title: Relationship of autonomic imbalance and circadian disruption with obesity and type 2 diabetes in resistant hypertensive patients.
abstract: BACKGROUND
  Hypertension, diabetes and obesity are not isolated findings, but a series of interacting interactive physiologic derangements. Taking into account genetic background and lifestyle behavior, AI (autonomic imbalance) could be a common root for RHTN (resistant hypertension) or RHTN plus type 2 diabetes (T2D) comorbidity development. Moreover, circadian disruption can lead to metabolic and vasomotor impairments such as obesity, insulin resistance and resistant hypertension. In order to better understand the triggered emergence of obesity and T2D comorbidity in resistant hypertension, we investigated the pattern of autonomic activity in the circadian rhythm in RHTN with and without type 2 diabetes (T2D), and its relationship with serum adiponectin concentration.
  
  
  METHODS
  Twenty five RHTN patients (15 non-T2D and 10 T2D, 15 males, 10 females; age range 34 to 70 years) were evaluated using the following parameters: BMI (body mass index), biochemical analysis, serum adiponectinemia, echocardiogram and ambulatory electrocardiograph heart rate variability (HRV) in time and frequency domains stratified into three periods: 24 hour, day time and night time.
  
  
  RESULTS
  Both groups demonstrated similar characteristics despite of the laboratory analysis concerning T2D like fasting glucose, HbA1c levels and hypertriglyceridemia. Both groups also revealed disruption of the circadian rhythm: inverted sympathetic and parasympathetic tones during day (parasympathetic > sympathetic tone) and night periods (sympathetic > parasympathetic tone). T2D group had increased BMI and serum triglyceride levels (mean 33.7 ± 4.0 vs 26.6 ± 3.7 kg/m² - p = 0.00; 254.8 ± 226.4 vs 108.6 ± 48.7 mg/dL - p = 0.04), lower levels of adiponectin (6729.7 ± 3381.5 vs 10911.5 ± 5554.0 ng/mL - p = 0.04) and greater autonomic imbalance evaluated by HRV parameters in time domain compared to non-T2D RHTN patients. Total patients had HRV correlated positively with serum adiponectin (r = 0.37 [95% CI -0.04 - 1.00] p = 0.03), negatively with HbA1c levels (r = -0.58 [95% CI -1.00 - -0.3] p = 0.00) and also adiponectin correlated negatively with HbA1c levels (r = -0.40 [95% CI -1.00 - -0.07] p = 0.02).
  
  
  CONCLUSIONS
  Type 2 diabetes comorbidity is associated with greater autonomic imbalance, lower adiponectin levels and greater BMI in RHTN patients. Similar circadian disruption was also found in both groups indicating the importance of lifestyle behavior in the genesis of RHTN.
authors.affiliation: Cardiovascular Pharmacology Laboratory, Faculty of Medical Sciences and Clinic Hospital, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil. leandro.martins@novartis.com
authors.forename: Leandro
authors.initials: L
authors.lastname: Boer-Martins
authors.forename: Valéria N
authors.initials: VN
authors.lastname: Figueiredo
authors.forename: Caroline
authors.initials: C
authors.lastname: Demacq
authors.forename: Luiz C
authors.initials: LC
authors.lastname: Martins
authors.forename: Fernanda
authors.initials: F
authors.lastname: Consolin-Colombo
authors.forename: Márcio J
authors.initials: MJ
authors.lastname: Figueiredo
authors.forename: Fernando P S
authors.initials: FP
authors.lastname: Cannavan
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D001938:Brazil / Q000453:epidemiology; D002940:Circadian Rhythm; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000503:physiopathology*; D004351:Drug Resistance; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000503:physiopathology*; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D000959:Antihypertensive Agents; D015415:Biomarkers; D006442:Glycated Hemoglobin; D014280:Triglycerides; C499918:ADIPOQ protein, human; C517652:hemoglobin A1c protein, human