19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Reduced HDL function in children and young adults with type 1 diabetes

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects.

          Methods

          Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL’s dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport.

          Results

          The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p < 0.001 and at follow-up, 0.34 (SD = 0.06) versus 0.36 (SD = 0.06)  %HAE/mg/dL, p = 0.003. HAE-apoA-I ratio was significantly and inversely correlated with HbA1c in the diabetes group. Over the 5 years of the study, the mean HAE-apoA-I ratio remained consistent in both groups. Individual changes were less than 15% for half of the study participants.

          Conclusions

          This study shows reduced HDL function, quantified as HAE-apoA-I ratio, in children and young adults with T1D compared with healthy control subjects. The differences in HDL function appeared shortly after disease onset and persisted over time.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

          The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes.

            Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms.

              The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic. © 2011 Macmillan Publishers Limited. All rights reserved
                Bookmark

                Author and article information

                Contributors
                martin.heier@medisin.uio.no
                mborja@chori.com
                UXBRUC@ous-hf.no
                UXINLJ@ous-hf.no
                h.d.margeirsdottir@medisin.uio.no
                k.f.hanssen@medisin.uio.no
                knut.dahl-jorgensen@medisin.uio.no
                moda@chori.com
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                6 July 2017
                6 July 2017
                2017
                : 16
                : 85
                Affiliations
                [1 ]ISNI 0000 0004 0433 7727, GRID grid.414016.6, , Children’s Hospital Oakland Research Institute, ; Oakland, CA USA
                [2 ]ISNI 0000 0004 1936 8921, GRID grid.5510.1, Faculty of Medicine, , University of Oslo, ; Oslo, Norway
                [3 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Oslo Centre for Biostatistics and Epidemiology, Research Support Services, , Oslo University Hospital, ; Oslo, Norway
                [4 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Center for Clinical Heart Research and Department of Cardiology, , Oslo University Hospital, ; Oslo, Norway
                [5 ]ISNI 0000 0000 9637 455X, GRID grid.411279.8, Department of Pediatric and Adolescent Medicine, , Akershus University Hospital, ; Lørenskog, Norway
                [6 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Department of Endocrinology, , Oslo University Hospital, ; Oslo, Norway
                [7 ]ISNI 0000 0004 0389 8485, GRID grid.55325.34, Pediatric Department, , Oslo University Hospital, ; Oslo, Norway
                Author information
                http://orcid.org/0000-0001-7807-194X
                Article
                570
                10.1186/s12933-017-0570-2
                5501001
                28683835
                f8bdaa37-70f2-463e-90a9-2d87d5eb8ecf
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 2 May 2017
                : 23 June 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100009471, EkstraStiftelsen Helse og Rehabilitering;
                Funded by: Oslo Diabetes Research Centre
                Funded by: FundRef http://dx.doi.org/10.13039/100011264, FP7 People: Marie-Curie Actions;
                Funded by: FundRef http://dx.doi.org/10.13039/100000968, American Heart Association;
                Award ID: 14POST1833018
                Award Recipient :
                Funded by: California Tobacco Related Disease Research Program
                Award ID: 21RT-0125
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2017

                Endocrinology & Diabetes
                high-density lipoprotein,type 1 diabetes,atherosclerosis,hdl function,hdl-apoa-i exchange

                Comments

                Comment on this article