Pancreatic exocrine insufficiency in diabetes is associated with autonomic dysfunction

Figures & data

Figure 1. The main theories for pathophysiological mechanisms leading to pancreatic exocrine insufficiency in diabetes. The illustration is modified after Zsóri et al. [1].

Figure 2. Inclusion flow chart.

Table 1. Clinical characteristics.

Variables	All patients	Pancreatic exocrine function			Cases / controls
		Reduced (FE-1 < 200)	Normal (FE-1 ≥ 200)	p Value	Cases	Controls	p Value
General demographics
n	59	12	47	–	8	13
Women, n	32 (54%)	6 (50%)	26 (55%)	.74	4 (50%)	4 (31%)	0.38
Age, yrs.	53 (15)	55 (9)	51 (16)	.52	57 (7)	49 (20)	0.11
Height, cm	171 (13)	170 (13)	172 (12)	.37	168 (20)	171 (8)	0.64
Weight, kg	84 (23)	79 (23)	85 (25)	.57	77 (28)	73 (12)	0.51
BMI, kg/m^2	27.2 (9.0)	26.4 (6.4)	28.1 (9.7)	.56	26.3 (6.4)	24.2 (2.6)	0.61
Diabetes status
Type 1 diabetes, n	31 (53%)	10 (83%)	21 (45%)	.02	7 (88%)	10 (77%)	0.55
Diabetes duration, yrs.	11 (20)	22 (33)	11 (17)	.08	22 (35)	23 (23)	0.83
HbA1c, % / mmol/mol	7.3 (1.4)/56 (15)	8.0 (1.7)/64 (18)	7.2 (1.1)/55 (12)	.79	7.2 (1.4)/55 (15)	7.5 (0.8)/58 (0.9)	0.55
Any late complications, n (%)	16 (27%)	4 (33 %)	12 (25%)	.59	2 (25%)	5 (39%)	0.53
Retinopathy, n (%)	12 (20%)	3 (25%)	9 (19%)	.65	1 (13%)	4 (31%)	0.34
Nephropathy, n (%)	8 (14%)	2 (17%)	6 (13%)	.73	1 (13%)	2 (15%)	0.85
Polyneuropathy, n (%)	8 (14%)	2 (17%)	6 (13%)	.73	1 (13%)	2 (15%)	0.85
Cardiovascular disease, n (%)	2 (3%)	1 (8.3%)	1 (2.1%)	.29	0	1 (8%)	0.42
Other parameters
Bristol stool scale, number	4 (1)	3 (1)	4 (2)	.09	3 (1)	4 (1)	0.58
Daily stool frequency, number	1.0 (0.5)	1.0 (0.8)	1.0 (0.5)	.19	1.0 (1.6)	1.0 (0.5)	0.68
Faecal Elastase-1, mg/g	449 (283)	125 (125)	491 (128)	<.001	79 (83)	444 (203)	<0.001
P-Glucose at test start, mmol/L	–	–	–	–	8.6 (2.0)	9.8 (3.5)	0.47

Data are given as median (IQR) unless otherwise indicated. Cases were defined as FE-1 < 200. Controls were recruited from participants with FE-1 ≥ 200. Abbreviations: IQR: Interquartile range; FE-1: Faecal Elastase-1; BMI: Body Mass Index; HbA1c: Glycosylated haemoglobin.

Figure 3. Heart-rate-variability parameters in cases (left) and controls: (a) Mean HR; (b) Mean NN; (c) SDNN; (d) RMSSD; (e) Total power; (f) VLF; (g) LF; (h) HF; (i) LF norm; (j) HF norm; (k) LF/HF ratio. Statistical significance of p≤.05 are marked by *. Results are given as median (IQR). Abbreviations: HR: Heart rate; SDNN: Standard deviation of NN intervals (inter-beat intervals where artefacts are removed); RMSSD: Root mean square of successive RR interval differences; VLF: Very low frequency; LF: Low frequency; HF: High frequency; LF norm: Low frequency normalized units; HF norm: High frequency normalized units; LF/HF ratio: Low frequency/high frequency ratio; IQR: Interquartile range.

Figure 4. Baroreflex sensitivity parameters in cases (left) and controls: (a) SD of HR; (b) Maximal variance of HR; (c) Mean variance of HR; (d) E/I ratio. Statistical significance of p≤.05 are marked by *Results are given as median (IQR). SD of HR: Standard deviation of heart rate; E/I ratio: Expiration/inspiration ratio; IQR: Interquartile range.

Table 2. Autonomic function tests.

Variables	Cases (n = 8)	Controls (n = 13)	p Value
HRV (time-domain measures)
Mean HR, bpm	59.2 (11.7)	65.7 (14.6)	.39
Mean NN, ms	1015.4 (209.0)	913.9 (239.7)	.39
SDNN, ms	31.1 (8.2)	49.3 (43.0)	.15
RMSSD, ms	16.9 (10.3)	25.8 (27.1)	.05
HRV (frequency-domain measures)
Total power, ms^2	298.8 (217.8)	427.1 (1709.4)	.13
VLF, ms^2	156.9 (103.2)	157.0 (456.2)	.77
LF, ms^2	72.0 (83.7)	231.1 (427.1)	.17
HF, ms^2	31.3 (43.0)	83.6 (176.4)	.04
LF norm, nu	74.7 (25.2)	66.6 (39.6)	.36
HF norm, nu	25.4 (25.2)	38.8 (38.4)	.28
LF/HF ratio	3.0 (4.4)	1.6 (4.6)	.26
Baroreflex sensitivity
SD of HR	2.3 (2.3)	5.1 (3.6)	.03
Maximal variance of HR	5.9 (7.3)	16.6 (11.2)	.01
Mean variance of HR	5.0 (6.5)	10.4 (11.1)	.03
E/I ratio	1.09 (0.08)	1.19 (0.21)	.02

Data are given as median (IQR). Abbreviations: IQR: Interquartile range; HRV: Heart rate variability; HR: Heart rate; Bpm: Beats per minute; SDNN: Standard deviation of NN intervals (inter-beat intervals where artefacts are removed); RMSSD: Root mean square of successive RR interval differences; VLF: Very low frequency; LF: Low frequency; HF: High frequency; LF norm: Low frequency normalized units; HF norm: High frequency normalized units; LF/HF ratio: Low frequency/high frequency ratio; SD of HR: Standard deviation of heart rate; E/I ratio: Expiration/inspiration ratio.

Zsóri G, Illés D, Terzin V, et al. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review. Pancreatology. 2018;18(5):559–565.

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