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IntroductionRisk 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.ObjectiveWe 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.MethodsGlucose 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 ResultsOne-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).ConclusionsAlthough 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.

Background. Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. Methods. We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999–2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. Results. The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10–4.24) than in males (AAMR: 1.12, 95% CI: 1.07–1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55–4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15–2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98–4.11) than in males (AAMR: 2.45, 95% CI: 2.39–2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97–3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02–3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28–4.44) than in females (AAMR: 2.31, 95% CI: 2.26–2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44–2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05–4.46) per 1,000,000 person-years in 2017. Conclusions. We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.

We show that estimates of the half-life of deviations from LOOP are biased when not taking into account the precision when aggregating over types of goods. Using a comprehensive dataset with monthly price data for 124 homogeneous products across regions in Denmark over the period 1997–2010 we find a large positive aggregation bias. On average, we find that the half-life is 8.4 months when taking the bias into account compared to 28.7 months when applying the standard method. The heterogeneity in estimated half-life can be explained by price stickiness, distance between regions and whether the good is traded or non-traded. This article is protected by copyright. All rights reserved.

The paper presents a general method for estimating a country’s level of fundamental house prices and its interaction with actual house prices. We set up a unified empirical model which can be used to analyze the time-series behavior of the fundamental house price and to test various hypotheses regarding its relation to the actual house price. Conditional forecasts from the model allow us to simulate policy experiments. To illustrate how the methods work, we apply it to data for Sweden. We find a tendency for actual house prices to converge on fundamental prices, albeit rather slowly. To achieve a significant fall in actual house prices it is necessary to increase the user cost substantially.

One-hour glucose (1h-PG) during an oral glucose tolerance test (OGTT) is an emerging biomarker for diagnosis and prediction of prediabetes (preDM) and type 2 diabetes (T2D). Our objectives were to: (1) use a longitudinal mathematical model to predict the pattern of glucose rise in 1h-PG and 2h-PG concentration with time and (2) test our predictions in a longitudinal cohort of 52 Pima Indians (baseline age, 26.5±5.8 years; BMI, 36.6±5.8 kg/m2) who were followed for 7.2±3.5 years. Model simulations suggested that the 1h-PG would pass the threshold of 155 mg/dl before the 2h-PG passed the threshold of 140 mg/dl for most individuals, and that the time difference could be as much as several years, depending on the balance of impairments in insulin resistance and early-phase insulin secretion. Using the longitudinal data set, we estimated the times of crossing the 1h-PG and 2h-PG thresholds by fitting a linear mixed effect model to trajectories of individual participants. Participants had a median of 6 (range 3-11) separate OGTTs, 1.7±0.8 years apart. For most participants (48/52), 1h-PG of 155 mg/dl was observed before 2h-PG reached 140 mg/dl (time difference, 1.9±2.0 years). Using the linear fits we also estimated that the average 1h-PG value would be 217 mg/dl (12.0 mmol/L) when 2h-PG reached 200 mg/dl (11.1 mmol/L). Overall, the times of crossing the 1h-PG threshold of 155 mg/dl and the 2h-PG threshold of 140 mg/dl were correlated, but 1h-PG crossed earlier, thus providing an earlier indication of future hyperglycemia. Additionally, since 1h-PG and 2h-PG rise together during the progression from preDM to T2DM, a 1h-PG of 217 mg/dl could be an alternative marker to the 2h-PG of 200 mg/dl for the diagnosis of T2D. Disclosure J. Ha: None. S.T. Chung: None. A.E. Sumner: None. M. Bergman: None. C. Bogardus: None. A. Sherman: None.

We investigate how European policy initiatives influenced market assessments of sovereign default risk and banking sector fragility during the sovereign debt crisis in four adversely affected countries — Portugal, Ireland, Spain and Italy. We focus on three broad groups of policies: (a) ECB policy actions (monetary and financial support), (b) EU programs (financial and fiscal rules as well as financial support in crisis countries), and (c) domestic austerity programs. We measure immediate market impact effects: what policies changed risk perceptions, using CDS spreads on sovereign bonds and banks in this assessment. We employ dynamic panel and event study methodologies in the empirical work. We find that a number of programs initially stabilized sovereign and bank bond markets (e.g. Outright Monetary Transactions program), although announcement and implementation impacts on markets differed in some cases (e.g. second Covered Market Bond Program). Actions designed to shore up sovereign markets often lowered risk assessments in bank bond markets and policies designed to ensure safety and soundness of the European banking system in some cases significantly impacted sovereign debt markets. Finally, a number of policies designed to stabilize markets had surprisingly little immediate impact on either sovereign or bank bond market risk assessments.

