bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target Fasting Plasma Glucose (FPG) without Nocturnal Hypoglycemia in Patients with Type 1 Diabetes or Type 2 Diabetes—Results from SWITCH Trials
Authors: WYSHAM CAROL H. , LANE WENDY , LADELUND STEEN , TUTKUNKARDAS DENIZ , HELLER SIMON 
Published: June 2018

Insulin degludec (degludec) is a basal insulin that results in a lower FPG than insulin glargine 100 units/mL (glargine U100), which may increase the risk of nocturnal hypoglycemia in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). This post-hoc analysis investigated the proportion of patients with T1D or T2D treated with degludec or glargine U100 meeting the ADA recommended upper limit of the pre-meal plasma glucose goal of &lt;130 mg/dL (&lt;7.2 mmol/L) at each visit (start and end of 16 week maintenance) without nocturnal hypoglycemia. Patients with T1D or T2D and with FPG measurements during the 16-week maintenance period of the SWITCH 1 (n=501) and SWITCH 2 (n=720) trials (randomized, double-blind, crossover, treat-to-target trials of patients treated with degludec or glargine U100) were included. Nocturnal hypoglycaemia was defined as any blood glucose-confirmed (&lt;56 mg/dL [&lt;3.1 mmol/L]) symptomatic event occurring from 00:01-05:59. In the SWITCH trials, significantly more patients with T1D or T2D treated with degludec achieved FPG target during the maintenance period, and did so without nocturnal hypoglycemia, compared with glargine U100 (Figure).

In conclusion, compared with glargine U100, treatment with degludec was associated with greater opportunity to reach target FPG without an increased risk of nocturnal hypoglycemia.

Disclosure
C.H. Wysham: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Insulet Corporation, Novo Nordisk Inc., Sanofi. W. Lane: Advisory Panel; Self; Novo Nordisk A/S, Insulet Corporation, Intarcia Therapeutics, Inc., Sanofi. Research Support; Self; Novo Nordisk A/S, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Sanofi, Dexcom, Inc.. Speaker's Bureau; Self; Novo Nordisk A/S, Insulet Corporation. S. Ladelund: Employee; Self; Novo Nordisk A/S, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Technical University of Denmark. Research Support; Self; Metropolitan University College, Denmark. D. Tutkunkardas: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. S. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Takeda, Sanofi-Aventis, Boehringer Ingelheim GmbH. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Eli Lilly and Company, Merck Sharp & Dohme Corp., Takeda, AstraZeneca, Boehringer Ingelheim GmbH.
Somatostatin Receptor II Antagonism Improves Glucagon Counterregulatory Responses to Recurrent Hypoglycemia in Male Sprague-Dawley Rats
Authors: RIDDELL MICHAEL , JAHANGIRIESMAILI MAHSA , MANDEL ERIN R. , GREENBERG CAYLEE A. , PASIEKA AOIBHE M. , TEICH TREVOR , CHAN OWEN , LIGGINS RICHARD T. 
Published: June 2018

Glucagon (GCN) helps prevent hypoglycemia when blood glucose levels drop; however, recurrent hypoglycemia attenuates GCN counterregulation to subsequent bouts of hypoglycemia. As somatostatin normally inhibits GCN secretion, we tested the hypothesis that a somatostatin receptor type 2 antagonist (SSTR2a), PRL-2903, improves GCN responses attenuated by recurrent hypoglycemia in healthy rats. Healthy male Sprague-Dawley rats (n=22) were made hypoglycemic on three consecutive days (days 1-3, blood glucose 1.7-2.2 mmol/L for ∼2 h) via exogenous insulin administration (10-, 8- and 5- U/kg of Humulin-R on days 1-3, respectively). GCN levels during hypoglycemia on day 3 were significantly lower than on day 1 (117±47 pg/mL vs. 184±77 [mean±SD] pg/mL; P=0.001), highlighting the role of recurrent hypoglycemia in counterregulatory failure. On day 4, rats were treated with either PRL-2903 (10 mg/kg IP; n=13) or vehicle (n=9) 1 h prior to the induction of hypoglycemia with 5 U/kg of R-insulin. GCN levels during hypoglycemia (i.e., glucose ≤3.5 mmol/L) were 2.5-fold higher (109±55 vs. 44±26 pg/mL; P=0.004) compared to vehicle, and time to reach hypoglycemia was 3.2-fold longer (64±45 vs. 20±10 min; P =0.001), with PRL-2903 pre-treatment. Interestingly, C-peptide levels were also lower (P=0.001) with PRL-2903 (0.35±0.22 ng/mL), compared to vehicle (0.63±0.21 ng/mL), inferring a lower insulin secretion during hypoglycemia with PRL-2903 treatment.
In conclusion, our data suggests that SSTR2a improves GCN responses following recurrent hypoglycemia, and that this improvement may be associated with a reduction in insulin secretion in healthy rats. Therefore, SSTR2a treatment may be a useful therapeutic approach to improve GCN counterregulatory responses to hypoglycemia.

Disclosure
M. Riddell: Speaker's Bureau; Self; Medtronic. Consultant; Self; Eli Lilly and Company, JAEB Center For Health Research, Xeris Pharmaceuticals, Inc.. Research Support; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; Zucara Theraputics. Other Relationship; Self; JDRF. M. Jahangiriesmaili: None. E.R. Mandel: None. C.A. Greenberg: None. A.M. Pasieka: None. T. Teich: None. O. Chan: None. R.T. Liggins: Employee; Self; Zucara Therapeuytics, Inc..
Severe Hypoglycemia Rates Are Highest among those with Suboptimal Reporting Behaviour—Results from the InHypo-DM Study
Authors: RATZKI-LEEWING ALEXANDRIA , BLACK JASON E. , MEQUANINT SELAM , AU NATALIE H. , RYAN BRIDGET L. , REICHERT SONJA M. , BROWN JUDITH B. , HARRIS STEWART 
Published: June 2018

Many patients fail to report severe hypoglycemia (SH) events to their healthcare provider (HCP). This limits the ability of HCPs to adjust treatment regimens and optimize glycemia. This study aimed to explore the independent association between patients’ disclosure of SH events to their HCP and self-reported rates of SH. Data were obtained from the InHypo-DM population-based study, Canada’s largest hypoglycemia-specific survey. To indicate SH disclosure, patients at risk for hypoglycemia rated how often they reported their SH events (using ADA definitions) to their HCP on a scale from Never to Always. Univariable analyses identified significant clinical or demographic confounders (p≤0.2). Based on the distribution of SH events, zero-inflated negative binomial (ZINB) regression was used to test the relationship between hypoglycemia disclosure and the retrospective incidence of SH events. A total of 552 people with T1DM (17%) or T2DM (83%) completed the InHypo-DM survey. Forty percent of respondents reported at least one or more SH events. The overall incidence rate of SH was 2.45 events/person-year. Thirty-four percent of respondents indicated that they always report SH events. Results of the ZINB model showed that the odds of experiencing any event was not significantly associated with disclosure behaviour (p=0.86). However, the rate of repeated events was almost double (IRR=1.9, 95% CI: 1.2 to 3.0, p=0.004) among individuals who under-reported their SH as compared to those who did not. These results persisted after adjusting for age, medication type, income, most recent HbA1c, and presence of comorbidities. This population-based study revealed a nearly two-fold higher rate of SH among those who under-report to their HCP. Thus, HCPs should be aware that patient reporting may not be a true reflection of SH events and make efforts to elicit accurate information regarding SH events from their patients, especially for those at risk for repeated SH.

Disclosure
A. Ratzki-Leewing: None. J.E. Black: None. S. Mequanint: None. N.H. Au: None. B.L. Ryan: None. S.M. Reichert: Other Relationship; Self; Novo Nordisk Inc., Sanofi, Abbott, AstraZeneca. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Merck & Co., Inc., Janssen Pharmaceuticals, Inc.. J.B. Brown: None. S. Harris: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Amgen Inc., Lilly/Boehringer Ingelheim, Abbott, Janssen. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Lilly/Boehringer Ingelheim, Abbott, Janssen. Research Support; Self; Novo Nordisk A/S, Sanofi, Merck, Abbott, AstraZeneca, Janssen. Other Relationship; Self; CIHR, CDA, The Lawson Foundation.
Decreasing Incidence of Postinsulin Hypoglycemia for Hyperkalemia Treatment
Authors: MACMASTER HEIDEMARIE W. , TRAN ALLEN , MONASH BRADLEY , MURRAY SARA G. , PRASAD PRIYA A. , RUSHAKOFF ROBERT J. 
Published: June 2018

Acute hyperkalemia (K = 5.1 mEq/L) treatment may include a 10 unit bolus of IV insulin regular. Nationally, this treatment results in a 20% rate of hypoglycemia and a 7% rate of severe hypoglycemia. At UCSF, after introduction of a updated hyperkalemia orderset (Revision a) that standardized blood glucose (BG) POCT pre-insulin administration and post-insulin administration (1, 2, 4, and 6 hours post-insulin), we found 21% of treatments resulted in hypoglycemia (&lt;70 mg/dl) with 92% of these occurring &lt;3 hours of insulin administration. After analysis for independent hypoglycemia risk factors, we further revised the hyperkalemia order set(Revision b) to: 1) weight-based insulin dosing 2) If pre-insulin BG &lt; 50 mg/dL, then add an additional dextrose 50% (50 mL) IV once one-hour post-insulin administration 3) If pre-insulin BG &gt;300 mg/dL, then remove dextrose 50% (50 mL) with insulin administration. There was a significant reduction in both hypoglycemia and severe hypoglycemia following implementation of the Revision b hyperkalemia orderset (Table).
Post-Insulin Hypoglycemia for Hyperkalemia TreatmentGlycemic Control - Post-Insulin for Hyperkalemia TreatmentHyperkalemia Orderset - Revision a (n=225) 01/01/16-03/19/17Hyperkalemia Orderset -Revision b (n=146) 03/30/17-09/30/17Hypoglycemia (&lt;70mg/dL)21%10%Severe Hypoglyemia (&lt;40 mg/dL)5%2%
In conclusion, we believe that an EMR hyperkalemia order set can help significantly reduce hypoglycemia events with predefined times for glucose monitoring, weight-based insulin dosing, standard glucose administration guidelines and prompts to warn providers of risks for hypoglycemia. This data supports optimization of glycemic control into the AHA hyperkalemia guidelines.

Disclosure
H.W. Macmaster: None. A. Tran: None. B. Monash: None. S.G. Murray: None. P.A. Prasad: None. R.J. Rushakoff: None.
Diabetes Mellitus and High Triglycerides Are Significant Predictors of Major Cardiovascular Events and Increased Health Care Costs and Resource Utilization—A Real-World Analysis of High-Risk Statin-Treated Patients
Authors: TOTH PETER P. , GRANOWITZ CRAIG B. , HULL MICHAEL , PHILIP SEPHY 
Published: June 2018

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in patients with diabetes. We investigated real-world impact of high triglycerides (TG) and diabetes on cardiovascular (CV) outcomes and costs.
Methods: This retrospective administrative claims multivariate analysis (controlled for patient characteristics and comorbidities) of the Optum Research Database included patients aged ≥45 years with diabetes and/or ASCVD who had a statin prescription filled in 2010, had continuous medical/pharmacy coverage, and were followed for ≥6 months up to March 2016. Patients with TG 200-499 mg/dL (n=13,411) and a comparator cohort with TG &lt;150 mg/dL and high-density lipoprotein cholesterol (HDL-C) &gt;40 mg/dL (n=32,506) were included.
Results: Multivariate analyses showed a 35% higher rate of occurrence of composite major CV events per unit time in the high-TG vs. comparator cohort (hazard ratio [HR] 1.349, 95% CI 1.225-1.485, P&lt;0.001). Diabetes was found to be a significant predictor of CV events, costs, and risk of inpatient hospital stay (Table).
Conclusions: In statin-treated patients with high CV risk, high TG and diabetes were found to be significant predictors of worse CV and health economic outcomes in a real-world setting.

Disclosure
P.P. Toth: Speaker's Bureau; Self; Amarin Corporation. Consultant; Self; Amarin Corporation. Speaker's Bureau; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Speaker's Bureau; Self; Kowa Pharmaceuticals America, Inc.. Consultant; Self; Kowa Pharmaceuticals America, Inc.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Speaker's Bureau; Self; Sanofi US, Novo Nordisk Inc. C.B. Granowitz: Employee; Self; Amarin Corporation. M. Hull: None. S. Philip: Stock/Shareholder; Self; Amarin Corporation. Employee; Self; Amarin Corporation.
Total Oxidative Index Is Associated with Glycated Hemoglobin, Low-Grade Inflammation, and Non-HDL Cholesterol in Type 2 Diabetes
Authors: DALAN RINKOO , GOH LIUH LING , TANG XIN , CHEW DANIEL E.K. , BOEHM BERNHARD 
Published: June 2018

Objectives: To study associations of established cardiovascular risk factors, inflammation and carotid artery intima-media thickness (CIMT) with oxidative stress in type 2 diabetes mellitus (T2DM).
Methods: We recruited 343 T2DM subjects from the three main ethnic groups in Singapore (Chinese: 196, Indians: 106, Malays: 41; Age: 54.7±10.4 years; Males: 46%). Measurements: Demographics, BMI, blood pressure, HbA1c, glucose and lipids; CIMT and C-reactive protein (hsCRP). Derivatives of reactive oxygen metabolites (dROMS) and total anti-oxidant status (TAC) was estimated by the automated clinical chemistry analyser (Diacron, Italy). The total oxidative index (OXY) was calculated as the difference between standardised dROMS and TAC values. The relationship between OXY, dROMS and TAC as dependent variable and age, gender, ethnicity, BMI, blood pressure, HbA1c, fasting lipids, log CRP and CIMT as co-variates was assessed using multiple regression analysis. Associations with gender and ethnicity were assessed by student’s t test and Kruskal Wallis test respectively.
Results: The mean OXY was higher in the females (0.2±1.3) compared to the males (0.2±1.0); p&lt;0.001 and highest in the Indians (0.3±1.2) when compared to Chinese (-0.1±1.2) and Malays (-0.1±1.0); p=0.01. OXY exhibited a linear relationship with HbA1c (β=0.09, p=0.01), Non-HDL cholesterol ((β=0.28, p&lt;0.001) and CRP (β=0.21, p&lt;0.001). dROMS associated with HbA1c (β=5.3, p=0.04) and CRP (β=14.80, p&lt;0.001) and TAC associated inversely with non-HDL-cholesterol (β= -121.4, p&lt;0.001). No association with CIMT was seen.
Conclusions: In T2DM, total oxidative stress is a function of HbA1c, non-HDL-Cholesterol and low-grade inflammation. HbA1c and inflammation increase reactive oxygen metabolites, whereas non-HDL cholesterol decreases the anti-oxidant potential. The mechanisms of oxidative stress generation, in particular in various ethnic groups, needs to be studied further.

Disclosure
R. Dalan: None. L. Goh: None. X. Tang: None. D.E.K. Chew: None. B. Boehm: None.
Amino Acid Metabolism Is Regulated by Glucagon Receptor Signaling in Mice
Authors: WINTHER-SOERENSEN MARIE , GALSGAARD KATRINE D. , KUHRE RUNE E. , PEDERSEN JENS , ALBRECHTSEN NICOLAI J. WEWER , HOLST JENS J. 
Published: June 2018

The pancreatic hormone glucagon contributes to diabetic hyperglycemia and glucagon receptor antagonists lower blood glucose in patients with type 2 diabetes. A liver-alpha cell axis has recently been identified which when disrupted leads to hypersecretion of glucagon and may contribute to the development of diabetes. Here, we investigated the hepatic effects of glucagon receptor signaling in rodents and hypothesized that intact glucagon receptor signaling is necessary for amino acid metabolism via non-transcriptional changes leading to increased ureagenesis. Female C57BL/6JRj mice (n=64) were given a glucagon receptor antagonist (GRA) or vehicle orally three hours prior to an intraperitoneal injection with amino acids (Vamin, 3.6 µmol/g body weight), glucagon (200 ng/g body weight), or both, and blood samples were obtained at 0, 4, 12, and 20 minutes after injection. GRA treated animals had a significant decrease in plasma urea (8.6±0.3 vs. 11.1±0.4 mmol/L, p&lt;0.0001) and blood glucose (8.1±0.2 vs. 9.0±0.2, p&lt;0.001 mmol/L) and a concomitant increase in plasma amino acids (3.5±0.1 vs. 2.7±0.1 mmol/L, p&lt;0.0001) and glucagon (32.5±3.5 vs. 12.5±1.7 pmol/L, p&lt;0.0001). In addition, amino acid-stimulated ureagenesis, reflected by increased plasma urea, was inhibited in GRA treated mice compared to controls (incremental area under the curve: 27.6±3.3 vs. 41.2±5.3 min × mmol/L, p&lt;0.05). Production of urea in perfused rat livers (n=6) increased rapidly upon administration of amino acids (1 mM) compared to baseline (683±254 vs. 518±198 pmol/min/100 g body weight, p&lt;0.05) and was further increased in response to amino acids + glucagon (10 nM) stimulation (846±229 vs. 518±198 pmol/min/100 g body weight, p&lt;0.001). Glucagon therefore acutely regulates hepatic amino acid metabolism through increased ureagenesis via non-transcriptional mechanism(s), and disruption of this, due to e.g., nonalcoholic liver disease, may therefore contribute to the diabetogenic effect of hyperglucagonemia.

Disclosure
M. Winther-Soerensen: None. K.D. Galsgaard: None. R.E. Kuhre: None. J. Pedersen: None. N.J. Wewer Albrechtsen: Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Other Relationship; Self; Mercodia, Alpco. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., AstraZeneca. Research Support; Self; Danish Diabetes Academy, Novo Nordisk Foundation. Other Relationship; Self; Antag Therapeutics. Other Relationship; Spouse/Partner; Antag Therapeutics.
Serum Uromodulin (SUMOD) Inversely Correlates with Aortic Stiffness in Type 1 Diabetes (T1D) Youth
Authors: WIROMRAT PATTARA , BJORNSTAD PETTER , RONCAL-JIMENEZ CARLOS ALBERTO , SCHÄFER MICHAL , BAUMGARTNER AMY , PYLE LAURA , CREE-GREEN MELANIE , REYES YESENIA GARCIA , BROWNE LORNA , JOHNSON RICHARD , NADEAU KRISTEN J. 
Published: June 2018

Lower SUMOD correlates with decreasing kidney function and atherosclerosis in adults with T1D, but its relationship with markers of arterial stiffness in youth with T1D is unknown. We sought to evaluate the relationship between SUMOD and central arterial stiffness in youth with T1D. Participants (n=49, 12-21 years old, 51% female, BMI 25.2±4.6 kg/m2, mean HbA1c8.6±1.4) were enrolled in EMERALD, a randomized controlled trial of metformin in youth with T1D. Post-hoc SUMOD was measured using Euroimmun ELISA kits from serum from the baseline visit. Ascending (AA) and descending aortic (DA) stiffness (pulse wave velocity [PWV] and strain) were determined by MRI at baseline and 3 months of follow-up. SUMOD positively correlated with AA strain (r: 0.37, p=0.04) and negatively with AA PWV (r: -0.41, p=0.03). According to SUMOD tertiles, participants in the lower tertile had higher AA PWV vs. the middle and high tertiles (Figure).
Lower baseline SUMOD also predicted worsening in AA PWV over 3 months (β±SE: -0.04±0.01, p=0.03) adjusting for age, sex, baseline AA PWV, treatment group (metformin vs. placebo) and estimated glomerular filtration rate. In T1D youth, decreased SUMOD is associated with increased aortic stiffness. Further research is needed in T1D youth to understand the pathogenesis of SUMOD in cardiovascular disease.

