Research Article: Impact of age at appendectomy on development of type 2 diabetes: A population-based cohort study

Date Published: October 16, 2018

Publisher: Public Library of Science

Author(s): Yang-Ming Lee, Chew-Teng Kor, Diko Zhou, Hsueh-Chou Lai, Chia-Chu Chang, Wen-Lung Ma, Yu Ru Kou.


Diabetes is a complex metabolic disease characterized by chronic low-grade inflammation in which genetic and environmental factors are involved. Growing evidence implicates that alterations of the gut microbiota potentially contribute to the emergence of metabolic diseases. The human appendix has more recently been recognized as a microbial reservoir for repopulating the gastrointestinal tract and an important part of the immune system. Thus, appendectomy may influence microbial ecology and immune function. This study investigated the association between appendectomy and type 2 diabetes risk.

We analyzed a cohort of 10954 patients who underwent appendectomy between 1998 and 2013 based on the Taiwan National Health Insurance Program database. A comparison cohort of 43815 persons without appendectomy was selected randomly and matched by sex, age, comorbidities, and index year. To ensure reliability of the results, a sensitivity analysis using a propensity score–matched study was performed. We observed the subsequent development of type 2 diabetes in both cohorts.

Although the overall incidence of type 2 diabetes in the appendectomy patients was 7.9% higher than that in the non-appendectomy patients, it was not statistically significant (95% confidence interval [CI], 0.997–1.168) after the adjustment of confounding factors. Multivariate regression analysis revealed that the adjusted hazard ratio (HR) of type 2 diabetes was 1.347 for appendectomy patients < 30 years of age (95% CI, 1.009–1.798) compared to non-appendectomy patients. The incidence of type 2 diabetes was higher within 3 years of post-appendectomy follow-up than for non-appendectomy patients (HR, 2.017; 95% CI, 1.07–3.802). Age impacted the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.002); in contrast, sex did not affect the association between appendectomy and type 2 diabetes risk (Pinteraction = 0.88). Our study results suggest that appendectomy increases type 2 diabetes risk, particularly when performed prior to middle age.

Partial Text

Diabetes is one of the most serious public health issues worldwide due to its rapidly increasing incidence and tremendous amount of various vascular complications. According to the International Diabetes Federation, in 2015, the 415 million individuals had diabetes, a figure that is estimated to increase to 642 million by 2040 [1] Diabetes is a complicated metabolic disease characterized by chronic inflammation [2, 3] that involves genetic and environmental factors. Insulin resistance, the core defect of metabolic diseases, is linked to low-grade inflammation; however, its detailed molecular mechanism remains to be determined. Recent studies have suggested that the gut microbiota play a fundamental role in metabolic disease development by modifying energy homeostasis [4–8]. Studies from animal models have shown that alterations in the gut microbiota contribute to the development of metabolic diseases by increasing endotoxemia-induced inflammation [9]. Furthermore, Cox et al. demonstrated that altering the intestinal microbiota in early life using low-dose penicillin switched the metabolic phenotype [10]. Ridaura et al. demonstrated that the microbiota derived from discordant obese twins affected murine metabolism [11].

Of the 15917 patients in the appendectomy group, 10954 patients remained after the exclusion of 2975 patients <18 or >100 years of age, 1538 patients with a history of DM, 201 patients with a prescription history of antidiabetic agents, eight patients who underwent bariatric surgery, and 241 patients who did not survive or completed <30 days of follow-up. There were a total of 43815 persons in the control group. In this large retrospective population-based cohort study, we found no statistically significant association between appendectomy and type 2 DM in the overall population (aHR, 1.079; 95% CI, 0.997–1.168). However, appendectomy increased the risk of type 2 DM among patients < 20 years (aHR, 2.45; 95% CI, 1.039–5.776) and those <30 years (aHR, 1.347; 95% CI, 1.009–1.798). In the random frequency-matched cohort, all confounding factors except Charlson Comorbidity Index score and number of visiting clinics were equally distributed in the appendectomy and control groups. To reduce selection bias, a multivariate regression analysis was conducted of a propensity score-matched cohort, which revealed that the adjusted HR of type 2 DM in the appendectomy patients < 20 years and those < 30 years were 2.52 (95% CI, 1.116–5.695) and 1.36 (95% CI, 1.02–1.813) compared to controls. Since the number of appendectomy patients < 20 years of age was limited, we may have overestimated the impact of age on appendectomy and the development of type 2 DM. Therefore, we concluded that appendectomy prior to 30 years of age is an independent risk factor for the development of type 2 DM. In conclusion, appendectomy performed in patients < 30 years is associated with the risk of type 2 DM independent of hypertension, hyperlipidemia, gout, polycystic ovaries, depression, GDM, depression, obesity, chronic pancreatitis, HBV, HCV, statins, atypical antipsychotics, HIV drugs, corticosteroids, and immunosuppressants. The results of this study implicate that the appendix protects against type 2 DM development before middle age. Further studies should be performed to clarify the role of appendectomy in the development of diabetes.   Source:


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