Diabetes risk assessment and prediction in Chinese

Abstract

The prevalence of diabetes has been rising worldwide and, in Hong Kong, was already 9.8%, in 1995, based on the 75-gram oral glucose tolerance test (OGTT). In 2010, the prevalence in China was 11.2%, when the HbA1c criterion was also included, with 70% being undiagnosed. Alarmingly, 50% of the adults in China have prediabetes, which is associated with an increased risk of future diabetes and cardiovascular diseases. Early detection and proper disease management should help in easing the impact of diabetes-related complications. Identification of the major risk factors, risk assessment tools development and evaluation of diagnostic tests for diabetes should help the planning of a better case-finding strategy, and were the foci of this thesis. All studies included in this thesis were based on the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), a long-term population-based prospective study (1995 - 2018). Data from the baseline and four reassessments of CRISPS clearly demonstrated obesity to be a key modifiable risk factor of diabetes. As obesity is associated with adipokine dysregulation which contributes to obesity-related insulin resistance, we investigated the association of circulating levels of several adipokines with incident diabetes in a prospective study of the CRISPS cohort. FGF21 was superior to other adipokines and could match the performance of 2-hour plasma glucose during OGTT in predicting incident diabetes in 9 years. The findings suggest that while various adipokines are mechanistically involved in the development of diabetes, FGF21 may have the greatest potential to be the biomarker for predicting diabetes and other obesity-related diseases. Non-laboratory-based diabetes risk assessment tools can help to identify individuals at risk of undiagnosed diabetes. We validated the two American Diabetes Association (ADA) recommended screening methods and found that the ADA risk test was the preferred test with high negative predictive value and fewer people would be submitted to confirmatory blood tests. We also developed a three-component risk score for screening of undiagnosed diabetes in Hong Kong. The score performed better than the ADA risk test when validated by an external cohort from Shaanxi. Moreover, individuals deemed as high-risk by this score but not found to have diabetes on initial blood tests were observed to have a higher chance of future diabetes development. The impact of including HbA1c in the diagnosis of diabetes and prediabetes was evaluated at the fourth CRISPS reassessment. We found that 54.5% of those with diabetes and 70.7% of the prediabetes participants were detected only by the HbA1c criteria, rendering it the better initial test compared with the OGTT. The large group of prediabetes individuals diagnosed only by HbA1c had cardiometabolic risk profiles intermediate between impaired fasting glucose/impaired glucose tolerance and normal participants. The HbA1c criteria hence have the advantage of early detection of at-risk participants who may benefit from prevention measures for cardiometabolic diseases. We have proposed a diabetes screening algorithm based on these findings, with the aim to facilitate early diagnosis of diabetes in Hong Kong, where the model of disease management has started to shift to a more preventive approach.