Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Original Article

Volume 10, Number 4, August 2017, pages 224-234

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

Figure 1. Association between GRP and abnormal glucose metabolism in patients after acute pancreatitis. GRP: gastrin-releasing peptide; CI: confidence interval; PR: prevalence ratio.

Figure 2. Associations between GRP and FBG (a) and HbA1c (b). FBG: fasting blood glucose; GRP: gastrin-releasing peptide; HbA1c: glycated hemoglobin A1c.

**Table 1.** Baseline Characteristics of Study Participants
Characteristic	NGM (n = 53)	AGM (n = 30)	Total (n = 83)	P
AGM: abnormal glucose metabolism; AP: acute pancreatitis; BMI: body mass index; FBG: fasting blood glucose; HbA1c: glycated hemoglobin A1c; NGM: normal glucose metabolism. *Data are presented as mean ± standard deviation (SD); †P-values < 0.05.
Age (years)*	47 ± 15	57 ± 13	51 ± 15	0.005†
Sex				0.485
Male	30	20	50
Female	23	10	33
Ethnicity				0.005†
NZ European	29	18	47
Maori	1	5	6
Pacific Islanders	2	1	3
Asian	4	5	9
Other	17	1	18
BMI (kg/m²)*	26.86 ± 4.82	29.93 ± 6.07	27.95 ± 5.46	0.016†
Etiology				0.906
Biliary	24	13	37
Alcohol	12	6	18
Other	17	11	28
Recurrence				0.448
No	40	20	60
Yes	13	10	23
Severity				< 0.001†
Mild	50	18	68
Moderate	2	9	11
Severe/critical	1	3	4
Duration from first attack of AP (months)*	33 ± 30	23 ± 19	30 ± 27	0.112
FBG (mmol/L)*	4.98 ± 0.29	5.87 ± 0.77	5.30 ± 0.67	< 0.001†
HbA1c (mmol/mol)*	33.57 ± 2.62	39.13 ± 3.00	35.58 ± 3.84	< 0.001†

Table 1. Baseline Characteristics of Study Participants

Characteristic

NGM (n = 53)

AGM (n = 30)

Total (n = 83)

AGM: abnormal glucose metabolism; AP: acute pancreatitis; BMI: body mass index; FBG: fasting blood glucose; HbA1c: glycated hemoglobin A1c; NGM: normal glucose metabolism. *Data are presented as mean ± standard deviation (SD); †P-values < 0.05.

Age (years)*

47 ± 15

57 ± 13

51 ± 15

0.005†

Sex

0.485

Male

Female

Ethnicity

0.005†

NZ European

Maori

Pacific Islanders

Asian

Other

BMI (kg/m²)*

26.86 ± 4.82

29.93 ± 6.07

27.95 ± 5.46

0.016†

Etiology

0.906

Biliary

Alcohol

Other

Recurrence

0.448

Yes

Severity

< 0.001†

Mild

Moderate

Severe/critical

Duration from first attack of AP (months)*

33 ± 30

23 ± 19

30 ± 27

0.112

FBG (mmol/L)*

4.98 ± 0.29

5.87 ± 0.77

5.30 ± 0.67

< 0.001†

HbA1c (mmol/mol)*

33.57 ± 2.62

39.13 ± 3.00

35.58 ± 3.84

< 0.001†

**Table 2.** Associations Between Gastrin-Releasing Peptide and Pancreatic Hormones
Pancreatic hormones	Gastrin-releasing peptide
Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Specifically, model 4 for amylin and insulin was adjusted for BMI and recurrence. Model 4 for glucagon was adjusted for age, sex, BMI, recurrence, and duration. Model 4 for pancreatic polypeptide was adjusted for sex, age, BMI, and recurrence. Model 4 for somatostatin was adjusted for age and recurrence.
Amylin
Model 1	-0.001 (-0.006, 0.005)	0.833
Model 2	0.000 (-0.005, 0.004)	0.885
Model 3	-0.001 (-0.005, 0.004)	0.793
Model 4	0.000 (-0.005, 0.005)	0.972
Glucagon
Model 1	-0.004 (-0.007, -0.002)	0.002*
Model 2	-0.004 (-0.006, -0.002)	0.001*
Model 3	-0.005 (-0.007, -0.003)	< 0.001*
Model 4	-0.005 (-0.007, -0.003)	< 0.001*
Insulin
Model 1	-0.001 (-0.004, 0.002)	0.602
Model 2	0.001 (-0.002, 0.004)	0.420
Model 3	0.002 (-0.001, 0.005)	0.249
Model 4	0.001 (-0.002, 0.004)	0.509
Pancreatic polypeptide
Model 1	-0.001 (-0.002, 0.001)	0.225
Model 2	-0.002 (-0.003, 0.000)	0.010*
Model 3	-0.002 (-0.003, -0.001)	< 0.001*
Model 4	-0.001 (-0.003, 0.000)	0.028*
Somatostatin
Model 1	-0.022 (-0.311, 0.267)	0.881
Model 2	-0.013 (-0.278, 0.253)	0.924
Model 3	-0.075 (-0.323, 0.174)	0.557
Model 4	-0.087 (-0.356, 0.183)	0.528

Table 2. Associations Between Gastrin-Releasing Peptide and Pancreatic Hormones

Pancreatic hormones

Gastrin-releasing peptide

β (95% CI)

Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Specifically, model 4 for amylin and insulin was adjusted for BMI and recurrence. Model 4 for glucagon was adjusted for age, sex, BMI, recurrence, and duration. Model 4 for pancreatic polypeptide was adjusted for sex, age, BMI, and recurrence. Model 4 for somatostatin was adjusted for age and recurrence.

Amylin

Model 1

-0.001 (-0.006, 0.005)

0.833

Model 2

0.000 (-0.005, 0.004)

0.885

Model 3

-0.001 (-0.005, 0.004)

0.793

Model 4

0.000 (-0.005, 0.005)

0.972

Glucagon

Model 1

-0.004 (-0.007, -0.002)

0.002*

Model 2

-0.004 (-0.006, -0.002)

0.001*

Model 3

-0.005 (-0.007, -0.003)

< 0.001*

Model 4

-0.005 (-0.007, -0.003)

< 0.001*

Insulin

Model 1

-0.001 (-0.004, 0.002)

0.602

Model 2

0.001 (-0.002, 0.004)

0.420

Model 3

0.002 (-0.001, 0.005)

0.249

Model 4

0.001 (-0.002, 0.004)

0.509

Pancreatic polypeptide

Model 1

-0.001 (-0.002, 0.001)

0.225

Model 2

-0.002 (-0.003, 0.000)

0.010*

Model 3

-0.002 (-0.003, -0.001)

< 0.001*

Model 4

-0.001 (-0.003, 0.000)

0.028*

Somatostatin

Model 1

-0.022 (-0.311, 0.267)

0.881

Model 2

-0.013 (-0.278, 0.253)

0.924

Model 3

-0.075 (-0.323, 0.174)

0.557

Model 4

-0.087 (-0.356, 0.183)

