bluuebunny/crossref_metadata_2025_split huggingface dataset:
345-OR: Exercise and Liraglutide Synergistically Attenuate Vascular Inflammation and Enhance Metabolic Insulin Action in Diet-Induced Obesity
Authors: LIU JIA , AYLOR KEVIN W. , LIU ZHENQI 
Published: June 2023

Endothelial oxidative stress and vascular inflammation induce microvascular insulin resistance which is an early event in diet-induced obesity and contributes to metabolic insulin resistance. To examine whether exercise and glucagon-like peptide 1 (GLP-1) receptor agonism, alone or in combination, modulate vascular and metabolic insulin actions during obesity development, we performed an euglycemic insulin clamp, in conjunction with contrast enhanced ultrasound, in adult male rats after 2 weeks of high-fat diet feeding with either access to running wheel (exercise), liraglutide (200 mg/kg subcutaneously twice daily), or the combination of both. Rats exhibited increased visceral adiposity and blunted microvascular responses (microvascular blood volume, flow velocity, and total flow) and metabolic insulin actions (glucose infusion rates). Exercise and liraglutide alone each improved muscle insulin sensitivity but their combination fully restored insulin-mediated glucose infusion rates. The combined exercise and liraglutide intervention enhanced insulin-mediated muscle microvascular perfusion, reduced perivascular macrophage accumulation and oxidative stress in the muscle, attenuated blood vessel inflammation and improved endothelial function, along with increased nucleus translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and phosphorylation of AMP-activated protein kinase (AMPK) and nitric oxide synthase (eNOS) in endothelial cells. We conclude that exercise and liraglutide synergistically enhance the metabolic actions of insulin and reduce vascular oxidative stress and inflammation in the early stage of obesity development. Our data suggest that early combination use of exercise and GLP-1 receptor agonism might be an effective strategy in preventing microvascular and metabolic insulin resistance and associated complications during the development of obesity.

Disclosure
J.Liu: None. K.W.Aylor: None. Z.Liu: None.

Funding
National Institutes of Health (R01DK125330), (R01DK1124344 to Z.L.)
35-OR: Incretin Production Is Impaired in Atypical Low BMI Diabetes Mellitus
Authors: JEBASINGH FELIX , ANOOP SHAJITH , KURIAN MATHEWS E. , SANDEEP VENKATA N. , CHRISTINA FLORY , JENNIFER SHIRLY , JOSE ARUN , CHRISTUDOSS PAMELA , REBEKAH GRACE , JIANG NANCY , HAWKINS MEREDITH , THOMAS NIHAL 
Published: June 2023

Introduction: Atypical Low BMI Diabetes Mellitus (ALBDM) constitutes an unclassified form of diabetes that is likely to be prevalent in low- and middle-income countries. Recently, we reported in Diabetes Care that such individuals demonstrate striking defects in insulin secretion, despite absence of visible pancreatic pathology (PMID: 35522035). This study aims to determine whether defects in the incretin axis might contribute to impaired insulin secretion in ALBDM.
Methodology: We assessed the glucagon and incretin (GLP-1, GIP, and Oxyntomodulin) responses to an oral glucose tolerance test (OGTT) in patients with ALBDM. Ten male subjects demonstrating features of ALBDM (n=10, age 33±8.3 years, BMI 18.5±1.1 kg/m2, HbA1c 7.5±0.7%) were compared with 7 healthy BMI-matched normoglycemic (HbA1c: 5.0±0.3%) controls. All subjects underwent an OGTT, with blood sampling for C-peptide and incretin levels at nine specific time points. Insulin secretion rate (ISR) was calculated by C-peptide deconvolution using ISEC software, and total secretion rate for incretins were calculated as area under the curve (AUC) using the Trapezoid method with linear interpolation.
Results: As we previously reported, ALBDM subjects displayed impaired insulin secretion (50% reduction in post-OGTT insulin AUC, p=0.007). There was a profound reduction of OGTT-stimulated rise in the incretins GLP-1 (80% reduction; p=0.055), GIP (79% reduction; p=0.02) and oxyntomodulin (75% reduction; p=0.007) in ALBDM subjects compared to controls. In ALBDM subjects, mild hyperglucagonemia was observed in the early postprandial phase at 15 min of the OGTT followed by slow postprandial suppression.
Conclusions: Significant reductions in levels of GLP-1, GIP and Oxyntomodulin and an accompanying early phase of hyperglucagonemia suggest potential defects in development and/or function of enteroendocrine cells, which may contribute to defective insulin secretion and hyperglycemia in patients with Atypical Low BMI Diabetes Mellitus.

