Association Between Famine Exposure In Early Life And Type 2 Diabetes And Hyperglycemia In Adulthood

BackgroundThe vast majority of the world's diabetes cases are type 2 diabetes(T2D).Type 2 diabetes is caused by insulin resistance,which results primarily from decreased activity,obesity,age,and a family history of diabetes.Obviously,genetics plays a crucial role in driving this disease,but environmental factors are equally important.Increasing experimental and epidemiological evidence shows that the risk for T2D can be affected by both adult environmental conditions(e.g.lifestyle)and conditions in early life.Some studies have shown that famine,characterized by long-term and continuous malnutrition,in early life may also have an effect on T2D.Barker suggested that the human body can be programmed by undernutrition,permanently changing the body's metabolism to enable survival during the fetal period,but that those changes could increase the risk of T2D in later life.Most studies have demonstrated an association between famine exposure in early life and T2D in adulthood;however,a study on the Siege of Leningrad did not show the same association.From the late 1950s to the early 1960s,China suffered a great famine,which lasted for a long time and affected a large area.The Great Chinese Famine is usually known as "Three Years of Natural Calamities"(1959-61),although it was not actually resolved until 1962.Almost every region in China suffered from this famine,but the severity of the famine varied in different regions.Moreover,rural areas suffered more from this famine than urban areas.Several studies on the association between the Great Chinese Famine and the risk of T2D or metabolic syndrome have been published.Unfortunately,few studies were conducted nationwide.Because the severity of the famine are varied in different regions,the results of these regional studies are usually limited.Objectives1.To explore the association between famine exposure in early life and the risk of T2D and hyperglycemia in adulthood.2.To explore the interaction between famine exposure cohorts and famine severity on the risk of hyperglycemia and T2D.MethodsThe present study was performed on 7262 participants who were born between 1 October 1949 and 1 July 1966,and who had never migrated from the province where they were born from baseline data collection for the China Health And Retirement Longitudinal Study(CHARLS)in 2011.Participants were divided according to birthdate into cohorts with fetal,late,middle,and early childhood exposure and no exposure to famine.1960 was the worst year of the Great Chinese Famine,and the excess death rate(EDR)due to the famine varied across regions;diabetes and hyperglycemia were defined by the American Diabetes Association 2010 criteria and data obtained from the blood samples in this survey,or by the self-reported data.Weighted Logistic regression models were used to analyze the association between famine exposure in early life and the risk of T2D and hyperglycemia in adulthood.In addition,we explored the interaction between age group of famine exposure and famine severity on the risk of hyperglycemia and T2D.Potential confounding factors were self-reported family economic status,residential area type,health status before 16 years of age,residential area type before 16 years of age,BMI,smoking status,alcohol consumption status,marriage status,educational level and waist circumference.Main results1.The risk of hyperglycemia was significantly higher for female exposed cohorts than female no exposure cohort(odds ratios[OR]and 95%confidence intervals[CIs]:1.556(1.219-1.987),1.360(1.038-1.782),1.466(1.137-1.890),and 1.349(1.024-1.778)for late,middle,early childhood and fetal exposure,respectively)after adjusting confounding factors.In contrast,we did not observe any association between famine exposure and hyperglycemia in males.Meanwhile,we observed that males in the early exposure cohorts had a lower risk of T2D than males in the no-exposure cohort(OR= 0.658,95%CI= 0.495-0.875)after adjusting confounding factors.No associations of famine exposure with T2D risk were found in females.2.No multiplicative interactions were found between famine exposure cohorts and famine severity on the risk of hyperglycemia and T2D.A positive additive interaction were found between famine exposure cohorts and famine severity on the risk of hyperglycemia,after adjusting the confounding factors,the results as follows:S=1.233,AP=3.8%,RERI=0.047.ConclusionsIn conclusion,exposure to famine during early life was found to increase the risk of hyperglycemia in female Chinese middle-aged and elderly residents,but decreased the risk of T2D in males who were exposed to famine during early-childhood.Meanwhile,a positive additive interaction were found between famine exposure cohorts and famine severity on the risk of hyperglycemia,after adjusting the confounding factors.