Faculty Bibliography

OBJECTIVE: To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS: We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (>/=8.6 mmol/L) versus 2-h (>/=7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement. RESULTS: Median age was 48 years (interquartile range [IQR] 48-49). During follow-up (median 33 years [IQR 24-37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90-3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (C index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality. CONCLUSIONS: The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.

AIMS/HYPOTHESIS: In addition to blood glucose concentrations measured in the fasting state and 2 h after an OGTT, intermediate measures during an OGTT may provide additional information regarding a person's risk of future diabetes and cardiovascular disease (CVD). First, we aimed to characterise heterogeneity of glycaemic patterns based on three time points during an OGTT. Second, we compared the incidences of diabetes and CVD and all-cause mortality rates among those with different patterns. METHODS: Our cohort study included 5861 participants without diabetes at baseline from the Danish Inter99 study. At baseline, all participants underwent an OGTT with measurements of plasma glucose levels at 0, 30 and 120 min. Latent class mixed-effects models were fitted to identify distinct patterns of glycaemic response during the OGTT. Information regarding incident diabetes, CVD and all-cause mortality rates during a median follow-up time of 11, 12 and 13 years, respectively, was extracted from national registers. Cox proportional hazard models with adjustment for several cardiometabolic risk factors were used to compare the risk of diabetes, CVD and all-cause mortality among individuals in the different latent classes. RESULTS: Four distinct glucose patterns during the OGTT were identified. One pattern was characterised by high 30 min but low 2 h glucose values. Participants with this pattern had an increased risk of developing diabetes compared with participants with lower 30 min and 2 h glucose levels (HR 4.1 [95% CI 2.2, 7.6]) and participants with higher 2 h but lower 30 min glucose levels (HR 1.5 [95% CI 1.0, 2.2]). Furthermore, the all-cause mortality rate differed between the groups with significantly higher rates in the two groups with elevated 30 min glucose. Only small non-significant differences in risk of future CVD were observed across latent classes after confounder adjustment. CONCLUSIONS/INTERPRETATION: Elevated 30 min glucose is associated with increased risk of diabetes and all-cause mortality rate independent of fasting and 2 h glucose levels. Therefore, subgroups at high risk may not be revealed when considering only fasting and 2 h glucose levels during an OGTT.

In view of the increasing burden of Type 2 diabetes on healthcare systems, considerable attention has been focused on identifying and treating individuals at high risk of the disease. This has led to the designation of 'prediabetes or intermediary hyperglycaemia', describing a fasting, 2-h plasma glucose (PG) or HbA1c level above the so-called normal range, but below that defining diabetes. According to the International Diabetes Federation, 318 million adults aged 20-79 years had prediabetes in 2015, and this is expected to rise to 481 million by 2040 [1]

AIM: The objective of the study was to compare the diagnosis of dysglycemic states by conventional oral glucose tolerance test (OGTT) criteria (fasting and 2-h plasma glucose) with the 1-h post-load plasma glucose level. MATERIAL AND METHODS: 34 individuals (mean age: 55+/-13years; BMI: 27.7+/-6.3kg/m2) at risk for prediabetes were administered a 75g OGTT. Individuals with normal glucose tolerance (NGT) or prediabetes were identified according to fasting and/or 2-h plasma glucose (PG) concentrations. Subsequently, subjects were divided in 2 groups: group 1 (n=21) with a 1-h PG<155mg/dl and group 2 (n=13) with a 1-h PG>/=155mg/dl. HOMA was performed to assess beta-cell function and insulin sensitivity. RESULTS: NGT or prediabetes based on conventional criteria correlated with the 1-h PG/=155mg/dl (p<0.001). Moreover, the 1-h PG>/=155mg/dl was associated with higher HbA1c levels (6.1+/-0.5 vs. 5.5+/-0.3%, p<0.001) and significantly impaired insulin secretion and hyperbolic product (BxS) on HOMA test vs. 1-h PG<155mg/dl. CONCLUSION: The 1-h post-load plasma glucose value >/=155mg/dl is strongly associated with conventional criteria for (pre)diabetes and alterations of beta-cell function.