This paper studies tax shifting of excise taxes on alcoholic and nonalcoholic beveragesin Denmark. We use a unique data set collected by Statistics Denmark focusing on sixepisodes of tax changes: three tax cuts and three tax hikes. We find that excise taxeson beer and soda are overshifted but those on liquor are undershifted. We also findthat the pass-through is inversely related to the size of the tax change and that there areasymmetric effects of tax changes on soda. Finally, the tax pass-through on beer and sodais an increasing function of the distance to the German border, This paper studies tax shifting of excise taxes on alcoholic and nonalcoholic beverages in Denmark. We use a unique data set collected by Statistics Denmark focusing on six episodes of tax changes: three tax cuts and three tax hikes. We find that excise taxes on beer and soda are overshifted but those on liquor are undershifted. We also find that the pass-through is inversely related to the size of the tax change and that there are asymmetric effects of tax changes on soda. Finally, the tax pass-through on beer and soda is an increasing function of the distance to the German border.

The above-referenced article contained an error in the far-right column heading in Table 2. The heading should read as follows: PPV % (TP/TP + …

New indices of fiscal rule strength are constructed and, using a dynamic panel econometric model for 27 EU countries over the period 1990–2012, we assess whether national fiscal rules alone help to promote sustainable public finances in the EU or whether they must be supported by good governance in order to be effective. We find that fiscal rules are effective in reducing structural primary deficits at all levels of government efficiency. However, the effect is smaller as government efficiency increases, indicating that fiscal rules and government efficiency are institutional substitutes in terms of promoting fiscal sustainability. We also find that balanced budget rules are the most effective form of fiscal rules. Multiple fiscal rules are found to enhance fiscal solvency. Other institutional features that enhance the effectiveness of fiscal rules are transparency of policies and commitment to implementation of fiscal programs. Supranational rules, however, do not affect the effectiveness of national fiscal rules in reducing the deficit bias. Our results are robust to alternative estimation methods and endogeneity assumptions.

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.

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.

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.

Context Early prediction of dysglycemia is crucial to prevent progression to type 2 diabetes. The 1-hour postload plasma glucose (PG) is reported to be a better predictor of dysglycemia than fasting plasma glucose (FPG), 2-hour PG, or glycated hemoglobin (HbA1c). Objective To evaluate the predictive performance of clinical markers, metabolites, HbA1c, and PG and serum insulin (INS) levels during a 75-g oral glucose tolerance test (OGTT). Design and Setting We measured PG and INS levels at 0, 30, 60, and 120 minutes during an OGTT in 543 participants 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 The 1-hour PG outperformed every individual marker except 30-minute PG or mannose, whose predictive performances were lower but not significantly worse. HbA1c was inferior to 1-hour 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 The 1-hour PG, alone or in combination with metabolic markers, is a robust predictor for determining the future risk of type 2 diabetes, outperforms the 2-hour PG, and is cheaper to measure than metabolites. Metabolites add to the predictive value of PG and HbA1c measurements. Shortening the standard 75-g OGTT to 1 hour improves its predictive value and clinical usability., We evaluated clinical risk factors, metabolites, HbA1c, and plasma glucose levels during an OGTT. The 1-hour glucose level either alone or together with metabolites robustly predicted type 2 diabetes.

