bluuebunny/crossref_metadata_2025 huggingface dataset:
1460-P: Predicting Atherosclerotic Cardiovascular Disease (ASCVD) Risk in Veterans with Diabetes
Authors: RAGHAVAN SRIDHARAN , HO YUK-LAM , POSNER DANIEL , VASSY JASON L. , GAGNON DAVID R. , PHILLIPS LAWRENCE S. , WILSON PETER W.
Published: June 2019

Estimating ASCVD risk in patients with diabetes could guide intensity of risk factor treatment, but existing risk calculators (2013 ACC/AHA ASCVD pooled cohort equations [PCE] and RECODe risk equations [RECODe]) have not been evaluated in a contemporary American population with diabetes. Using validated phenotyping algorithms, we evaluated prediction models for the development of a composite “hard” ASCVD outcome (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death) over 5 years in 184,823 diabetic U.S. Veterans without baseline ASCVD receiving primary care in the VA 2002-2007 (2.4% women, 19.5% black, mean age 61 years, 9851 ASCVD events). We compared discrimination using the C-statistic and calibration using the Greenwood-Nam-D’Agostino test (GND) of the PCE variables (sex, age, race, cholesterol, blood pressure [BP], smoking status, BP medications, statin treatment, and aspirin), RECODe, and a series of models using PCE variables with VA sample-specific coefficients. Models with PCE variables and VA-specific coefficients had better discrimination (C=0.642) than the PCE (C=0.582) or RECODe (C=0.633). Successive addition of hemoglobin A1c, estimated glomerular filtration rate, diabetes medications, and statin therapy improved the model (full model, C=0.669), with only minimal enhancement by semisupervised variable selection using LASSO (C=0.672). The C-statistic of the full model was similar in those <60 or ≥60 years old, but predicted risk was higher for black than for white patients, and for men than for women. The full model also had improved calibration (GND p=0.82) compared to the PCE and RECODe (p<0.0001 for both; higher p indicates better calibration).

Conclusion: Health system-specific tailoring of prediction equations provides improved discrimination and calibration compared to existing models. This risk predictor could be embedded in the electronic health record and used to guide intensification of treatment aimed to improve ASCVD outcomes.

Disclosure

S. Raghavan: None. Y. Ho: None. D. Posner: None. J.L. Vassy: None. D.R. Gagnon: None. L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc. P.W. Wilson: None.

Funding

U.S. Department of Veterans Affairs; American Heart Association
1468-P: Cause-Specific Mortality over 30 Years among Chinese with Newly Diagnosed Diabetes: The Da Qing IGT and Diabetes Study
Authors: AN YALI , ZHANG PING , WANG JINPING , GONG QIUHONG , ZHANG BO , CHEN YANYAN , GREGG EDWARD , BENNETT PETER H. , LI GUANGWEI
Published: June 2019

Despite its growing prevalence in China, the extent to which diabetes leads to excess mortality and its underlying causes are ill-defined. Six-hundred and six persons with newly diagnosed diabetes (NDD) and a comparison group of 494 with normal glucose tolerance (NGT) were identified in 1986 by screening 110,660 adults aged 25-74 years who agreed to participate in The Da Qing IGT and Diabetes study. A follow-up study of the original study participants was conducted in 2016. We compared death rates and causes of death between the two groups during 30 years of follow-up. Four-hundred and forty (71.7%) participants with NDD and 153 (31.0%) with NGT died. Overall mortality (rates/1,000 person-years + 95% CI) were much higher in those with NDD than with NGT, 40.8 (35.6-46.5) vs.15.8 (13.0-19.1) in men (P< 0.0001), and 30.4 (26.4-34.9) vs. 6.9 (5.0-9.3) in women (P<0.0001). Earlier age at diagnosis of diabetes was significantly related to the relative risk of death (RR (+95% CI)), 5.0 (2.9-8.6) in those diagnosed at age 25∼39y, 3.2 (2.3-4.4)] at 40∼49y, and 2.8 (2.1-3.6) at 50∼74y. Cardiovascular disease (CVD) was the predominant cause of death in those with diabetes (66.5% in men and 62.8% in women), almost half of which was due to stroke (52.1% in men and 40.6% in women). After age-sex adjustment, the NDDs had significant increased mortality from CVD (RR 3.9 [95% CI, 2.9-5.2]), renal failure (RR 15.6 [95% CI, 6.3-38.9]), infection (RR 4.2 [95% CI, 2.0-8.5]), and cancer (RR 1.5 [95% CI, 1.0-2.3]).

In conclusion, diabetes is associated with substantially increased risks of death in Chinese adults, especially from CVD, renal failure, infection and cancer. Earlier age at diagnosis leads to greater relative risk of death.

Disclosure

Y. An: None. P. Zhang: None. J. Wang: None. Q. Gong: None. B. Zhang: None. Y. Chen: None. E. Gregg: None. P.H. Bennett: Consultant; Self; World Health Organization. Stock/Shareholder; Self; Becton, Dickinson and Company, Eli Lilly and Company, Pfizer Inc., UnitedHealth Group Inc. Other Relationship; Self; American Diabetes Association, Centers for Disease Control and Prevention, European Association for the Study of Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. G. Li: None.

