bluuebunny/crossref_metadata_2025_split huggingface dataset:
1439-P: Risk of Dementia and Cognitive Dysfunction in Individuals with Diabetes or Elevated Blood Glucose in Four Large Cohorts
Authors: WIUM-ANDERSEN IDA , JØRGEN RUNGBY , BALSLEV MARTIN , RGENSEN JØ , OSLER MERETE , WIUM-ANDERSEN MARIE 
Published: June 2019

Objective: To determine risk of dementia in both patients with type 1 or type 2 diabetes and in individuals without a diagnosis of dementia but with glycosylated hemoglobin, type A1C (HbA1c) of ≥ 6,5% (48 mmol/mol).
Method: In this register- and cohort-based study, we included all incident diabetes cases registered in the National Diabetes Registry in Denmark from January 2000 through December 2012 (n=151,413) and a reference population, adult participants from the Glostrup cohort (n=16,801), the ADDITION Study (n=26,586) and Copenhagen Aging and Midlife Biobank (n=5,408). Using these cohorts, we analyzed if a diagnosis of type 1 or type 2 diabetes in the National Diabetes Registry or HbA1c level of ≥ 6,5% in the cohorts increased risk of dementia in the Danish National Patient Registry or cognitive performance assessed by the Intelligenz-Struktur-Test 2000R.
Results: Both type 1 and type 2 diabetes were associated with increased risk of dementia with the highest risk estimates for dementia diagnosed before age 65. Self-reported diabetes or high HbA1c levels were associated with lower cognitive performance (p=0.004), while high HbA1c was associated with increased risk of dementia in the Glostrup cohort but not in the ADDITION study.
Conclusions: Both type 1 and type 2 diabetes are associated with increased risk of dementia, however results for screening detected high HbA1c were equivocal.

Disclosure
I. Wium-Andersen: None. J. Rungby: None. M. Jørgensen: None. M. Osler: None. M. Wium-Andersen: None.

Funding
Jaschafonden; Lundbeck Foundation; Danish Medical Association; Danish Diabetes Association; M.D. Gerhard Linds Grant; Lundbeck Foundation/Novo Nordisk Foundation; Family Hede Nielsen Foundation; Holger Rabitz and Wife Doris Mary, born Phillip’s Memorial Foundation
1454-P: Cerebral Glutathione Is Associated with Insulin Resistance in Older Individuals
Authors: PACH JOLANTA J. , GROSKREUTZ DEREK , LEVENTHAL JESSICA , KNIGHT MARI-LYNET , JAIN KANIKA , HWA JOHN , JIANG LIHONG , GRAAF ROBIN DE , HWANG JANICE 
Published: June 2019

Glutathione (GSH) is the primary defense against oxidative stress through its role in reducing reactive oxygen species (ROS) in the body, and its levels have been shown to be lower in both metabolic disease and aging. In this study, we sought to determine whether GSH levels in the human brain are lower in older individuals and whether these levels are associated with metabolic changes that come with age, such as increasing insulin resistance. 14 young (age 30.1 ±3.2 years, BMI 26.1 ±0.8 kg/m2, A1c 5.3% ±0.1, HOMA-IR 1.6 mg(μU)/dL(mL) ±0.2) and 9 old (age 73.7 ±1.8, BMI 28.1 ±1.6, A1c 5.6 ±0.1, HOMA-IR 2.9 ±0.7) individuals underwent an oral glucose tolerance test as well as magnetic resonance spectroscopy (MRS) scanning at 4T for measurement of intracerebral GSH levels in the prefrontal cortex and striatum. Older individuals had higher levels of plasma ROS compared to younger individuals (P&lt;0.001); however, there were no differences in plasma GSH levels (P=0.15). Intracerebral GSH levels (normalized to creatine(cr)) were not different between groups (P=0.76 prefrontal cortex, P=0.53 striatum). Amongst the older individuals, cerebral GSH/cr levels correlated inversely with HOMA-IR in both the striatum (r = -0.74, P=0.04) as well as prefrontal cortex (r= -0.95, P&lt;0.001). Moreover, amongst older individuals, intracerebral GSH levels correlated inversely with performance on several measures of visual-spatial memory including the spatial working memory task (ρ= -0.9, P=0.003). There were no relationships between HOMA-IR and cerebral GSH levels amongst the younger individuals. Our findings indicate that amongst older individuals, increased insulin resistance is associated with diminished intracerebral GSH levels as well as visual-spatial cognitive deficits. These findings suggest that intracerebral GSH levels may be a useful marker for assessing the impact of metabolic dysfunction on neurocognitive function.

Disclosure
J.J. Pach: None. D. Groskreutz: None. J. Leventhal: None. M. Knight: None. K. Jain: None. J. Hwa: None. L. Jiang: None. R. de Graaf: None. J. Hwang: None.

Funding
National Institutes of Health (P30AG021342)
1456-P: Cardiovascular Outcomes in Subjects with Acute Myocardial Infarction (AMI) and Newly Discovered Abnormal Glucose Tolerance (AGT): A Meta-analysis
Authors: LAICHUTHAI NITCHAKARN , DEFRONZO RALPH A. 
Published: June 2019

Aims: To study: (1) the prevalence of newly discovered AGT in subjects presented with AMI and (2) the risk of recurrent major adverse cardiovascular events (MACE and mortality) in this population.
Methods: Electronic databases were searched. Studies were included for analysis if: (1) they were prospective or retrospective studies in AMI subjects without known history of diabetes; (2) diagnosis of AGT was made with FPG, 2-hour PG (OGTT) or A1c, (3) provided incidence of MACE and/or all-cause mortality in newly discovered AGT subjects compared with NGT subjects. AGT was further divided into prediabetes and diabetes. Pooled prevalence and hazard ratios (HR) were calculated using random-effect model.
Results: Total of41,677 subjects from 20 studies were included in the analysis. Median follow-up time was 3.7 ±2.8 years. The pooled prevalence of newly discovered AGT in AMI subjects was 49.3%. Compared to NGT, subjects with AGT had higher risk of mortality (HR = 1.66, 95% CI 1.34-2.05, p&lt;0.001) and MACE (HR = 1.80, 95% CI 1.40-2.31, p&lt;0.001). Compared to NGT, prediabetes group had higher risk for mortality (HR = 1.82, 95% CI 1.30-2.54, p&lt;0.001) and MACE (HR = 1.67, 95% CI 1.24-2.26, p&lt;0.001). Of note, prediabetes subjects had a higher risk of MACE compared to subjects with newly diagnosed diabetes (HR = 1.76, 95% CI 1.35-2.29, p&lt;0.001), whereas there was no difference in all-cause mortality between prediabetes and diabetes subjects (HR = 0.97 95% CI 0.60-1.55, p=NS).
Conclusion: This meta-analysis showed a high prevalence of newly discovered AGT in patients with AMI. The increased risk in MACE and mortality was observed before the onset of diabetes, i.e., in prediabetes. The discovery of AGT in patients who present with an AMI is a strong predictor for mortality and MACE. Since prediabetes and diabetes subjects are at the same high CV risk, factors other than hyperglycemia must explain the markedly increased incidence of MACE and all-cause mortality.

Disclosure
N. Laichuthai: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.
1465-P: Cardiovascular Risk Factors among Young Adults with Diabetes in the U.S.
Authors: SAYDAH SHARON , MERCADO CARLA , SIEGEL KAREN R. , GREGG EDWARD W. , IMPERATORE GIUSEPPINA 
Published: June 2019

Although the prevalence of diabetes (DM) among young adults age 18 to 44 years in the United States (U.S.) has increased in the past two decades, little is known about how cardiovascular disease (CVD) risk factors for DM complications in this age group compare to older adults with DM. We used data from the National Health and Nutrition Examination Survey from 2007-2016 to characterize young adults with and without DM by CVD risk factors and compared the differences to middle- aged and older adults (aged ≥45 years). DM was defined by self-report or by A1c levels ≥ 6.5% among those without self-reported diabetes. Measures included demographics, health insurance, and CVD risk factors. Absolute difference in difference was calculated as the difference in prevalence by DM status among young adults minus the difference by DM status among middle-aged and older adults. Among young adults in the U.S., DM prevalence was 3.5%, corresponding to 3.6 million people with DM. As expected, participants of both age groups with DM had higher levels of adiposity, hypertension, high cholesterol, and chronic kidney disease (CKD), and lower levels of physical activity, compared to those without (Table). However, the difference in adiposity and high cholesterol by DM status was greater among young adults compared to middle-aged and older adults. Young adults with DM have a high burden of CVD risk factors that could lead to future increases in morbidity and mortality.

Disclosure
S. Saydah: None. C. Mercado: None. K.R. Siegel: None. E.W. Gregg: None. G. Imperatore: None.
1466-P: Estimating Cardiovascular Risk in People with Type 2 Diabetes and Cardiovascular Disease: UKPDS Outcomes Model
Authors: COLEMAN RUTH L. , GRAY ALASTAIR M. , MCGUIRE DARREN K. , HOLMAN RURY R. 
Published: June 2019

Background and Aims: Type 2 diabetes (T2D) cardiovascular (CV) risk calculators focus mainly on those without CVD. We evaluated a T2D clinical outcomes simulation model (UKPDS Outcomes Model v2 [OM2]) estimates of CV risk in TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) participants with T2D and CVD.
Materials and Methods: We compared estimated 3-year CV event and all-cause mortality (ACM) rates with observed rates. Covariates included: sex, ethnicity, age, diabetes duration, atrial fibrillation, albuminuria; baseline plus annual measures of smoking, HDL and LDL-cholesterol, weight, systolic blood pressure, HbA1c, heart rate, white cell count, haemoglobin, estimated glomerular filtration rate; and prior history of ischaemic heart disease, heart failure, amputation, blindness, kidney failure, stroke, myocardial infarction (MI) or diabetic foot ulcer.
Results: 1491/14671 (10.2%) participants experienced ≥1 major CV event over median 3.0 years follow-up. Predicted compared with observed rates were 6.4% vs. 5.1% for CV death, 7.7% vs. 4.2% ≥1 MI event and 3.5% vs. 2.5% for ≥1 stroke event (Table). Discrimination was fair (aROC&gt;0.6) for stroke, CV death and ACM, but poor for MI. Simulated relative risks matched those observed.
Conclusion: OM2 overestimates absolute CV and ACM risk in TECOS participants, but correctly simulates the lack of sitagliptin impact.

Disclosure
R.L. Coleman: None. A.M. Gray: Advisory Panel; Self; Sanofi-Aventis. D.K. McGuire: Consultant; Self; Eisai Co., Ltd., Eli Lilly and Company, Pfizer Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. 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.
1467-P: National Trends in the Use of Lipid-Lowering Drugs among Type 2 Diabetes Patients in Denmark from 1997 to 2017
Authors: RØNN PERNILLE F , CARSTENSEN BENDIX , KNUDSEN JAKOB S. , PERSSON FREDERIK , JØRGENSEN MARIT E 
Published: June 2019

Background: Lipid-lowering drug (LLD) treatment is important for cardiovascular risk reduction in type 2 diabetes. Statins are first choice of treatment but increasing public concern of side effects may have changed the prescription patterns of LLDs. We mapped trends in LLD usage among type 2 diabetes patients in Denmark from 1997 to 2017.
Methods: The study population was defined as all persons registered with type 2 diabetes in the national registers in the period 1997 through 2017. All redeemed LLDs (ATC-codes: C10) were extracted from the Register of Medicinal Product Statistics. Medication coverage at any given day was calculated based on amount purchased and doses prescribed if recorded; otherwise on Defined Daily Dose.
Results: A total of 420,751 persons living in Denmark with type 2 diabetes was included. Out of these, 266,385 (63%) individuals redeemed at least two LLD prescriptions in the period. The proportion covered by LLDs increased from 24% in 1997 to 58% in 2013, where after it declined (Figure 1). By 2017, 35% of the population was on simvastatin, 15% on atorvastatin, 4% on rosuvastatin, 2% on ezetemibe and 1% on other drugs.
Conclusion: Changing guidelines has had a clear impact on the actual use of LLDs among type 2 diabetes patients, but the declining tendency emphasize that there is still room for improvement. There was, however, not a noteworthy shift from statins to other drugs.
Figure 1.

Disclosure
P.F. Rønn: Research Support; Self; Amgen AB. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. J.S. Knudsen: None. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

Funding
Amgen AB
1493-P: Sickle Cell Trait, Hemoglobin C Trait, and Glucose-6-Phosphate Dehydrogenase Deficiency Contribute to Decreased Detection of Hyperglycemia by A1C
Authors: BRIKER SARA M. , HORLYCK-ROMANOVSKY MARGRETHE F. , ADUWO JESSICA Y. , MUGENI REGINE , DUBOSE CHRISTOPHER , MABUNDO LILIAN , CHUNG STEPHANIE T. , HA JOON , SHERMAN ARTHUR , SUMNER ANNE E. 
Published: June 2019

A1C is easier to perform than an OGTT, but A1C has a lower rate of detection of diabetes (DM) and prediabetes (preDM). Underperformance of A1C in the detection of hyperglycemia may be magnified in Africans. Three single gene mutations common in Africa, specifically sickle cell trait (SCT), hemoglobin C (HbC) trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency may lead to artefactually low A1C levels. Our goals were: (1) compare DM and preDM prevalence diagnosed by either A1C or OGTT; (2) evaluate whether SCT, HbC trait or G6PD deficiency impact A1C levels. Participants were 421 African-born blacks living in America (male: 66% (276/421), age: 38±10y (mean±SD)). A1C and OGTT were done with repeat studies done in 105 participants 11±7 days later. Diagnosis of DM and preDM required meeting either A1C criteria or glucose guidelines for the OGTT. G6PD activity was assayed in 50 consecutively enrolled participants. DM prevalence was 8% (32/421). Detection of DM by A1C-alone, A1C and OGTT and OGTT-alone were: 16% (5/32), 16% (5/32), and 68% (22/32), respectively. PreDM prevalence was 42% (177/421) with detection rates by A1C-alone, A1C and OGTT and OGTT-alone: 28% (49/177), 30% (53/177) and 42% (75/177), respectively. Repeat testing gave similar results. Among people with DM, 40% (13/32) had either SCT or HbC trait. A1C failed in 77% (10/13) of people with both DM and either SCT or HbC trait. Overall, A1C was 3 times more likely to fail in the detection of DM if either SCT or HbC trait was present (Odds Ratio 3.5 (95% CI: 1.7, 7.5), P&lt;0.01). Prevalence of G6PD deficiency was 16% (8/50). At similar levels of glycemia, A1C levels were lower with G6PD deficiency (4.3±0.1 vs. 5.5±1.0%, P&lt;0.01). Working with African-born blacks living in America, we found that if only A1C was performed, 68% with DM and 42% with preDM would be undiagnosed. SCT, HbC trait and G6PD deficiency contribute to inappropriately low A1C levels and missed opportunity to detect hyperglycemia.

Disclosure
S.M. Briker: None. M.F. Horlyck-Romanovsky: None. J.Y. Aduwo: None. R. Mugeni: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. J. Ha: None. A. Sherman: None. A.E. Sumner: None.
15-LB: Diabetes Duration Did Not Moderate the Reduction in Severe Hypoglycemia Seen with Degludec vs. Glargine U100 in DEVOTE
Authors: ALEXOPOULOS ANASTASIA-STEFANIA , KVIST KAJSA , HACHMANN-NIELSEN ELISE , BUSE JOHN B. 
Published: June 2019

Hypoglycemia is associated with significant morbidity in type 2 diabetes (T2D). Progression of T2D leads to declining counterregulatory responses and heightened hypoglycemia risk. In this secondary analysis of data from DEVOTE, a CVOT with 7637 patients with T2D at high risk of cardiovascular events, we investigated diabetes duration as a moderator of severe hypoglycemia (SH) with use of glargine U100 (IGlar U100) versus insulin degludec. Patients in DEVOTE were categorized by diabetes duration in years: &lt;10, 10-15, 15-20 and ≥20. Prevalence of SH was examined by treatment arm (Table) using a negative binomial model with log-observation time as an offset term, and diabetes duration categories as moderators. Both proportion of patients with SH events and rate of SH increased with progression of disease in both arms. Degludec preserved its relative benefit over IGlar U100 for SH across diabetes duration groups, even in less progressed disease groups, i.e., an observed 52% relative risk reduction for degludec vs. IGlar U100 for patients within 10 years of disease onset (95% CI: 0.29; 0.81). There was no significant difference in treatment ratios across categories (p-value for interaction=0.50). Similar findings were confirmed in the SWITCH 2 trial (data not shown). Thus, diabetes duration did not moderate the relative reduction in rate of SH for degludec vs. IGlar U100 in DEVOTE.

Disclosure
A. Alexopoulos: None. K. Kvist: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc.

Funding
Novo Nordisk A/S
1510-P: A1C-Modified Atherosclerosis Risk in Communities Prediction Equation for Diabetes Can Be Replaced in Africans by Fasting Glucose
Authors: HORLYCK-ROMANOVSKY MARGRETHE F. , MUGENI REGINE , ADUWO JESSICA Y. , BRIKER SARA M. , DUBOSE CHRISTOPHER , MABUNDO LILIAN , CHUNG STEPHANIE T. , HA JOON , SHERMAN ARTHUR , SUMNER ANNE E. 
Published: June 2019

In Africa 70% of people living with diabetes (DM) are undiagnosed. To address this challenge, prediction equations must be tested in Africans. As the A1C-modified Atherosclerosis Risk in Communities (ARIC) DM prediction equation was optimized in African Americans, our goal was to test in Africans: 1) ability of the equation to detect undiagnosed DM; 2) contribution of each biochemical variable to the equation; 3) independent value of each biochemical variable. The equation has 5 clinical and 4 biochemical variables: HDL, TG, A1C and fasting plasma glucose (FPG). Participants were 421 African-born blacks living in the U.S. (66% male; age 38±10y (mean ±SD); BMI 27.5±4.4 kg/m2). OGTT was performed. DM diagnosis required 2h glucose ≥200 mg/dL. Area under the receiver operating characteristic curve (AROC) predicted DM. Youden Index estimated optimal cut points. DM occurred in 6% (27/421). AROC for the full equation was 0.84. Only with FPG excluded from the equation did the AROC decline (P&lt;0.01) (Table 1A). Single predictor variables HDL, TG, A1C had low AROC. However, FPG as a single predictor had AROC 0.89 and was equivalent to the full equation (Table 1B). Thus, DM was identified by the full equation in 78% (21/27) and by FPG alone in 81% (22/27). Optimal cut point for FPG was 100 mg/dL. For the detection of DM, FPG ≥100 mg/dL performed as well as the A1C-modified ARIC equation.

Disclosure
M.F. Horlyck-Romanovsky: None. R. Mugeni: None. J.Y. Aduwo: None. S.M. Briker: None. C. DuBose: None. L. Mabundo: None. S.T. Chung: None. J. Ha: None. A. Sherman: None. A.E. Sumner: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Minority Health and Health Disparities
1513-P: The Severe Insulin-Resistant Diabetes Cluster Features Higher Liver Fat Content, but Also an Accelerated Risk of Liver Fibrosis over Five Years after Diagnosis
Authors: ZAHARIA OANA P. , STRASSBURGER KLAUS , KUPRIYANOVA YULIYA , KARUSHEVA YANISLAVA , ANTONIOU SOFIA , BODIS KALMAN , ASPLUND OLOF , BURKART VOLKER , MUESSIG KARSTEN , HWANG JONG-HEE , KUSS OLIVER , GROOP LEIF , AHLQVIST EMMA , SZENDROEDI JULIA , RODEN MICHAEL 
Published: June 2019

Cluster analysis using age, BMI, glycemia and homeostasis model estimates (HOMA-IR, -B) revealed distinct risk profiles for progression of diabetic nephropathy in large cohorts, but its relevance for other diabetes-related comorbidities remains unclear. We aimed to (i) examine whether intensified phenotyping would confirm the results of this cluster analysis and (ii) test the hypothesis that liver fat content (HCL), as marker of nonalcoholic fatty liver disease (NAFLD), differs among clusters at diabetes diagnosis and during follow-up. Thus, this cluster analysis was applied to recent-onset patients with non-autoimmune diabetes of the German Diabetes Study. This identified 286 mild age-related (MARD, 44%), 268 mild obesity-related (MOD, 42%), 66 severe insulin-resistant (SIRD, 10%) and 27 severe insulin-deficient (SIDD, 4%) diabetes patients. Furthermore, whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, HCL by magnetic resonance spectroscopy and hepatic fibrosis by a noninvasive score (NAFLD-FS). Congruently, whole-body insulin sensitivity was lowest in SIRD compared to MOD, SIDD and MARD (4.3±2.0 vs. 5.6±2.4, 6.5±2.6, 7.6±2.8 mg*kg-¹*min-¹, all p&lt;0.05). In SIRD, HCL (14±4%) was higher than in SIDD (5±2%), MOD (9±1%) and MARD (7±1%) (all p&lt;0.05). In SIRD, HCL negatively correlated with whole-body insulin sensitivity (r=-0.27, p&lt;0.05). NAFLD-FS was highest in SIRD (0.4) compared to SIDD (-2.9), MOD (-0.8) and MARD (-0.8) (all p&lt;0.05). At the 5-year follow-up (n=159), whole-body insulin sensitivity remained lowest in SIRD (p&lt;0.05 vs. all clusters) with no difference in changes between clusters. Also, significant fibrosis (NAFLD-FS &gt;0.6) was highest in SIRD (21%) compared to SIDD (0%), MOD (16%) and MARD (11%).
In conclusion, patients of the SIRD cluster exhibit higher prevalence of steatosis at diagnosis and increased risk of NAFLD progression over 5 years.

Disclosure
O.P. Zaharia: None. K. Strassburger: None. Y. Kupriyanova: None. Y. Karusheva: None. S. Antoniou: None. K. Bodis: None. O. Asplund: Research Support; Self; Eli Lilly and Company. V. Burkart: None. K. Muessig: None. J. Hwang: None. O. Kuss: None. L. Groop: None. E. Ahlqvist: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc.

Funding
German Ministry of Culture and Science of the State of North Rhine-Westphalia; German Federal Ministry of Health; German Federal Ministry of Education and Research