Ram Jagannathan

Elevated 1-hour plasma glucose levels are associated with dysglycemia, impaired beta-cell function, and insulin sensitivity: a pilot study from a real world health care setting

Individuals with prediabetes, namely impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), are at increased risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, only 30–40 % of those with IFG/IGT eventually develop T2DM [1–3]. In fact, about 40 % of individuals who develop T2DM after 10 years have Normal Glucose Tolerance (NGT) at baseline [3], indicating that the conventional fasting and 2-h oral glucose tolerance test (OGTT) do not recognize most high-risk individuals. Recently, population-based studies have consistently shown that 1-h post-load glucose (PG) levels may be a better predictor of T2DM and associated complications [4– 7]. Furthermore, NGT individuals with elevated 1-h PG[ 8.6 mmol/l were found to be more insulin resistant, and have worse beta-cell function and an atherogenic profile similar to those with prediabetes [8, 9]. These results were from a research setting using well-defined cohorts. There is sparse information regarding the performance of a 1-h OGTT in a health care setting where the population may be more heterogeneous. Therefore, we investigated the pathophysiological associations of NGT with elevated 1 h ([8.6) glucose levels with dysglycemic conditions in a cohort of outpatients undergoing screening for T2DM.

One-hour post-load plasma glucose level during the OGTT predicts dysglycemia

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 24years 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.

Enhanced predictive capability of a 1-hour oral glucose tolerance test : A prospective population-based cohort study

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 (Harrell concordance 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.

Examining the Proportion of Dietary Phosphorus From Plants, Animals, and Food Additives Excreted in Urine

Phosphorus bioavailability is an emerging topic of interest in the field of renal nutrition that has important research and clinical implications. Estimates of phosphorus bioavailability, based on digestibility, indicate that bioavailability of phosphorus increases from plants to animals to food additives. In this commentary, we examined the proportion of dietary phosphorus from plants, animals, and food additives excreted in urine from four controlled-feeding studies conducted in healthy adults and patients with chronic kidney disease. As expected, a smaller proportion of phosphorus from plant foods was excreted in urine compared to animal foods. However, contrary to expectations, phosphorus from food additives appeared to be incompletely absorbed. The apparent discrepancy between digestibility of phosphorus additives and the proportion excreted in urine suggests a need for human balance studies to determine the bioavailability of different sources of phosphorus.

Reducing the prevalence of dysglycemia: is the time ripe to test the effectiveness of intervention in high-risk individuals with elevated 1 h post-load glucose levels?

Identifying the earliest time point on the prediabetic continuum is critical to avoid progressive deterioration in β-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 β-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.

Use of 1-h post-load plasma glucose concentration to identify individuals at high risk of developing Type 2 diabetes