Funding

Centers for Disease Control and Prevention/Chinese Center for Disease Control and Prevention (5U19GH000636-05)
147-LB: PATAS, an Adipocyte-Targeted Peptide Approach to Treat Type 2 Diabetes and Associated Comorbidities
Authors: MARION VINCENT
Published: June 2019

Studying rare genetic disorders, associating type 2 diabetes, is a valuable approach to decipher disease origins as a specific causal gene can be linked to the diabetic phenotype. Understanding the related protein functions favors the discovery of new pathways, hence the design of new therapies. We focused on an ultra-rare genetic disorder, the Alström syndrome, associated with severe early-onset type 2 diabetes, obesity, steatosis and generalized fibrosis and for which a unique gene is consistently found mutated in ALMS patients, ALMS1 gene. Combining clinical, multiomics and in vivo mouse data, we discovered that ALMS1 regulates the ultimate steps of insulin signaling in the adipocyte, controlling fusion of GLUT4 sorting vesicles with the plasma membrane. ALMS1 binds to αPKC in the GLUT4 sorting vesicles vicinity and, under insulin stimulus, releases αPKC to trigger GLUT4 plasma membrane entry and glucose absorption. ALMS1 inactivation specifically inhibits adipocyte’s glucose absorption. In mice, the diabetic, steatotic and fibrotic phenotypes were linked to switching adipocyte energy tropism from glucose to lipids corelated with fatty acid transporters’ upregulation like FATP2 in the adipocyte; also observed in ALMS patients’ adipocytes. This change in fuel source in the adipocyte is the underlying cause for the observed metabolic disorders in vivo; primarily mediated through lipid signaling. Insulin-independent glucose absorption was achieved in normal adipocytes using a cell-penetrant, stapled peptide termed PATAS that targets ALMS1/αPKC protein interaction and in vivo can restore physiological adipocyte’s glucose energy tropism. Several in-house and outsourced experiments have demonstrated that PATAS administration significantly improves glucose intolerance, fasting blood glucose levels, liver steatosis and fibrosis in different mouse and rat models thereby making PATAS a potential novel drug to treat type 2 diabetes and its associated complications.

Disclosure

V. Marion: Research Support; Self; Rhythm Pharmaceuticals, Inc. Stock/Shareholder; Self; ALMS THERAPEUTICS.
1472-P: Association between Triglycerides and Residual Cardiovascular (CVD) Risk in Patients with Type 2 Diabetes and Established CVD: An Analysis of the BARI2D Trial
Authors: PAGIDIPATI NEHA , NAVAR ANN MARIE , MULDER HILLARY , WOJDYLA DANIEL M. , PHILIP SEPHY , GRANOWITZ CRAIG B.
Published: June 2019

Background: While hypertriglyceridemia is a known risk factor for developing CVD, whether it poses residual risk in patients with type 2 diabetes mellitus (T2DM) and established CVD is under-studied.

Methods: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, we examined 2,307 patients with T2DM and CVD to determine the association of baseline fasting triglyceride (TG) levels with MACE (time to CV death, myocardial infarction (MI), or stroke) or CV death over a mean follow-up of 5.0 years.

Results: At baseline, the mean fasting TG was 181 mg/dl with a median (Q1, Q3) of 148 (104, 219) mg/dl. Overall, 49.3% had TG≥ 150 mg/dl (N=1,167). Compared with those with TG<150 mg/dl, they were younger, more frequently Caucasian and with higher BMI. In unadjusted models, TGs were significantly associated with MACE and CV death (Table). This association did not remain after adjustment for multiple factors, including nonHDLc.

Conclusions: In this analysis of patients with T2DM and known CVD, TGs were relatively high and were associated with CV outcomes, but not when other risk factors were taken into account. Thus, while TGs are clearly a marker of those with residual high risk for CV events in T2DM, whether they specifically need to be lowered awaits well conducted clinical trials.

Disclosure

N. Pagidipati: Research Support; Self; Amarin Corporation, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Regenerative Medical Solutions, Sanofi. A. Navar: Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; Amarin Corporation, Amgen Inc., Regeneron Pharmaceuticals, Sanofi. H. Mulder: None. D.M. Wojdyla: None. S. Philip: Employee; Self; Amarin Corporation. Stock/Shareholder; Self; Amarin Corporation. C.B. Granowitz: Employee; Self; Amarin Pharma Inc. Stock/Shareholder; Self; Amarin Pharma Inc.

Funding

Amarin Corporation
1478-P: Impact of Prior Cerebrovascular Disease (CVD) and Glucose Tolerance Status on Incident CVD in Japanese
Authors: YANAGISAWA DAICHI , FUJIHARA KAZUYA , OSAWA TAEKO , KITAZAWA MASARU , YAMAMOTO MASAHIKO , MATSUBAYASHI YASUHIRO , YAMANAKA NAUTA , KODAMA SATORU , SONE HIROHITO
Published: June 2019

Although both a glucose metabolism abnormality and prior cerebrovascular disease (CVD) are major predictors of CVD, few studies have compared their impact on a subsequent CVD event. Also, few studies evaluated risk of prediabetes separately from nondiabetic categories. Thus, the impact of diabetes mellitus (DM) on subsequent CVD compared to normal glucose tolerance (NGT) could have been underestimated. We analyzed a nationwide claims-based database of 290,865 participants in 2008-14. Participants were classified as having NGT, prediabetes or DM based on fasting plasma glucose, HbA1c and use of antihypoglycemic agents (185,648 with NGT; 87,867 with prediabetes; 17,350 with DM). Participants were also classified as with or without prior CVD based on ICD-10 and questionnaires (1,944 with prior CVD; 288,921 without prior CVD). Cox regression model showed that prediabetes and DM confers about 1.1- and 1.4-fold excess risk for CVD, respectively, compared to NGT without prior CVD. Prediabetes and DM does not increase risk for CVD compared to NGT with prior CVD (Table). Prior CVD confers a 4-7-fold excess risk for CVD regardless of glucose tolerance status. Hazard ratio of CVD in NGT with prior CVD was 4 times higher than in DM without prior CVD. This implies that prediabetes and DM increase CVD only in those without prior CVD. Prior CVD confers a higher risk for subsequent CVD regardless of glucose tolerance status.

Disclosure

D. Yanagisawa: None. K. Fujihara: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. Y. Matsubayashi: None. N. Yamanaka: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
1479-P: Predictors of Incident Hospitalization for Heart Failure in the ACE Trial Population
Authors: SCOTT CHARLES A.B. , MCMURRAY JOHN J. , RYDÉN LARS , SUN YIHONG , TENDERA MICHAL , COLEMAN RUTH L. , HOLMAN RURY R.
Published: June 2019

Background and Aims: Heart failure (HF) is a deadly complication of type 2 diabetes but little is known about its incidence in patients with coronary heart disease (CHD) and impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify baseline variables predictive of incident hospitalization for HF (hHF) or HF-death during median 5.0 years follow-up in this Chinese population with CHD and IGT.

