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Risk of acute pancreatitis in type 2 diabetes and risk reduction on anti-diabetic drugs: a population-based cohort study in Taiwan

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Risk and Preventive Medication of Acute Pancreatitis in Patients with Type 2 Diabetes Mellitus in Taiwan: A

Population-based Cohort Study

Journal: American Journal of Gastroenterology Manuscript ID: AJG-10-2337

Manuscript Type: Original Contributions Keywords: Pancreas, Diabetes Manuscript Section: Pancreatic

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Type of manuscript:Original clinical study

Manuscript title: Risk and Preventive Medication of Acute Pancreatitis in Patients with Type 2 Diabetes Mellitus in Taiwan: A Population-based Cohort Study

Shih-Wei Lai, M.D.1; Chih-Hsin Muo, MS2; Kuan-Fu Liao, M.D.3; Fung-Chang Sung, Ph.D., MPH2; Pei-Chun Chen, Ph.D., MSPH2;

Running head:Acute pancreatitis and Type 2 diabetes mellitus

Current Author Addresses:

1Department of Family Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung city, 404, Taiwan

2Department of Public Health and Management Office for Health Data, China Medical University, No. 91, Hsueh-Shih Road, Taichung city, 404, Taiwan

3Department of Internal Medicine, Taichung Tzu Chi General Hospital, No.66, Sec. 1, Fongsing Rd., Tanzih Township, Taichung County, 427, Taiwan

Corresponding author:

Pei-Chun Chen, Ph.D., MSPH Assistant Professor

Department of Public Health

China Medical University College of Public Health No.91, Hsueh-Shih Road, Taichung city, 404, Taiwan Phone: 886-4-2205-3366 ext 2119; fax: 886-4-2205-4070 E-mail: peichun@mail.cmu.edu.tw

Word count: 249 in abstract, 2163 in text, 4 tables, 1 figure and 19 references

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Study Highlights

Type 2 DM increases the risk of acute pancreatitis. Anti-diabetic drugs can reduce the risk.

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Abstract

Objectives. To assess the risk and preventive medication of acute pancreatitis for

patients with Type 2 diabetes mellitus (DM).

Methods. From the claims data of one million randomly sampled from 23 million enrollees of

the Taiwan National Health Insurance, we identified 19,518 adult patients with newly diagnosed

Type 2 DM in 2000–2005. We also identified 78,072 patients without the disease, frequency

matched with sex and age during the same period as controls. Both groups were followed up until

the end of 2008 to measure the incidences of acute pancreatitis and the effectiveness of

anti-diabetes medication in reducing the risk.

Results. Both cohorts were similar in sex and age distributions. Patients with Type 2

DM had an incidence rate of acute pancreatitis 1.95-fold greater than non-diabetics

(27.7 vs. 14.2 per 10,000 person-years). Results of the multivariable Cox model

analysis showed a slightly decreased hazard ratio (HR) of 1.89 (95% confidence

interval (CI) = 1.65–2.18). Alcoholism (HR = 6.92, 95% CI = 3.28–14.6), gallstones

(HR = 2.52, 95% CI = 1.35–4.72), and hepatitis C infection (HR = 3.35, 95% CI =

1.72–6.52) were also significant factors predicting acute pancreatitis. Patients taking

biguanides, sulfonylureas, thiazolidinediones, or alpha-glucosidase inhibitors were

benefited with 37% to 56% of risk reduction of the disease.

Conclusions. There is a higher risk of acute pancreatitis in patients with Type 2 DM

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in Taiwan. Alcoholism, gallstones, and hepatitis C infection are the other risk factors

for the disease. Anti-diabetic drugs can reduce the risk.