Disclosure
F.Jebasingh: None. N.Jiang: None. M.Hawkins: None. N.Thomas: None. S.Anoop: None. M.E.Kurian: None. V.N.Sandeep: None. F.Christina: None. S.Jennifer: None. A.Jose: None. P.Christudoss: None. G.Rebekah: None.

Funding
Endocrine Society of India
356-OR: Accuracy Evaluation of an Implantable CGM with Chemistry Improvements in a 365-Day Feasibility Study
Authors: AL-KHAWI LUJAIN , SANCHEZ PATRICIA , HUFFSTETLER PHILIP , VELVADAPU VENKATA N. , MASCIOTTI JAMES M. , TWEDEN KATHERINE S. , KAUFMAN FRANCINE R. 
Published: June 2023

Background: The prospective, multi-center PROMISE study demonstrated safety and accuracy of the 180-day Eversense E3 CGM System in adults with diabetes. Subsequently, the implantable E3 CGM sensor material and protective chemistries were advanced to improve the sensor signal maintenance. This analysis compares this Modified CGM System accuracy obtained from a feasibility study to that of the E3 CGM System using data from the PROMISE study.
Methods: A 365-day feasibility study was conducted to assess accuracy of CGM to SMBG measurements using the CONTOUR Next One meter for 32 Modified E3 sensors inserted in 32 subjects through 365 days. Results were compared to the CGM-SMBG pairs of E3 sensors from 30 subjects evaluated in the PROMISE study through 180 days.
Results: Modified E3 CGM System accuracy to SMBG through day 365 was equivalent to that of the E3 CGM System through day 180 as shown in the Table below.

Table: Accuracy to SMBG measurements of the Modified E3 sensors compared to that of E3 control sensors (Mean MARD increase of ~1.4% when SMBG is used as reference compared to YSI)
Conclusion: Modifications to the E3 sensor prolonged the longevity of the sensor from 180 days to 365 days while maintaining accuracy, suggesting that a fully implanted CGM System could provide accurate data over a one-year time period.

Disclosure
L.Al-khawi: Employee; Senseonics. P.Sanchez: Employee; Senseonics. P.Huffstetler: None. V.N.Velvadapu: None. J.M.Masciotti: None. K.S.Tweden: Employee; Senseonics. F.R.Kaufman: Consultant; MannKind Corporation, Twin Health, Stock/Shareholder; Senseonics.
357-OR: Continuous Glucose Monitoring in Diabetes Patients with Cognitive Impairment
Authors: KOTECHA PAREETA , CHEN WEI-HAN , LI YUJIA , DONAHOO WILLIAM T. , BIAN JIANG , GUO JINGCHUAN 
Published: June 2023

Objective: Continuous glucose monitoring (CGM) is beneficial in individuals at high risk of hypoglycemia or hypoglycemic events. Cognitive impairment can affect diabetes management and lead to poor health outcomes. We aimed to (1) assess the association between CGM use and all-cause mortality among diabetes patients with cognitive impairment and dementia, and (2) determine disparities in the use of CGM in this population.
Methods: We used 2016-2020 electronic health records data from the University of Florida Health System and identified patients who (1) had diagnoses of both diabetes and cognitive impairment (i.e., mild cognitive impairment or Alzheimer's disease and related dementias) and (2) were insulin users. We examined CGM use by race/ethnicity and insurance status; and applied multiple logistic regression to examine the association of CGM use with all-cause mortality.
Results: Of 1995 eligible patients (mean age 70.5±9.9 years, 56.9% non-Hispanic White (NHW), 37.5% non-Hispanic Black (NHB), and 5.6% others), 51 (2.6%) were CGM users and 566 (28.9%) died in a median follow up of 697 days. Black patients were less likely to use CGM compared to White patients (29.4% vs. 37.7% were Black among CGM users vs. non-users, respectively). Medicaid/uninsured patients were less likely to use CGM compared to Medicare/private insurance patients (1.9% vs. 11% were Medicaid/uninsured patients among CGM users vs. non-users, respectively). After adjusting for demographic and clinical characteristics in insulin users, CGM users were associated with a significantly lower risk of all-cause mortality compared to non-CGM users (adjusted OR (95% CI):0.2 (0.1-0.6)).
Conclusion: The use of CGM was associated with improved survival among diabetes patients who were insulin users and had cognitive impairment. However, racial and socioeconomic disparities in the use of CGM were observed, which may exacerbate existing inequities in diabetes care and outcomes.

