Epidemiology of Type 2 Diabetes

Type 2 diabetes has been diagnosed based on elevated glycemic levels that are quantified using different laboratory means in random, fasting or post-challenge status. The evolution of the diagnostic criteria for type 2 diabetes can be roughly divided into three different development stages according to the scientific basis upon which the criteria was developed. In 1950s to 1960s the diagnostic cut-off values were set solely on the basis of statistical estimate (mean±2SD). The reports of the bimodal distribution of fasting and 2h post-load glucose concentrations in certain populations and their relationships with retinopathy provided clinical evidence for making the diagnostic criteria for diabetes in 1979. On the basis of findings from studies on prevalence of retinopathy in 1990s the current diagnostic criteria was made based on either glucose or HbA1c levels. Although the definitions were evidence based, classifications of individuals with hyperglycemia based on different glycemic assays and criteria are not completely concordant. In this chapter the important scientific events and the milestones achieved during the evolution of the diagnostic criteria are traced back which may serve as a stimulus for the future research to improve the diagnostic criteria for diabetes.

Type 2 diabetes mellitus, with an increasing prevalence in both developing and developed countries, has become one of the major health threats to the human being. According to the International Diabetes Federation (IDF), the number of patients with diabetes is 285 million in the year of 2010 and will rise to 438 million in 2030. The greater increase will occur in the developing countries than in developed world. Most recent data have shown that the prevalence of diabetes increased about 9 folds from 1980 (1.0%) to 2008 (9.7%) in China. This explosive increase in prevalence of diabetes is mostly attributed to the increase in risk profiles at a population level including population aging, obesity, physically inactive and unhealthy diet. Diabetes prevention programs that target lifestyle intervention are urgently needed.

Under increasing burden of diabetes and in the light of evidences it is clear that diabetes and its complication are preventable, screening for diabetes, which aims at early detecting and treating patients with diabetes to reduce the diabetic complications, and at the same time identifying individuals at high risk for diabetes to prevent or delay the onset of diabetes, has been recommended by several professional organizations such as the World Health Organization, the International Diabetes Federation, and the American Diabetes Association. Various screening programs have been developed and conducted by applying different screening tools including fasting or random capillary blood glucose tests, fasting and post challenge plasma glucose tests, HbA1c test, and a number of risk assessment questionnaires (or scores). The cost-effectiveness and the impact on the participants of these screening programs have not been fully evaluated, but the screening tests used in these programs have been validated in terms of discrimination, calibration and reclassification of individuals with and without the events.

Obesity is a well known major modifiable risk factor for type 2 diabetes and as many as 25 other chronic conditions. The prevalences of obesity and obesity-related metabolic disorders, such as type 2 diabetes and many others, are increasing in both the developed and the developing world. Public health programmes that encourage people at individual and community levels to adopt healthy lifestyle are urgently needed to tackle the globally felt burden imposed by obesity. Based on current evidence BMI or Waist Circumference (WC) or Waist-To-Hip Ratio (WHR) predict or are associated with type 2 diabetes independently. It remains an open question as to which of these obesity indicators is best at predicting type 2 diabetes. Therefore both BMI and WC can be used as surrogate measures of obesity. The fact that diabetes prevalence varies markedly among different ethnic groups for the same BMI or WC suggests uniform cutoff values can not be applied on a worldwide basis. Longitudinal studies are needed to clarify the mechanism by which body composition, body fat distribution, genetic, social, cultural and behavioural factors predispose individuals to type 2 diabetes.

Dyslipidemia is one of the major risk factors for Cardiovascular Disease (CVD) that coexists with diabetes. It plays an important role in the development and progress of atherosclerosis, the underlying pathogenesis of CVD. Hyperglycemia is associated with adverse lipid profiles. An atherogenic lipid profile, consisting of high Triglycerides (TG) and small dense Low-Density Lipoprotein Cholesterol (LDL-C) and low High-Density Lipoprotein Cholesterol (HDL-C), is common not only in patients with overt diabetes but also in individuals with prediabetes. The impact of dyslipidemia on risk of CVD in patients with hyperglycemia has been extensively studied. Reduced HDL-C is well documented as an independent predictor of CVD events, the role of TG as an independent risk factor for CVD is, however, controversial. Recently, the interest to use novel parameters such as total cholesterol (TC) to HDL ratio (TC/HDL-C), non- HDL-cholesterol (non-HDL-C), apolipoprotein B (apoB) and apolipoprotein A (apoA) to assess CVD risk has increased. This chapter provides a comprehensive review of the physiology, pathophysiology, prognosis and management of dyslipidemia in individuals with different glycemic levels. The ethnic differences in occurrence of dyslipidemia are also addressed.

We began this chapter by summarizing the definition of hyperuricemia and its increasing prevalence in different ethnic groups that accompany the increase in obesity, diabetes and metabolic syndrome worldwide. This was followed by a discussion on complex associations between serum Uric Acid (UA) and Fasting and 2-hour Plasma Glucose (FPG and 2hPG) in both pre-diabetes and diabetic patients. The UA-glucose association was positive in the low FPG and low 2hPG distributions, but negative in the upper FPG and 2hPG distributions. In spite of inconsistent findings among studies, most prospective data found that higher levels of baseline UA predicted a future risk of developing type 2 diabetes independently. The direction of causality between value of UA and the development of type 2 diabetes is, however, uncertain. Further studies to investigate the pathophysiological mechanism underlying the relationship between glucose, UA and cardio-metabolic risk factors are gravely needed.

It has been proposed that diabetes was associated with an increased risk of cancer mortality and morbidity. Complex mechanisms are involved in the association between diabetes and cancer. Metformin has been suggested to reduce the risk of cancer incidence (Hazard ratio 0.63 (95% CI 0.53- 0.75)) or cancer mortality (Hazard ratio 0.43 (95% CI 0.23-0.80)), but insulin or sulfonylurea is suspected to increase the risk of cancer incidence (Hazard ratio 1.36 (95% CI 1.19-1.54)) or cancer mortality (Hazard ratio 1.30 (95% CI 1.10-1.60)). Evidences on these issues are reviewed and summarized in this chapter.

Both micro-vascular and macro-vascular complications increase premature deaths in patients with diabetes. Hypertension, Coronary Heart Disease (CHD) and ischemic stroke are known to be highly prevalent among patients with diabetes. Cardiovascular Disease (CVD) accounts for 80% of deaths in people suffering from diabetes. There is strong evidence that diabetes is an independent risk factor for cardiovascular mortality. In addition, non-diabetic hyperglycemia defined as Impaired Fasting Glucose (IFG) or Impaired Glucose Tolerance (IGT) was also associated with risk of CVD in some, but not in all studies. Randomized controlled clinical trials have confirmed that intensive glucose control can reduce the risk of micro-vascular complications among patients with diabetes. However, whether intensive glycemic control is of great benefit to CVD reduction among patients with diabetes or impaired glucose tolerance is still inconclusive. The association between glycemic levels and risk of hypertension, CHD and ischemic stroke will be discussed in this chapter.