Longitudinal assessment of pancreatic exocrine dysfunction in type 1 diabetes

Table 1 Characteristics and outcomes

Clinical characteristics and FEC	Time 1, n = 106
Baseline characteristics
Age (year)	46.2 ± 11.8
Male sex	53 (50)
Smoking	29 (27.3)
Alcohol	19 (17.9)
DM characteristics and control
DM duration in years	19.3 ± 9.7
HbA1c (%)	7.8 ± 1
DM-related complications1	45 (42.5)
Retinopathy	42 (39.6)
Kidney disease	18 (17)
Neuropathy	15 (14.2)
Cardiovascular disease	1 (0.9)
Peripheral artery disease	3 (2.8)
Fecal elastase concentration (µg/g), median (IQR)	239.5 (266)
> 200	62 (58.5)
100-200	21 (19.8)
< 100	23 (21.7)
Gastrointestinal symptoms
No	66 (62.3)
Yes2	40 (37.7)
Diarrhea	6 (5.7)
Abdominal pain	5 (4.7)
Dyspepsia	33 (31.1)
Nutritional status
BMI (kg/m2)	25.2 ± 4.4

¹Some patients presented more than one diabetes-related complication.

²Some patients reported more than one symptom.

Data were showed as mean ± SD or n (%). FEC: Fecal elastase concentration; BMI: Body mass index; DM: Diabetes mellitus; HbA1c: Glycated hemoglobin; IQR: Interquartile range (Q1-Q3).

Table 2 Baseline nutritional parameters

Clinical and blood nutritional parameters	Valid cases	mean ± SD	Below normal limit, n (%)
BMI (kg/m2)	106	25.2 ± 4.4	1 (0.9)
Hemoglobin (g/dL)	106	14.1 ± 1.3	4 (3.8)
Mean corpuscular volume (fL)	106	92.6 ± 5.9	2 (1.9)
Lymphocytes (× 109/L)	106	1842 ± 524	1 (0.9)
Prothrombin activity (%)	105	98.3 ± 4	0
Total proteins (g/dL)	106	6.97 ± 0.42	5 (4.7)
Albumin (g/dL)	106	4.38 ± 0.28	0
Prealbumin (mg/dL)	102	20.9 ± 4.7	50 (49)
Retinol-binding protein (mg/dL)	101	3.2 ± 1.2	48 (47)
Transferrin (mg/dL)	103	233 ± 42	6 (5.8)
Ferritin (µg/L)	103	92 ± 88	16 (15.1)
Cholesterol (mg/dL)	106	181 ± 34	1 (0.9)
Triglycerides (mg/dL)	105	68 ± 33	0
Folic acid (µg/L)	104	11.5 ± 4.7	2 (1.9)
Cobalamin (ng/L)	104	444 ± 259	7 (6.7)
Vitamin A (mg/L)	100	0.38 ± 0.17	12 (12)
Vitamin D (ng/L)	99	25 ± 10	32 (32.3)
Vitamin E (mg/dL)	100	1.34 ± 0.34	0
Phosphate (mg/dL)	106	3.6 ± 0.6	5 (4.7)
Calcium (mg/dL)	106	10.2 ± 7.7	1 (0.9)
Iron (mg/dL)	103	84 ± 34	20 (19.4)
Zinc (µg/dL)	97	76 ± 14	6 (6.2)
Magnesium (mg/dL)	101	1.89 ± 0.19	1 (0.9)

Some tests were not available in a subset of patients. BMI: Body mass index.

Table 3 Univariate and multivariate analysis of risk factors and clinical characteristics for low fecal elastase concentration