Disclosure
P.Kotecha: Employee; Novo Nordisk Global Business Services. W.Chen: None. Y.Li: None. W.T.Donahoo: None. J.Bian: None. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.
358-OR: Better Adherence to Real-Time Continuous Glucose Monitoring (rtCGM) than to Intermittently Scanned CGM (isCGM) among People with Type 2 Diabetes (PWT2D) on Intensive Insulin Therapy (IIT)
Authors: NEMLEKAR POORVA , HANNAH KATIA , NORMAN GREGORY J. 
Published: June 2023

Background: For PWT2D, medication regimen adherence is associated with improved glycemic control and reduced health care utilization. However, little is known about CGM adherence for managing T2D, and how it varies by type of CGM.
Materials and Methods: A retrospective analysis of Merative’s MarketScan® US healthcare claims data was conducted. The cohort included CGM-naïve PWT2D on IIT who initiated rtCGM or isCGM between 1/1/2017 through 12/31/2020 (index date=earliest observed pharmacy claim). Adherence was defined as having ≥80% proportion of days covered (PDC) by pharmacy claims. Inclusion criteria were adults ≥30 years of age with T2D, using bolus insulin, with continuous health plan enrollment coverage 12 months before (baseline) and 12 months after the index date (follow-up), and no evidence of prior CGM use. The association between CGM adherence and change in A1C was examined in a subset of 663 patients with 6-month baseline and 6-month follow-up laboratory values.
Results: The rtCGM group (n=2,349) was [mean (SD)] 49.2 (8.0) years of age and 48% female, while the isCGM group (n=8,881) was 50.4 (8.0) years of age and 48% female. Average PDC was 85% (26%) for the rtCGM group and 68% (32%) for the isCGM group. A total of 76.2% of the rtCGM group and 50.6% of the isCGM group met the ≥80% PDC level of adherence. A multivariate logistic regression model showed the odds of adherence were three times greater for rtCGM compared to isCGM (OR=3.2, 95% CI 2.8-3.5, p&lt;0.001). Those adherent to CGM, regardless of device type, had a greater decrease in A1C (-0.94%) compared to those who did not meet the adherence criterion (-0.54%) (p&lt;0.001).
Conclusions: These findings indicate that for PWT2D on IIT, adherence to rtCGM is higher than to isCGM. The association between adherence and reduced A1C suggests patients can improve glycemic control with consistent use of CGM.

Disclosure
P.Nemlekar: Employee; Dexcom, Inc. K.Hannah: Employee; Dexcom, Inc. G.J.Norman: Employee; Dexcom, Inc.

Funding
Dexcom, Inc.
36-LB: Dulce Digital-Me—A Randomized Comparative Effectiveness Trial of Static vs. Adaptive Digital Interventions for Hispanic Adults with Diabetes
Authors: PHILIS-TSIMIKAS ATHENA , FORTMANN ADDIE L. , CLARK TAYLOR , SPIERLING BAGSIC SAMANTHA R. , FARCAS EMILIA , ROESCH SCOTT , SCHULTZ JAMES H. , GILMER TODD P. , GODINO JOB G. , SAVIN KIMBERLY L. , JONES JENNIFER A. , CHICHMARENKO MARIYA , SANDOVAL HALEY , GALLO LINDA 
Published: June 2023

