0.602); the differences were statistically significant (p=0.005). The dyslipidemia parameters reveal that there was no significant difference in the groups for the change in LDL-C (p=0.36), total cholesterol (p=0.16) and HDL-C (p=0.11). The DMP group had significant elevation in HDL-C (11.8%, p=0.001). DMP with compulsory periodic interventions is useful as a better glycemic management tool and resource optimisation, as done in DMP, in an emerging economy would be useful model to emulate even for the developed world to manage the cost of diabetes care.

Disclosure
I. Kuberan: None. S. Rao: None. N. Wadhwa: None.
Mitochondrial Glycerol 3-Phosphate Dehydrogenase Improves Skeletal Muscle Regeneration in Obesity and Diabetes
Authors: QU HUA , ZHENG YI 
Published: June 2018

While adult mammalian skeletal muscle is stable due to its post-mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, leading to the loss of muscle function, and contributing to the global burden of these diseases. However, the underlying mechanisms behind the impairment are not well defined. Here we identify mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH deletion (mGPDH-/-) attenuated skeletal muscle regeneration in vitro and in vivo while mGPDH overexpression improved the insufficient regeneration in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese (HFD, ob/ob) and diabetic (STZ) mice by AAV led to a significant improvement in their muscle regeneration (Figure 1). Our study provides a new mechanism and potential therapeutic target for skeletal muscle regeneration impairment.

Disclosure
H. Qu: None. Y. Zheng: None.
Higher Dietary Intake of Vitamin D Is Associated with Lower Incidence of Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , TANAKA SACHIKO , KAMADA CHIEMI , YOSHIMURA YUKIO , ARAKI ATSUSHI , MORIYA TATSUMI , KATAYAMA SHIGEHIRO , SONE HIROHITO 
Published: June 2018

Evidence for optimal dietary intake of vitamin D for prevention of diabetic complications is sparse although associations between low vitamin D intake and high incidence of diabetes and vitamin D supplementation and improvement in insulin resistance were reported. We aimed to investigate the relationship between vitamin D intake and the incidence of diabetes complications in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c≥6.5%. The present analysis was conducted as a multicenter prospective study on the incidence of and risk factors for macro- and microvascular complications among 22Japanese patients with type 2 diabetes from outpatient clinics in 59 university and general hospitals in Japan.Analyzed were 1516 responders to a baseline dietary survey assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 8-year risk of nephropathy, retinopathy, and cardiovascular disease (CVD). Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean vitamin D intake in quartiles ranged from 5.4 to 18.7μg/day. After adjusting for confounders, HRs of diabetic nephropathy in the 2nd, 3rd, and 4th quartiles for vitamin D intake compared with the 1st quartile were 0.7 (95% confidence interval 0.4-1.3, p=0.29), 1.2 (0.6-2.2, p=0.61), and 0.33 (0.14-0.79, p=0.01), respectively. There was no significant associations of vitamin D intake with retinopathy and CVD in the 2nd to 4th quartiles relative to the first quartile (retinopathy: 1.2 (0.9-1.6, 0.4), 0.8 (0.5-1.2, p=0.23), and 0.7 (0.5-1.0, p=0.08); CVD: 1.1 (0.7-1.7, p=0.83), 1.2 (0.7-2.0, p=0.62), and 0.7 (0.4-1.3, p=0.22)). Findings suggested that high vitamin D intake was associated with a lower incidence of diabetes nephropathy among Japanese patients with type 2 diabetes.

Disclosure
C. Horikawa: None. R. Aida: None. S. Tanaka: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. A. Araki: None. T. Moriya: None. S. Katayama: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Risk of Nonalcoholic Fatty Liver Disease (NAFLD)-Related Liver Complications in the Diabetic Population in Israel
Authors: GOLDSHTEIN INBAL , FERNANDES GAIL , CHODICK GABRIEL , RAJPATHAK SWAPNIL , KARASIK AVRAHAM 
Published: June 2018

In the absence of early non-invasive diagnostic tools, the burden of NAFLD and its related complications in the diabetic (DM) population remains unclear. Using longitudinal data and defined criteria to identify NAFLD patients, this study evaluated the incidence of NAFLD-related liver complication in DM vs. non-DM population. The study utilized the computerized database of a nationally representative payer-provider health fund, including all members enrolled in year 2000 (index) without viral hepatitis or excess alcohol intake. NAFLD was defined as at least 2 of the following criteria: 2+ measurements of elevated liver enzymes (&gt;2 upper normal limit), NAFLD Fibrosis score&gt;-1.455, coded NAFLD Diagnoses, or imaging evidence using natural language processing of 1 million ultrasonography text reports. Cirrhosis, liver transplant and hepatocellular carcinoma (HCC), were detected by diagnoses, procedures, and the national cancer registry. DM was defined using a previously validated registry. Incidence density rates based on person years (PY) since index were compared between NAFLD cases vs. age and sex matched controls (2:1 ratio). The incidence was further stratified by the presence of DM. The total population included 1,083,4subjects with a mean follow-up of 15.1 years (SD=4.2).Out of these, n=61,644 were identified as NAFLD, with a mean age of 52.1 years (SD=13.6) and 23.4% with DM when they met the criteria for NAFLD. The incidence of cirrhosis, HCC and liver transplant was substantially higher in NAFLD cases as compared with matched controls with rate ratios of 5.6 (95% CI: 5.2-6.0), 1.3 (1.2-1.4) and 3.9 (2.9-5.2) respectively. After stratification by DM, rate ratios were 2.2 (95% CI: 2.0-2.3) for cirrhosis, 2.1 (1.8-2.5) for HCC and 2.5 (1.7-3.5) for liver transplant in NAFLD with DM vs. NAFLD without DM. This study shows that patients identified with NAFLD had higher rates of liver complications and these rates were increased among patients with DM.

