2.1 Study population
The Kailuan study is an ongoing prospective cohort (trial registration number: ChiCTR-TNC-11001489) study in Tangshan, China (14,15). In 2006 to 2007, a total of 101,510 participants (≥ 18 years, including retired individuals) from Kailuan community received questionnaires and the first survey at Kailuan General Hospital and 10 affiliated hospitals. Following surveys were provided every 2 years since 2006.
In this study, we included participants who participated in at least one survey from 2006 to 2017 and were born in the destructive zone of the Great Tangshan earthquake between 28 July 1974 and 4 May 1979. Criteria for birth dates was based on the Tangshan earthquake date (i.e., July 28, 1976) and gestation period of 280 days. According to the date of the Tangshan earthquake and birth date of each participant, participants born between 04 May 1977 and 04 May 1979 were defined as nonexposed group, and participants born between 28 July 1974 and 04 May 1977 were defined as exposed group. Meanwhile, exposed group were further divided into fetal exposed group with participants born between 28 July 1976 and 04 May 1977, infant exposed group with participants born between 28 July 1975 and 28 July 1976, and early childhood exposed group with participants born between 28 July 1974 and 28 July 1975.
Meanwhile, we excluded participants who were not born in the destructive zone of the Great Tangshan earthquake; without location of birth; or with DM at the baseline.
Ultimately, a total of 7,568 eligible participants were included in this study. The study followed the Declaration of Helsinki and was approved by the Ethics Committee of the Kailuan Medical Group. All participants gave their written informed consent.
2.2 Earthquake exposure
The Tangshan earthquake was a natural disaster resulting from a magnitude 7.6 earthquake that hit the region around Tangshan, Hebei, People's Republic of China on 28 July 1976. The magnitude of the Tangshan earthquake is indicated by the extent of felt zones: up to 1,100 km away, across most of northeastern China, and even in Mongolia and Korea (16). In and around Beijing, 140 kilometers from the epicenter, the shaking reached an intensity of VI on the Chinese intensity scale (16). It is a kind of severe natural catastrophic event that can cause adverse physiological and mental responses. There is no definite conclusion about the mechanism of the Tangshan earthquake, the predominant mechanism is the plate movement. Tangshan lies at the intersection of the Bohai-Zhangjiakou Fault Zone (BZFZ) and the Tangshan-Cixian-Ninghe Fault Zone, which is the most important intraplate seismic belt within the Huabei Basin. In the northern Huabei Basin, the Yanliao epsilon-shaped structure is composed of the Huairou-Sanhe-Tangshan-Jinzhou-Xialiaohe arcuate structure belt and the NS-trending Tangshan-Fengnan uplift. The backbone of Tangshan-Fengnan uplift pushed southward and made the compressive stress concentrate at the apex of the arcuate structure belt (17). The stress would be released when it exceeded the limiting value and caused the Tangshan earthquake.
In this study, earthquake exposure was defined by the date of the Tangshan earthquake and birth date of each participant. Earthquake severity was measured by seismic intensity according to the New Chinese Seismic Intensity Scale in 1957 (18, 11), and varied from I (not felt) to XI (disastrous).The category of the seismic intensity in prefecture level were divided into three groups: destructive, felt and not felt. Destructive zones comprised prefectures where the intensity was destructive to disastrous (V–XI) (11). We selected individuals who were born in the Tangshan earthquake destructive zones, and had similar characteristics of socio-economic status, living habits. Moreover, we defined the place of birth of participants based on individual identity card information in questionnaire.
2.3 Health data collection
DM was defined as either a self-reported physician diagnosi, or taking antidiabetic medication, or fasting blood glucose (FBG) ≥7.0 mmol/L in physical examination (19). Self-report of a physician diagnosis and an antidiabetic medication were collected by questionnaires provided by the survey among Kailuan General Hospital and 10 affiliated hospitals participants. Fasting blood glucose was measured using the hexokinase/glucose-6-phosphate dehydrogenase method (Mind Bioengineering Co Ltd, Shanghai, China) (20).
Data on birth date, gender, education level, physical exercise, smoking status, alcohol consumption were collected using a self-reported questionnaire, as detailed previously (18, 14, 15). Higher education level was defined as high school and above. Regular physical activity was defined as exercise ≥ 3 times/week for a duration of ≥ 30min each (21). Current smoker was defined as smoking at least one cigarette on average in a recent year (19). Drinking status was defined according to average alcohol consumption in the past year, as detailed elsewhere (19).
Blood pressure was measured by physical examination in the morning and prohibited coffee, tea, or physical exercise within 30 minutes before measurement. Measurement of blood pressure was repeated for 3 times, with each measurement interval of 1 to 2 minutes, and the mean value was taken. Height and weight were measured by trained nurses, and body mass index (BMI) was calculated as weight (kg)/height2 (m2). Biochemical evaluation used the same fasting blood sample taken in the morning. Concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were measured at Kailuan General Hospital and 10 affiliated hospitals using an autoanalyzer (Hitachi 747; Hitachi, Tokyo, Japan).
2.4 Statistical Analyses
For baseline characteristics of the study participants’ description, mean standard deviation (SD) was used for normally distributed variables. Number and percentage (%) were used to describe categorical variables. Pearson χ2 test for categorical variables and Student t test or Mann-Whitney U test for continuous variables were used to compare the characteristics of the participants across baseline groups. The follow-up period was defined from the baseline survey to the onset of DM or the last visit on December 31, 2017. Incidence density of DM was calculated during the follow-up.
Multivariate cox regression model was used to compare the risk of incident DM with earthquake exposure. Hazard ratios (HRs) with 95% CIs were calculated, with nonexposed individuals as the reference category. Model 1 adjusted for gender (male or female). Model 2 additionally adjusted for body mass index (≥ 24 kg/m2 or < 24 kg/m2), smoking status (smoker or non-smoker), alcohol consumption (drinker or non-drinker), physical exercise (yes or no), and high education level (below high school or high school or above). Model 3 included model 2 and additionally adjusted for systolic pressure (continuous variables), triglycerides (continuous variables), high-density lipoprotein (continuous variables), and low-density lipoprotein (continuous variables).
We further compared the risk of incident DM with stratification of earthquake exposure (fetal exposure, infant exposure, and age exposed group of 1-2 year), with the nonexposed group as the reference category. To demonstrate the possible interaction of earthquake exposure in the development of DM, we generated interaction terms using the cross products of earthquake exposure with baseline BMI, smoking status, alcohol consumption and regular physical exercise into multivariate cox regression model, respectively. The P for interaction was calculated based on the number of exposure groups (nonexposed and exposed) and the number of subgroups for each modifier in the subgroup analysis. Additionally, we assumed that the missing data were random and used multiple imputations by chained equations to impute each missing data (22).
All analyses were conducted using SAS (Version 9.4; SAS Institute, Cary, NC), and a two-tailed P<0.05 was considered as statistically significant.