Faculty Bibliography

OBJECTIVE:One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS/METHODS:. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS:Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS:The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.

Evidence from populations at risk for type 1 diabetes, type 2 diabetes or gestational diabetes substantiates the 1-hour plasma glucose as a sensitive alternative marker for identifying high-risk individuals when ß-cell function is relatively more functional. An elevated 1-hour plasma glucose could therefore diagnose dysglycemia and risk for complications across the glycemic spectrum. Reducing the 2-hour oral glucose tolerance test to 1-hour would reduce the burden on patients, likely reduce costs, and enhance its accessibility in practice.

Whether an OGTT reproducibly detects either type 2 diabetes (T2D) or prediabetes in Africans in unknown. Therefore, 131 Africans had two OGTT. Diagnostic reproducibility for T2D was excellent (κ = 0.84), but only moderate for prediabetes (κ = 0.51). A single OGTT positive for T2D may be sufficient to guide clinical care and inform epidemiologic study design. ClinicalTrials.gov Identifier: NCT00001853.

Many healthcare providers screen high-risk individuals exclusively with an HbA1c despite its insensitivity for detecting dysglycemia. The two cases presented describe the inherent caveats of interpreting HbA1c without performing an oral glucose tolerance test (OGTT). The first case reflects the risk of over-diagnosing type 2 diabetes (T2D) in an older African American male in whom HbA1c levels, although variable, were primarily in the mid- prediabetes range (5.7-6.4% [39-46 mmol/mol]) for many years although the initial OGTT demonstrated borderline impaired fasting glucose (IFG) with a fasting plasma glucose (FPG) of 102 mg/dl [5.7 mmol/L]) without evidence for impaired glucose tolerance (IGT) (2-hour glucose >140-199 mg/dl ([7.8 -11.1 mmol/L]). As subsequent HbA1c levels were diagnostic of T2D (6.5-6.6% [48-49 mmol/mol]), a second OGTT performed was normal. The second case illustrates the risk of under-diagnosing T2D in a male with HIV having normal HbA1c levels over many years who underwent an OGTT when mild prediabetes [HbA1c = 5.7% (39 mmol/mol)] developed which was diagnostic of T2D. To avoid inadvertent mistreatment, it is therefore essential to perform an OGTT, despite its limitations, in high-risk individuals particularly when glucose or fructosamine and HbA1c values are discordant. Innate differences in the relationship between fructosamine or fasting glucose to HbA1c are demonstrated by the glycation gap or hemoglobin glycation index.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians, Inc., and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes the establishment of a Diabetes Prevention Clinic for veterans with prediabetes.

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Prediabetes is a highly prevalent metabolic disorder. Screening is mandatory, since this condition is associated, in the absence of treatment, with an increased risk of developing diabetes and related complications, in particular cardiovascular. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose and/or glycemia at 120 min of a 75-gram oral glucose tolerance tests [OGTT] and/or the glycated hemoglobin [HbA1c]). Substantial recently published data suggests that diagnosis of prediabetes based on current criteria is already "delayed" in the natural evolution of dysglycemia. In contrast, a glucose level greater than 155 mg/dL (8.6 mmol/L) at 60 minute of the OGTT could be an earlier marker for risk of hyperglycemia than the 120 minute value, in individuals with normal glucose tolerance, before "prediabetes" is detected as conventionally defined. This parameter is also associated with better performance in terms of prediction of diabetes, macroangiopathy and mortality, when compared with conventional tests. The 1-hour postload OGTT could therefore replace current criteria for diagnosis of early metabolic abnormalities, in particular in the presence of discordant results from traditional first line tests (fasting glucose and HbA1c), leading to a more rapid therapeutic intervention.

INTRODUCTION:Risk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown. OBJECTIVE:We performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L. METHODS:Glucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic. RESULTS:One-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628). CONCLUSIONS:Although dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.