Which biochemical assay is best for measuring diabetes prevalence?
Authors: Lydia E Makaroff, David Cavan
Journal: The Lancet Diabetes & Endocrinology (2015)

Accurate assessments of diabetes prevalence are needed to allocate resources for treating patients and monitoring treatment coverage. Researchers need methods of making population-wide assessments of diabetes that are cost effective, precise, and reliable. Because up to half of all diabetes cases might be undiagnosed,1International Diabetes FederationIDF Diabetes Atlas 6th edition update for 2014. International Diabetes Federation, Brussels, Belgium2014http://www.idf.org/diabetesatlasGoogle Scholar one of three biochemical tests are used to estimate diabetes prevalence. Fasting plasma glucose (FPG) is a measure of glucose concentrations after the person has refrained from eating or drinking anything other than water for 12 h. The oral glucose tolerance test (OGTT) measures the changes in blood glucose after a fixed amount of glucose has been administered. HbA1c does not directly measure blood glucose, but represents the average amount of glucose in the blood in the past 2–3 months.2American Diabetes AssociationDiagnosis and classification of diabetes mellitus.Diabetes Care. 2014; 37: S81-S90Crossref PubMed Scopus (3675) Google Scholar The degree to which these different measures correlate in diverse geographical and ethnic populations has largely been unanswered. The question of whether these measures give comparable results is particularly important when comparing data from resource-poor countries. Diabetes affects an estimated 8·3% of adults (aged 20–79 years) worldwide, and varies with geographical region, from 5·1% in sub-Saharan Africa to 11·4% in North America and the Caribbean.1International Diabetes FederationIDF Diabetes Atlas 6th edition update for 2014. International Diabetes Federation, Brussels, Belgium2014http://www.idf.org/diabetesatlasGoogle Scholar At present, high quality diabetes surveys are available for only 57% of 221 countries and territories worldwide, and only 19% of countries have OGTT-based results.1International Diabetes FederationIDF Diabetes Atlas 6th edition update for 2014. International Diabetes Federation, Brussels, Belgium2014http://www.idf.org/diabetesatlasGoogle Scholar Instead, many countries with limited resources use the simple and standardised WHO STEPwise approach to Surveillance (STEPS) protocol for risk factor surveillance, published in 2005. The STEPS core risk factors include demographic information, health behaviours, BMI, waist circumference, and blood pressure. WHO recommends that well-resourced countries also analyse FPG, with an optional module for OGTT.3WHO Noncommunicable Diseases and Mental HealthWHO STEPS surveillance manual: the WHO STEPwise approach to chronic disease risk factor surveillance. World Health Organization, Geneva, Switzerland2005http://apps.who.int//iris/handle/10665/43376Google Scholar When it was first correlated to FPG in the late 1970s, HbA1c was unstandardised.4Koenig RJ Peterson CM Jones RL Saudek C Lehrman M Cerami A Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus.N Engl J Med. 1976; 295: 417-420Crossref PubMed Scopus (1049) Google Scholar However, by 2009, technology had improved to such a degree that an international expert committee appointed by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation recommended that a standardised HbA1c test done in a laboratory could be used to diagnose type 2 diabetes.5The International Expert CommitteeInternational Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes.Diabetes Care. 2009; 32: 1327-1334Crossref PubMed Scopus (2387) Google Scholar An HbA1c of 6·5% (48 mmol/mol) or higher is diagnostic for diabetes, although a value below this threshold does not exclude diabetes. In The Lancet Diabetes & Endocrinology, the NCD Risk Factor Collaboration has done a global meta-analysis of various methods of assessing national and subnational prevalence of diabetes.6NCD Risk Factor Collaboration (NCD-RisC)Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participants. Lancet Diabetes Endocrinol; published online June 22.http://dx.doi.org/10.1016/S2213-8587(15)00129-1Google Scholar They concluded that prevalence estimates based on FPG only and those based on FPG or 2hOGTT had a very strong correlation (r=0·98), and HbA1c-based definitions had a lower (although still strong) correlation (r=0·91) with FPG-based definitions. Prevalence based on HbA1c was lower than prevalence based on FPG in 42·8% of cases and higher in 41·5%. HbA1c was less sensitive than FPG only and than FPG or 2hOGTT for detecting undiagnosed diabetes. The identification of previously undiagnosed diabetes based on HbA1c had a pooled specificity (true negative rate) of 99·7% and a pooled sensitivity (true positive rate) of 52·8% compared with FPG, and a sensitivity of 30·5% compared with FPG or 2hOGTT.6NCD Risk Factor Collaboration (NCD-RisC)Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participants. Lancet Diabetes Endocrinol; published online June 22.http://dx.doi.org/10.1016/S2213-8587(15)00129-1Google Scholar These results will affect the design of epidemiological studies. Researchers should consider resources and population characteristics when deciding whether to use FPG, OGTT, or HbA1c tests. Testing FPG is faster than testing OGTT, and needs less equipment and staff training. However, it does require the person to have fasted, which cannot be guaranteed. An HbA1c test can be done at any time, requires no fasting or glucose consumption, and the sample is relatively stable at room temperature. However, the HbA1c test must be standardised and done in a certified laboratory, and cannot be used in a population with a condition that changes red blood cell turnover, such as chronic malaria.5The International Expert CommitteeInternational Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes.Diabetes Care. 2009; 32: 1327-1334Crossref PubMed Scopus (2387) Google Scholar Furthermore, the NCD Risk Factor Collaboration reported that the relation between glucose-based and HbA1c-based prevalences varied with national income, year of study, and BMI.6NCD Risk Factor Collaboration (NCD-RisC)Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participants. Lancet Diabetes Endocrinol; published online June 22.http://dx.doi.org/10.1016/S2213-8587(15)00129-1Google Scholar This finding, together with the reduced sensitivity in detecting undiagnosed diabetes, suggests that, under existing diagnostic criteria, an HbA1c test should be supplemented with a glucose-based test in assessments of population-level prevalence. Nevertheless, the high degree of correlation reported by the NCD Risk Factor Collaboration suggests some flexibility might be possible in using different measurement strategies in different contexts, increasing the ease of producing a worldwide estimate of present and future epidemiological patterns for diabetes. DC and LEM are employed by an organisation that receives funding from AstraZeneca, Bayer HealthCare, BD, Boehringer Ingelheim, Bupa, Julphar Diabetes, Landmark Group, Lilly Diabetes, Medtronic, Merck, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Diabetes, Servier, and Takeda. Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331 288 participantsDifferent biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA1c-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test. Full-Text PDF Open Access