Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

AIMS/HYPOTHESIS: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. METHODS: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. RESULTS: In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states. CONCLUSIONS/INTERPRETATION: These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

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 ß-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.

Using root metaphors to analyze communication between nurses and patients: a qualitative study.

BACKGROUND: Metaphors in communication can serve to convey individuals' backgrounds, contexts, experiences, and worldviews. Metaphors used in a health care setting can help achieve consensual communication in professional-patient relationships. Patients use metaphors to describe symptoms, or how disease affects them. Health professionals draw on shared understanding of such metaphors to better comprehend and meet patient needs, and to communicate information that patients can more easily integrate into their lives. This study incorporated a theoretical framework based on four worldviews, each with an underlying foundational metaphor (root metaphor). The use of these root metaphors (formism, mechanism, contextualism, and organicism) can have an explanatory function and serve to impart new meanings, as each type of metaphor can lead to a particular interpretation. The study aimed to extract and discuss the root metaphors, with a view to analyzing the communication between health professionals and patients. METHODS: In a case study in Spain over a six-month period, we analyzed the content of recorded, transcribed interviews conducted by one nurse with 32 patients who had chronic illnesses. We inductively extracted five categories that emerged from the interviews: blood sugar, cholesterol, exercise, blood pressure, and diet. We then examined these categories from the standpoint of each of the four root metaphors using two approaches: A series (deductive) and an emergent (inductive) approach. RESULTS: The results show that the nurse tended to primarily use two worldviews: mechanism and formism. In contrast, patients tended to favor mechanism when discussing cholesterol, blood pressure, and blood sugar levels, whereas contextualism was predominant when the category was diet or exercise. CONCLUSIONS: This study adds to the existing literature on health professionals and patients' communication. It shows how the use of Pepper's root metaphors help to analyze the communication between the nurse and patients. Furthermore, it shows they are both using different root metaphors when they are talking about illness and treatments especially regarding blood sugar, cholesterol, exercise, blood pressure, and diet. Further qualitative and quantitative studies are needed to solidly these findings.

Adipokines, hormones related to body composition, and insulin resistance in HIV fat redistribution syndrome.

BACKGROUND: Lipodystrophies are characterized by adipose tissue redistribution, insulin resistance (IR) and metabolic complications. Adipokines and hormones related to body composition may play an important role linking these alterations. Our aim was to evaluate adipocyte-derived hormones (adiponectin, leptin, resistin, TNF-α, PAI-1) and ghrelin plasma levels and their relationship with IR in HIV-infected patients according to the presence of lipodystrophy and fat redistribution. METHODS: Anthropometric and metabolic parameters, HOMA-IR, body composition by DXA and CT, and adipokines were evaluated in 217 HIV-infected patients on cART and 74 controls. Fat mass ratio defined lipodystrophy (L-FMR) was defined as the ratio of the percentage of the trunk fat mass to the percentage of the lower limb fat mass by DXA. Patient's fat redistribution was classified into 4 different groups according the presence or absence of either clinical lipoatrophy or abdominal prominence: no lipodystrophy, isolated central fat accumulation (ICFA), isolated lipoatrophy and mixed forms (MXF). The associations between adipokines levels and anthropometric, metabolic and body composition were estimated by Spearman correlation. RESULTS: Leptin levels were lower in patients with FMR-L and isolated lipoatrophy, and higher in those with ICFA and MXF. Positive correlations were found between leptin and body fat (total, trunk, leg, arm fat evaluated by DXA, and total, visceral (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratio evaluated by CT) regardless of FMR-L, and with HOMA-IR only in patients with FMR-L. Adiponectin correlated negatively with VAT, and its mean levels were lower in patients with ICFA and higher in those with no lipodystrophy. Resistin was not correlated with adipose tissue but positively correlated with HOMA-IR in FMR-L patients. PAI-1 levels were higher in MXF-patients and their levels were positively correlated with VAT in those with FMR-L. Ghrelin was higher in HIV-infected patients than controls despite BMI-matching. CONCLUSION: The overall body fat reduction in HIV lipoatrophy was associated with low leptin plasma levels, and visceral fat accumulation was mainly associated with decreased plasma levels of adiponectin.

Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients.

BACKGROUND: HIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT. METHODS: Cross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher's exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models. RESULTS: L-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p=0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95%CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95%CI: 0.732-0.817) in those with lipodystrophy (p=0.671). CONCLUSIONS: HIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.

Two types of abdominal pain as the initial presentation of Takayasu arteritis: A case report.