Methods: Independent predictors of hHF/HF-death were determined using a Cox proportional hazards model. Patients were censored at first hHF event, HF-death or end of follow-up. The 16 variables tested included age, gender, BMI, smoking, plasma creatinine, prior cardiovascular events, fasting and 2-hour postload glucose and HbA1c. Those with a univariate hHF association (P<0.10) were considered for inclusion in the model, with P values <0.05 required for retention in the multivariable model.

Results: Of the 6522 ACE participants, 6278 had no prior HF. They were mean (SD) 64.2 (8.0) years old, BMI 25.4 (3.1) kg/m2 and 73% were male. Of these, 111 (1.8%) had ≥1 episode of adjudicated hHF. Significant independent hHF/HF-death predictors were age, plasma creatinine, prior myocardial infarction (MI) and prior atrial fibrillation (AF) (Table).

Conclusion: In Chinese patients with CHD and IGT, those at higher risk of hHF/HF-death were older with higher plasma creatinine values, prior MI and prior AF.

Disclosure

C.A.B. Scott: None. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Amgen Inc., AstraZeneca, Bayer AG, Bayer AG, Bristol-Myers Squibb Company, DalCor Pharmaceuticals, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Theracos, Inc., Vifor Pharma. L. Rydén: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker's Bureau; Self; Bayer AG. Other Relationship; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Y. Sun: None. M. Tendera: Consultant; Self; Bayer AG, Servier. R.L. Coleman: None. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.
1482-P: Low-Density Lipoprotein Cholesterol (LDL-C) Management in Patients with Atherosclerotic Cardiovascular Diseases (ASCVD) and Preexisting Diabetes in Alberta, Canada
Authors: CHEN GUANMIN , FARRIS MEGAN S. , COWLING TARA , TAI MING-HUI , PINTO LIONEL , COLGAN STEPHEN , ROGOZA RAINA , ANDERSON TODD J.
Published: June 2019

Background: Lipid-lowering therapy (LLT) reduces the risk of CV events, however, limited real-world data exist on the management of LDL-C in patients with ASCVD and pre-existing diabetes in Canada. Our study describes the clinical characteristics and LDL-C management of patients with ASCVD and diabetes using health system data in Alberta.

Methods: A retrospective study was conducted linking multiple health system datasets to examine clinical characteristics and LDL-C levels in those receiving LLT (e.g., statins) after the first LDL-C test. Patients with ASCVD were identified using ICD diagnostic codes between 2011-2015. Similarly, diabetes status was assessed in the year prior to ASCVD diagnosis. LDL-C was assessed at the first (index) and second (follow-up) tests during the study period. LDL-C levels were evaluated based on a threshold of 2.0 mmol/L, as per the 2016 Canadian blood cholesterol management guidelines.

Results: Among 144,607 patients with ASCVD and a prescription for LLT (mean age=66.3; 66% male), 27,540 (19.0%) patients were identified with diabetes. Patients with diabetes were more likely to have stroke, myocardial infarction, or peripheral arterial disease. Congestive heart failure and hypertension were found in 26.8% and 87.8% of patients with diabetes compared to 12.5% and 71.5% in those without, respectively. Of the patients with diabetes who had an index and follow-up LDL-C test (n=18,214), 35.0% (n=6,380) did not achieve the guideline specified LDL-C threshold at index. At follow-up (mean=238.9 days after index), 49.0% (n=3,129) of those who did not achieve threshold at index failed to meet the threshold.

Conclusions: Nearly half of patients above the LDL-C threshold at the index test did not achieve threshold at the follow-up test, despite receiving LLT. Multifaceted interventions may be required to improve cholesterol management of patients with ASCVD and diabetes in Alberta.

Disclosure

G. Chen: Consultant; Self; Medlior Health Outcomes Research Ltd. M.S. Farris: Employee; Self; Medlior Health Outcomes Research Ltd. T. Cowling: Stock/Shareholder; Self; Medlior Health Outcomes Research Ltd. M. Tai: Employee; Self; Amgen Inc. L. Pinto: Employee; Self; Amgen Inc. S. Colgan: Employee; Self; Amgen Inc. R. Rogoza: Employee; Self; Amgen Inc. Stock/Shareholder; Self; Amgen Inc. T.J. Anderson: None.
1485-P: Defining a Hierarchy of Mortality Risk in Metabolic Syndrome
Authors: VISARIA AAYUSH , AMOROSA LOUIS F.
Published: June 2019

Purpose: ATP III defined metabolic syndrome (MetS) as at least three of five criteria (waist circumference [WC], elevated fasting glucose [FG], low HDL [HDL], high triglycerides [TG], elevated blood pressure [BP]). We developed a novel score to account for the differing all-cause mortality hazards of individual criteria and to better reflect the increased mortality with increasing number of criteria.

Methods: A population of 2,392 non-pregnant individuals >20 years with data on demographics, MetS criteria, smoking status, and mortality were included in this secondary analysis of NHANES III (1988-1994). Outcomes included all-cause mortality as of Dec. 31st, 2011. Cox hazard models were run adjusting for potential confounders and accounting for the complex survey design. Hazard weights for each criterion were developed using univariate Cox models and summed for an overall score.

