Serum indicators are measurable factors that reflect the normal physiological state of an organism. For example, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) are biomarkers of liver function; creatinine (Cr) and urea nitrogen are biomarkers of renal function; triiodothyronine (FT3) and free thyroxine (FT4) are biomarkers of thyroid function; and high-density lipoprotein (HDL), low-density protein (LDL), glucose, and glycosylated hemoglobin (HbA1C) are related to metabolic function. Some biomarkers of gastric function, such as pepsinogen (PG), have also been recognized. PGI is produced in the stomach by the body and fundus, and PGII is produced primarily in the oxyntic gland mucosa of the stomach, the gastric antrum, and the duodenum. Several studies have found that PGI and PGII are secreted into the gastric lumen and 1% of them are also leaked into circulating blood [
Interactions between organs are vital for allowing the body to adjust the function of each organ according to the needs of the body as a whole. Associations between serological indicators reflecting different organ functions are thus also important for revealing intrinsic links between different organs. Changes in gastric function may affect absorption, resulting in malnutrition and a consequent decline in immune function, thus increasing susceptibility to other diseases [
This retrospective study was conducted during 2009 to 2012 at The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province. A total of 823 participants (518 men, 305 women; median age, 49 years; range 25–84) from the health checkup center of the hospital were enrolled in the study. All the participants have the information of PGI, PGII, gastrin-17 and blood glucose, lipids (glucose, triglyceride (TG), LDL, and HDL) and kidney function (Cr and urea nitrogen), liver function (ALT and ALP), thyroid function (FT3, FT4, TSH, TPOAb, and thyroglobulin antibody (TGAb)). However, information on HbA1C was only acquired for 57 participants.
The collection of data from the laboratory information system was approved by the Human Ethics Review Committee of The First Affiliated Hospital of China Medical University (Shenyang, China). Written or verbal consent was not considered necessary for the secondary use of data and because the data analyzed were deidentified.
We compared the concentrations of gastric function indicators among participants grouped according to the quartiles of extragastric indicators’ levels. All statistical analyses were performed with SPSS version 13.0 software (SPSS, Chicago, IL, USA). The distribution of variables was assessed by the Kolmogorov-Smirnov test. Non-normally distributed variables were analyzed using the median and interquartile range. An ordinal logistic regression model was applied to analyze the relationships between gastric function and other biomarkers among the three groups adjusted for sex, age, and
A total of 823 patients with serum indicators of gastric and extragastric functions were included. The distributions and normal reference ranges of the selected characteristics are shown in Table
Baseline characteristics.
Parameters | Median (interquartile range) | Normal range | Minimum and maximum value | Kolmogorov-Smirnov test |
---|---|---|---|---|
sPGI (microg/L) | 94.9 (73–119.4) | 70–150 | 13.9, 583.4 | 0.000 |
sPGII (microg/L) | 7.5 (5.3–12) | ≥10.25 | 1.3, 98.1 | 0.000 |
PGI/II | 12.06 (8.9–15.45) | ≥7 | 1.52, 53 | 0.023 |
sG17 (pmol/L) | 2.2 (0.9–5.9) | ≤5 | 0.0, 150.1 | 0.000 |
Cr ( |
68 (56–77) | 59–104 | 37, 394 | 0.000 |
Ure (mmol/L) | 5.18 (4.45–6.1) | 2.85–7.14 | 2.31, 15.28 | 0.003 |
ALT (U/L) | 21 (15–32) | 9–50 | 6, 765 | 0.000 |
ALP (U/L) | 67 (56–79) | 45–125 | 30, 208 | 0.000 |
FT3 (pmol/L) | 4.64 (4.26–5.0) | 2.63–5.70 | 2.79, 39.63 | 0.000 |
TSH (mIU/L) | 1.63 (1.13–2.37) | 0.35–4.94 | 0.00, 65.58 | 0.000 |
TPOAb (IU/mL) | 0.29 (0.09–0.78) | 0.00–5.61 | 0.00, 952.8 | 0.000 |
TGAb (IU/mL) | 1.2 (0.71–2.58) | 0.00–4.11 | 0.00, 908.3 | 0.000 |
TG (mmol/L) | 1.43 (0.96–2.14) | 0.00–1.70 | 0.31, 32.92 | 0.000 |
HDL (mmol/L) | 1.23 (1.04–1.46) | 0.91–1.92 | 0.52, 2.91 | 0.000 |
LDL (mmol/L) | 3.2 ± 0.84 | 0.00–3.64 | 0.35, 7.41 | 0.195 |
Glu (mmol/L) | 5.53 (5.19–6.17) | 3.90–6.10 | 4.07, 18.24 | 0.000 |
HbA1C (mmol/mol) | 6.68 ± 1.49 | 3.90–6.10 | 4.8, 11.9 | 0.053 |
Serum PGI, PGII, PGI/II, and gastrin-17 concentrations across four Cr or urea nitrogen levels are shown in Table
The correlations between gastric function indicators and Cr and urea nitrogen levels in serum.
