1. α-Glukosidase-Inhibitors
Heart rate variability (HRV) in type 2 diabetics with improved glycemic control under Pioglitazone therapy: results of the ETAPP Study
Martin Schönauer 1, Christina.Kautz 2, Ulrike Schönauer1, Josef Niebauer4 Andreas Thomas 3
1 Diabetic Center August-Bebel-Str. 71, Leipzig, Germany 2 Universität Leipzig, Germany 3 Medtronic GmbH, Emaunuel-Letze-Str. 20, Düsseldorf, Germany,
4 Privatuniversität Salzburg, Institut für Sportmedizin, Salk-Institut, Lindhofstr. 20, A-5020 Salzburg, Austria
OBJECTIVES
ABSTRACT
Development of HRV Disturbation during the study
315 patients (168f/147m) were assigned either to an intervention group, receiving 30mg/day Pioglitazone (PIO n=227), or a control group (Control n=88). Median age at baseline 60,3+8,2 years, BMI: 31,3+5,3 kg/m2, fasting blood glucose: 6,7+1,3 mmol/l, HbA1c: 6,9+1,0%, triglycerides: 2,55+1,14 mmol/l, total cholesterol: 5,19+1,03 mmol/l, HDL: 1,14+0,30 mmol/l, LDL: 2,83+0,86 mmol/l, RRsyst.: mmHg, RRdiast.: mmHg. The interpretation of the HRV patterns revealed that 70% of the patients had signs of a cardiovascular autonomic diabetic neuropathy (CADN). Apart from the prescription of pioglitazone, the glycaemic and antihypertensive therapy was optimized in both groups.
Aim of the ETAPP Study was an early stratification of the cardiovascular risk of insulin independent type 2 diabetics with a short anamnesis under office conditions. Between October 2003 and March 2004 patients with type 2 diabetes from the east of Germany, treated by 102 general practitioners, were recruited. Laboratory parameters (fasting blood glucose, HbA1c, triglycerides, HDL, LDL, VLDL) and blood pressure were determined. Heart rate variability (HRV) was evaluated by power spectral analysis with the transportable VariaCardio®TF5 in a modified orthostatic test (5 min supine, 5 min standing, min supine).
Month 12
Month 0
Pioglitazone
Control no
mild
medium
severe
RESULTS
Following significant changes from baseline to week 52 were established (PIO vs. Control): fasting plasma glucose: -0,75+1,44 mmol/l vs. +0,13+1,63 mmol/l (p<0,001), HbA1c: ‑0,63+0,71% vs. +0,07+0,59% (p<0,001), triglycerides: -0,49+1,00 mmol/l vs. ‑0,04+1,19 mmol/l (p<0,001), HDL: +0,13+0,24 mmol/l vs. -0,06+0,28 mmol/l (p<0,001), LDL: -0,21+0,79 mmol/l vs. 0,04+0,77 mmol/l (p<0,05), BMI: +0,7+1,5 kg/m2 vs. -0,2+1,6 kg/m2 (p<0,001). As a sign for autonomic cardiac dysfunction, HRV improved significantly in the Pioglitazone group as opposed to the control group (p<0,001):
Cardiovascular Risk Profil
BMI >
25 kg/m2
30 kg/m2
35 kg/m2
40 kg/m2
Hyper-tension
Dys-lipidemia
Glycemic Control and Blood Pressure Control
CONCLUSION
PIO
Control
Month 0
Month 12
Month 0
Month 0
Month 12
PIO
Control
RRsyst
RRdiast
These results show that an additional medication with the insulin sensitizer Pioglitazone in sufficient treated type-2-diabetics further optimises the metabolic control and moreover improves the heart rate variability which is associated with an increased cardiovascular mortality risk. In summery, the short-term analysis of HRV is a sensible method and necessary for risk stratification as suggested in the guidelines of the ADA.
Antidiabetic Therapy at the beginning
Metformin
Sulfonyl-uria (SH)
Metformin + SH
konservativ
(Diet and Sports)
Glinids
α-Glukosidase-Inhibitors
REFERENCES
(1) Howorka K, Pumprla J, Schabmann A: Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. Journal of the Autonomic Nervous System –172
(2) Boulton AJM et al.: Diabetic Neuropathies, A statement by the American Diabetes Association. Diabetes Care 2005; 28:
Setting:
(1) ECG:
R-R
Intervals
(2) R-R Intervals Variability
(3) Spectral Analysis of R-R Intervals Variability
Symp.
(+Parasymp.)
Parasymp. LF HF
VLF
supine
standing
Short-term analysis of HRV: modified orthostatic stress
Typical examples of HRV in case of autonomic dysfunction
normal
light stadium (beginning)
medium (advanced stadium)
worst stadium