Results: There were 991 deaths from all causes among the 2,393 individuals over 250-months. Among those with MetS, increasing number of criteria coincided with increasing mortality hazards compared to those with 0 criteria (3: aHR=1.47, 95% CI [1.18, 1.83]; 4: aHR=1.77 [1.42, 2.21]; 5: aHR=2.39 [1.89, 3.02]). In our model individual criterion mortality hazards were rounded and assigned as points. The sum of the points of the criteria formed a weighted score. From highest to lowest hazard, the criteria hierarchy was BP (5 points), FG (3), WC (2), TG (1), and HDL (1) for a total possible score of 12 points. Scores 6 points and above had similar or higher hazard to those with traditional MetS when compared to normals (Score of 6: aHR= 1.50 [1.20, 1.88] vs. MetS: aHR: 1.29 [1.17, 1.42]). Increasing points corresponded to increasing mortality hazard; those with 10-12 points had nearly double the hazard as normals (aHR= 2.07 [1.54, 2.79]).

Conclusion: The developed weighted score is a more comprehensive ranking which assesses aggregate mortality hazard and may better assess all-cause mortality hazard in U.S. adults than current MetS diagnostic criteria.

Disclosure

A. Visaria: None. L.F. Amorosa: None.
1491-P: Increase in HbA1c at Time of Diagnosis Upon Change to New Diagnostic Criteria in Denmark
Authors: CARSTENSEN BENDIX , RØNN PERNILLE F. , JØRGENSEN MARIT E.
Published: June 2019

Introduction: In 2011 the diagnostic criteria for diabetes in Denmark was changed from an oral glucose tolerance test (OGTT) to HbA1c. Several studies have shown that the OGTT identifies diabetes at a lower HbA1c level than the current threshold. Several countries have seen a decreasing type 2 diabetes incidence after 2011, possibly related to new diagnostic criteria. It is therefore conceivable that the HbA1c level at the time of diagnosis should be increasing after 2011. We investigated the level of HbA1c in newly diagnosed type2 diabetes patients in Denmark in the period 2010-16, to test this conjecture.

Methods: We obtained HbA1c measurements from the national laboratory database which contains person-identifiable laboratory measurements on all Danish citizens. These were linked to a national register on all type 2 diabetes patients, which was based on national health care registers. We chose the HbA1c measurement closest to the date of diabetes, but only in a window from 3 months before to 1 month after diagnosis.

Results: Information on HbA1c was available for 98,010 out of 132,534 persons with type 2 diabetes registered in the period 2010-16 incl. The overall level of HbA1c was stable in the period 2010-13, but from 2013 we saw weak increase in the median HbA1c at diagnosis, most pronounced for men (48 to 56 mmol/mol) compared to women (47 to 52 mmol/mol). But the 90th percentile of HbA1c increased in the period 2013-16 for men from 78 to 101 and for women from 65 to 88 mmol/mol, while percentiles of HbA1c below the median were stable.

Conclusion: HbA1c at diagnosis increased in the period 2013-16, presumably because the diagnosis is made at a more advanced state when using HbA1c as criterion as compared to OGTT. In the same period the incidence rates of type 2 diabetes was increasing to 2011, then declining till 2015 and after that increased again. Future studies will show whether changes in HbA1c levels influences the prevalence, incidence and mortality of persons included as diabetes patients in the register.

Disclosure

B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. P.F. Rønn: Research Support; Self; Amgen AB. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.
1494-P: Glycated Albumin May Be an Effective Alternative to A1C in the Presence of Hemoglobin C Trait
Authors: BRIKER SARA M. , HORLYCK-ROMANOVSKY MARGRETHE F. , MUGENI REGINE , ADUWO JESSICA Y. , DUBOSE CHRISTOPHER , SUMNER ANNE E.
Published: June 2019

Hemoglobin C (HbC) trait is a heterozygous hemoglobinopathy common in West Africa. Due to interference with the HPLC assay, heterozygous hemoglobinopathies such as HbC trait may lead to readings for A1C which are artefactually low. Therefore, the value of A1C as a diagnostic test may be compromised. Glycated albumin (GA) may be an effective alternate to A1C because it is a nonfasting measure of glycemia which is not impacted by Hb variants. No study has focused on HbC trait and evaluated the ability of A1C and GA to detect glucose tolerance status. Our goals were to evaluate the diagnostic efficacy of A1C and GA in the detection of dysglycemia in the 4% (13/366) of African-born blacks enrolled in the Africans in America Study who had HbC trait documented by hemoglobin electrophoresis. OGTT was performed in the 13 participants (age 37±7y (mean±SD), BMI 26.9±3.4 kg/m2). Glucose tolerance status was defined by the OGTT. The ability of A1C≥5.7% and GA≥14.2% to diagnose dysglycemia was evaluated. Both A1C≥5.7% and GA≥14.2% represent the upper quartile cut-off for their distribution in the Africans in America cohort. Mean A1C was 4.8±0.7%, range 3.1- 5.6%. Mean GA was 13.9±1.3%, range 11.9 - 15.4%. Thirty-nine % (5/13) of the participants had prediabetes and 8% (1/13) had diabetes. However, A1C was <5.7% in all participants. Therefore, for A1C sensitivity and specificity were 0% and 100% resp. In contrast, for GA the sensitivity and specificity were 83% and 71%, resp. Although the number of individuals with HbC trait in our cohort was small, our findings suggest that GA may be an important screening test to be used in populations with a high prevalence of HbC trait.