Gastric function | Cr level quartilesa |
|
Urea level quartilesb |
| ||||||
---|---|---|---|---|---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( |
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | |||
PGI | 79.7 (66.6–109.75) | 92.75 (72.3–119.73) | 96.65 (75.15–117.55) | 105.15 (80.9–129.8) | 0.044 | 86.15 (67.43–110.45) | 96.2 (73.4–121.88) | 94.4 (72.2–115.7) | 99.8 (80.4–129.5) | 0.305 |
PGII | 6.5 (4.86–10.75) | 7.81 (5.1–12.45) | 7.75 (5.5–12.3) | 8.4 (5.8–13.23) | 0.024 | 7.2 (5.0–11.7) | 7.25 (5.4–11) | 7.4 (5.0–13.1) | 8.25 (5.73–12.2) | 0.160 |
PGI/II | 11.97 (8.52–15.62) | 12.03 (8.79–15.14) | 12.03 (9.05–15.46) | 12.27 (9.27–15.67) | 0.047 | 11.89 (8.47–14.93) | 12.67 (9.35–15.86) | 11.68 (8.35–15.15) | 12.3 (9.1–15.7) | 0.993 |
G17 | 2.4 (0.98–6.6) | 2.45 (0.94–5.73) | 1.78 (0.69–5.34) | 2.18 (0.8–6.63) | 0.101 | 1.65 (0.85–5.64) | 2.05 (0.78–5.2) | 2.9 (0.8–7.6) | 2.55 (1.0–5.9) | 0.416 |
Cr: creatinine.
bQuartile 1 (2.31–4.45 mmol/L); quartile 2 (4.46–5.18 mmol/L); quartile 3 (5.19–6.10 mmol/L); quartile 4 (6.11–15.28 mmol/L).
The values listed in the table are median and interquartile range.
Serum PGI, PGII, PGI/II, and gastrin-17 concentrations across four serum ALT and ALP levels are shown in Table
The correlation between gastric function indicators and ALT and ALP levels in serum.
Gastric function | ALT level quartilesa |
|
ALP level quartilesb |
| ||||||
---|---|---|---|---|---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( |
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | |||
PGI | 89.7 (69.9–115.85) | 97.95 (76.08–121.7) | 96.2 (72.28–121.7) | 95.3 (72.3–119.4) | 0.923 | 89 (70.3–118.5) | 95.95 (77.05–116.48) | 96.7 (73–123.85) | 95.5 (73.65–122.88) | 0.397 |
PGII | 7.25 (5.18–13.03) | 7.6 (5.53–11.53) | 7.21 (5.18–12.13) | 7.8 (5.1–12) | 0.640 | 7.3 (5.0–12.5) | 7.2 (5.3–11) | 8.05 (5.58–12.6) | 7.6 (5.3–12.03) | 0.331 |
PGI/II | 11.69 (8.01–15.29) | 12.41 (9.56–15.7) | 12.17 (8.59–15.05) | 12.1 (8.9–15.64) | 0.639 | 12.04 (8.57–15.69) | 12.92 (9.13–15.67) | 11.64 (8.76–15.37) | 11.98 (8.9–15.3) | 0.947 |
G17 | 2.28 (0.9–6.63) | 2.35 (0.86–5.55) | 2.35 (0.83–6.14) | 1.9 (0.9–5.4) | 0.267 | 2.1 (0.6–5.7) | 1.65 (0.8–5.38) | 2.6 (1.14–6.36) | 2.53 (0.99–6.31) | 0.146 |
ALT: aminotransferase; ALP: alkaline phosphatase.
aQuartile 1 (6–15 U/L); quartile 2 (16–22 U/L); quartile 3 (23–32 U/L); quartile 4 (33–765 U/L).
bQuartile 1 (30–56 U/L); quartile 2 (57–67 U/L); quartile 3 (68–79 U/L); quartile 4 (80–208 U/L).