Disclosure
P. Wiromrat: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. C. Roncal-Jimenez: None. M. Schäfer: None. A. Baumgartner: None. L. Pyle: None. M. Cree-Green: None. Y. Garcia Reyes: None. L. Browne: None. R. Johnson: Board Member; Self; XORT Therapeutics. Stock/Shareholder; Self; Colorado Research Partners LLC. Consultant; Self; Danone Research Foundation. K.J. Nadeau: None.
Do Greenlandic Carriers of the TBC1D4 p.Arg684Ter Variant Have Increased Risk of Cardiovascular Disease?
Authors: JØRGENSEN MARIT E. , TVERMOSEGAARD MARIA , RØNN PERNILLE F. , BJERREGAARD PETER , DAHL-PETERSEN INGER K. , LARSEN CHRISTINA V. , PEDERSEN MICHAEL L. , ALBRECHTSEN ANDERS , MOLTKE IDA , GRARUP NIELS , HANSEN TORBEN 
Published: June 2018

Background: The nonsense polymorphism p.Arg684Ter in the TBC1D4 gene is associated with severe skeletal muscle insulin resistance and postprandial hyperglycemia in the Greenlandic population. Homozygous carriers have an increased risk for type 2 diabetes (odds ratio of 10.3) and the variant has an allele frequency of 17% with 4% homozygous carriers in the population. However, we do not know, if p.Arg684Ter carrier status also confers a greater risk of cardiovascular disease (CVD). Thus the aim is to investigate if carriers of the variant are more at risk of CVD than non-carriers.
Materials and Methods: The study included adult participants in the Inuit Health in Transition study completed in the years 2005-2010 with sampling from 12 regions in Greenland (n= 3115) and the B99 study conducted from 1999-2001 (n=1401). Outcome was a first time CVD event from the Greenlandic Patien Register or the Causes of Death Register. Incidence rates of CVD were estimated by Poisson regression for wild type, heterozygous and homozygous carriers followed until the end of 2013, adjusted for European admixture proportion, age, sex, smoking, lipids, blood pressure, lipid- and blood pressure lowering drugs, blood glucose and known diabetes.
Results: During a median follow-up time of 7 years [IQR: 5.0, 10.0], 273 had an incident CVD event, 13 events among homozygous (HO), and 78 events among heterozygous (HE) carriers. Both in crude and adjusted analyses, there was a higher risk of incident CVD with p.Arg684Ter carrier status, although not statistically significant, with unadjusted incidence rate ratios (IRR) of 2.2 [CI 0.3- 15.5] for HO vs. WT; multivariable adjusted IRR 1.6 [0.12-19.5] for HO vs. WT. The same pattern was seen for HE vs. WT.
Conclusions: Overall, there was a trend towards increased risk of incident CVD with the TBC1D4 p.Arg684Ter variant although not statistically significant. Lack of statistical power may partly explain this, and replication in a larger sample or longer follow-up is needed.

Disclosure
M.E. Jørgensen: Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca, Amgen Inc.. M. Tvermosegaard: None. P.F. Rønn: Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. P. Bjerregaard: None. I.K. Dahl-Petersen: None. C.V. Larsen: None. M.L. Pedersen: None. A. Albrechtsen: None. I. Moltke: None. N. Grarup: None. T. Hansen: None.