Oral Presentation Neuropathophysiology - an ISH satellite 2012

The relation of glucose metabolism to left ventricular mass and function and sympathetic nervous system activity in obese subjects with metabolic syndrome (#8)

Nora E Straznicky 1 , Mariee T Grima 1 , Carolina I Sari 1 , Sofie Karapanagiotidis 2 , Chiew Wong 2 , Nina Eikelis 1 , Katrina Richards 1 , Paul J Nestel 3 , John B Dixon 1 , Gavin W Lambert 1 , Markus P Schlaich 4 , Elisabeth A Lambert 1
  1. Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia
  2. Alfred Baker Medical Unit, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia
  3. Cardiovascular Nutrition Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne , VIC, Australia
  4. Neurovascular Hypertension & Kidney Disease Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, VIC, Australia

BACKGROUND- Early changes of cardiac structure and function have been reported in pre-diabetic and diabetic populations however the contribution of the sympathetic nervous system (SNS) to these changes has yet to be delineated.

METHODS- Un-medicated subjects with ATP III metabolic syndrome, classified as impaired glucose tolerant (IGT, n=31) or treatment naïve type 2 diabetic (n=25, T2D) and matched for age (mean 58 ± 1 yr), gender, BMI (32.2 ± 0.5 kg/m2) and blood pressure (137 ± 2/77 ± 1 mmHg) were studied. They underwent standard oral glucose tolerance test, echocardiography, and assessments of whole-body noradrenaline kinetics. Insulin sensitivity was determined by euglycaemic hyperinsulinemic clamp (M value) in a subset of subjects (20 IGT, 13 T2D).

RESULTS- T2D subjects had higher left ventricular mass index (LVMI, 93.6 ± 3.5 versus 77.2 ± 3.4 g/m2, P=0.002) and Doppler derived isovolumetric relaxation (119 ± 6 versus 106 ± 4 msec, P=0.04) and deceleration times (231 ± 10 versus 200 ± 7 msec, P=0.02) and lower early/late transmitral flow velocity (E/A, 0.86 ± 0.04 versus 1.07 ± 0.06, P=0.02) compared to IGT. Arterial noradrenaline concentration was higher in the T2D group (287 ± 31 versus 217 ± 15 pg/ml, P=0.05), whereas plasma noradrenaline clearance was reduced (1.94 ± 0.11 versus 2.26 ± 0.10 L/min, P=0.02). M value correlated with LV septal thickness (r=-0.46, P=0.007). Whole-body noradrenaline spillover rate correlated with LVMI in the T2D subgroup (r=0.47, P=0.03). In the pooled cohort, LVMI was independently predicted by pulse pressure (r=0.38, P=0.004) and E/A ratio by age (r=-0.47, P=0.003) and 2h plasma glucose (r=-0.38, P=0.005).

CONCLUSIONS- Transition from IGT to T2D is associated with cardiac enlargement and diastolic dysfunction, which relate to metabolic, hemodynamic and autonomic alterations.

DISCLOSURES-This study was funded by a Heart Foundation Grant-in-Aid (G11M5892).