Epidemiological Characteristics and The Effect of Severe Hypoglycemia on the Risks of Cardiovascular Disease and All-cause Mortality in Patients with Type 1 Diabetes Mellitus

Abstract

The incidence rate of Type 1 diabetes (T1DM) increased rapidly in most Western countries during last decades Hygiene hypothesis is one of the major hypotheses explaining the variation of incidence rate Most T1DM is diagnosed at young age but the population incidence of childhood T1DM and the major complication severe hypoglycemia were rarely reported in Asian Severe hypoglycemia is the major obstacle in glycemic controls Whether there is a long-term association and a dose-gradient relationship between severe hypoglycemia and subsequent risks of all-cause mortality and cardiovascular disease (CVD) incidence is still inconclusive We retrieved our data from Taiwan’s National Health Insurance Research Database (NHIRD) from 2003 to 2008 to report annual incidence rate of childhood T1DM By counting the newly-diagnosed T1DM registered in the list of Catastrophic Illness Database in NHIRD and using the population statistics from Taiwan’s government we reported the incidence rate and clinical features of childhood T1DM and examined the association of the incidence rate of T1DM with child-population density and urbanization level of living areas in an ecological study Besides a T1DM　cohort was followed from 2003 to 2011 with a mean follow-up period of 6 2 years to estimate the incidence rate and frequency of severe hypoglycemia under the assumption of Poisson distribution The possible risk factors for the incidence of severe hypoglycemia in T1DM cases were examined Furthermore by taking all-cause mortality and cardiovascular disease (CVD) incidence as separate outcomes we employed incidence density sampling matching method to conduct two nested case-control studies in which the exposure status of severe hypoglycemia in three time-windows (1-year 1-3 years and 3-5 years) prior to the two adverse outcomes were determined and associated with the risks of all-cause mortality and CVD incidence The dose-gradient effect of severe hypoglycemia within 5 years was also investigated In addition we also conducted two cohort studies one with a fixed-time exposure status of severe hypoglycemia and the other one with time-dependent exposure status of severe hypoglycemia The independent effect of severe hypoglycemia on all-cause mortality and CVD incidence were assessed in the three aforementioned three studies with adjustment or matched for age at first diagnosis sex socioeconomic factors and severity of diabetes The childhood incidence rate was 5 3 per 105 persons in Taiwan from 2003 to 2008 An increased incidence rate of T1DM was associated with female sex older age and lived in the areas with lowest child-population density Diabetic ketoacidosis was still the most important cause for hospitalization The incidence rate of severe hypoglycemia in T1DM was 2 80 persons per100 person-years (PYs) and 6 03 episodes per 100 PYs An increased incidence rate of severe hypoglycemia was associated with female sex older age and lower monthly-income based insurance premium Moreover according to results of the nested case-control design the risk of all-cause mortality was associated with history of severe hypoglycemia occurred in 1-year 1-3 years and 3-5 years prior to death but the risk of CVD incidence was only associated with history of severe hypoglycemia occurred in the previous year A higher frequency of severe hypoglycemia occurred within 5 years was associated with a higher risk of all-cause mortality and CVD incidence The prior history of severe hypoglycemia was associated with both short-term and long-term risks of all-cause mortality in the two cohort studies On the other hand severe hypoglycemia was found to be associated with CVD incidence in the cohort study with time-dependent exposure status of severe hypoglycemia but only significantly associated with the risk of CVD incidence in 3-4 year of follow-up in the cohort design with fixed-time exposure status of severe hypoglycemia In conclusion the incidence rate of childhood T1DM in Taiwan was relatively low compared to most Western countries Among patients with T1DM female sex older age of first diagnosis and lower income level were associated with an increased risk of severe hypoglycemia Prior history of severe hypoglycemia was associated with both short-term and long-term risk of all-cause mortality and short-term adverse effect on CVD incidence Higher frequency of severe hypoglycemia attack was associated with elevated risks of all-cause mortality and CVD incidence Clinicians and patients with T1DM should put emphasis on the prevention of severe hypoglycemia while managing glycemic control

Date of Award	2016 Feb 15
Original language	English
Supervisor	Chung-Yi Li (Supervisor)