We compared the effectiveness of Dulce Digital (DD), a diabetes education text messaging program, versus Dulce Digital-Me (DD-Me), which included DD text messaging plus algorithm-driven, personalized goal-setting and feedback, in improving diabetes outcomes in Hispanic adults with type 2 diabetes (T2D). In this open-label comparative effectiveness trial, Hispanic adults with T2D were randomized (1:1:1) to receive DD, or the more personalized DD-Me approach delivered via automated, algorithm-driven text messaging (DD-Me_Auto) or telephonic communication from a health coach (DD-Me_Tel) across 6-months as part of existing primary care. Changes in clinical (HbA1c—primary) and patient reported outcomes were examined over 12 months. We enrolled N=310 Hispanic participants (69.7% female; M=52.1±10.2 years; 93.2% Spanish preferred; HbA1c M= 9.3±1.6 %) to receive DD (n=107), DD-Me_Auto (n=106) or DD-Me_Tel (n=97). Mixed models revealed no difference between DD and DD-Me (combined Auto+Tel) in rate of HbA1c change across 6- or 12-months, ps&gt;0.05. All groups showed clinically and statistically significant improvements in HbA1c across 6-months [DD ∆ = -0.17% per month post baseline (95% CI -0.22,-0.10); DD-Me_Auto ∆= -0.20% (95% CI -0.26,-0.14); DD-Me_Tel ∆ = -0.15% (95% CI -0.20,-0.10), ps&lt;.001]. Effect sizes were slightly attenuated, but remained statistically significant at 12-months (∆ HbA1c= -0.08% to -0.05% per month; ps &lt; 0.001). Self-management behaviors and diabetes distress improved across 12-months in all groups. DD-Me (combined) showed greater improvement in medication adherence versus DD over time (Bint=-0.20, 95% CI -0.33,-0.01, p&lt; 0.01). Two low-cost digital interventions for Hispanic adults with low income and T2D had similar and clinically significant effects on HbA1c across 12 months. Simple digital approaches can be integrated within primary care-based chronic care models to reduce diabetes disparities.

Disclosure
A. Philis-tsimikas: Advisory Panel; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Medtronic, Research Support; Novo Nordisk A/S, Lilly, Viking Therapeutics, NIH - National Institutes of Health. K. L. Savin: None. J. A. Jones: None. M. Chichmarenko: None. H. Sandoval: None. L. Gallo: None. A. L. Fortmann: Employee; Dexcom, Inc. T. Clark: None. S. R. Spierling bagsic: None. E. Farcas: None. S. Roesch: None. J. H. Schultz: None. T. P. Gilmer: None. J. G. Godino: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK1123221UL1, TR002550)
360-OR: Continuous Glucose Monitoring–Guided Insulin Administration in Subjects with Type 2 Diabetes in Long-Term Care Facilities—A Randomized Clinical Trial
Authors: IDREES THAER , CASTRO-REVOREDO IRIS A. , OH HYUNGSEOK , GAVALLER MONICA D. , ZABALA ZOHYRA , MORENO EMMELIN M. , MOAZZAMI BOBAK , GALINDO RODOLFO J. , CABB ELENA , JOHNSON THEODORE M. , PENG LIMIN , UMPIERREZ GUILLERMO 
Published: June 2023

The efficacy of real-time continuous glucose monitoring (rt-CGM) in adjusting insulin therapy in long-term care facilities (LTCF) has not been evaluated. Accordingly, we randomized 100 insulin-treated subjects with T2D in LTCF. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with treatment adjusted based on POC results; while in the rt-CGM group (Dexcom G6), treatment adjustment was based on daily CGM profile. Treatment adjustment was performed by the LTC medical team, with a target glucose of 140-180 mg/dL, and a duration of intervention up to 60 days. Primary endpoint was difference between groups in time in range (TIR, 70-180 mg/dL). Results: There were no significant differences in TIR (53.38%±30.16 vs 48.81%±28.03, p=0.40), mean daily glucose (185±44 vs 191 ±47 mg/dL, p=0.72), patients with % CGM values &lt;54 mg/dL (0.23±0.8% vs 0.56±2.2 %, p=0.88), with a trend in reducing time below range (TBR &lt;70 mg/dL) (0.83±2.6 % vs 1.18±3.5%, p= 0.51), between CGM and POC group. Conclusion: The results of this pilot randomized study indicate that the use of Dexcom G6 rtCGM is safe and effective in guiding diabetes therapy in long-term care facilities, resulting in a similar improvement in glycemic control (TIR) without differences in hypoglycemia.