The values listed in the table are median and interquartile range.
Serum PGI, PGII, PGI/II, and gastrin-17 concentrations across four serum levels of T3, T4, TSH, TPOAb, and TGAb levels are shown in Table
(a) The correlation between gastric function indicators and T3 and T4 levels in serum. (b) The correlation between gastric function parameters and TSH, TPOAb, and TGAb levels in serum.
Gastric function | T3 level quartilesa |
| |||
---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
PGI | 94.2 (72.2–121.9) | 92.5 (71.23–112) | 94.9 (75.55–122.45) | 96.15 (72.4–119.95) | 0.399 |
PGII | 7.2 (5.3–13.1) | 7 (5–10.77) | 8.15 (5.63–12.9) | 8.15 (5.2–12.23) | 0.629 |
PGI/II | 12.15 (8.73–16.08) | 12.7 (9.39–15.89) | 11.47 (8.83–14.59) | 12.01 (8.74–15.52) | 0.094 |
G17 | 2.6 (0.9–5.7) | 2.08 (0.9–5.26) | 2.3 (0.81–7.7) | 1.95 (0.9–6.05) | 0.151 |
|
|||||
Gastric function | T4 level quartilesb |
| |||
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
|
|||||
PGI | 96.1 (73–119.8) | 91.8 (73–113.3) | 92.7 (72.9–117.7) | 98.85 (72.78–127) | 0.506 |
PGII | 7.6 (5.2–12.3) | 6.7 (5.25–11.1) | 7.7 (5.3–12.2) | 7.96 (5.5–12.55) | 0.542 |
PGI/II | 12.2 (8.9–15.31) | 12.38 (9.44–15.59) | 12.31 (8.36–15.61) | 11.82 (8.64–15.55) | 0.820 |
G17 | 2.55 (0.8–5.9) | 2.1 (0.9–5.08) | 2.1 (0.8–5.8) | 2.28 (0.95–7.6) | 0.059 |
T3: triiodothyronine; T4: tetraiodothyroxide.
aQuartile 1 (2.79–4.26 pmol/L); quartile 2 (4.27–4.64 pmol/L); quartile 3 (4.65–5.00 pmol/L); quartile 4 (5.01–39.63 pmol/L).
bQuartile 1 (7.31–13.22 U/L); quartile 2 (13.23–14.28 U/L); quartile 3 (14.29–15.44 U/L); quartile 4 (15.45–40.89 U/L).
The values listed in the table are median and interquartile range.
Gastric function | TSH level quartilesc |
| |||
---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
PGI | 98.35 (75.65–122) | 95.05 (72.8–117.9) | 91.7 (71.68–122.45) | 90.8 (71.8–119.4) | 0.516 |
PGII | 8.15 (5.68–13.53) | 7.8 (5.5–11.4) | 7 (5–11.7) | 6.9 (5.1–12) | 0.093 |
PGI/II | 11.54 (8.38–15.34) | 12.05 (9.5–15.1) | 12.09 (9.07–15.6) | 12.68 (8.93–15.53) | 0.047 |
G17 | 2.88 (1.09–7.35) | 2.7 (1.04–5.3) | 1.78 (0.76–6.18) | 2 (0.7–5.3) | 0.334 |
|
|||||
Gastric function | TPOAb level quartilesd |
| |||
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
|
|||||
PGI | 100.85 (75.1–125.78) | 93.1 (74.05–118) | 96.9 (73.33–124.75) | 84 (68.98–111.4) | 0.008 |
PGII | 7.8 (5.5–11.9) | 7.3 (5.1–12) | 8.65 (5.7–14.08) | 6.95 (5–10.78) | 0.420 |
PGI/II | 12.86 (9.63–15.8) | 12.13 (8.97–15.54) | 11.08 (8.07–14.49) | 12.17 (9.33–15.57) | 0.58 |
G17 | 2.63 (1.04–6.3) | 2.05 (0.73–5.43) | 2.58 (1.1–6.75) | 1.83 (0.6–5.39) | 0.990 |
|
|||||
Gastric function | TGAb level quartilese |
| |||
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
|
|||||
PGI | 92.9 (72.2–121.45) | 98.65 (77.08–121.83) | 92.4 (74.55–120.85) | 91.7 (69.2–118.25) | 0.23 |
PGII | 8.4 (5.1–12.38) | 7.8 (5.68–12.53) | 7.3 (5.15–11.05) | 6.8 (5.2–11.68) | 0.37 |
PGI/II | 11.88 (8.78–15.02) | 12.51 (9.17–15.57) | 12.04 (8.92–15.96) | 12.09 (8.56–15.29) | 0.21 |
G17 | 2.98 (1.11–7.28) | 2.1 (0.99–5.31) | 2.05 (0.8–5.55) | 1.83 (0.7–5.35) | 0.07 |
TSH: thyroid stimulating hormone; TPOAb: thyroid peroxidase antibody; TGAb: thyroglobulin antibody.