Key words: acute pancreatitis; alcoholism; gallstones; Type 2 diabetes mellitus

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Introduction

Acute pancreatitis is a condition of pancreatic inflammation with varied incidence

among populations. In a systematic review, Yadav et al. [1] found that the annual

incidence of acute pancreatitis ranged 4.2–45.3 per 100,000 in Europeans from

1966–2005. The annual incidence in California increased from 33.2 per 100,000 in

1994 to 43.8 per 100,000 in 2001 [2]. Fagenholz et al. [3] found that the

hospitalization rate for acute pancreatitis in the US increased from 40 per 100,000 in

1988 to 70 per 100,000 in 2003. Clinically, acute pancreatitis is often associated with

significant co-morbidity and substantial mortality rates. The overall fatality of the

disease ranges approximately from 2%–5% [3–5].

The etiology of acute pancreatitis is undoubtedly multifactorial. Extant

epidemiological studies have shown that gallstones, hypertriglyceridemia, obesity,

viral hepatitis, and lifestyle are significant factors associated with acute pancreatitis

[6–9]. Two large cohort studies have demonstrated that patients with Type 2 diabetes

mellitus (DM) are at a higher risk for acute pancreatitis [9,10]. The retrospective

cohort analysis of the US claims data found a 2.83-fold greater risk of acute

pancreatitis for Type 2 DM patients than non-DM persons [10]. The analysis of the

UK General Practice Research Database also showed a 1.49-fold increased risk for

Type 2 DM patients [9]; however, both cohort studies were limited to Western

populations and had no data on preventive measures.

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The prevalence of DM in Taiwan was approximately 8.2%–11.4% in 1986–2002

[11–13]. Since 2009, the disease has become the fifth leading cause of death [14]. No

cohort study has explored the association between acute pancreatitis and Type 2 DM

in Asian populations. Assessment of this association requires a large population size.

We took the advantage of a large dataset available from the National Health Insurance

(NHI) program in Taiwan to conduct a follow-up assessment of this association. We

estimated the incidence of acute pancreatitis among patients with Type 2 DM relative

to a population without diabetes. We also characterized other risk factors associated

with acute pancreatitis, and investigated whether anti-diabetic drugs are beneficial in

reducing risk.

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Materials and Methods

Data sources

The NHI program was reformed from 13 insurance-related systems of Taiwan in

March 1995. By the end of 2008, this insurance program covered more than 99% of

the entire population of Taiwan (23 million) [15]. We obtained a dataset of

reimbursement claims from the National Health Research Institutes (NHRI), which

manages the NHI databank. The dataset represented the registry of a randomly

sampled cohort of one million people enrolled in the NHI system with claims from

1996–2008. This dataset included information on ambulatory cares, in-patient care,

dental services, prescription drugs, medical institutions, physicians, and registration

entries, with individual personal identification coded for public access. Limited data

on personal socio-demographic status, such as sex, birth date, affiliation to insured

occupational group, income level for insurance fee estimate, and residential area, were

also available.

Criteria and definition

The criteria of diseases were defined according to the International Classification of

Diseases 9th Revision, Clinical Modification (ICD-9-CM). We used a retrospective

cohort design to identify patients aged 20 and older newly diagnosed with Type 2 DM

(ICD-9 codes 250 x 0 or 250 x 2) and currently using anti-diabetic drugs in

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2000–2005. The anti-diabetes drugs included biguanides, sulfonylureas,

thiazolidinediones, alpha-glucosidase inhibitors, D-phenylalanine derivatives,

dipeptidyl peptidase 4 inhibitors, incretin mimetic agents, and insulin. For each DM

case, we randomly selected four persons without medical claims for diabetes

frequency matching with age (every five-year span) and sex in the same time period.

Patients with known history of pancreatic cancer, chronic pancreatitis, Type 1 DM,

and gestational diabetes were excluded from this study. To measure the incidence of

acute pancreatitis (ICD-9 codes 577.0), both Type 2 diabetic and non-diabetic cohorts

were followed up until the end of 2008, or were censored because of death or

withdrawal from the insurance program. The entry study index date for a study

subject was defined by the date the individual was identified from the claims data.