Disclosure
T.Idrees: None. T.M.Johnson: Consultant; Astellas Pharma Inc., Research Support; Dexcom, Inc. L.Peng: None. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter. I.A.Castro-revoredo: None. H.Oh: None. M.D.Gavaller: None. Z.Zabala: None. E.M.Moreno: None. B.Moazzami: None. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. E.Cabb: None.

Funding
Dexcom, Inc. (IIS-2020-119_6X)
364-OR: Unsupervised Approach Systematically Analyzes the Multiomics Profiles Associated with T2D Insulin Insensitivity—An IMI-RHAPSODY Study
Authors: LI SHIYING , IBBERSON MARK , RUTTER GUY A. , PEARSON EWAN , SLIEKER RODERICK , BEULENS JOLINE , HANSEN MICHAEL K. , KUZNETSOV DMITRY , GERL MATHIAS J. , DRAGAN IULIAN J. , SIMONS KAI , DONNELLY LOUISE A. , TRAN VAN DU T. , MEHL FLORENCE , 'T HART LEEN M. 
Published: June 2023

Considerable heterogeneity exists in Type 2 diabetes disease onset and subsequent outcomes. Multi-omics analysis may provide a means to better assess inter-patient variations and design personalised approaches. Previous T2D biomarker discovery mainly focused on associating biomarkers with clinical pre-assigned patients. Here, we attempt to group T2D patients with similar multi-omics profiles using a multi-omics integrating clustering approach, Similarity Network Fusion (SNF). Each T2D subgroup’s unique omics profiles were then associated with T2D progression. In both cohorts, 180 and 1195 circulating lipids and proteins from a total of 1,134 subjects in DCS and GoDARTS cohorts group patients into two subgroups. Two subgroups are likely to represent the different stages of T2D insulin insensitivity with differences at HOMA2 (p=0.0008;4.2e-11;1.1e-09, -B, -IR and -S, DCS), C-peptide (p=3.7e-11;2.5e-06) and overall disease progression (HR=0.6;0.7). This is the first study solely relying on integrated lipidomics and proteomics to capture the stages of T2D insulin insensitivity, allowing potential novel biomarker discovery which may be masked by traditional approaches. In both cohorts, a number of discriminative omics features can be observed. Immune proteins, such as IL-18R, CLP, IL-1R and COD antigen showed strong but differing associations with insulin insensitivity, which may be related to the inflammation associated with T2D. Moreover, growth factors such as GHR and IGFs also exhibit strong associations with the present study. For lipids, patients with less severe insulin insensitivity exhibit elevated levels of sphingomyelins. In conclusion, we systematically analysed the multi-omics profiles associated with T2D insulin insensitivity. The molecular signatures may be used to investigate molecular mechanisms underpinning progression and provide insights for precision medicine.

Disclosure
S.Li: None. I.J.Dragan: None. K.Simons: Other Relationship; Lipotype, I have no there compoanz. L.A.Donnelly: None. V.T.Tran: None. F.Mehl: None. L.M.'t hart: Research Support; European Union. M.Ibberson: Consultant; Novo Nordisk Foundation. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. E.Pearson: Speaker's Bureau; Novo Nordisk, Lilly, Illumina. R.Slieker: None. J.Beulens: None. M.K.Hansen: None. D.Kuznetsov: None. M.J.Gerl: Employee; Lipotype GmbH.
367-OR: E-cigarette Vaping Exposure Increases Adipose 11ß-HSD1 Expression and Disturbs Glucose Homeostasis in Mice
Authors: WANG JIAN , LIU JENNY , WANG YING , KIM SAMUEL C.J. , ESPINAL ELIZABETH , YANG RONG , ZHONG HUI , SHAO XUESI M. , LUTFY KABIRULLAH , FRIEDMAN THEODORE , JIANG MEISHENG , LIU YANJUN 
Published: June 2023