cQuartile 1 (0–1.13 mIU/L); quartile 2 (1.14–1.63 mIU/L); quartile 3 (1.64–2.37 mIU/L); quartile 4 (2.38–65.58 mIU/L).
dQuartile 1 (0–0.10 IU/mL); quartile 2 (0.11–0.29 U/mL); quartile 3 (0.30–0.78 U/mL); quartile 4 (0.79–952.8 IU/mL).
eQuartile 1 (0–0.7 IU/mL); quartile 2 (0.72–1.20 IU/mL); quartile 3 (1.21–2.58 IU/mL); quartile 4 (2.59–908.3 IU/mL).
Serum PGI, PGII, PGI/II, and gastrin-17 concentrations across four serum levels of TG, HDL, and LDL are shown in Table
The correlation between gastric function parameters and TG, LDL, and HDL levels in serum.
Gastric function | TG level quartilesa |
| |||
---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
PGI | 89.15 (69.18–113.78) | 98 (74–126) | 95.3 (73.9–121.85) | 96.1 (73.35–123.15) | 0.8 |
PGII | 6.7 (4.98–11.63) | 7.7 (5.6–13.7) | 7.6 (5.35–11.4) | 8.3 (5.3–12) | 0.75 |
PGI/II | 12.31 (8.86–15.65) | 11.81 (8.39–15.3) | 12.21 (8.97–15.55) | 12.13 (9.37–15.42) | 0.48 |
G17 | 1.73 (0.78–4.85) | 2.1 (0.85–6.7) | 2.35 (0.8–6.1) | 2.7 (1.1–6.85) | 0.04 |
|
|||||
Gastric function | LDL level quartilesb |
| |||
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
|
|||||
PGI | 98.25 (75.78–125.53) | 89.3 (70.9–119.25) | 91.85 (72.18–112.35) | 96.55 (72.48–123.4) | 0.045 |
PGII | 8.25 (5.73–12.4) | 7.22 (5.1–12.25) | 7.25 (5.2–11.73) | 7.34 (5.13–11.95) | 0.165 |
PGI/II | 12.00 (8.91–14.95) | 12.3 (8.92–15.82) | 11.94 (8.84–15.32) | 12.12 (8.92–15.67) | 0.29 |
G17 | 2.38 (1–5.49) | 2.2 (0.83–6.8) | 2.05 (0.89–5.71) | 2.38 (0.8–6) | 0.412 |
|
|||||
Gastric function | HDL level quartilesc |
| |||
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | ||
|
|||||
PGI | 95.7 (73.58–123.4) | 97.7 (73.7–120.4) | 95 (74.05–122.1) | 89.7 (69.9–114) | 0.57 |
PGII | 7.8 (5.3–11.3) | 8.3 (5.2–13.1) | 7.1 (5.3–13) | 7 (5.1–11.25) | 0.92 |
PGI/II | 12.66 (9.9–15.83) | 11.63 (8.34–15.33) | 12.18 (8.96–15.49) | 11.86 (8.54–15.31) | 0.170 |
G17 | 2.1 (0.94–6.23) | 2.55 (0.95–6.6) | 2.1 (0.73–6.45) | 2.3 (0.85–4.88) | 0.13 |
TG: triglyceride; LDL: low-density lipoprotein, HDL: high-density lipoprotein.
aQuartile 1 (0.31–0.96 mmol/L); quartile 2 (0.97–1.42 mmol/L); quartile 3 (1.43–2.12 mmol/L); quartile 4 (2.13–32.92 mmol/L).
bQuartile 1 (0.35–2.66 mmol/L); quartile 2 (2.67–3.15 mmol/L); quartile 3 (3.16–3.69 mmol/L); quartile 4 (3.70–7.41 mmol/L).
cQuartile 1 (0.52–1.04 mmol/L); quartile 2 (1.05–1.23 mmol/L); quartile 3 (1.24–1.46 mmol/L); quartile 4 (1.47–2.91 mmol/L).
