Diabetes, Insulin Use, and Helicobacter Pylori Eradication
This is a retrospective cohort study using the reimbursement databases of the NHI of Taiwan. According to the Ministry of Interior, >98.0% of the Taiwanese population in 2005 (22,770,383: 11,562,440 men and 11,207,943 women) were covered by the NHI. A random sample of 1,000,000 insurants in 2005 was created by the National Health Research Institute. The National Health Research Institute is the only institute approved, as per local regulations, for conducting sampling of a representative sample of the whole population for the year 2005 with a predetermined sample size of 1,000,000 individuals. The reimbursement databases of these individuals were retrieved and could be provided for academic research after approval. The identification information was scrambled for the protection of the privacy of the individuals.
Figure 1 shows a flowchart for selecting cases for the study. After excluding subjects <25 years old, patients with T1DM (in Taiwan, patients with T1DM were issued a "Severe Morbidity Card" after certified diagnosis), living region unknown, cases with a diagnosis of gastric cancer and cases receiving HP eradication before 2005, the data of 601,441 subjects were analyzed.
(Enlarge Image)
Figure 1.
Flowchart showing the procedures in the calculation of the annual incidence of Helicobacter pylori eradication in 2005 in Taiwan using the National Health Insurance database.
The reimbursement databases were available back to 1996. Identification number, sex, birth date, medications and diagnostic codes based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) were retrieved. Diabetes was coded 250.1–250.9 and gastric cancer 151. The comorbidities (ICD-9-CM codes) included hypertension (401–405), chronic obstructive pulmonary disease (490–496, a surrogate for smoking), stroke (430–438), nephropathy (580–589), ischemic heart disease (410–414), peripheral arterial disease (250.7, 785.4, 443.81, 440–448), eye disease (250.5, 362.0, 369, 366.41, 365.44), obesity (278) and dyslipidemia (272.0–272.4).
Medications included statin, fibrate, angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, calcium channel blocker, sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone. The NHI insurants were classified according to occupation and this served as a surrogate for socioeconomic status. The living region served as a surrogate for geographical distribution of some environmental exposure. Occupation was categorized as I: civil servants, teachers, employees of governmental or private business, professionals and technicians; II: people without particular employers, self-employed or seamen, III: farmers or fishermen; and IV: low-income families supported by social welfare or veterans. Living region was categorized as Taipei, Northern, Central, Southern and Kao-Ping/Eastern.
The methods for identifying patients receiving HP eradication therapy in a previous study were followed. The details for all therapeutic regimens are shown in the supplementary Table 1 of this earlier paper. In brief, HP eradication therapy was defined as a combination use of proton pump inhibitor or H2 receptor blockers, plus clarithromycin or metronidazole, plus amoxicillin or tetracycline, with or without bismuth, in the same prescription order for 7–14 days.
Diabetes status and insulin use were considered as the exposures of interest and HP eradication as the outcome in the study. To assure the correctness of temporal order of exposure and outcome, age, diabetes status, diabetes duration, use of insulin or other medications, and comorbidities were recorded as a status or diagnosis before January 1, 2005; and HP eradication was recorded as a first event occurring in the year 2005. PES done in 2005 and from 1997 to 2005 were both analyzed. The purpose to include PES done in 2005 was to assure the temporal proximity of performing PES which might be related to the conduction of HP eradication.
The baseline characteristics between diabetic and non-diabetic subjects were compared by Student's t test for continuous variables and by Chi square test for categorical variables.
Chi square test examined the differences of annual incidence of HP eradication among subgroups of age (25–44, 45–54, 55–64 and ≥65 years), sex, diabetes (for all subjects), insulin use (for diabetic patients only), occupation and living region, for all subjects and for the diabetic patients only separately, before and after excluding patients with diabetes diagnosed <5 years (Figure 1).
Logistic regression estimated the mutually-adjusted odds ratios for HP eradication in all subjects and in the diabetic patients only. For the diabetic patients only, the independent variables included age, sex, PES (1997–2005), the above-mentioned comorbidities, living region, occupation and all the above-mentioned medications. For all subjects, the independent variables included age, sex, diabetes, PES (1997–2005), the above-mentioned comorbidities, medications other than anti-diabetic therapies (i.e., statin, fibrate, angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, calcium channel blocker), living region and occupation.
Additional logistic models were created to examine whether the magnitude of the odds ratios for diabetes status (for all subjects), diabetes duration (for all subjects) and insulin use (for the diabetic patients only) might change by including different sets of covariates. Model I was adjusted for age and sex; model II for age, sex, occupation and living region; model III for age, sex, occupation, living region, PES (in 2005), hypertension, chronic obstructive pulmonary disease, stroke, nephropathy, ischemic heart disease, peripheral arterial disease, eye disease, obesity and dyslipidemia; model IV for age, sex, occupation, living region, PES (in 2005), hypertension, chronic obstructive pulmonary disease, stroke, nephropathy, ischemic heart disease, peripheral arterial disease, eye disease, obesity, dyslipidemia, statin, fibrate, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and calcium channel blocker (model IV in diabetic patients only was additionally adjusted for oral anti-diabetic agents including sulfonylurea, metformin, acarbose, pioglitazone and rosiglitazone).
Analyses were conducted using SAS statistical software, version 9.1 (SAS Institute, Cary, NC). Data were expressed as mean (standard deviation) for continuous variables or number (%) for categorical variables. P < 0.05 was considered statistically significant.