Disclosure

S.M. Briker: None. M.F. Horlyck-Romanovsky: None. R. Mugeni: None. J.Y. Aduwo: None. C. DuBose: None. A.E. Sumner: None.
150-OR: BioChaperone Pramlintide Insulin (BCPramIns), a New Co-Formulation of Pramlintide (PRAM) and Human Insulin (INS), Improves Postprandial Blood Glucose (BG) vs. Both Separate Injections of PRAM+INS and Insulin Lispro (LIS) in Subjects with T1D
Authors: MEIFFREN GRÉGORY , SEROUSSI CYRIL , RANSON AYMERIC , CHARVET RICHARD , GAUDIER MARTIN , ANDERSEN GRIT , ZIJLSTRA ERIC , DEVRIES J. HANS , HEISE TIM , SOULA RÉMI , SOULA OLIVIER
Published: June 2019

BCPramIns is developed to leverage the beneficial effects of PRAM on post-prandial BG control in a convenient co-formulation with INS. This double-blind, randomized cross-over study investigated pharmacodynamics, pharmacokinetics and safety of BCPramIns in 24 subjects with T1DM [mean±SD age 41±10 years; BMI 25±2.3 kg/m²; HbA1c 7.2±0.6%] who received fixed doses of 7.5 IU INS and 45 µg PRAM either as a single injection of BCPramIns or separate injections (PRAM+INS) before a mixed meal tolerance test in comparison to 7.5 U insulin lispro (LIS) with BCPramIns, BG excursions in the first 2 hours post-meal were reduced by 97% (p<0.0001) and 82% (NS) compared to LIS and PRAM+INS, respectively (Table). Time to maximum BG was prolonged by BCPramIns compared to LIS and slightly delayed compared to PRAM+INS, (5.00h vs. 3.00h and 4.25h respectively, Table). Insulin exposure was similar between BCPramIns and PRAM+INS (AUCINS_0-6h 87 vs. 86 mU*h/L), indicating no impairment in insulin absorption with BCPramIns. Six adverse events occurred with BCPramIns, 4 with PRAM+INS and 3 with LIS. Hypoglycemia during dosing visit days were balanced between the three treatment groups (4-3-3).

In conclusion, BCPramIns was well tolerated and improved postprandial BG versus LIS.

Disclosure

G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. R. Charvet: None. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. G. Andersen: None. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S. Employee; Self; Profil Institute for Metabolic Research. Research Support; Self; Medtronic. Speaker's Bureau; Self; Novo Nordisk A/S. T. Heise: Advisory Panel; Self; Mylan. Research Support; Self; ADOCIA, Boehringer Ingelheim International GmbH, Dance Biopharm Holdings Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Johnson & Johnson, MedImmune, Mylan, Nordic Bioscience, Novo Nordisk A/S, Pfizer Inc., Poxel, Saniona, Sanofi, Wockhardt, Zealand Pharma A/S. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. R. Soula: Board Member; Self; Cellnovo. Employee; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. Employee; Self; ADOCIA. Stock/Shareholder; Spouse/Partner; ADOCIA. Stock/Shareholder; Self; ADOCIA.
1505-P: Plasma Glucose Level at 1h Post 75g OGTT Is the Best Predictor of the Development of Glucose Intolerance in Subjects with Normal Glucose Tolerance—The Toon Health Study
Authors: TAKAKADO MISAKI , TAKATA YASUNORI , HADATE TOSHIMI , MATSUSHITA YUMI , KAWAMURA RYOICHI , MARUYAMA KOUTATSU , SAITO ISAO , OSAWA HARUHIKO
Published: June 2019

Background: Although glucose intolerance (GI) is diagnosed by fasting and 2h plasma glucose (PG) levels during a 75g OGTT, the upper limit of 1h PG level remains to be undefined in subjects with NGT. Previous report focusing on changes from NGT + IGT to diabetes has reported that 1h PG with ≥155 mg/dl is the risk for future diabetes in the world. However, IGT is well known as a risk factor for cardiovascular disease, few studies have focused on changes from NGT to GI. We therefore conducted a 5-year prospective study intended for NGT subjects to clarify the best predictor of the development of GI.

Methods: To diagnose GI, we performed a 75gOGTT. We enrolled 1383 NGT subjects from The Toon Health Study. Finally, we analyzed 981 individuals with NGT who had a repeat health checkup. To investigate valuable predictive factors of progression of GI, we performed ROC curve analyses and compared fasting PG, 1h post OGTT, 2h post OGTT, and HbA1c.

Results: ROC curve analyses revealed that 1h post OGTT was the best predictor of the development of GI in NGT (sensitivity 66%, specificity 74%, at a cutoff value of 149 mg/dl). In NGT with 1h PG>149mg/dl, odd ratio for the development of GI was 4.7 (95% CI: 3.25-6.80) compared to the reference after adjustment for age, sex, and BMI (p<0.0001).

Conclusions: PG level at 1h post 75g OGTT was the best predictor of the development of GI in NGT.

Disclosure

M. Takakado: None. Y. Takata: None. T. Hadate: None. Y. Matsushita: None. R. Kawamura: None. K. Maruyama: None. I. Saito: None. H. Osawa: None.
1517-P: A Longitudinal Study of a Panel of Adipokines and Gestational Diabetes Risk
Authors: FRANCIS ELLEN C. , LI MENGYING , HINKLE STEFANIE , CHEN JINBO , CHEN LIWEI , ZHANG CUILIN
Published: June 2019

Prospective studies with measurement of a comprehensive panel of adipokines in early pregnancy and gestational diabetes (GDM) risk are sparse, and studies of adipokines for prediction of GDM are limited. We investigated a panel of adipokines in relation to GDM risk. In a nested case-control study within the NICHD Fetal Growth Studies-Singleton cohort (2009-2013), we identified 107 GDM cases and selected 214 controls matched on age, race/ethnicity, and gestational week (GW) at blood draw. Plasma Leptin, Soluble Leptin Receptor (sOB-R), Free Leptin, Chemerin, Fatty Acid Binding Protein 4 (FABP4), Retinol Binding Protein 4, Adiponectin, Omentin1, and Vaspin were measured prior to GDM at GWs 10-14, 15-26. Adjusting for maternal age, GW of blood collection, nulliparity, and family history of diabetes, conditional logistic analysis was performed to estimate adjusted odds ratios (aOR) for associations of adipokines with GDM. Receiver-operating-characteristic (ROC) curves assessed the predictive value of adipokines for GDM diagnosis. Leptin, Free Leptin, Chemerin, and FABP4 concentrations were significantly higher. Adiponectin, and sOB-R were significantly lower among cases than controls. At GW 10-14, Adiponectin, and sOB-R were significantly and inversely related to GDM risk. For example, across increasing quartiles of sOB-R the aOR were 1.00 (ref), 0.37 (0.19, 0.74), 0.28 (0.13, 0.59), and 0.24 (0.11, 0.52) (Ptrend≤.0001). In contrast, Leptin, Free Leptin, Chemerin, and FABP4 were significantly and positively associated with GDM risk. In general, associations of adipokines with GDM were stronger at GW 15-26. In addition, at GW 15-26, sOB-R significantly improved GDM prediction over conventional risk factors (age, GW, race, nulliparity, family history of diabetes, prepregnancy BMI) and glucose (P = 0.02). A panel of adipokines may be implicated in the pathogenesis of GDM with significant associations and incremental predictive value detected in early pregnancy before GDM is usually screened for.

