title: Effects of induced hyperinsulinaemia with and without hyperglycaemia on measures of cardiac vagal control.
abstract: OBJECTIVE
  We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control.
  
  
  METHODS
  Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine).
  
  
  RESULTS
  Serum insulin level was positively associated with HR at all time points during the clamps except the first-phase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log10HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures.
  
  
  CONCLUSIONS
  Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.
authors: Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands.
authors: M
authors: M
authors: Berkelaar
authors: E M W
authors: EM
authors: Eekhoff
authors: A M C
authors: AM
authors: Simonis-Bik
authors: D I
authors: DI
authors: Boomsma
authors: M
authors: M
authors: Diamant
authors: R G
authors: RG
authors: Ijzerman
authors: J M
authors: JM
authors: Dekker
authors: L M
authors: LM
authors: 't Hart
authors: E J C
authors: EJ
authors: de Geus
mesh_terms: D000328:Adult; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D004562:Electrocardiography; D005215:Fasting; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D015309:Glucose Clamp Technique; D006321:Heart / Q000502:physiology; D006339:Heart Rate; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D006946:Hyperinsulinism / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects*
chemical_list: D007328:Insulin; D052216:Glucagon-Like Peptide 1
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