Electronic cigarette (E-cigs) use may increase the prediabetic risk, but the underlying mechanisms remain underexplored. Pre-receptor activation of glucocorticoids (GCs) via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissues has been identified as an important mediator of insulin resistance and type 2 diabetes. However, little is known about the effects of E-cig vaping on 11β-HSD1 and glucose homeostasis. To address this issue, we conducted animal model studies with mice exposed to aerosolized PBS, nicotine-free or nicotine-containing E-cigs, with concurrent exposure to either vehicle or the GC receptor (GR) antagonist RU486. We observed that exposure of E-cig vaping nicotine for 4 weeks increased 11β-HSD1 expression and induced lipase HSL and ATGL abundance within the adipose tissues with induction of hypercortisolemia in response to elevated plasma nicotine levels in mice compared with those of aerosolized E-cig vaping vehicle or PBS controls. Induction of adipose 11β-HSD1 was correlated with elevated the expression of hepatic gluconeogenic enzymes PEPCK and G6Pase and corresponded to the elevated fasting glucose levels. Moreover, E-cig vaping nicotine also increased glucose intolerance, but decreased the glucose-lowing effects of insulin and elevated plasma FFA levels in mice compared with PBS controls. However, E-cig vapor without nicotine did not affect these metabolic parameters. Furthermore, RU486 treatment attenuated E-cig vaping nicotine-induced adipose 11β-HSD1 and lipase expression. In addition, RU486 also attenuated the E-cig-mediated activation of hepatic PEPCK and G6Pase and decreased plasma FFA levels, but did not change the elevated plasma corticosterone levels in mice on E-cig vaping nicotine. These data indicate that E-cig vapor exposure harmfully affects glucose homeostasis and these effects may arise, in part, from aerosol nicotine-induced adipose 11β-HSD1 and GR expression.

Disclosure
J.Wang: None. T.Friedman: None. M.Jiang: None. Y.Liu: None. J.Liu: None. Y.Wang: None. S.C.J.Kim: None. E.Espinal: None. R.Yang: None. H.Zhong: None. X.M.Shao: None. K.Lutfy: None.

Funding
Tobacco-Related Disease Research Program (T31IR1603)
368-OR: Life Expectancy and Causes of Death after Bariatric Surgery or Usual Care in Patients Stratified by Baseline Type 2 Diabetes in the Swedish Obese Subjects Study
Authors: SJÖHOLM KAJSA , ANDERSSON ASSARSSON JOHANNA C. , TAUBE MAGDALENA , CARLSSON EKANDER LENA 
Published: June 2023

Introduction: Patients with and without type 2 diabetes (T2D) differ in terms of metabolic disturbances and cardiovascular risk factors. Thus, it is possible that the increased survival after surgical obesity treatment is due to reduction of different causes of death. Here, we determined mortality and causes of death after bariatric surgery in relation to baseline T2D status in the prospective controlled Swedish Obese Subjects (SOS) study.
Methods: Deaths after bariatric surgery or usual care were determined in subgroups defined by baseline T2D (n=697) or non-T2D (n=3335) during a median follow-up of 26 years. The Swedish Cause of Death Register, case sheets and autopsy reports were assessed to determine the direct cause of death. Analyses were adjusted for preselected risk factors (age, sex, BMI and smoking at baseline, and year of inclusion in the study).
Results In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0 and 1.6, 0.5-2.7 years, respectively) and lower overall mortality (adjusted hazard ratio (adjHR)=0.77, 95% CI 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (p for interaction 0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR=0.65, 95% CI 0.46-0.91; and 0.70, 0.55-0.88, respectively (p for interaction 0.516)).
Conclusions: Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.

Disclosure
K.Sjöholm: None. J.C.Andersson assarsson: None. M.Taube: None. L.Carlsson ekander: None.

Funding
Swedish Research Council; Swedish State; Swedish Heart and Lung Foundation; Swedish Diabetes Foundation; Adlerbert Research Foundation