BACKGROUND: Takayasu arteritis (TA) is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Diagnosis is usually delayed in most patients owing to the absence of typical clinical manifestations in the acute phase until the development of substantial arterial symptoms. The purpose of this case report is to describe abdominal pain being an uncommon symptom in TA. LEARNING OBJECTIVE: The clinical presentation of TA can be non-specific and can have serious consequences if the diagnosis is delayed, helping the clinicians who can treat with such patients (emergency medicine, cardiologist, or medical personnel).

Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glucose disturbances and insulin resistance.

INTRODUCTION: Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes. AIMS: To compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations. DESIGN: Cross-sectional cohort study. METHODS: We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults. RESULTS: Patients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found. CONCLUSIONS: IR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.

Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients.

BACKGROUND: In HIV-infected patients, combination antiretroviral therapy (cART) is associated with clinical lipodystrophy (CL) and metabolic abnormalities (MA). This study aimed to evaluate the prevalence of the metabolic syndrome (MS) and its components, and to determine whether patients with or without CL had a different prevalence of MA. METHODS: We evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score. RESULTS: CL was present in 58.7% of the patients. The prevalence of the MS was 52.2% (ATPIII) and 43.2% (IDF), and it was not significantly different between patients with (W) or without (WT) CL, regardless of the definition used (ATPIII WCL 52.9% vs WT CL 51.1%; p = 0.738; IDF WCL 41.3% vs WTCL 46.0%; p = 0.379). Moderate concordance was observed between the 2 definitions (kappa = 0.484; p < 0.001) and after gender stratification there was good concordance in women (kappa = 0.759; p < 0.001). Patients with CL had lower waist circumference and HDL-C and higher triglycerides levels. In women, CL was significantly associated with MS, hypertriglyceridemia and low HDL cholesterol independently of age, cART and BMI. Patients with CL had a significantly higher risk of coronary heart disease at 10 years, measured by the Framingham risk score, than patients without CL. Those with CL and with MS had higher frequencies of moderate and high risk categories than those without MS. CONCLUSIONS: The prevalence of the MS was high in these HIV-infected patients with an age average of 40 years and this finding could explain why HIV patients have an increased risk for cardiovascular disease (CVD).

Loss of postprandial insulin clearance control by Insulin-degrading enzyme drives dysmetabolism traits.

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored. We hypothesized that IDE governs postprandial IC and hepatic IDE dysfunction amplifies dysmetabolic responses and prediabetes traits such as hepatic steatosis. In a European/Portuguese population-based cohort, IDE SNPs were strongly associated with postprandial IC in normoglycemic men but to a considerably lesser extent in women or in subjects with prediabetes. Liver-specific knockout-mice (LS-IDE KO) under normal chow diet (NCD), showed reduced postprandial IC with glucose intolerance and under high fat diet (HFD) were more susceptible to hepatic steatosis than control mice. This suggests that regulation of IC by IDE contributes to liver metabolic resilience. In agreement, LS-IDE KO hepatocytes revealed reduction of Glut2 expression levels with consequent impairment of glucose uptake and upregulation of CD36, a major hepatic free fatty acid transporter. Together these findings provide strong evidence that dysfunctional IC due to abnormal IDE regulation directly impairs postprandial hepatic glucose disposal and increases susceptibility to dysmetabolic conditions in the setting of Western diet/lifestyle.

Fat mass ratio: an objective tool to define lipodystrophy in hiv-infected patients under antiretroviral therapy.

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66-0.82], p<0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63-0.86], p<0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Genomic Epidemiology of Salmonella Infantis in Ecuador: From Poultry Farms to Human Infections.

Salmonella enterica is one of the most important foodborne pathogens around the world. In the last years, S. enterica serovar Infantis has become an important emerging pathogen in many countries, often as multidrug resistant clones. To understand the importance of S. enterica in the broiler industry in Ecuador, we performed a study based on phenotypic and WGS data of isolates from poultry farms, chicken carcasses and humans. We showed a high prevalence of S. enterica in poultry farms (41.4%) and chicken carcasses (55.5%), but a low prevalence (1.98%) in human samples. S. Infantis was shown to be the most prevalent serovar with a 98.2, 97.8, and 50% in farms, foods, and humans, respectively, presenting multidrug resistant patterns. All sequenced S. Infantis isolates belonged to ST32. For the first time, a pESI-related megaplasmid was identified in Ecuadorian samples. This plasmid contains genes of antimicrobial resistance, virulence factors, and environmental stress tolerance. Genomic analysis showed a low divergence of S. Infantis strains in the three analyzed components. The results from this study provide important information about genetic elements that may help understand the molecular epidemiology of S. Infantis in Ecuador.

A randomized double-blind study comparing the efficacy and safety of orlistat versus placebo in obese patients with mild to moderate hypercholesterolemia.

INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

Ecuadorian mainland industrial poultry production is free of H5/H7 Avian influenza virus: National surveillance program in 2016.

Avian influenza (AI) is a disease caused by influenza viruses type A that belong to the Orthomyxoviridae family. AI induces high economic losses in poultry production worldwide. Due to a possible outbreak, a national surveillance program was needed. From April to July 2016, 152 industrial poultry farms were randomly sampled. All samples were analyzed by competitive ELISA for Influenza type A viruses. Suspicious and positive sera were further analyzed by Hemagglutination Inhibition (HI) in order to serotype H5 or H7 low pathogenic avian influenza virus (LPAIV). The farms sampled showed 94.08%, 3.95% and 1.97% of negative, positive and suspicious results, respectively. However, serotyping revealed all positive and suspicious samples were negative to H5/H7 LPAIV. Our results show the absence of AI in the mainland Ecuadorian industrial poultry production.

[Utility of omentoplasty for poststernotomy mediastinitis secondary to myocardial revascularization surgery]. / Utilidad de la omentoplastia en el tratamiento de la esternomediastinitis secundaria a cirugía de revascularización miocárdica.

Acute poststernotomy mediastinitis is a serious complication of cardiac surgery and is associated with high mortality. Conservative treatment with local debridement, irrigating-suction systems, and specific antibiotic therapy is sometimes inadequate. Omentoplasty is occasionally used for reconstruction and the treatment of various chest diseases. This useful procedure is most often indicated for suppurative processes and radionecrosis, to complement myoplasty, or to cover a chest wall prosthesis. When used to treat poststernotomy mediastinitis secondary to cardiac surgery, omentoplasty improves control of infection and prognosis. We describe 2 cases of poststernotomy mediastinitis secondary to cardiac revascularization surgery in which omentoplasty was an effective treatment. Excellent control of infection was achieved.

Thyroid diseases, dyslipidemia and cardiovascular pathology.

INTRODUCTION: The relationship between thyroid hormones and lipids has long been studied, having been first described more than 70 years ago. Since then, much new information has been discovered, which justifies a reevaluation of the relationship between thyroid pathology and dyslipidemia. Thyroid hormones play an important role in regulating lipid metabolism, and thyroid dysfunction can result in lipid abnormalities which increase the risk of endothelial dysfunction, hypertension and cardiovascular disease. METHODOLOGY: A review of the literature was carried out on the association between thyroid diseases, lipid profile and cardiovascular risk, using the Medline database and textbooks. Articles in English and Portuguese published between 1980 and 2007 were selected. Data collection took place between 2003 and 2007. RESULTS: The increased cardiovascular risk in thyroid dysfunction is related to lipid profile, endothelial dysfunction, metabolic, hormonal and hemodynamic changes and coagulation disturbances. Because of its high prevalence in the population hypothyroidism is the principal functional disorder. Lipid anomalies associated with hypothyroidism are at least partially responsible for the increase in coronary heart disease. CONCLUSION: The clinical benefit of treating subclinical hyperthyroidism is still the subject of debate, but treatment appears to be associated with beneficial effects on lipi d profile and cardiovascular function. Further studies are required to clarify the influence of various degrees of thyroid dysfunction in the development of atherosclerosis and cardiovascular morbidity.

Detection of Activation Sequences in Spiking-Bursting Neurons by means of the Recognition of Intraburst Neural Signatures.

Bursting activity is present in many cells of different nervous systems playing important roles in neural information processing. Multiple assemblies of bursting neurons act cooperatively to produce coordinated spatio-temporal patterns of sequential activity. A major goal in neuroscience is unveiling the mechanisms underlying neural information processing based on this sequential dynamics. Experimental findings have revealed the presence of precise cell-type-specific intraburst firing patterns in the activity of some bursting neurons. This characteristic neural signature coexists with the information encoded in other aspects of the spiking-bursting signals, and its functional meaning is still unknown. We investigate the ability of a neuron conductance-based model to detect specific presynaptic activation sequences taking advantage of intraburst fingerprints identifying the source of the signals building up a sequential pattern of activity. Our simulations point out that a reader neuron could use this information to contextualize incoming signals and accordingly compute a characteristic response by relying on precise phase relationships among the activity of different emitters. This would provide individual neurons enhanced capabilities to control and negotiate sequential dynamics. In this regard, we discuss the possible implications of the proposed contextualization mechanism for neural information processing.

The 1-h post-load plasma glucose as a novel biomarker for diagnosing dysglycemia.

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As ß-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 ß-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.

Petition to replace current OGTT criteria for diagnosing prediabetes with the 1-hour post-load plasma glucose ≥ 155 mg/dl (8.6 mmol/L).

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.

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 ß-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 ß-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.