Methods
Study Population
This is a retrospective cohort study using the reimbursement databases of the NHI of Taiwan. According to the Ministry of Interior, >98.0% of the Taiwanese population in 2005 (22,770,383: 11,562,440 men and 11,207,943 women) were covered by the NHI. A random sample of 1,000,000 insurants in 2005 was created by the National Health Research Institute. The National Health Research Institute is the only institute approved, as per local regulations, for conducting sampling of a representative sample of the whole population for the year 2005 with a predetermined sample size of 1,000,000 individuals. The reimbursement databases of these individuals were retrieved and could be provided for academic research after approval. The identification information was scrambled for the protection of the privacy of the individuals.
Figure 1 shows a flowchart for selecting cases for the study. After excluding subjects <25 years old, patients with T1DM (in Taiwan, patients with T1DM were issued a "Severe Morbidity Card" after certified diagnosis), living region unknown, cases with a diagnosis of gastric cancer and cases receiving HP eradication before 2005, the data of 601,441 subjects were analyzed.
(Enlarge Image)
Figure 1.
Flowchart showing the procedures in the calculation of the annual incidence of Helicobacter pylori eradication in 2005 in Taiwan using the National Health Insurance database.
Data Retrieved From NHI Databases
The reimbursement databases were available back to 1996. Identification number, sex, birth date, medications and diagnostic codes based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) were retrieved. Diabetes was coded 250.1–250.9 and gastric cancer 151. The comorbidities (ICD-9-CM codes) included hypertension (401–405), chronic obstructive pulmonary disease (490–496, a surrogate for smoking), stroke (430–438), nephropathy (580–589), ischemic heart disease (410–414), peripheral arterial disease (250.7, 785.4, 443.81, 440–448), eye disease (250.5, 362.0, 369, 366.41, 365.44), obesity (278) and dyslipidemia (272.0–272.4).
Medications included statin, fibrate, angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, calcium channel blocker, sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone. The NHI insurants were classified according to occupation and this served as a surrogate for socioeconomic status. The living region served as a surrogate for geographical distribution of some environmental exposure. Occupation was categorized as I: civil servants, teachers, employees of governmental or private business, professionals and technicians; II: people without particular employers, self-employed or seamen, III: farmers or fishermen; and IV: low-income families supported by social welfare or veterans. Living region was categorized as Taipei, Northern, Central, Southern and Kao-Ping/Eastern.
The methods for identifying patients receiving HP eradication therapy in a previous study were followed. The details for all therapeutic regimens are shown in the supplementary Table 1 of this earlier paper. In brief, HP eradication therapy was defined as a combination use of proton pump inhibitor or H2 receptor blockers, plus clarithromycin or metronidazole, plus amoxicillin or tetracycline, with or without bismuth, in the same prescription order for 7–14 days.
Statistical Analyses
Diabetes status and insulin use were considered as the exposures of interest and HP eradication as the outcome in the study. To assure the correctness of temporal order of exposure and outcome, age, diabetes status, diabetes duration, use of insulin or other medications, and comorbidities were recorded as a status or diagnosis before January 1, 2005; and HP eradication was recorded as a first event occurring in the year 2005. PES done in 2005 and from 1997 to 2005 were both analyzed. The purpose to include PES done in 2005 was to assure the temporal proximity of performing PES which might be related to the conduction of HP eradication.
The baseline characteristics between diabetic and non-diabetic subjects were compared by Student's t test for continuous variables and by Chi square test for categorical variables.
Chi square test examined the differences of annual incidence of HP eradication among subgroups of age (25–44, 45–54, 55–64 and ≥65 years), sex, diabetes (for all subjects), insulin use (for diabetic patients only), occupation and living region, for all subjects and for the diabetic patients only separately, before and after excluding patients with diabetes diagnosed <5 years (Figure 1).
Logistic regression estimated the mutually-adjusted odds ratios for HP eradication in all subjects and in the diabetic patients only. For the diabetic patients only, the independent variables included age, sex, PES (1997–2005), the above-mentioned comorbidities, living region, occupation and all the above-mentioned medications. For all subjects, the independent variables included age, sex, diabetes, PES (1997–2005), the above-mentioned comorbidities, medications other than anti-diabetic therapies (i.e., statin, fibrate, angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, calcium channel blocker), living region and occupation.
Additional logistic models were created to examine whether the magnitude of the odds ratios for diabetes status (for all subjects), diabetes duration (for all subjects) and insulin use (for the diabetic patients only) might change by including different sets of covariates. Model I was adjusted for age and sex; model II for age, sex, occupation and living region; model III for age, sex, occupation, living region, PES (in 2005), hypertension, chronic obstructive pulmonary disease, stroke, nephropathy, ischemic heart disease, peripheral arterial disease, eye disease, obesity and dyslipidemia; model IV for age, sex, occupation, living region, PES (in 2005), hypertension, chronic obstructive pulmonary disease, stroke, nephropathy, ischemic heart disease, peripheral arterial disease, eye disease, obesity, dyslipidemia, statin, fibrate, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and calcium channel blocker (model IV in diabetic patients only was additionally adjusted for oral anti-diabetic agents including sulfonylurea, metformin, acarbose, pioglitazone and rosiglitazone).
Analyses were conducted using SAS statistical software, version 9.1 (SAS Institute, Cary, NC). Data were expressed as mean (standard deviation) for continuous variables or number (%) for categorical variables. P < 0.05 was considered statistically significant.
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