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

Background: We previously evaluated metabolic markers (alpha-hydroxybutyrate, bradykinin hydroxyproline, mannose, alpha-tocopherol, 10:1 carnitine, and X-12063) for the early prediction of type 2 diabetes (T2D). The present study compared glucose measurements at different time points during an oral glucose tolerance test (OGTT) with the metabolites for predicting future T2D. Methods: Fasting (FPG), 30, 60, and 120 minute plasma glucose (PG) levels were measured in 543 individuals from the Botnia Prospective Study, 146 of whom progressed to T2D within a 10 year period. Machine learning based predictive models for the future risk of T2D were built based on (1) OGTT-derived glucose measurements, (2) clinical risk factors (age, sex, body mass index, and family history of T2D, (3) metabolites, (4) combinations of PG levels and metabolites, (5) combinations of PG levels and clinical risk factors, and (6) combinations of PG levels, clinical risk factors, and metabolites. The metabolites were also correlated with the PG levels. Results: The 1-h PG predictive performance (area under the receiver operating characteristic curve, AUC = 0.76, sensitivity = 0.70, specificity = 0.69) was superior to FPG, 2-h PG, or individual metabolites, and was as good as the multivariate model with all six metabolites (AUC = 0.78, DeLong’s p = 0.24). The combined predictive model that included the 1-h PG, clinical risk factors, and six metabolites (AUC = 0.81, sensitivity = 0.74, specificity = 0.75) significantly improved the predictive performance beyond the 1-h PG alone (p = 0.02) and the combined model with clinical risk factors and six metabolites (p = 0.02). Conclusion: The 1-h PG predicts risk for T2D better than FPG or the 2-h PG. Although several multivariate models containing the metabolites improved the prediction performance beyond the 1-h PG, the 1-h PG alone was on par, and is a more practical biomarker. Shortening the OGTT to 1 hour provides a better and simpler assessment of T2D risk than the current OGTT. Disclosure G. Peddinti: None. T. Tuomi: None. M. Bergman: None. L. Groop: None.

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.

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.

Diagnosis of type 2 diabetes and prediabetes is mandatory. Chronic hyperglycemia in diabetes is associated with long-term micro- and macrovascular as well as with neurological complications. Prediabetes predisposes patients to develop diabetes and macrovascular disease. Diagnosis of diabetes is established on (at least) one of the following criteria: a fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/l), a casual plasma glucose ≥ 200 mg/dl (11.1 mmol/l) in the presence of symptoms, a 2-h plasma glucose during the 75-g oral glucose tolerance test (OGTT) ≥ 200 mg/dl (11.1 mmol/l) and/or an HbA1c ≥ 6.5%. Prediabetes is defined by the Position Statement of the American Diabetes Association as a fasting plasma glucose between 100 and 125 mg/dl (5.6 - 6.9 mmol/l) [a condition called Impaired Fasting Glucose] and/or by a 2-h plasma glucose during OGTT 140 - 199 mg/dl (7.8 - 11.0 mmol) [Impaired Glucose Tolerance] and/or a HbA1c level 5.7 - 6.4%, with however some potential discordance between tests. The threshold of fasting plasma glucose defining Impaired Fasting Glucose as well as the adequacy of HbA1c as a correct diagnostic tool for prediabetes is still debated.

We investigate whether fiscal rules help to reduce the extent of policy procyclicality—how government expenditure policy responds to GDP-- in a dynamic panel framework with 81 advanced, emerging and developing countries over 1985–2012. We construct two new fiscal rule indices and investigate whether rules help to dampen procyclical policies. We condition our empirical specifications on the degree to which governments appear able to manage and enforce fiscal rules. We find that fiscal rules are very effective in reducing procyclicality of policy once a minimum threshold of government efficiency/quality has been reached. Government efficiency alone is not enough to reduce procyclicality of fiscal policy. However, high government efficiency combined with strong fiscal rules is a potent combination facilitating counter-cyclical policy responses to GDP movements.

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.

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 s-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.

This is a rare case of a peripherally inserted central catheter (PICC) that was found to be in the pericardiacophrenic vein on a post-procedure chest X-ray. An 82-year-old man was admitted to the medical ICU for severe sepsis with shock and a PICC was placed for vasopressor support. Malpositioning of a central venous catheter can lead to catastrophic results including, perforation, pericardial effusion and tamponade.