Statistical analysis

We estimated the incidence rate as the number of acute pancreatitis identified and

divided by the total follow-up person-years for each cohort by sex, specific age, and

follow-up years. Cox proportional hazard analysis was used to estimate the hazard

ratio (HR) of acute pancreatitis and 95% confidence intervals (CI) for patients with

Type 2 DM compared with non-DM people. Univariate and multivariate models were

used to assess the risk levels associated with demographic factors and co-morbidities

identified in the baseline. The potential co-morbidities included obesity,

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hypertriglyceridemia, alcoholism, gallstones, hepatitis B infection, and hepatitis C

infection. Data analyses also compared the risk of acute pancreatitis associated with

anti-diabetes medication. The statistical significance level was set at two-sided

probability value of < 0.05. All analyses used the SAS software version 9.1 (SAS

Institute Inc., Cary, North Carolina).

Ethical considerations

All individual personal data in the insurance reimbursement claims data were

scrambled to secure patient privacy for public access. This study was exempted from

a full review by the Institution Review Board.

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Results

Baseline characteristics of the study population

Eligible study subjects consisted of 19,518 patients in Type 2 diabetic cohort and

78,072 persons in non-diabetic cohort, with similar sex and age distributions and

mean ages of 56.7 years (Table 1). The Type 2 diabetic cohort had higher prevalence

of obesity, hypertriglyceridemia, alcoholism, gallstones, hepatitis B, and hepatitis C

infections at the baseline (P < 0.0001).

During the follow-up period, the incidence of acute pancreatitis was 1.95-fold greater

in Type 2 diabetic cohort than in non-diabetic cohort (27.7 vs. 14.2 per 10,000

person-years), with the adjusted HR decreased slightly to 1.89 (Table 2). The

sex-specific hazard ratio (HR) shows that men were at higher risk than women. The

age-specific HR was higher in Type 2 diabetic subjects aged 20–39 years (HR = 5.48,

95% CI = 3.64–8.25), followed by aged 40–64 (HR = 2.02, 95% CI = 1.66–2.45), and

aged 65 years and older (HR = 1.34, 95% CI = 1.05–1.71), compared with

non-diabetic age-matched group. The risk of acute pancreatitis was higher in patients

with a diabetic duration of more than five years (HR = 2.40, 95% CI = 1.78–3.25).

The cumulative incidence of acute pancreatitis was twofold higher in diabetic patients

than the non-diabetic group during the entire follow-up period, and the difference

increased with follow-up time (Figure 1).

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Co-morbidity and acute pancreatitis by univariate and multivariate Cox

proportional hazard analysis

Adjusted hazard ratios and 95% confidence intervals of acute pancreatitis associated

with Type 2 DM and co-morbidities are shown in Table 3. The age- and sex-adjusted

HR of acute pancreatitis for patients with Type 2 DM was reduced slightly to 1.89

(95% CI = 1.65–2.18). Hyperlipidemia, alcoholism, gallstones and hepatitis C

infection were identified as co-morbidities independently associated with acute

pancreatitis. The risk increased further for the diabetic patients with alcoholism (HR =

6.92, 95% CI = 3.28–14.6) and hepatitis C infection (HR = 3.35, 95% CI = 1.72–6.52),

but not hyperlipidemia and gallstones.

Influence of anti-diabetic drugs on the risk of acute pancreatitis

Table 4 shows the effectiveness of taking anti-diabetic drugs in reducing the risk of

acute pancreatitis. Controlling for sex, age, and co-morbidities, the results show that

HR of developing acute pancreatitis were 0.46 (95% CI = 0.35–0.61) for those taking

biguanides, 0.63 (95% CI = 0.47–0.83) for sulfonylureas, 0.63 (95% CI = 0.46–0.87)

for thiazolidinediones, and 0.44 (95% CI = 0.31–0.62) for alpha-glucosidase

inhibitors. The beneficial effect of using insulin was not statistically significant (HR =

0.81, 95% CI = 0.64–1.02).