Identifying the earliest time point on the prediabetic continuum is critical to avoid progressive deterioration in beta-cell function. Progressively rising glucose levels even within the "normal range" occur considerably late in the evolution to diabetes thus presenting an important opportunity for earlier diagnosis, treatment, and possible reversal. An elevated 1 h postprandial glucose level, not detected by current diagnostic standards, may provide an opportunity for the early identification of those at risk. When the 1 h post-load glucose level is elevated, lifestyle intervention may have the greatest benefit for preserving beta-cell function and prevent further progression to prediabetes and diabetes. In view of the considerable consistent epidemiologic data in large disparate populations supporting the predictive capacity of the1 h post-load value for predicting progression to diabetes and mortality, the time is therefore ripe to evaluate this hypothesis in a large, prospective multicenter randomized trial with lifestyle intervention.

The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders.

AIMS: The present study assessed the longitudinal association of an elevated 1-h plasma glucose [1-h-PG >8.6mmol/l (155mg/dl)] with and without impaired glucose tolerance [IGT; 2-h-PG 7.8-11.0mmol/l (140-199mg/dl)] with cumulative incident of diabetes and prediabetes over 25years in a non-diabetic cohort. METHODS: From 1979 to 1984, 1970 non-diabetic men and women completed an oral glucose tolerance test (OGTT), physical and biochemical measurements as well as a questionnaire related to lifestyle and medical background. During the years 2000-2004, 853 survivors of the original cohort were interviewed and re-examined for glycemic progression. RESULTS: Individuals with 1-h-PG >8.6mmol/l (155mg/dl) but with 2-h-PG <7.8mmol/l (140mg/dl) had a significantly elevated risk, compared to those with both 1-h-PG 8.6mmol/l (155mg/dl) and 2-h-PG <7.8mmol/l (140mg/dl), for both diabetes [OR:4.35 (95%CI: 2.50-7.73)] and prediabetes outcomes [OR:1.87 (95%CI 1.09-3.26)], adjusted for sex and age, smoking, body mass index, blood pressure, fasting blood glucose and insulin. CONCLUSIONS: The risk for diabetes associated with a 1-h level >8.6mmol/l (155mg/dl) is increased and further worsened in the presence of IGT. Identifying individuals at risk with a 1-h-PG glucose level during an OGTT is recommended.

BACKGROUND: To study the ability of the 30-minute plasma glucose (30 min-PG) during an oral glucose tolerance test (OGTT) to predict the future risk of type 2 diabetes (T2DM), among Asian Indians with impaired glucose tolerance (IGT). METHODS: For the present analyses, we utilized data from 753 participants from two diabetes primary prevention studies, having complete data at the end of the study periods, including 236 from Indian Diabetes Prevention Programme-1 (IDPP-1) and 517 from the 2013 study. Baseline 30-min PG values were divided into tertiles: T1 < 9.1 mmol/l (<163.0 mg/dl); T2 9.2-10.4 mmol/l (164.0-187.0 mg/dl) and T3 > 10.4 mmol/l(>/=188 mg/dl).The predictive values of tertiles of 30-min PG for incident diabetes were assessed using Cox regression analyses RESULTS: At the end of the studies 230 (30.5%) participants developed diabetes. Participants with higher levels of 30-min PG were more likely to have increased fasting, 2hrPG and HbA1c levels, increased prevalence to impaired fasting glucose (IFG), and decreased beta cell function. The progression rate of diabetes increased with increasing tertiles of 30-min PG. Cox's regression analysis showed that 30-min PG was an independent predictor of incident diabetes after adjustment for an array of covariates (HR:1.44 [1.01-2.06]) CONCLUSIONS: This prospective analysis demonstrates, for the first time, an independent association between an elevated 30-min PG level and incident diabetes among Asian Indians with IGT. Predictive utility of glycemic thresholds at various time points other than the traditional fasting and 2 hr PG values should therefore merit further consideration.