Disclosure

E.C. Francis: None. M. Li: None. S. Hinkle: None. J. Chen: None. L. Chen: None. C. Zhang: None.

Funding

National Institutes of Health
152-LB: Sodium-Glucose Cotransporter Inhibitor Impairs Adhesion of Cancer Cells by Increasing Shedding and Dephosphorylation of Discoid Domain Receptor
Authors: OKADA JUNICHI , OKADA SHUICHI , YAMADA MASANOBU
Published: June 2019

Dapagliflozin, a selective inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is used clinically to reduce circulating glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose from the kidney. Dapagliflozin is metabolized and inactivated by UDP glucuronosyltransferase 1 family, Polypeptidase A9 (UGT1A9). Dapagliflozin treatment of HCT116 cells that express SGLT2 but not UGT1A9 display loss of cell adhesion whereas HepG2 cells that express both UGT1A9 and SGLT2 are resistant to dapagliflozin. Knockdown of UGT1A9 in HepG2 cells increased dapagliflozin sensitivity whereas overexpression of UTG1A9 in HCT116 cells protect against dapagliflozin-dependent loss of cell adhesion. Dapagliflozin treatment had no effect on the cellular interaction with fibronectin, vitronectin, or laminin but induced a loss of interaction with collagen I and IV. In parallel, dapagliflozin treatment reduced the protein levels of the discoidin domain receptor 1 (DDR1) concomitant with Y792 dephosphorylation and appearance of cleaved DDR1. Concomitant with these observations, dapagliflozin increased sheddase and tyrosine phosphatase activities. Physiologically, dapagliflozin reduced tumor burden of HCT116 cells in chick chorioallantoic membrane assays. Taken together, these data present a new potential role for dapagliflozin therapy as an anti-cancer reagent in tumor cells that express SGLT2 but not UGT1A9.

Disclosure

J. Okada: None. S. Okada: None. M. Yamada: None.
1522-P: Serum Mac-2 Binding Protein Glycosylation Isomer Level and the Risk of Type 2 Diabetes in a Japanese Community: The Hisayama Study
Authors: HIGASHIOKA MAYU , HIRAKAWA YOICHIRO , YOSHINARI MASAHITO , HONDA TAKANORI , SAKATA SATOKO , SHIBATA MAO , YOSHIDA DAIGO , HATA JUN , KITAZONO TAKANARI , OSAWA HARUHIKO , NINOMIYA TOSHIHARU
Published: June 2019

Background: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker of chronic liver disease including liver fibrosis. Chronic liver disease has been acknowledged to cause glucose intolerance. However, few studies have addressed the association between serum M2BPGi levels and the risk of type 2 diabetes (T2D).

Methods: A total of 2,143 participants aged 40-79 years without diabetes were followed-up for a median of 7.0 years. Serum M2BPGi levels were measured at baseline and were categorized into quartiles: ≤ 0.40; 0.41-0.55; 0.56-0.75; and ≥0.76 (cut-off index). A Cox’s proportional hazards model was used to estimate hazard ratios (HRs) and their 95% CIs for the incident T2D with the adjustment for confounders-namely age, sex, family history of diabetes, systolic blood pressure, use of antihypertensive agents, serum total and HDL cholesterol, serum triglyceride, use of lipid-modifying agents, BMI, smoking, drinking, regular exercise, and fasting plasma glucose. The impact of serum M2BPGi levels on the predictive ability of incident T2D was evaluated with Harrell’s C statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).

Results: During follow-up periods, 219 subjects developed T2D. The multivariable-adjusted HR (95% CI) of developing T2D increased significantly with higher serum M2BPGi levels (p for trend=0.03), being 1.00 (reference) in Q1, 1.38 (0.89-2.15) in Q2, 1.51 (0.95-2.39) in Q3, 1.70 (1.07-2.70) in Q4. The predictive ability of incident T2D was improved by adding serum M2BPGi level to the model comprising aforementioned confounders: Harrell’s c-statistics from 0.787 to 0.795 (p=0.03), cNRI 0.19 (p=0.03), and IDI 0.004 (p=0.07).

Conclusion: Our findings suggest that higher serum M2BPGi level was a significant risk factor for T2D in the general Japanese population. Measuring serum M2BPGi level may be effective to detect the high-risk population of T2D.

Disclosure

M. Higashioka: None. Y. Hirakawa: None. M. Yoshinari: None. T. Honda: None. S. Sakata: None. M. Shibata: None. D. Yoshida: None. J. Hata: None. T. Kitazono: None. H. Osawa: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.
1526-P: Delayed Heart Rate Recovery after Exercise as a Risk Factor of Incident Metabolic Syndrome: A Retrospective Cohort Study
Authors: YU TAE YANG , JIN SANG-MAN , HUR KYU YEON , BAE JI CHEOL , JEE JAEHWAN , KIM JAE HYEON , LEE MOON-KYU
Published: June 2019

Background: There have been several cross-sectional studies reporting that delayed heart rate recovery (HRR) after exercise is associated with the development of the metabolic syndrome (MetS). However, there have been few longitudinal studies. We evaluated the longitudinal association of delayed HRR following a graded exercise treadmill test (GTX) with the incident MetS including metabolic parameters as adjusting factors.