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Discussion

Though not utterly novel, to the best of our knowledge, this is the first

population-based cohort study that simultaneously determines the risk of developing

acute pancreatitis and the effectiveness of anti-diabetic medication in reducing the

risk for diabetic patients in Taiwan. In the present study, the incidence of acute

pancreatitis in Type 2 diabetic cohort was approximately two-fold greater than that in

non-diabetic cohort, a moderate risk consistent with previous studies [9-10]. The

incidence of acute pancreatitis measured by sex and age was consistently higher in

patients with Type 2 DM. The age-specific incidence also showed that Type 2

diabetic patients 20–39 years of age had the highest incidence rate ratio compared to

non-diabetics, which was consistent with the finding of Noel et al. [10]. This indicates

that the risk of acute pancreatitis is relatively great for young patients of DM.

The risk of developing acute pancreatitis in patients with Type 2 DM varied

moderately among studies. The multivariate Cox model analysis in this study

measured an adjusted HR slightly higher than the finding of 1.49-fold in the UK

General Practice Research Database (GPRD) study [9]; however, it was lower than

the HR of 2.83 in the study using a US insurance claims database [10]. Although the

biological mechanism between Type 2 DM and acute pancreatitis could not be proven

from this observational study, these cohort studies suggest that patients with Type 2

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We also found that patients with both DM and hepatitis C infection were at higher

risk to develop acute pancreatitis. A previous study has reported that patients with

acute hepatitis A, B, and E infections are at higher risk of acute pancreatitis [8],

without mentioning the risk for hepatitis C. Some case reports have shown that

interferon therapy in patients with chronic hepatitis C infection can induce acute

pancreatitis [16, 17]. In this study, 50 patients with chronic hepatitis C infection

received interferon therapy; however, no patient developed acute pancreatitis during

the follow-up period (data not shown). Because there was no data of hepatitis C RNA

in this dataset, we cannot posit a plausible biological explanation for why patients

with hepatitis C infection are at an elevated risk of acute pancreatitis. However, our

data show that patients having both hepatitis C and Type 2 diabetes at a higher risk of

acute pancreatitis.

Epidemiological studies have consistently reported the association between acute

pancreatitis with other co-morbidities, particularly gallstones and alcohol

consumption [6, 7]. Our study also demonstrates the evidence of a slight additional

effect from diabetes to those with co-morbidity of alcoholism, with an HR increase

from 6.05 to 6.92. This indicates that alcoholism has a greater influence than Type 2

diabetes in the risk of developing acute pancreatitis. No such additional effects were

evident in patients with both gallstones and diabetes.

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In further analysis, we found that patients using biguanides, sulfonylureas,

thiazolidinediones, or alpha-glucosidase inhibitors had 37%–56% reduction of acute

pancreatitis risk. Using insulin decreased risk of developing acute pancreatitis;

however, the association was not statistically significant. Gonzalez-Perez et al. found

that diabetic patients had decreased risks of developing acute pancreatitis using

insulin [odds ratio (OR) = 0.34, 95% CI = 0.13–0.91] or long-term (more than 3 years)

use of metformin (OR = 0.5, 95% CI = 0.28–0.91) [18]. In contrast, Gonzalez-Perez

et al. also found patients taking sulfonylureas for more than 3 years were at higher

risk (OR) = 1.66, 95% CI = 1.01–2.74) [18]. Because of lack of prospective studies,

we cannot posit any further explanation regarding the relation of anti-diabetic drugs to

the risk of acute pancreatitis. Further studies are required to explore the implication of

anti-diabetic drugs on acute pancreatitis.

Our study has several strengths. This study was based on a Taiwan

population-based study with a large sample size and with an increased statistical

power testing significant. The representative large sample size increased the validity

of identifying rare diseases such as acute pancreatitis for this study.

The limitations in the present study should be noted. A number of suspected risk

factors of acute pancreatitis, such as cigarette smoke, were not available. This was due

to the inherent limitation of insurance dataset. However, women in Taiwan rarely

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smoke, and account for less than 5% of the smokers [19]. Smoking is not likely an

important risk factor associated with acute pancreatitis because the risk difference

between men and women in this study is small.

