Faculty Bibliography

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.
Copyright

Context/UNASSIGNED:Early prediction of dysglycaemia is crucial to prevent progression to type 2 diabetes. The one-hour post-load plasma glucose (1-h PG) has been reported a better predictor of dysglycaemia than fasting plasma glucose (FPG), 2-h PG, or glycated haemoglobin (HbA1c). Objective/UNASSIGNED:To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and plasma glucose (PG) and serum insulin (INS) levels during a 75-gram oral glucose tolerance test (OGTT). Design and Setting/UNASSIGNED:We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 individuals in the Botnia Prospective Study, 146 of whom progressed to type 2 diabetes within a 10-year follow-up period. Using combinations of variables, we evaluated 1527 predictive models for progression to type 2 diabetes. Results/UNASSIGNED:The 1-h PG outperformed every individual marker except 30-min PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c performed inferior to 1-h PG according to DeLong test p-value but not false discovery rate. Combining the metabolic markers with PG measurements and HbA1c significantly improved the predictive models, and mannose was found to be a robust metabolic marker. Conclusions/UNASSIGNED:The 1-h PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes outperforms the 2-h PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-gram OGTT to one hour improves its predictive value as well as clinical usability.

Weight loss reduces the risk of type 2 diabetes mellitus (T2D) in overweight and obese individuals. Although the physiological response to food varies among individuals, standard dietary interventions use a "one-size-fits-all" approach. The Personal Diet Study aims to evaluate two dietary interventions targeting weight loss in people with prediabetes and T2D: (1) a low-fat diet, and (2) a personalized diet using a machine-learning algorithm that predicts glycemic response to meals. Changes in body weight, body composition, and resting energy expenditure will be compared over a 6-month intervention period and a subsequent 6-month observation period intended to assess maintenance effects. The behavioral intervention is delivered via mobile health technology using the Social Cognitive Theory. Here, we describe the design, interventions, and methods used.

Over-nutrition and its late consequences are a dominant theme in medicine today. In addition to the health hazards brought on by over-nutrition, the medical community has recently accumulated a roster of health benefits with obesity, grouped under "obesity paradox." Throughout the world and throughout history until the 20^th century, under-nutrition was a dominant evolutionary force. Under-nutrition brings with it a mix of benefits and detriments that are opposite to and continuous with those of over-nutrition. This continuum yields J-shaped or U-shaped curves relating body mass index to mortality. The overweight have an elevated risk of dying in middle age of degenerative diseases while the underweight are at increased risk of premature death from infectious conditions. Micronutrient deficiencies, major concerns of nutritional science in the 20^th century, are being neglected. This "hidden hunger" is now surprisingly prevalent in all weight groups, even among the overweight. Because micronutrient replacement is safe, inexpensive, and predictably effective, it is now an exceptionally attractive target for therapy across the spectrum of weight and age. Nutrition-related conditions worthy of special attention from caregivers include excess vitamin A, excess vitamin D, and deficiency of magnesium.

Many individuals with prediabetes, as presently defined, will progress to diabetes (T2D) despite the considerable benefit of lifestyle modification. Therefore, it is paramount to screen individuals at increased risk with a more sensitive method capable of identifying prediabetes at an even earlier time point in the lengthy trajectory to T2D. This petition reviews findings demonstrating that the 1-hour (1-h) postload plasma glucose (PG) ≥ 155 mg/dl (8.6 mmol/l) in those with normal glucose tolerance (NGT) during an oral glucose tolerance test (OGTT) is highly predictive for detecting progression to T2D, micro- and macrovascular complications and mortality in individuals at increased risk. Furthermore, the STOP Diabetes study documented effective interventions that reduce the future risk of T2D in those with NGT and a 1-h PG ≥ 155 mg/dl (8·6 mmol/L). The 1-h OGTT represents a valuable opportunity to extend the proven benefit of diabetes prevention to the sizeable and growing population of individuals at increased risk of progression to T2D. The substantial evidence provided in this petition strongly supports redefining current diagnostic criteria for prediabetes with the elevated 1-h PG level. The authors therefore advocate a 1-h OGTT to detect prediabetes and hence, thwart the global diabetes epidemic.

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycemia and proposes that the 1-hour post-load glucose level during the 75 gram OGTT may serve as a novel biomarker to detect dysglycemia 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 HbA1_cor 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 OGTT making it more acceptable in a clinical setting.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7-6.4% (37-47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when ß-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs.