Table 1.

Prevalence of cardiac autonomic neuropathy as reported in major studies

Ref.	Year	Country	N of subjects	Type of DM	Population characteristics	Diagnostic test	Criteria applied	Prevalence(%)	Comments
O’Brien et al[111]	1991	United Kingdom	506	IDDM	Mean age 45 yr, mean DM duration 15 yr, female 42%	HRV in response to (1) rest (2) single deep breath (3) Valsalva manoeuvre or (4) standing	At least two positive of the tests mentioned in the previous column	17	Prevalence of CAN was associated with the presence of other DM complications
Ziegler et al[223]	1992	Germany	130	Newly diagnosed IDDM		CV of HRV, low- and mid- frequency bands of spectral analysis, MCR, Valsalva manoeuvre or lying-to standing	At least three positive of the tests mentioned in the previous column	7.7
		Austria	647	Total IDDM				25.3
		Switzerland	524	Non-IDDM				34.3
Kennedy et al[11]	1995	United States	290	IDDM	Listed pancreas transplantation recipients	HRV Valsalva manoeuvre		90 88
DCCT research group[19]	1998	United States	1441	IDDM (1) primary prevention cohort (absence of end–organ damage such as retinopathy and microalbuminuria) (2) secondary intervention cohort (mild/ moderate retinopathy +/- microalbuminuria)	Mean age 27 yr, female 47% duration of DM 1-5 yr (mean 2.6) primary prevention cohort 1-15 yr (mean 8.8) secondary intervention cohort	HRV	R-R variation < 15	1.6-6.2	These figures represent baseline characteristics
						Valsalva manoeuvre	Valsalva ratio < 1.5	5.5-6.3
						Postural BP	Diastolic BP drop > 10 mmHg	0
Kempler et al[28] (EURODIAB IDDM)	2002	16 European countries	3250	T1DM	Mean age 32 yr, mean DM duration 14 yr, female 49%	(1) R-R response to standing (2) Postural BP	R-R ratio < 1.04 or drop > 20 mmHg in systolic BP	36	Correlation with age, DM duration and HbA1c
Gaede et al[5,224] (the Steno type 2 study)	2003	Denmark	160	T2DM	Mean age 55 yr, female 27%, HbA1C 8.8% at baseline	(1) R-R response to breathing (2)Postural BP	R-R variation < 6 or drop > 25 mmHg in systolic BP	27.5	This figure represents baseline findings
Valensi et al[27]	2003	France	245	T1DM	Mean age 39.6 yr, mean DM duration 8.6 yr, female 43%	R-R response to	Criteria for abnormal tests were based on Armstrong et al[225]		Rate of moderate/severe CAN was higher in T1DM (18.2% and 4.8%) than in T2DM (12.3% and 2.3%) (P = 0.031)
			151	T2DM		(1) deep breathing		21.2
						(2) Valsalva and		20.7
						(3) standing		33.5
							At least two positive tests (classed as moderate CAN)	20
Low et al[23]	2004	United States	83	T1DM	Mean age 59 yr, white 99%, female 48%	(1) Sudomotor axon-reflex test (2) Valsalva manoeuvre (3) BP and HR response to standing (4) R-R response to deep breathing	CASS ≥ 1 in two domains or ≥ 2 in one domain (sudomotor, cardiovagal, adrenergic)	54	This study focuses on DAN but encompasses several cardiac autonomic tests
			148	T2DM				73
Pop-Busui et al[18] (DCCT/EDIC study)	2009	United States	620	IDDM-former intensive Tx group IDDM-former conventional Tx group	Mean age 47 yr in both groups, mean DM duration 26 yr, female 49% and 46% respectively	R-R response to (1) deep breathing (2) Valsalva manoeuvre (3) postural BP	R-R < 15 or R-R 15-19.9 and Valsalva ratio < 1.5 or drop > 15 mmHg in diastolic BP	29	13/14 yr post closeout of DCCT
			591					35

DM: Diabetes mellitus; IDDM: Insulin dependent diabetes mellitus; CV: Coefficient of variation; MCR: Mean circular resultant; HRV: Heart rate variability; BP: Blood pressure; CAN: Cardiac autonomic neuropathy; CASS: Composite Autonomic Severity Score; DCCT: Diabetes Control and Complications Trial; T1DM: Type 1 diabetes mellitus.