Variables	Univariate analysis			Multivariate analysis
	Normal FEC, n = 62	Abnormal FEC, n = 44	P value	OR	95%CI	P value
Age (year)	45.1 ± 11.7	47.3 ± 11.8	0.364
Male sex	26 (41.9)	27 (61.4)	0.049	3.14	1.30-8.06	0.013
Female sex	36 (58.1)	17 (38.6)
Smoking	13 (21)	16 (36.4)	0.080
Alcohol	7 (11.3)	12 (27.3)	0.035
DM duration (year)	18.4 ± 10	20.8 ± 10.8	0.244
DM-related complications	19 (30.6)	26 (59.1)	0.004
Retinopathy	17 (27.4)	25 (56.8)	0.002	2.63	1.09-6.44	0.032
Kidney disease	8 (12.9)	10 (22.7)	0.184
Neuropathy	7 (11.3)	8 (18.2)	0.316
Cardiovascular disease	0	1 (2.3)	0.415
Peripheral arteriopathy	1 (1.6)	2 (4.5)	0.569
HbA1c (%)	7.6 ± 0.9	8.1 ± 1.1	0.017	1.83	1.15-3.06	0.015
Gastrointestinal symptoms	27 (43.5)	13 (29.5)	0.143
BMI (kg/m2)	24.7 ± 3.9	26 ± 4.9	0.183
Serum nutritional markers
Hemoglobin (g/dL)	13.9 ± 1.3	14.3 ± 1.2	0.124
Mean corpuscular volume (fL)	92.2 ± 6.5	93.1 ± 5.8	0.449
Lymphocytes (× 106/L)	1713 ± 566	1920 ± 578	0.068
Prothrombin index	98.1 ± 4.1	98.6 ± 4.0	0.491
Total proteins (g/L)	7.0 ± 0.4	6.9 ± 0.4	0.507
Albumin (g/dL)	4.4 ± 0.3	4.4 ± 0.3	0.441
Prealbumin (mg/dL)	20.9 ± 5.4	20.8 ± 3.6	0.880
Retinol binding protein (mg/dL)	3.2 ± 1.3	3.2 ± 1.0	0.864
Transferrin (mg/dL)	232.9 ± 42.2	232.8 ± 42.9	0.995
Ferritin (µg/L)	100.5 ± 96.8	79.2 ± 71.2	0.226
Cholesterol (mg/dL)	180 ± 34.5	182 ± 33	0.798
Triglycerides (mg/dL)	64.3 ± 26.9	62.9 ± 40.4	0.220
Vitamin A (mg/L)	0.4 ± 0.2	0.4 ± 0.1	0.913
Vitamin D (ng/mL)	26.6 ± 10.3	23.7 ± 9.6	0.161
Vitamin E (mg/L)	13.3 ± 3.0	13.6 ± 3.9	0.642
Vitamin B12 (ng/L)	504.5 ± 286	367.5 ± 183	0.006
Folic acid (µg/L)	11.4 ± 5.2	11.7 ± 4.1	0.790
Calcium (mg/L)	9.4 ± 0.4	9.6 ± 0.3	0.027
Iron (mg/dL)	79.6 ± 31.5	91.1 ± 37.5	0.093
Magnesium (mg/dL)	1.9 ± 0.2	1.9 ± 0.2	0.180
Zinc (µg/dL)	75.3 ± 14.5	76.3 ± 13.5	0.742

Data were showed as mean ± SD or n (%). DM: Diabetes mellitus; FEC: Fecal elastase concentration; HbA1c: Glycated hemoglobin; BMI: Body mass index; OR: Odds ratio; 95%CI: 95% confidence interval.

Table 4 Clinical and laboratory characteristics of the patients at both timepoints

Characteristics	Timepoint 1, n = 66	Timepoint 2, n = 66	P value
Age (year)	47 ± 11.2	55.4 ± 11.3	< 0.001
Male sex	29 (44)	29 (44)	1
Female sex	37 (56)	37 (56)
Smoking	17 (25.8)	12 (18.2)	0.125
Alcohol	14 (21.2)	7 (10.6)	0.016
DM duration in years	19.3 ± 9.7	27.6 ± 9.6	< 0.001
DM-related complications	31 (47)	41 (62.1)	0.006
Retinopathy	29 (43.9)	33 (50)	0.344
Kidney disease	12 (18.2)	15 (22.7)	0.375
Neuropathy	9 (13.6)	14 (21.2)	0.063
Cardiovascular disease	1 (1.5)	2 (3)	1
Peripheral arteriopathy	1 (1.5)	4 (6.1)	0.250
HbA1c (%)	7.7 ± 1	7.5 ± 0.8	0.020
Fecal elastase (µg/g), median (IQR)	227.5 (253)	171.5 (246)	0.094
Fecal elastase group (µg/g)			0.035
> 200	39 (59.1)	27 (40.9)
100-200	13 (19.7)	20 (30.3)
< 100	14 (21.2)	19 (28.8)
Gastrointestinal symptoms	25 (37.9)	17 (25.8)	0.077
Dyspepsia	21 (31.8)	15 (22.7)	0.180
Diarrhea	4 (6.1)	3 (4.5)	1
Abdominal pain	3 (4.5)	2 (3)	1
BMI (kg/m2)	25.4 (4.4)	25.8 (4.6)	0.110
Nutritional markers below LLN1
Prealbumin	34 (52.3)	35 (53.8)	0.835
Retinol binding protein	34 (52.3)	20 (31.7)	0.003
Vitamin A	7 (10.8)	2 (3.1)	0.125
Vitamin D	21 (32.8)	37 (56.9)	0.007

¹Only parameters with a frequency of ≥ 10% cases in any of the time points are displayed in the table.

Data were showed as mean ± SD or n (%). DM: Diabetes mellitus; HbA1c: Glycated hemoglobin; BMI: Body mass index; IQR: Interquartile range (Q1-Q3); LLN: Lower limit of normal.