0.528

**Table 3.** Associations Between Gastrin-Releasing Peptide and Gut Hormones
Gut hormones	Gastrin-releasing peptide
Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Specifically, model 4 for cholecystokinin, gastric-inhibitory peptide, gastrin, ghrelin, glucagon-like peptide-1 and 2, oxyntomodulin, secretin, and vasoactive intestinal peptide was adjusted for BMI and recurrence. Model 4 for glicentin was adjusted for BMI, recurrence, and duration. Model 4 for peptide YY was adjusted for age, BMI, recurrence, and duration.
Cholecystokinin
Model 1	0.036 (-0.341, 0.413)	0.852
Model 2	-0.050 (-0.410, 0.310)	0.785
Model 3	-0.021 (-0.372, 0.330)	0.907
Model 4	0.037 (-0.330, 0.404)	0.844
Gastric-inhibitory peptide
Model 1	-0.001 (-0.002, 0.001)	0.223
Model 2	-0.001 (-0.003, 0.000)	0.054
Model 3	-0.002 (-0.004, -0.001)	0.001*
Model 4	-0.001 (-0.003, 0.000)	0.065
Gastrin
Model 1	0.000 (0.000, 0.000)	0.610
Model 2	0.000 (0.000, 0.000)	0.463
Model 3	0.000 (0.000, 0.000)	0.543
Model 4	0.000 (0.000, 0.000)	0.677
Ghrelin
Model 1	-0.011 (-0.025, 0.004)	0.142
Model 2	-0.008 (-0.022, 0.007)	0.302
Model 3	-0.012 (-0.026, 0.001)	0.077
Model 4	-0.010 (-0.024, 0.005)	0.180
Glicentin
Model 1	-0.005 (-0.012, 0.002)	0.175
Model 2	-0.006 (-0.013, 0.001)	0.081
Model 3	-0.007 (-0.014, -0.001)	0.024*
Model 4	-0.004 (-0.010, 0.003)	0.282
Glucagon-like peptide-1
Model 1	0.001 (-0.001, 0.002)	0.322
Model 2	0.000 (-0.001, 0.002)	0.845
Model 3	0.000 (-0.001, 0.002)	0.754
Model 4	0.000 (-0.001, 0.002)	0.588
Glucagon-like peptide-2
Model 1	0.022 (-0.010, 0.054)	0.181
Model 2	0.017 (-0.015, 0.048)	0.300
Model 3	0.016 (-0.015, 0.046)	0.318
Model 4	0.021 (-0.009, 0.051)	0.175
Oxyntomodulin
Model 1	0.005 (-0.007, 0.017)	0.403
Model 2	0.001 (-0.010, 0.013)	0.839
Model 3	0.001 (-0.010, 0.012)	0.840
Model 4	0.004 (-0.007, 0.016)	0.464
Peptide YY
Model 1	-0.001 ( -0.002, 0.000)	0.055
Model 2	-0.001 (-0.002, 0.000)	0.026*
Model 3	-0.002 (-0.003, -0.001)	< 0.001*
Model 4	-0.002 (-0.003, -0.001)	0.003*
Secretin
Model 1	0.088 (-2.688, 2.845)	0.950
Model 2	-0.390 (-2.994, 2.215)	0.769
Model 3	-0.932 (-3.560, 1.696)	0.487
Model 4	-0.097 (-2.722, 2.528)	0.942
Vasoactive intestinal peptide
Model 1	0.351 (-0.271, 0.973)	0.269
Model 2	0.245 (-0.343, 0.833)	0.414
Model 3	0.367 (-0.253, 0.987)	0.246
Model 4	0.497 (-0.082, 1.076)	0.092

Table 3. Associations Between Gastrin-Releasing Peptide and Gut Hormones

Gut hormones

Gastrin-releasing peptide

β (95% CI)

Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Specifically, model 4 for cholecystokinin, gastric-inhibitory peptide, gastrin, ghrelin, glucagon-like peptide-1 and 2, oxyntomodulin, secretin, and vasoactive intestinal peptide was adjusted for BMI and recurrence. Model 4 for glicentin was adjusted for BMI, recurrence, and duration. Model 4 for peptide YY was adjusted for age, BMI, recurrence, and duration.

Cholecystokinin

Model 1

0.036 (-0.341, 0.413)

0.852

Model 2

-0.050 (-0.410, 0.310)

0.785

Model 3

-0.021 (-0.372, 0.330)

0.907

Model 4

0.037 (-0.330, 0.404)

0.844

Gastric-inhibitory peptide

Model 1

-0.001 (-0.002, 0.001)

0.223

Model 2

-0.001 (-0.003, 0.000)

0.054

Model 3

-0.002 (-0.004, -0.001)

0.001*

Model 4

-0.001 (-0.003, 0.000)

0.065

Gastrin

Model 1

0.000 (0.000, 0.000)

0.610

Model 2

0.000 (0.000, 0.000)

0.463

Model 3

0.000 (0.000, 0.000)

0.543

Model 4

0.000 (0.000, 0.000)

0.677

Ghrelin

Model 1

-0.011 (-0.025, 0.004)

0.142

Model 2

-0.008 (-0.022, 0.007)

0.302

Model 3

-0.012 (-0.026, 0.001)

0.077

Model 4

-0.010 (-0.024, 0.005)

0.180

Glicentin

Model 1

-0.005 (-0.012, 0.002)

0.175

Model 2

-0.006 (-0.013, 0.001)

0.081

Model 3

-0.007 (-0.014, -0.001)

0.024*

Model 4

-0.004 (-0.010, 0.003)

0.282

Glucagon-like peptide-1

Model 1

0.001 (-0.001, 0.002)

0.322

Model 2

0.000 (-0.001, 0.002)

0.845

Model 3

0.000 (-0.001, 0.002)

0.754

Model 4

0.000 (-0.001, 0.002)

