The online version of this article (https://doi.org/10.1186/s12872-017-0738-4) contains supplementary material, which is available to authorized users.
Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects.
Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests.
CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels of 30/15 and VAL in CGL vs. healthy individuals. A significant positive correlation was observed between leptin and 30/15 coefficient (r = 0.396; p = 0.036) after adjusting for insulin resistance and triglycerides. Autonomic cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and albumin/creatinine ratio in CGL cases.
We observed a high prevalence of CAN in young patients with CGL, suggesting that insulin resistance, hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN development. Additional studies are needed to evaluate the role of leptinemia in the physiopathogenesis of the condition.
Additional file 1: Table S1. Molecular results of the AGPAT2 and BSCL2 genes in patients with generalized congenital lipodystrophy. Table S2. Results of the cardiovascular autonomic tests of patients with congenital generalized lipodystrophy. Table S3. Symptoms of dysautonomia in patients with congenital generalized lipodistrophy and type 1 diabetes as well as healthy individuals. Table S4. Evaluation of the cardiometabolic parameters and cardiovascular autonomic tests in patients with lipodystrophy and type 1 diabetes. (DOCX 36 kb)12872_2017_738_MOESM1_ESM.docx
Lima JG, Nobrega LH, de Lima NN, do Nascimento Santos MG, Baracho MF, Jeronimo SM. Clinical and laboratory data of a large series of patients with congenital generalized lipodystrophy. Diabetol Metab Syndr. 2016;8:23. PubMed PMID: 26985241. Pubmed Central PMCID: Pmc4793761. Epub 2016/03/18. eng CrossRefPubMedPubMedCentral
Rolim LC, de Souza JS, Dib SA. Tests for Early Diagnosis of Cardiovascular Autonomic Neuropathy: Critical Analysis and Relevance. Front Endocrinol. 2013;4:173. PubMed PMID: 24273533. Epub 2013/11/11. eng
Gomes MB, Coral M, Cobas RA, Dib SA, Canani LH, Nery M, et al. Prevalence of adults with type 1 diabetes who meet the goals of care in daily clinical practice: a nationwide multicenter study in Brazil. Diabetes Res Clin Pract. 2012;97(1):63–70. PubMed PMID: 22397904. Epub 2012/03/09. eng CrossRefPubMed
National High Blood Pressure Education P. The seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Bethesda: National Heart, Lung, and Blood Institute (US); 2004.
Tanner JM. Growth at adolescence. 2nd Ed. Ofxord: Blackwell; 1962.
ADA. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Suppl 1):S81-90. PubMed PMID: 24357215. Epub 2013/12/21. eng.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143–421. PubMed PMID: 12485966. Epub 2002/12/18. eng
Garcia Cuartero B, Garcia Lacalle C, Jimenez Lobo C, Gonzalez Vergaz A, Calvo Rey C, Alcazar Villar MJ, et al. [The HOMA and QUICKI indexes, and insulin and C-peptide levels in healthy children. Cut off points to identify metabolic syndrome in healthy children]. An Pediatr (Barc). 2007 May;66(5):481-90. PubMed PMID: 17517203. Epub 2007/05/23. Indice HOMA y QUICKI, insulina y peptido C en ninos sanos. Puntos de corte de riesgo cardiovascular. spa.
Geloneze B, Tambascia MA. Avaliação laboratorial e diagnóstico da resistência insulínica. Arquivos Brasileiros de Endocrinologia & Metabologia. 2006;50:208–15. CrossRef
Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, et al. Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med. 1992;9(2):166–75. PubMed PMID: 1563252. Epub 1992/03/01. eng CrossRefPubMed
Panzer C, Lauer MS, Brieke A, Blackstone E, Hoogwerf B. Association of fasting plasma glucose with heart rate recovery in healthy adults: a population-based study. Diabetes. 2002 Mar;51(3):803-7. PubMed PMID: 11872683. Epub 2002/03/02. eng.
Laitinen T, Lindstrom J, Eriksson J, Ilanne-Parikka P, Aunola S, Keinanen-Kiukaanniemi S, et al. Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance. Diabet Med. 2011;28(6):699–704. PubMed PMID: 21388444. Epub 2011/03/11. eng CrossRefPubMed
Van De Borne P, Hausberg M, Hoffman RP, Mark AL, Anderson EA. Hyperinsulinemia produces cardiac vagal withdrawal and nonuniform sympathetic activation in normal subjects. Am J Phys. 1999;276(1 Pt 2):R178–83. PubMed PMID: 9887192. Epub 1999/01/14. eng
Lindmark S, Wiklund U, Bjerle P, Eriksson JW. Does the autonomic nervous system play a role in the development of insulin resistance? A study on heart rate variability in first-degree relatives of type 2 diabetes patients and control subjects. Diabet Med. 2003;20(5):399–405. PubMed PMID: 12752490. Epub 2003/05/20. eng CrossRefPubMed
McCall KD, Holliday D, Dickerson E, Wallace B, Schwartz AL, Schwartz C, et al. Phenylmethimazole blocks palmitate-mediated induction of inflammatory cytokine pathways in 3T3L1 adipocytes and RAW 264.7 macrophages. J Endocrinol. 2010;207(3):343–53. PubMed PMID: 20813836. Epub 2010/09/04. eng CrossRefPubMed
Rodriguez AJ, Nunes Vdos S, Mastronardi CA, Neeman T, Paz-Filho GJ. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of controlled cross-sectional studies. J Diabetes Complicat. 2016;30(2):357–67. CrossRefPubMed
Bertog SC, Sobotka PA, Sievert H. Renal denervation for hypertension. J Am Coll Cardiol Intv. 2012;5(3):249–58. CrossRef
Ito D, Suzuki N. [Seipin/BSCL2-related motor neuron disease: Seipinopathy is a novel conformational disease associated with endoplasmic reticulum stress]. Rinsho Shinkeigaku. 2007 Jun;47(6):329-35. PubMed PMID: 17633104. Epub 2007/07/18. jpn.
Ewing D. Analysis of heart rate variability and other non-invasive tests with special reference to diabetes mellitus. Autonomic failure. 1992;16:312–33.
Smith SA. Reduced sinus arrhythmia in diabetic autonomic neuropathy: diagnostic value of an age-related normal range. Br Med J (Clin Res Ed). 1982 Dec 4;285(6355):1599-601. PubMed PMID: 6814668. Pubmed Central PMCID: Pmc1500796. eng.
Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task force of the European Society of Cardiology and the north American Society of Pacing and Electrophysiology. Circulation. 1996;93(5):1043–65. PubMed PMID: 8598068. Epub 1996/03/01. eng
- Early commitment of cardiovascular autonomic modulation in Brazilian patients with congenital generalized lipodystrophy
Clarisse Mourão Melo Ponte
Virgínia Oliveira Fernandes
Maria Helane Costa Gurgel
Izabella Tamira Galdino Farias Vasconcelos
Lia Beatriz de Azevedo Souza Karbage
Christiane Bezerra Rocha Liberato
Carlos Antônio Negrato
Marília de Brito Gomes
Ana Paula Dias Rangel Montenegro
Renan Magalhães Montenegro Júnior
- BioMed Central
Neu im Fachgebiet Kardiologie
Mail Icon II