Conclusion

Patients with Type 2 diabetes mellitus are at an elevated risk of acute pancreatitis,

and the risk is relatively greater for young patients. Patients infected with hepatitis C

and who suffer from alcoholism may be at additional risk. In contrast, we have also

found that anti-diabetic drugs demonstrate an effective mechanism of reducing the

risk of acute pancreatitis, particularly for those taking biguanides, sulfonylureas,

thiazolidinediones, or alpha-glucosidase inhibitors.

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Funding

This study was supported in part by grants of the Department of Health, Taiwan

(DOH 97-HP-1101, 2008-2010), Clinical Trial and Research Center of Excellence

(DOH99-TD-B-111-004) and Cancer Research Center of Excellence

(DOH99-TD-C-111-005), the National Science Council (NSC 98-2621-M-039 -001)

and the China Medical University Hospital (1MS1). The funding agencies had no role

in the study design, data collection and analysis, decision to publish, or preparation of

the manuscript.

Acknowledgement

The authors thank the National Health Research Institute in Taiwan for providing us

the insurance claims data.

Conflict of Interest Statement

The authors disclose no conflicts of interest.

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References

1. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas. 2006;33(4):323-30.

2. Frey CF, Zhou H, Harvey DJ, White RH.The incidence and case-fatality rates of acute biliary, alcoholic, and idiopathic pancreatitis in California, 1994-2001.

Pancreas. 2006;33(4):336-44.

3. Fagenholz PJ, Castillo CF, Harris NS, Pelletier AJ, Camargo CA Jr.

Increasing United States hospital admissions for acute pancreatitis, 1988-2003.

Ann Epidemiol. 2007;17(7):491-7.

4. Lowenfels AB, Maisonneuve P, Sullivan T. The changing character of acute pancreatitis: epidemiology, etiology, and prognosis. Curr Gastroenterol Rep.

2009;11(2):97-103.

5. Fu CY, Yeh CN, Hsu JT, Jan YY, Hwang TL. Timing of mortality in severe acute pancreatitis: experience from 643 patients. World J Gastroenterol 2007;13(13):1966-9.

6. Chang MC, Su CH, Sun MS, Huang SC, Chiu CT, Chen MC, Lee KT, Lin CC, Lin JT. Etiology of acute pancreatitis--a multi-center study in Taiwan.

Hepatogastroenterology. 2003;50(53):1655-7.

7. Chen CH, Dai CY, Hou NJ, Chen SC, Chuang WL, Yu ML. Etiology, severity and recurrence of acute pancreatitis in southern Taiwan. J Formos Med Assoc.

2006;105(7):550-5.

8. Jain P, Nijhawan S, Rai RR, Nepalia S, Mathur A. Acute pancreatitis in acute viral hepatitis. World J Gastroenterol. 2007;13(43):5741-4.

9. Girman CJ, Kou TD, Cai B, Alexander CM, O'Neill EA, Williams-Herman DE, et al: Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab. 2010;12(9):766-71.

10. Noel RA, Braun DK, Patterson RE, Bloomgren GL.Increased risk of acute pancreatitis and biliary disease observed in patients with type 2 diabetes: a retrospective cohort study. Diabetes Care. 2009;32(5):834-8.

11. Tai TY, Yang CL, Chang CJ, Chang SM, Chen YH, Lin BJ, et al. Epidemiology of diabetes mellitus among adults in Taiwan. J Med Assoc Thai. 1987;70 (Suppl 2):42-8.

12. Chou P, Chen HH, Hsiao KJ. Community-based epidemiological study on diabetes in Pu-Li, Taiwan. Diabetes Care 1992;15:81-9.

13. Lai SW, Ng KC. Descriptive Analysis of Diabetes Mellitus in Patients Receiving Health Checkups—A Hospital-based Study. Changhua J Med.

2004;9(Suppl ):267-71.