0.588

Glucagon-like peptide-2

Model 1

0.022 (-0.010, 0.054)

0.181

Model 2

0.017 (-0.015, 0.048)

0.300

Model 3

0.016 (-0.015, 0.046)

0.318

Model 4

0.021 (-0.009, 0.051)

0.175

Oxyntomodulin

Model 1

0.005 (-0.007, 0.017)

0.403

Model 2

0.001 (-0.010, 0.013)

0.839

Model 3

0.001 (-0.010, 0.012)

0.840

Model 4

0.004 (-0.007, 0.016)

0.464

Peptide YY

Model 1

-0.001 ( -0.002, 0.000)

0.055

Model 2

-0.001 (-0.002, 0.000)

0.026*

Model 3

-0.002 (-0.003, -0.001)

< 0.001*

Model 4

-0.002 (-0.003, -0.001)

0.003*

Secretin

Model 1

0.088 (-2.688, 2.845)

0.950

Model 2

-0.390 (-2.994, 2.215)

0.769

Model 3

-0.932 (-3.560, 1.696)

0.487

Model 4

-0.097 (-2.722, 2.528)

0.942

Vasoactive intestinal peptide

Model 1

0.351 (-0.271, 0.973)

0.269

Model 2

0.245 (-0.343, 0.833)

0.414

Model 3

0.367 (-0.253, 0.987)

0.246

Model 4

0.497 (-0.082, 1.076)

0.092

**Table 4.** Associations Between Gastrin-Releasing Peptide and Cytokines
Cytokine	Gastrin-releasing peptide
Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Model 4 for interleukin-6 was adjusted for BMI and recurrence. Model 4 for monocyte chemoattractant protein-1 was adjusted for BMI, recurrence, and duration. Model 4 for tumor necrosis factor α was adjusted for age, BMI, and recurrence.
Interleukin-6
Model 1	-0.001 (-0.006, 0.005)	0.749
Model 2	-0.004 (-0.009, 0.002)	0.211
Model 3	-0.005 (-0.010, 0.001)	0.108
Model 4	0.000 (-0.006, 0.005)	0.901
Monocyte chemoattract protein-1
Model 1	-0.002 (-0.004, 0.000)	0.024*
Model 2	-0.003 (-0.005, -0.001)	0.001*
Model 3	-0.003 (-0.005, -0.002)	< 0.001*
Model 4	-0.002 (-0.004, 0.000)	0.017*
Tumor necrosis factor-α
Model 1	-0.034 (-0.063, -0.005)	0.023*
Model 2	-0.036 (-0.065, -0.007)	0.015*
Model 3	-0.050 (-0.078, -0.023)	< 0.001*
Model 4	-0.039 (-0.069, -0.010)	0.008*

Table 4. Associations Between Gastrin-Releasing Peptide and Cytokines

Cytokine

Gastrin-releasing peptide

β (95% CI)

Data are presented as β coefficients (95% CI). *P-values < 0.05. Model 1 was the unadjusted model. Model 2 was adjusted for age, sex, ethnicity, and BMI. Model 3 was adjusted for age, sex, ethnicity, BMI, etiology, severity, duration, and recurrence. Model 4 was adjusted for those confounders found to be significant in model 3. Model 4 for interleukin-6 was adjusted for BMI and recurrence. Model 4 for monocyte chemoattractant protein-1 was adjusted for BMI, recurrence, and duration. Model 4 for tumor necrosis factor α was adjusted for age, BMI, and recurrence.

Interleukin-6

Model 1

-0.001 (-0.006, 0.005)

0.749

Model 2

-0.004 (-0.009, 0.002)

0.211

Model 3

-0.005 (-0.010, 0.001)

0.108

Model 4

0.000 (-0.006, 0.005)

0.901

Monocyte chemoattract protein-1

Model 1

-0.002 (-0.004, 0.000)

0.024*

Model 2

-0.003 (-0.005, -0.001)

0.001*

Model 3

-0.003 (-0.005, -0.002)

< 0.001*

Model 4

-0.002 (-0.004, 0.000)

0.017*

Tumor necrosis factor-α

Model 1

-0.034 (-0.063, -0.005)

0.023*

Model 2

-0.036 (-0.065, -0.007)

0.015*

Model 3

-0.050 (-0.078, -0.023)

< 0.001*

Model 4

-0.039 (-0.069, -0.010)

0.008*