Search

Background: The mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls., Methods: Post-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82 Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS)., Results: Mean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA 1c , body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16)., Conclusion: A lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden., Competing Interests: PR reports having received research grants from Astra Zeneca and Novo Nordisk and given lectures for Astra Zeneca, Mundipharma and Boehringer Ingelheim and has served as a consultant for Astra Zeneca, Bayer, Eli Lilly, Boehringer Ingelheim, Astellas, Gilead, Sanofi Aventis Vifor, and Novo Nordisk, all fees given to Steno Diabetes Center. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laursen, Rasmussen, Zobel, Hasbak, von Scholten, Holmvang, Ripa, Hansen, Frimodt-Moeller, Kjaer, Rossing and Hansen.)

Background: Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall., Methods: Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [ 64 Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [ 64 Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUV max ); and means of the maximum values (mSUV max ), both values were calculated at the level of each participant and each individual coronary-segment., Results: SUV max and mSUV max values decreased significantly in the liraglutide group both at the participant level (SUV max : p=0.013; mSUV max : p=0.004) and at the coronary-segment level (SUV max : p=0.001; mSUV max : p<0.0001). No change was observed in the placebo group neither at the participant level (SUV max : p=0.69; mSUV max : p=0.67) or at the coronary-segment level (SUV max : p=0.49; mSUV max : p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUV max : p=0.076; mSUV max : p=0.077) and the coronary segment level (SUV max : p=0.13; mSUV max : p=0.11) a borderline significant difference was observed. Baseline SUV max [ 64 Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045)., Conclusion: Liraglutide treatment for 26-weeks caused a significant reduction in [ 64 Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [ 64 Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP., Competing Interests: AK has received consultancy fees from Novo Nordisk and is an inventor on a patent of [64Cu]Cu-DOTATATE. RR, BS, TH, and PR have shares in Novo Nordisk A/S. BS and EZ are now employees of Novo Nordisk A/S. PR has received the following: Consultancy and/or speaking fees (to Steno Diabetes Center Copenhagen) from AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novo Nordisk and Sanofi Aventis; Research grants to institution from AbbVie, AstraZeneca and Novo Nordisk. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jensen, Zobel, von Scholten, Rotbain Curovic, Hansen, Rossing, Kjaer and Ripa.)