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. G. Chodick: None. S. Rajpathak: Employee; Self; Merck & Co., Inc. 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.
White Matter Differences and Neurodevelopment Outcomes in Patients with KATP Channel-Related Diabetes
Authors: LEMELMAN MICHELLE B. , WREN-JARVIS JAMIE , SCOTT MEGAN N. , MARTIN RYAN , CARMODY DAVID , WROBLEWSKI KRISTEN , KEEDY SARAH , GREELEY SIRI ATMA W. 
Published: June 2018

Background: Patients with KATP channel related diabetes (KATP-DM) experience improved glycemic control with sulfonylurea therapy, but the degree of improvement in their spectrum of neurological dysfunction remains unclear. We hypothesized that patients with KATP-DM have differences in brain white matter and associated neurodevelopmental impairments when compared to those with type 1 diabetes or sibling controls.
Methods: Subjects (8-20 years old) from the Monogenic Diabetes Registry at the University of Chicago included those with KATP-DM (n=8), type 1 or other non-KATP diabetes (n=7), and sibling controls (n=6). All participants had brain MRI with diffusion tensor imagining (DTI) on a 3T Philips Achieva Quasar scanner. Fractional anisotropy (FA) was used as an indirect measurement of myelin in the brain. Subjects also participated in validated neurodevelopmental assessments.
Results: Nonparametric Kruskal-Willis testing of analyzable DTI data [4 KATP-DM, 5 T1DM, 3 siblings] revealed that FA values of the corpus callosum were not statistically different (p=0.58). However, DTI of the white matter tracks in the right hippocampus approached a significant difference among the three groups (p=0.07). Third ventricular volumes among all three groups [9 KATP-DM, 7 T1DM, 5 siblings] were significantly different (p=0.05). Significant differences between groups as determined by one-way ANOVA were found in Perceptual IQ (F (2,14)=4.862, p=.025); visual motor integration (F (2,14)=5.579, p=.017); and graphomotor coordination (F (2,14)=5.399, p=.018).
Conclusion: In this first study using quantitative MRI methods in patients with KATP-DM, DTI revealed no overall difference but possible regional variation in FA, while ventricular volume and neurodevelopmental function were different among this cohort. Larger studies are needed to assess the potential differences in brain white matter as well as the benefits of early sulfonylurea therapy on neurologic development.

Disclosure
M.B. Lemelman: None. J. Wren-Jarvis: None. M.N. Scott: None. R. Martin: None. D. Carmody: Research Support; Self; Novo Nordisk Inc.. K. Wroblewski: None. S. Keedy: None. S.W. Greeley: Research Support; Self; Novo Nordisk Inc..
Effects of Bariatric Surgery on FGF-19 and FGF-21 Levels on Obese Diabetic Women
Authors: AZHARIAN SAHAR , MURPHY ALICE , MCTERNAN PHILIP G. , PIYA MILAN K. , TRIPATHI GYANENDRA 
Published: June 2018

Background: Fibroblast growth factor 19 (FGF-19) and FGF-21 regulate glucose tolerance and insulin sensitivity, which in type 2 diabetes mellitus (T2DM) conditions becomes dysregulated. Whilst weight loss can restore this functionality, bariatric surgery can have a specific impact due to mechanical changes on gut/liver physiology. We aimed to analyse the effects of different bariatric surgeries: sleeve gastrectomy (SG), laparoscopic adjusted gastric banding (LAGB) and biliopancreatic diversion (BPD) on changes in FGF-19 and FGF-21 levels.
Methods: Obese and T2DM women (n=41 BMI&gt;35 Kg/m2) undergoing SG (n=14), LABG (n=13), and BPD (n=14) participated in an ethics approved study. Anthropometry, biochemical data, and adipose tissue (AT) biopsies were collected before and 6 months after surgery. FGF-19, FGF-21 levels and AT inflammation (TLR2, MYD88, TRAF6, IKK and NFkb) was assessed.
Results: Post surgery SG led to 63% reduction in FGF-21 whilst LABG and BPD led to 41% and 4% decrease respectively. There was a significant differences in FGF-21 levels between SG and BPD (p=0.021). Moreover, FGF-21 change in SG positivly correlated with changes in glucose (p=0.019), insulin (p=0.047), HOMA-IR (p=0.022) and triglyceride (p=0.027); absent in BPD and LABG. FGF-21 levels in SG appeared as a significant predictor of HOMA-IR change post surgery (p&lt;0.05). FGF-19 levels post surgery increased by 31% in SG compared to 10% rise in BPD and 39% decrease in LAGB with significant differences between SG and LAGB (p=0.012). FGF-19 change in BPD inversly correlated with changes in weight (p=0.012), BMI (p=0.037), waist circumfrance (p=0.044); absent in SG and LAGB.
Inflamatory markers post surgery were significantly reduced in all surgeries (TLR2: p&lt;0.01, MYD88: p&lt;0.01, TRAF6: p&lt;0.01, IKK: p&lt;0.01 and NFkb: p&lt;0.01).
Conclusion: SG appears to have a beneficial influence on FGF-21 and FGF-19 levels irrespective of reduced AT inflammation. Our FGF findings therfore suggests that SG provides better glucose homeostatis outcomes than LAGB and BPD.

Disclosure
S. Azharian: None. A. Murphy: None. P.G. McTernan: None. M.K. Piya: None. G. Tripathi: None.