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]. There is currently no international agreement on the definition of prediabetes. Because the American Diabetes Association, WHO and International Expert Committee have differing recommendations for diagnosing prediabetes, consensus is required to avoid confusion [2]. In clinical practice, neither impaired fasting glucose nor impaired glucose tolerance are considered clinical entities but rather as risk categories for development of Type 2 diabetes and cardiovascular disease. These definitions have varying sensitivities and specificities which, importantly, identify different, although overlapping, populations. Furthermore, longitudinal studies have shown that ~50–60% of those with prediabetes did not progress to diabetes, whereas ~30– 40% of people with diabetes had normal glucose tolerance at baseline [3]. More precise diagnostic measures are therefore needed to better stratify high-risk individuals. With this background, large-scale epidemiological and clinical studies have consistently demonstrated the superiority of an elevated 1-h post-load PG concentration [1-h PG ≥ 155 mg/dl (8.6 mmol/l)] during the 75 g oral glucose tolerance test in identifying high-risk individuals. AbdulGhani and DeFronzo [4] showed that 1-h PG concentration was superior to fasting, 2-h PG and HbA1c levels for predicting incident diabetes over 7–8 years in a high-risk Mexican-American cohort [4]. They also suggested the potential benefit of using elevated 1-h PG concentration in conjunction with Adult Treatment Panel III criteria for metabolic syndrome to stratify high-risk individuals [4]. The secondary analyses of the Malm€ o Preventive Project and Botnia study found that 1-h PG concentration was superior in predicting Type 2 diabetes; 1-h PG alone was superior to a prediction model consisting of conventional risk factors such as age, sex, BMI and parental history of diabetes [5]. Furthermore, 1-h PG performed significantly better than 2-h PG over 30 years [6]. These findings may be explained by the sensitivity of 1-h PG concentration for predicting b-cell functional integrity, paramount for preserving normal glucose tolerance, before progressive dysfunction occurs, leading to prediabetes or diabetes. Based on receiver-operating characteristic analysis, elevated 1-h PG level appears to be more specific and sensitive than either HbA1c or glucose thresholds in determining early changes in b cells. The decline in insulin sensitivity therefore occurs in the absence of prediabetes, the presence of which can result in further worsening and progressive deterioration with Type 2 diabetes. An elevated 1-h PG concentration should therefore be diagnosed before prediabetes becomes manifest [7]. A sub-analysis of the Diabetes Prevention Program showed that lifestyle intervention was more effective in those with preserved b-cell function at baseline [8]. Consistent with this, we found that pancreatic b-cell dysfunction occurs prior to prediabetes in those with normal glucose tolerance who have an elevated 1-h PG concentration [7]. We also demonstrated the importance of the elevated 1-h PG level for defining a high-risk population. In a real-life clinical setting, when comparing the accuracy of HbA1c and elevated 1-h PG with that of 2-h PG during the 75-g oral glucose tolerance test, the level of agreement was twofold greater for elevated 1-h PG than HbA1c categories defined by the American Diabetes Association [39–46 mmol/mol (5.7–6.4%)] and the International Expert Correspondence to: Michael Bergman. E-mail: michael.bergman@nyumc.org

Novel biomarkers for prediabetes, diabetes, and associated complications

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.

Lessons learned from the 1-hour post-load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1‐hour post‐load glucose level during the 75‐g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1‐hour post‐load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β‐cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2‐hour post‐load glucose values. An elevated 1‐hour post‐load glucose level was a better predictor of type 2 diabetes than isolated 2‐hour post‐load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1‐hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2‐hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1‐hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1‐hour post‐load level. Measurement of the 1‐hour PG level would increase the likelihood of identifying a larger, high‐risk group with the additional practical advantage of potentially replacing the conventional 2‐hour oral glucose tolerance test making it more acceptable in a clinical setting.

An elevated 1-h post- load glucose level during the oral glucose tolerance test detects prediabetes

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 β-cell function and insulin sensitivity. RESULTS NGT or prediabetes based on conventional criteria correlated with the 1-h PG<or≥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 β-cell function.

Sleep duration and physical activity profiles associated with self-reported stroke in the United States: Application of Bayesian Belief Network Modeling techniques.

Introduction: Physical activity (PA) and sleep are associated with cerebrovascular disease and events like stroke. Though the interrelationships between PA, sleep, and other stroke risk factors have been studied, we are unclear about the associations of different types, frequency and duration of PA, sleep behavioral patterns (short, average and long sleep durations), within the context of stroke-related clinical, behavioral, and socio-demographic risk factors. The current study utilized Bayesian Belief Network analysis (BBN), a type of machine learning analysis, to develop profiles of physical activity (duration, intensity, and frequency) and sleep duration associated with or no history of stroke, given the influence of multiple stroke predictors and correlates. Such a model allowed us to develop a predictive classification model of stroke which can be used in post-stroke risk stratification and developing targeted stroke rehabilitation care based on an individuals profile. Method: Analysis was based on the 2004–2013 National Health Interview Survey (n = 288,888). Bayesian BBN was used to model the omnidirectional relationships of sleep duration and physical activity to history of stroke. Demographic, behavioral, health/medical, and psychosocial factors were considered as well as sleep duration [defined as short < 7 h. and long ≥ 9 h, referenced to healthy sleep (7–8 h)], and intensity (moderate and vigorous) and frequency (times/week) of physical activity. Results: Of the sample, 48.1% were ≤ 45 years; 55.7% female; 77.4% were White; 15.9%, Black/African American; and 45.3% reported an annual income <