Methods: A retrospective longitudinal cohort study of participants without MetS, diabetes or cardiovascular diseases has been designed. HRR was calculated as peak heart rate minus heart rate after a 1-minute rest (HRR 1), heart rate after a 2-minute rest (HRR 2), and heart rate after a 3-minute rest (HRR 3). To investigate the association between HRR and incident MetS, multivariate Cox proportional hazards analysis was performed.

Results: During 9,683 person-years of follow-up between 2006 and 2012, there were 676 (31.2%) incident cases of the MetS. After adjustment for age, sex, smoking status, baseline heart rate, peak heart rate, peak oxygen uptake, hs-CRP, waist circumference, systolic blood pressure, TG, LDL-C, HDL-C, fasting plasma glucose, HOMA-IR, and HbA1c, the hazard ratios (HR) [95% confidence interval (CI)] of incident MetS comparing the first and second tertiles to the third tertile of HRR 3 were 1.492 (1.146-1.943) and 1.277 (1.004-1.624) (P for trend = 0.003). As a continuous variable, after full adjustments, the HR (95% CI) of incident MetS associated with each 1-second decrease in HRR3 was 1.015 (1.005 -1.026) (P = 0.004).

Conclusion: Delayed HRR 3 after exercise could predict incident MetS, even after adjusting for metabolic parameters. However, HRR 1 and HRR 2 have not shown the statistic significance.

Disclosure

T. Yu: None. S. Jin: None. K. Hur: None. J. Bae: None. J. Jee: None. J. Kim: None. M. Lee: None.
1527-P: Race/Ethnic-Specific Association between BMI and Incident Type 2 Diabetes (T2DM): Evidence from the Multiethnic Study of Atherosclerosis
Authors: RODRIGUEZ LUIS A. , BRADSHAW PATRICK T. , SHIBOSKI STEPHEN , FERNANDEZ ALICIA , VITTINGHOFF ERIC , HERRINGTON DAVID M. , DING JINGZHONG , KANAYA ALKA M.
Published: June 2019

Objective: We evaluated whether the longitudinal association between BMI and 10-year risk of developing T2DM occurred at lower BMI points among Chinese Americans, Hispanics, and African Americans compared to whites.

Research Design and Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (2000-2013), a cohort of adults ages 45-85 without cardiovascular disease at baseline. Incident T2DM was defined as fasting glucose ≥126 mg/dL and/or use of a diabetes medication. We used multivariable Weibull regressions adjusting for age, sex, education, dietary quality (Alternative Healthy Eating Index and kcal/day), and exercise to estimate the association between BMI and incident T2DM by race/ethnicity. BMI was modelled with a 3-knot restricted cubic spline to capture non-linear associations.

Results: Among 4,541 participants without prevalent T2DM, 557 incident T2DM cases occurred in a median 9.1 years of follow-up. The corresponding BMI points and their respective 95% CIs for a 10% risk of T2DM over 10 years were 22.2 (20.4, 24), 24.5 (21, 28), 25.5 (24.2, 26.8) and 28 (26.5, 29.5) for Chinese-Americans, Hispanics, African Americans, and whites, respectively.

Conclusion: Race/ethnic minority groups develop T2DM at lower BMI compared to whites. Our findings support the ADA-recommended BMI≥23 for Asians and BMI≥25 for other groups for T2DM screening.

Disclosure

L.A. Rodriguez: None. P.T. Bradshaw: None. S. Shiboski: None. A. Fernandez: None. E. Vittinghoff: None. D.M. Herrington: None. J. Ding: None. A.M. Kanaya: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (F31DK115029)
1528-P: The Utility of MODY Probability Calculator in Polish Patients with Diabetes
Authors: HOHENDORFF JERZY , ZAPALA BARBARA , SOLECKA IWONA , UCIEKLAK DAMIAN , LUDWIG-SLOMCZYNSKA AGNIESZKA , MATEJKO BARTłOMIEJ , MROZINSKA SANDRA , MALECKI MACIEJ , SZOPA MAGDALENA
Published: June 2019

MODY accounts for 1-2% of all diabetes cases. There are more than 20 genes linked with MODY. Unfortunately, ca. 90% of MODY cases are misdiagnosed as type 1 or type 2 diabetes. A proper diagnosis of the type of diabetes is crucial for the use of a tailored treatment. Next-generation sequencing (NGS) enables simultaneous testing of a set of genes responsible for MODY. However, this method is still not reimbursed in many countries and patients' selection for testing should be performed preciously. In 2012, an easy-to-use tool have been developed in Exeter, UK, to support the identification of cases appropriate for genetic testing in the British population. The aim of the study was to assess the utility of MODY Probability Calculator (MODY-PC) in Polish patients.

We have performed a retrospective analysis of 152 probands who were qualified for genetic testing between 2006 and 2018. Patients were recruited for MODY testing according to the classical clinical guidelines that include early age of diagnosis (≤35 years) and a positive, multigenerational family history. If Sanger sequencing for most likely gene was negative, NGS of a set of 28 genes was performed. MODY Probability was calculated on the website: www.diabetesgenes.org.

The study group consists of 64 GCK-, 37 HNF1A-MODY and 51 NGS-negative patients. The mean positive predictive value (PPV) was 66,6±17,7, 46,7±27,3 and 53,3±26,3% for GCK-, HNF-MODY and NGS-negative, respectively. The optimal statistical cut-off point to distinguish between MODY and NGS-negative patients was 58% (AUC: 0,568, 95% CI: 0,47-0,67). In such settings, in the analyzed group sensitivity and specificity was 64,4% and 49,0%, respectively. When using cut-off point of PPV for genetic testing of 25% sensitivity was 87,1% and specificity 17,6%.

In the analyzed group of probands that were qualified for genetic testing based on clinical features the use of MODY-PC would not substantially improve patients' selection process for genetic testing. Further improvement of MODY-PC is desirable.