Background We describe the relationship between dysglycemia and long-term mortality and elucidate the relationship between blood glucose levels during an oral glucose tolerance test (OGTT) and haemoglobin A1 (HbA1) and mortality. Methods A cohort of 1410 individuals was followed for 33 years since 1980. Fasting and post-OGTT glucose parameters were used to categorize the cohort according to baseline glycemic status. Results The mortality rate increased from 43% in normoglycemic individuals to 53.3, 61.7, 72.9 and 88.0% in those with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and diabetes, respectively. The highest mortality rate, compared with the normoglycemic category, was observed in individuals with IFG/IGT and diabetes according to a Cox proportional hazard model (HR = 1.38, 95%CI 1.10–1.74 and HR = 2.14, 95%CI 1.70–2.70, respectively), followed by individuals with IGT and IFG, but this did not reach statistical significance. We speculate that the IFG group may represent a mixture of individuals en route from normal to the next two categories as well as another cohort whose glucose levels are stably set at the upper reaches of the normal distribution. Significant differences were found between 1 and 2 h glucose values (p

This Commentary briefly reviews the background of prediabetes including its definition and pathophysiology and describes as well the natural course of glycemic deterioration as it follows a continuum. Research efforts in identifying glucose and other biomarkers for the early detection of high-risk individuals are summarized.

Objective Oral anticoagulants (OAC) are effective in the prevention of thromboembolic events but are underused. The 1st year following the beginning of vitamin K antagonists is associated with higher bleeding rate, especially in patients with international normalized ratio (INR) of > 4, leading to discontinuation of OAC. We hypothesized that the decision to discontinue OAC during the 1st year in patients with events of overanticoagulation is not fully justified. Setting A retrospective study of the association between warfarin overanticoagulation during the 1st year of treatment and the outcome and complications in patients admitted to an internal medicine department with iNR > 4. Subjects A cohort of 249 patients was divided according to OAC treatment duration: ≤12 months (group I, n = 72; mean age, 79.1 years) and > 12 months (group II, n = 177; mean age, 78.3 years). Results International normalized ratio upon admission was higher in group I (INR, 6.88 versus 6.16; P = 0.003). Patients in group I were overanticoagulated for a longer period (46.4% versus 18.5%; P 0.001) but had lower time in therapeutic range (39.0% versus 60.2%; P = 0.001). The frequency of INR monitoring was higher in group I. The incidence of major and minor bleeding events and survival was similar. Conclusions Patients who are admitted with INR > 4 during the 1st year of OAC therapy are overanticoagulated for a longer period, have lower time in therapeutic range, but do not present with higher incidence of bleeding events, all compared with patients treated for longer than 12 months. Stricter INR monitoring and careful patient selection may prevent the discontinuation of OAC.

The aim of the study was to examine the effect of androgen deprivation drugs, i.e. leuprolide and bicalutamide on the immune cross-talk between human peripheral blood mononuclear cells (PBMC) and cells from PC-3 and LNCaP human prostate cancer lines. PBMC, PC-3 and LNCaP were separately incubated without and with two androgen-deprivation drugs, i.e. leuprolide and bicalutamide, and the secretion of IL-1β, IL-6, IL-1ra and IL-10 was examined. In addition, the effect of both drugs on the production of those cytokines was carried out after 24 hours incubation of PBMC with both types of cancer cells. Leuprolide or bicalutamide did not affect the production of the cytokines by PBMC or by the prostate cancer cells from the two lines. Incubation of PBMC with PC-3 or LNCaP cells caused increased production of IL-1β, IL-6 and IL-10 as compared with PBMC incubated without malignant cells. While 10(-7) M and 10(-8) M of leuprolide caused a decreased secretion of IL-1β by PBMC previously incubated with prostate cancer cells without the drug, bicalutamide did not affect this PBMC activity at any drug concentration. This observation suggests the existence of an additional mechanism explaining the effect of androgen deprivation therapy in prostate cancer patients.

In view of the global shift from communicable to chronic, non-communicable diseases including obesity, prediabetes, and type 2 diabetes mellitus, the increasing prevalence of the latter creates a considerable challenge to the clinician and public health infrastructure. Despite the substantial research efforts in the last 10-15 years highlighting the considerable benefit of lifestyle modification in thwarting the insidious progression to diabetes and its complications, many individuals will ineluctably progress even when initially responsive. Furthermore, the vast majority of individuals with prediabetes remain undiagnosed and untreated. Therefore, the responsibilities of the medical and public health communities involve identifying new methods for screening and identifying those at risk as well as refining therapeutic approaches availing as many high-risk individuals as possible to novel treatment modalities.

BACKGROUND The incidence of left ventricular hypertrophy (LVH) in primary aldosteronism (PA) is higher than in essential hypertension. LVH is an independent cardiovascular risk factor. Treatment of PA with mineralocorticoid receptor blockers (MRBs) improves LVH. Previous studies included relatively small groups, low incidence of LVH and used high MRB dose. We tested the hypothesis that long-term regression of LVH in PA/low-renin hypertension may be achieved with low-dose MRB. METHODS Forty-eight patients (male/female 28/20, age 61.4 years, range 47-84) had PA (low renin, high aldosterone and high aldosterone/renin ratio, n=24) or low-renin hypertension (low renin, normal aldosterone and high aldosterone/renin ratio, n=24). All had either LVH or concentric remodelling. All had an echocardiogram both at baseline and at 1 year after the initiation of spironolactone. A subgroup of 29 patients had an echocardiogram at baseline, 1 year (range 0.5-1.5) and 3 years (range 1.8-7). RESULTS At baseline, spironolactone was commenced in all patients. The dose was 33.3±13.7 and 29.0±11.7 mg/day at 1 year and 3 years, respectively. A total of 73% of the patients received ≤37.5 mg/day. Introduction of spironolactone enabled the reduction of other antihypertensive medications (from 2.6±1.2 to 1.5±1.0 at 1 year). At 1 year, systolic and diastolic blood pressure decreased (149.3±14.1 to 126.2±12.0 mmHg, P

Background: Various cytokines are increased in hemodialysis (HD) patients, and are considered prognostic markers. Metabolic acidosis is common among chronic HD patients and is associated with survival. The relationship between acidosis and cytokines in HD patients has not been fully explored. The study aim was to measure pro- and anti-inflammatory cytokines in HD patients, with relation to bicarbonate levels. Methods: Forty-seven stable HD patients were included (male/female 28/19, mean age 70.4 ± 14.5 years). Blood tests were taken before a midweek dialysis session. Cytokine secretion from peripheral blood mononuclear cells was measured. Results: Acidosis versus no acidosis (serum HCO3- 21.5 ± 0.2 vs. 24.9 ± 0.3 mEq/l, p < 0.001) was associated with decreased secretion of the anti-inflammatory interleukin-10 (IL-10, 1.16 ± 0.11 vs. 1.71 ± 0.20 ng/ml, p = 0.023). Patients with acidosis had higher parathyroid hormone (PTH), calcium-phosphate product, protein intake and transferrin. Higher IL-10 was associated with increased IL-6 secretion, higher bicarbonate, younger age and lower PTH. Conclusions: In stable chronic HD patients, a possible direct relation exists between metabolic acidosis and IL-10.

Summary HbA1c testing has become an accepted means of diagnosing diabetes as an alternative to blood glucose levels. However, population-based norms of glucose and of HbA1c levels do not enable the detection of diabetes at an early enough stage to thwart complications. Personal trajectories of glucose levels show steep increases a number of years prior to diabetes diagnosis. Here, we hypothesize that a comparable time-dependent deviation in an individual's HbA1c level may be an early manifestation of disease that should prompt lifestyle modifications. We predict that analysis of personal trajectories of glucose and of HbA1c will promote earlier intervention and a greater reduction in disease complications than current standards, which are based on population-based norms. Copyright © 2012 John Wiley & Sons, Ltd.

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.

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 ± 13 years; BMI: 27.7 ± 6.3 kg/m2) at risk for prediabetes were administered a 75 g 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

The present study assessed the longitudinal association of an elevated 1-h plasma glucose [1-h-PG8.6mmol/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.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.Individuals with 1-h-PG8.6mmol/l (155mg/dl) but with 2-h-PG7.8mmol/l (140mg/dl) had a significantly elevated risk, compared to those with both 1-h-PG ⩽8.6mmol/l (155mg/dl) and 2-h-PG7.8mmol/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.The risk for diabetes associated with a 1-h level8.6mmol/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.