Diagnosis and validation in epidemiological studies

The diagnosis of diabetes in epidemiological field surveys is logistically more complex than the diagnosis of diabetes in clinical settings. Additional challenges include the feasibility of carrying out repeated glucose plasma measures on the same population sample (World Health Organization, 2006), processing a large number of blood specimens, and the high cost and inconvenience for both the study participants and the research team (Gavin et al., 1997). In 1997, the ADA recommended that estimates of diabetes incidence and prevalence in epidemiological studies should be made using a FPG test with the diagnostic level set at > 7.0mmol/l. This recommendation was based on this test’s good reproducibility, its low within-person variability, and its low cost compared to the ‘gold standard’ OGTT (Gavin et al., 1997).

Although many epidemiological studies have used the FPG test to diagnose both the incidence and prevalence of T2DM (Fox et al., 2007, Aekplakorn et al., 2011, Wang et al., 2009), this diagnostic method has been found to have flaws. Findings from seven Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe studies showed that the prevalence of diabetes diagnosed by the FPG test was much lower than the prevalence found by diagnosing with the 2 hour plasma glucose test (DECODE Study Group and European Diabetes Epidemiology Study Group, 1998). In addition to this, the FPG test has also been criticized for its low sensitivity for diagnosing mild to moderate degrees of impaired glucose tolerance and for its requirement of a long fast that cannot be guaranteed with multiple participants (King and Rewers, 1993).

The WHO has recommended the use of the OGTT, measuring the plasma glucose level 2 hours after a 75-g oral glucose load, for the diagnosis of impaired glucose tolerance and diabetes in epidemiological studies (field studies carried out in non-clinical settings). This recommendation reflects the higher specificity and sensitivity of the 2-hour OGTT when compared to the FPG test (King and Rewers, 1993). For example, the OGTT was more sensitive than the HbA1c test and the FPG test for diagnosing diabetes among Asian Americans (Herman and Zimmet, 2012).

Notwithstanding the wide use of the 2 hour OGTT in epidemiological studies (Ramachandran et al., 2004, Singh et al., 1998, Peng et al., 2000), in recent years both the ADA and the WHO have noted the advantages of using the HbA1c test to diagnose Chapter 1 :Introduction

diabetes (Chen et al., 2012a). This observation applies when haemoglobin dynamics are normal and a certified laboratory A1c test is used (American Diabetes Association, 2013). An A1c diagnosis is convenient for the participant as it does not require a fast, or 2-hour time point for blood collection. As well, the A1c test has low day-to-day variation and diagnostic levels can be set to correspond to detectable retinopathy. However, the A1c test has several problems. Not only is it a more expensive test than the FPG, it may not be feasible in some developing countries due to lack of accessible laboratories that conduct the test using a certified method. Furthermore, epidemiological studies have found that glycation rates may vary by ethnicity. One study found that even when FPG levels were matched, African Americans with and without diabetes had higher HbA1c levels than non-Hispanic whites (American Diabetes Association, 2012). Furthermore, A1c levels increase with age, and as such may be less reliable for diagnosing diabetes in older patients (Huang et al., 2013). A1c levels are also affected by abnormal haemoglobins, high red cell turnover, anemia, and pregnancy (American Diabetes Association, 2012).

Recognizing the limitations of selecting the appropriate diagnostic criteria, recent incidence and prevalence cohort studies of diabetes have used a combination of diagnostic criteria. These have included medication use (Chang et al., 2010), self-reported doctor diagnosis (Maskarinec et al., 2009), and/or hospital records (Okura et al., 2004), as well as the FPG test and OGTT (Wang and Hoy, 2004), and/or HBA1c (Gribble et al., 2012). Evidently the diagnosis of diabetes and glucose intolerance in epidemiological studies is complex and will depend largely on the type of study being conducted, the attributes of the participants involved (e.g. ethnicity, age, pregnancy, hemoglobinopathy, and anemia), and the resources available in the country and area of study. The diagnostic criteria selected will have implications for the incidence and prevalence findings, and for the comparability and validity of these findings (NCD Risk Factor Collaboration, 2016).

1.4.2.1 Self-reported diabetes

Self-report of doctor diagnosis is one of the most common methods used to measure diabetes in observational studies of populations (Rylander et al., 2014, Kurotani et al., 2013, Schneider et al., 2012, Minges et al., 2011). Although self-report is convenient, non-intrusive, and requires fewer resources, its validity and reliability may be in question

(Comino et al., 2013). Issues around the reliability and validity of a self-reported health condition may include the misunderstanding of the questionnaire, lack of formal diagnosis or treatment, an individual’s personal characteristics (i.e. age and sex), and/or the type of disease in question (Goto et al., 2013, Okura et al., 2004, Kriegsman et al., 1996).

A few studies have measured the reliability and validity of self-reported diagnosis of diabetes by assessing its level of agreement with other ‘gold standards’. These measures have included physical examinations and medical records (Pastorino et al., 2014, Kriegsman et al., 1996, Haapanen et al., 1997), of which medical records have been found to have an agreement with self-report as high as 98% (Manson et al., 1991). Medical records have also been linked, revealing that self-report has 81% sensitivity and 98% specificity for diabetes recorded in patient admission records combined with medical and diagnostic service records)(Comino et al., 2013). Using fasting glucose or medication use as the gold standard, self-report has moderate sensitivity (59-71%) and high specificity (96-97%) for prevalent diabetes and a similar performance for incident diabetes (62-80% sensitivity and 87-89% specificity).

Self-report has also been tested against HbA1c measurement (59-64% sensitivity and 84- 87% specificity for incident diabetes) (Schneider et al., 2012), and against fasting glucose or OGTT or HbA1c (70% sensitivity point estimate and 97% specificity point estimate) (Goto et al., 2013). It has also been tested against telephone interview by a study physician and/or using a combination of these measures (Pradhan et al., 2001). Overall, the findings from these studies suggest that self-report detects diabetes with a moderate to high sensitivity and specificity (Schneider et al., 2012, Pastorino et al., 2014). This accuracy of self-report has been attributed to the well-defined diagnostic criteria of diabetes and the requirement for treatment after diagnosis (Margolis et al., 2008, Schneider et al., 2012).

However, these findings may not be generalizable to all study populations. Some of these validation studies were carried out with cohorts that only included women (Manson et al., 1991, Rylander et al., 2014, Pradhan et al., 2001), a specific age range (Comino et al., 2013, Goldman et al., 2003) and/or of specific ethnicity (Odegaard and Pereira, 2013). The few studies that have assessed the validity of self-reported diabetes in Asian Chapter 1 :Introduction

populations suggest that Asian populations may have higher levels of misreporting than Western populations, which may link to traditional cultural beliefs (Goto et al., 2013) Therefore, the validity of self-reported diabetes needs to be assessed in each study population before being used for epidemiological investigations.