14. Department of Health, Taiwan: Main Causes of Death in 2009 [cited 2010

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September 1]. Available from URL:

http://www.doh.gov.tw/CHT2006/DM/DM2_2.aspx?now_fod_list_no=11122&c lass_no=440&level_no=3

15. Bureau of National Health Insurance, Department of Health, Taiwan. [cited 2010 September]

http://www.nhi.gov.tw/webdata/AttachFiles/Attach_14258_2_97-ch.pdf

16. Eland IA, Rasch MC, Sturkenboom MJ, Bekkering FC, Brouwer JT, Delwaide J, Belaiche J, Houbiers G, Stricker BH. Acute pancreatitis attributed to the use of interferon alfa-2b. Gastroenterology. 2000;119(1):230-3.

17. Chaudhari S, Park J, Anand BS, Pimstone NR, Dieterich DT, Batash S, Bini EJ.

Acute pancreatitis associated with interferon and ribavirin therapy in patients with chronic hepatitis C. Dig Dis Sci. 2004;49(6):1000-6.

18. Gonzalez-Perez A, Schlienger RG, García Rodríguez LA. Acute pancreatitis in association with type 2 diabetes and anti-diabetic drugs: a population-based cohort study. Diabetes Care. 2010 Sep 10. [Epub ahead of print]

19. Chao-Chia Hung, Lee-Lan Yen, Wen-Chi Wu. Association of parents’ alcohol use and family interaction with the initiation of alcohol use by sixth graders: A preliminary study in Taiwan. BMC Public Health 2009;9:172-175.

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1

Table 1. Baseline characteristics between Type 2 diabetic cohort and non-diabetic cohort identified in 2000–2005

Type 2 diabetes No

N=78,072

Yes N=19,518

N % n % P value*

Sex 1.00

Women 35,092 (45.0) 8,773 (45.0) Men 42,980 (55.0) 10,745 (55.0)

Age group (years) 1.00

20–39 7,772 (10.0) 1,943 (10.0) 40–64 48,012 (61.4) 12,003 (61.4)

≥65 22,288 (28.6) 5,572 (28.6)

Mean (SD) (years) 56.7 (13.7) 56.8 (13.3) 0.80 Baseline co-morbidity

Obesity 402 (0.5) 505 (2.6) <0.0001 Hypertriglyceridemia 441 (0.6) 421 (2.2) <0.0001 Alcoholism 404 (0.5) 158 (0.8) <0.0001 Gallstones 1,525 (2.0) 511 (2.6) <0.0001 Hepatitis B 1,509 (1.9) 508 (2.6) <0.0001 Hepatitis C 859 (1.1) 328 (1.7) <0.0001

*Chi-square test comparing patients with and without Type 2 diabetes.

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Table 2. Incidence density of acute pancreatitis estimated by sex, age, and follow-up years for Type 2 diabetic and non-diabetic cohorts identified in 2000–2005

Non-diabetes Type 2 diabetes N Cases Person-

years

Incidence N Cases Person- years

Incidence HR (95% CI)

All 78,072 621 436,653 14.2 19,518 295 106,512 27.7 1.95 (1.70–2.24) Sex

Women 35,092 258 198,319 13.0 8,773 121 48,534 24.9 1.92 (1.54–2.38) Men 42,980 363 238,334 15.2 10,745 174 57,978 30.0 1.97 (1.65–2.36) Age, years

20–39 7,772 40 44,678 8.95 1,943 54 10,996 49.1 5.48 (3.64–8.25) 40–64 48,012 314 276,147 11.4 12,003 155 67,605 22.9 2.02 (1.66–2.45)

≥ 65 22,288 267 115,827 23.1 5,572 86 27,911 30.8 1.34 (1.05–1.71) Follow-up

<1 years 78,072 104 77,332 13.5 19,518 46 19,205 24.0 1.78 (1.26–2.52) 1 76,607 113 75,890 14.9 18,931 54 18,685 28.9 1.94 (1.40–2.68) 2 75,202 98 74,490 13.2 18,464 47 18,261 25.7 1.96 (1.38–2.77) 3 73,744 100 66,893 15.0 18,031 43 16,295 26.4 1.77 (1.24–2.52) 4 60,304 89 53,131 16.8 14,645 38 12,884 29.5 1.76 (1.20–2.57)

≥ 5 46,381 117 88,916 13.2 11,212 67 21,182 31.6 2.40 (1.78–3.25)

Incidence rate: per 10,000 person-years.