Serum PGI, PGII, PGI/II, and G17 concentrations across four serum levels of glucose and HbA1C are shown in Table
The correlation between gastric function indicators and Glu and HbA1C levels in serum.
Gastric function | Glu level quartilesa |
|
HbA1C level quartilesb |
| ||||||
---|---|---|---|---|---|---|---|---|---|---|
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( |
Q1 ( |
Q2 ( |
Q3 ( |
Q4 ( | |||
PGI | 91.95 (72.88–116.5) | 95.2 (72.6–116.03) | 94.3 (72.63–122.73) | 96.1 (73.1–123.8) | 0.191 | 97.1 (87.1–121.6) | 103.1 (83.58–137.73) | 108 (77.6–137) | 86.5 (70.2–127.05) | 0.723 |
PGII | 7.0 (5.4–11.45) | 7.8 (5.5–12.98) | 7.5 (5.3–13.03) | 7.38 (5–11.5) | 0.125 | 9.81 (5.89–13.4) | 9.66 (6.75–12.52) | 7.7 (5.6–13.4) | 7.6 (4.9–10.86) | 0.153 |
PGI/II | 11.98 (9.35–15.31) | 11.75 (8.48–15) | 11.98 (8.67–15.33) | 12.67 (9.29–16.39) | 0.016 | 9.9 (7.29–13.4) | 11.81 (9.62–13.71) | 13.02 (11.1–15) | 13.54 (12.05–16.22) | 0.046 |
G17 | 2.05 (0.95–5.4) | 2.35 (0.8–6.28) | 2.1 (0.8–6.63) | 2.4 (0.9–5.5) | 0.608 | 1.85 (0.6–5.9) | 3.78 (0.4–5.74) | 2.6 (0.5–5.4) | 1.9 (0.9–6.2) | 0.549 |
Glu: glucose; HbA1C: glycated hemoglobin.
aQuartile 1 (4.07–5.19 mmol/L); quartile 2 (5.20–5.53 mmol/L); quartile 3 (5.54–6.17 mmol/L); quartile 4 (6.18–18.24 mmol/L).
bQuartile 1 (4.8–5.6 mmol/L); quartile 2 (5.7–6.1 mmol/L); quartile 3 (6.2–7.2 mmol/L); quartile 4 (7.3–11.9 mmol/L).
The present study explored the correlations between serum indicators of gastric function, including PGI, PGII, PGI/II, and gastrin-17, and multiple serum biomarkers of extragastric functions in a Chinese health checkup population. Our results suggest that serum PG and G17 levels were associated with kidney function, thyroid function, blood glucose, and lipids but not with liver function. To date, just one similar article had been published in a Japanese population, which investigated the relationship just only between PGI/II ratio and limited extragastric indicators including glucose, triacylglycerol, uric acid, cholinesterase, and hemoglobin [
Serum indicators including PGI, PGII, and G-17 may reflect the morphologic and functional changes in the stomach, and their use as “serological biopsy” for gastric diseases has been reported for over 20 years [
Cr and urea nitrogen are useful and inexpensive method of evaluating renal dysfunction. A high serum Cr concentration may indicate a failure of diseased kidneys to filter Cr from the blood effectively. A previous study also found that serum PG I concentrations were elevated as the renal function declined [
An immunological association between autoimmune thyroid diseases (AITD) and autoimmune gastritis (AIG) was first suggested in the early 1960s [
Gastrointestinal hormones have function to optimize the process of intestinal digestion and absorption of nutrients [
In accordance with some previous studies, our results showed that the serum PGI/II ratio was positively associated with glucose and HbA1C levels. Tanaka et al. demonstrated that a lack of gastric acid in AG influences the absorption of a variety of nutrients. Sipponen and Härkönen showed that AG may be a risk factor for malabsorption of dietary and supplementary calcium and may therefore increase the risk of osteoporosis on the long term [
There were several limitations to our study. First, although the correlations between serum indicators of gastric and extragastric functions were adjusted by sex, age, and
In conclusion, our results suggest that serum PG and G17 levels were associated with blood glucose and lipids and kidney function thyroid function but not with liver function. Serum indicators reflecting gastric function may correlate not only with primary diseases, but also with other extragastric diseases.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Yuehua Gong and Wei Wang contributed equally to this work.
This research is supported by grants from The National Basic Research Development Program of China (973 Program no. 2010CB529304) and Science Technology Project in Liaoning Province (nos. 2007225001-1 and 2011225002).