Disclosure

J. Hohendorff: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Novo Nordisk A/S, Sanofi-Aventis. B. Zapala: None. I. Solecka: None. D. Ucieklak: None. A. Ludwig-Slomczynska: None. B. Matejko: Research Support; Self; Roche Diabetes Care. Other Relationship; Self; Ascensia Diabetes Care. S. Mrozinska: Other Relationship; Self; EGIS Polska. M. Malecki: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Bioton, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Merck & Co., Inc. M. Szopa: None.

Funding

Polish Diabetes Association (2016 to M.S.); Jagiellonian University Medical College (K/ZDS/006219 to M.S.), (K/ZDS/005596 to M.M.)
153-LB: Pharmacokinetics, Pharmacodynamics, and Tolerability of Single- and Multiple-Dose of Janagliflozin, a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor, in Healthy Chinese Subjects
Authors: LIU HONGZHONG , SONG LING , XIAO XINHUA , JIANG JI , HU PEI , LIU DONGYANG
Published: June 2019

Objectives: Janagliflozin (JGZ) is a novel SGLT2 inhibitor for the treatment of type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. The purposes of the studies were 1) to investigate the PK, PD, and tolerability of JGZ in healthy Chinese subjects, 2) to provide a guidance for the selection of dosing regimens in further clinical studies.

Methods: Two randomized, double-blind, placebo-controlled studies were sequentially conducted, including one single-ascending dose (SAD) study and one multiple-ascending dose (MAD) study. In the SAD study, 56 subjects were randomized to receive 10, 25, 50, 100, 200, 300, or 450 mg JGZ or placebo. In the MAD study, 42 subjects were randomized to receive 50, 100, 200 mg JGZ or placebo as loading dose on Day 1, and then 25, 50, 100 mg JGZ or placebo once-daily from Day 2 to Day 14. The blood and urine samples were collected at prespecified time points, and the PK parameters, PD response exhibited in 24 h urinary glucose excretion (UGE), and tolerability were assessed.

Results: JGZ was readily absorbed with Tmax being 2.0∼4.5 h. The mean steady-state T1/2 was about 26∼30 h. The plasma exposure of JGZ increased in a roughly dose-dependent manner. The mean 24 h UGE ranged from about 18∼85 g in SAD study, with a dose-dependent increasing trend. The mean 24 h UGE were approximately 40, 43, and 50 g at steady state with 25, 50, and 100 mg JGZ, respectively, indicating no significant increase over the dose range of 25 to 100 mg. The adverse events in both studies were mostly mild with no serious adverse event or adverse event leading to discontinuation.

Conclusions: In healthy Chinese subjects, JGZ was generally well tolerated and had favorable PK and PD profiles supporting a once-daily dosing regimen. The present studies suggest JGZ 25 and 50 mg could be the clinically recommended doses, which need to be further investigated in T2DM patients.

Disclosure

H. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. L. Song: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. X. Xiao: None. J. Jiang: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. P. Hu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China. D. Liu: Research Support; Self; XuanZhu Pharma Co., Ltd., Jinan, Shandong, China.

Funding

XuanZhu Pharma Co., Ltd.
153-OR: Early Progression to Diabetes or Regression to Normal Glucose Tolerance among People with Impaired Glucose Tolerance Affects Long-Term Outcomes: Thirty-Year Follow-Up of Da Qing Diabetes Prevention Study
Authors: CHEN YANYAN , ZHANG PING , WANG JINPING , GONG QIUHONG , AN YALI , GREGG EDWARD , BENNETT PETER H. , LI GUANGWEI
Published: June 2019

Responses to lifestyle interventions in people with impaired glucose tolerance (IGT) may differ during the intervention phase: some progress to diabetes, some regress to normal glucose tolerance (NGT) and some retain IGT. Whether these different responses to intervention influence subsequent outcomes is uncertain. In 1986, 576 persons with IGT in Da Qing, China, were randomized to control or intervention (diet, exercise, diet plus exercise) groups for a six-year lifestyle intervention. In 1992, of 540 participants who completed the intervention, 252 (46.7%) had progressed to diabetes, 174 (32.2%) regressed to NGT, and 114 (21.1%) remained as having IGT. In 2016, we conducted a 30-year follow-up study to assess the intervention effect on CVD events, defined as the first occurrence of non-fatal or fatal stroke, myocardial infarction or heart failure, and composite microvascular complications, defined as the first occurrence of severe retinopathy, nephropathy or neuropathy. We compared the difference in those outcomes between the three groups. The 30-year cumulative incidence of CVD was 65.6% (95% CI 58.7-71.5) in the participants with diabetes, 46.1% (95% CI 48.0-53.8) in those with NGT, and 50.6% (95% CI 40.5-59.9) in those with IGT. The corresponding incidence of microvascular complications was 44.3% (95% CI 36.8-51.4), 23.1%, (95% CI 15.7-31.4), and 31.2% (95% CI 21.1-41.7). Adjusting for age and sex, those who had developed diabetes had significantly higher risks than those who had reverted to NGT for both CVD (HR = 1.57, 95% CI 1.18-2.07, P = 0.002) and composite microvascular complications (HR = 2.53, 95% CI 1.62-3.93, P < 0.0001). Our results indicate that delaying the development of diabetes in people with IGT is likely to reduce the incidence of both macro and microvascular adverse outcomes.

Disclosure

Y. Chen: None. P. Zhang: None. J. Wang: None. Q. Gong: None. Y. An: None. E. Gregg: None. P.H. Bennett: Consultant; Self; World Health Organization. Stock/Shareholder; Self; Becton, Dickinson and Company, Eli Lilly and Company, Pfizer Inc., UnitedHealth Group Inc. Other Relationship; Self; American Diabetes Association, Centers for Disease Control and Prevention, European Association for the Study of Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. G. Li: None.

Funding

Centers for Disease Control and Prevention/Chinese Center for Disease Control and Prevention (5U19GH000636-05)