HR (hazard ratio): Type 2 diabetes vs. non-diabetes (95% CI) Cases of outpatient services for acute pancreatitis.

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Table 3. Interaction effect on acute pancreatitis between diabetes and co-morbidities

Non-diabetes Type 2 diabetes

Cases Incidence HR (95% CI) Cases Incidence Adjusted HR

(95% CI)

All 621 14.2 1.00 (reference) 295 27.7 1.89 (1.65–2.18)

Hypertriglyceridemia

No 612 14.1 1.00 (reference) 290 27.8 1.93 (1.68–2.22)

Yes 9 39.0 2.39 (1.24–4.62) 5 22.1 1.45 (0.60–3.49)

Alcoholism

No 606 13.9 1.00 (reference) 288 27.2 1.92 (1.67–2.21)

Yes 15 80.5 6.05 (3.62–10.1) 7 96.0 6.92 (3.28–14.6)

Gallstones

No 577 13.4 1.00 (reference) 285 27.4 2.01 (1.74–2.32)

Yes 44 58.2 3.78 (2.77–5.15) 10 40.2 2.52 (1.35–4.72)

Hepatitis C

No 607 14.0 1.00 (reference) 286 27.2 1.90 (1.65–2.19)

Yes 14 34.7 2.03 (1.18–3.47) 9 59.3 3.35 (1.72–6.52)

Incidence: per 10,000 person-years.

HR: adjusted for age, sex and co-morbidities.

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Table 4. Cox model measured hazard ratios and 95% confidence intervals of acute pancreatitis associated with anti-diabetic drugs identified in 2000–2005

N Case Person-year Incidence Crude HR

(95% CI) Adjusted HR

(95% CI)

Insulin

Non-use 7,892 124 39,770 31.2 1.00 (reference) 1.00 (reference) Use 11,626 171 66,741 25.6 0.81 (0.64–1.02) 0.81 (0.64–1.02) Biguanide

Non-use 3,161 73 14,488 50.4 1.00 (reference) 1.00 (reference) Use 16,357 222 92,023 24.1 0.47 (0.36–0.62) 0.46 (0.35–0.61) Sulfonylurea

Non-use 3,348 62 15,403 33.8 1.00 (reference) 1.00 (reference) Use 16,170 233 91,109 25.6 0.62 (0.47–0.83) 0.63 (0.47–0.83) Thiazolidinedione

Non-use 15,721 250 83,143 30.1 1.00 (reference) 1.00 (reference) Use 3,797 45 23,368 19.3 0.63 (0.46–0.87) 0.63 (0.46–0.87) Alpha-glucosidase

inhibitor

Non-use 15,098 257 80,072 32.1 1.00 (reference) 1.00 (reference) Use 4,420 38 26,440 14.4 0.44 (0.32–0.62) 0.44 (0.31–0.62) Adjusted HR: adjusted for age, sex, and co-morbidities.

Incidence: per 10,000 person-years.

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Figure 1. Cumulative incidence of acute pancreatitis

for patients with Type 2 diabetes mellitus and

數據

Table 1. Baseline characteristics between Type 2 diabetic cohort  and non-diabetic cohort identified in 2000–2005
Table 2. Incidence density of acute pancreatitis estimated by sex, age, and follow-up years for Type 2 diabetic  and non-diabetic cohorts identified in 2000–2005
Table 3. Interaction effect on acute pancreatitis between diabetes and co-morbidities
Table 4. Cox model measured hazard ratios and 95% confidence intervals of acute  pancreatitis associated with anti-diabetic drugs identified in 2000–2005
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