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QUESTION: In a multiethnic cohort randomly assembled in Canada, is a combination of fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) more accurate than FPG alone for diagnosing impaired glucose tolerance (IGT) and diabetes?
Optimal diagnostic criteria using FPG, 2 hour post glucose load plasma glucose, and HbA1c to identify patients with IGT and diabetes were determined (using the 1998 WHO diagnostic criteria as the “gold standard”) and compared. Cut points were determined from receiver operating characteristic curves.
3 cities in Canada.
936 Canadians of South Asian, Chinese, and European descent.
Description of tests and diagnostic standard
FPG and 2 hour post glucose load (ie, after ingestion of 75 g of oral glucose) plasma glucose were measured using enzymatic methods with a hexokinase reference. HbA1c was analysed using high performance liquid chromatography. The 1998 WHO diagnostic criteria were used as the “gold standard” to classify the participants into 3 categories: normal (FPG <7.0 mmol/l and a 2 h glucose <7.8 mmol/l), IGT (FPG <7.0 mmol/l and a 2 h glucose 7.8–11.0 mmol/l), or diabetic (FPG ≥7.0 mmol/l or a 2 hour glucose ≥11.1 mmol/l). The American Diabetes Association criteria were also applied, and participants were classified into the 3 categories: normal (FPG <6.1 mmol/l), impaired fasting glucose (FPG 6.1–6.9 mmol/l), or diabetic (FPG ≥7.0 mmol/l).
Main outcome measures
Sensitivity and specificity, and positive and negative likelihood ratios.
According to WHO criteria, 6.4% and 15.2% of participants had diabetes and IGT, respectively. FPG and HbA1c optimal cut points, with the corresponding sensitivity and specificity and positive and negative likelihood ratios for diagnosing diabetes, are in the table; combining FPG and HbA1c improved the specificity and positive likelihood ratio (table). The American Diabetes Association criteria had a sensitivity of 48% (95% CI 36 to 61) for diagnosing diabetes. FPG or HbA1c alone or in combination did not yield satisfactory diagnostic properties for diagnosing IGT.
In a multiethnic cohort randomly assembled in Canada, a combination of fasting plasma glucose and glycosylated haemoglobin had greater specificity and positive likelihood ratio than fasting plasma glucose alone for diagnosing diabetes.
In the study by Anand et al, the overall sensitivity of fasting glucose (American Diabetes Association recommendations) for diagnosing diabetes was low (48%). A dual cut point of FPG ≥5.7 mmol/l and HbA1c ≥5.9% had a sensitivity of 72% and a specificity of 95%, and in South Asian people 85% and 91%, respectively.
In clinical practice, we prefer to know which patients with normal or impaired FPG have diabetes according to the oral glucose tolerance test (OGTT). Patients with cardiovascular risk factors and increased risk of mortality cluster in this group.1–2 If they have abnormal glucose metabolism, different follow up and management may be required. In patients with FPG <7.0 mmol/l, can we limit further work up for diabetes to those at high risk of diabetes, or with cardiovascular risk factors or impaired FPG? Because of the burden of screening a large population we have no other choice, although in certain populations the FPG levels might miss a small percentage of patients with diabetes. If we decide to continue beyond determination of FPG levels, do we offer an OGTT, determination of HbA1c, or close follow up with repeated determinations of FPG? OGTT may offer better sensitivity and specificity for development of macrovascular and microvascular complications of diabetes. Besides the high cost, HbA1c measurement requires additional testing to evaluate its performance.
Although the question about screening does not have clear cut answers, some conclusions may be drawn: Firstly, persons with normal or impaired FPG should be stratified according to their risk of diabetes. Factors to consider include ethnic origin, obesity, and family history. A formal index should be developed and validated for that purpose. Secondly, persons at high risk of diabetes and cardiovascular morbidity should be closely followed even if FPG is normal. Thirdly, the decision to use OGTT, or a combination of FPG values and HbA1c or close follow up depends on the local population, as well as the cost of the tests. Fourthly, serious and continuous effort should be made in these patients to modify risk factors and maintain healthy life styles.
Sources of funding: not stated.
For correspondence: Dr S S Anand, McMaster University, Hamilton, ON, Canada.
Abstract and commentary also appear in ACP Journal Club.