Complete laboratory diagnosis of Insulin Autoimmune Syndrome.

The definition of Insulin autoimmune syndrome includes the presence of high levels of blood insulin and insulin autoantibodies. We encountered a 45-years-old white man with a high insulin serum value that do not fit with the C-peptide result. To discard or to confirm an analytical interference and diagnose a possible Insulin Autoimmune Syndrome we performed the following investigations: dilution linearity test, heterophilic antibody blocking, polyethylene glycol precipitation, measurements with alternative assays, and gel filtration chromatography by size exclusion. The latter technique confirmed that most of the insulin was complexed with a 150-kDa protein, corresponding to immunoglobulin G, identified as insulin autoantibodies. These antibodies were responsible for hypoglycemia attacks in the patient, who had a previous autoimmune disease. This case highlights the importance of carefully analyzing the results and ruling out possible interferences, as well as considering all kinds of pathologies, even if they are infrequent.

Prevalence of undiagnosed diabetes and prediabetes related to periodontitis and its risk factors in elderly individuals.

OBJECTIVE: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic and to find common risk factors. METHODS: Male patients, older than 50 years, attended their first dental visit to the School of Dentistry for a period of two years, and it was proposed to evaluate undiagnosed type 2 diabetes mellitus. Periodontal, biochemical, microbiological examinations, nutritional profile, and physical activity were performed. RESULTS: A total of 106 patients were examined, 6 (5.6%) had diabetes, and 37 (34.9%) had prediabetes without prior diagnosis. The severity of periodontitis was greater in patients with diabetes. Most of the patients were overweight and had increased systolic blood pressure. Patients with prediabetes and periodontitis had a low adherence to the Mediterranean diet. Tannerella forsythia was present in more patients with periodontitis, and the prevalence of Aggregatibacter actinomycetemcomitans is practically absent in groups with periodontitis, except for the group with diabetes. CONCLUSIONS: In the population studied, the prevalence of patients without a diagnosis of diabetes and prediabetes was very high and underestimated. The increased severity of periodontitis in patients with diabetes and in conjunction with the high level of cortisol seen in patients with periodontitis, especially those with diabetes, emphasize the dysregulation of the immunoinflammatory system. CLINICAL SIGNIFICANCE: It is essential to add all this data to our dental practice to cover patient health with a broader landscape.

Periodontitis and Other Risk Factors Related to Myocardial Infarction and Its Follow-Up.

The main issue in the prevention of myocardial infarction (MI) is to reduce risk factors. Periodontal disease is related to cardiovascular disease and both share risk factors. The purpose of this study is to investigate whether periodontitis can be considered a risk factor for MI and common risk factors in a case-control study and in a prospective follow-up study in patients with MI. The test group (MIG) was made up of 144 males who had MI in the previous 48 h. The control group (CG) was composed of 138 males without MI. Both groups were subdivided according to the presence or absence of stage III and IV of periodontitis. General data; Mediterranean diet and physical activity screening; periodontal data; and biochemical, microbiological and cardiological parameters were recorded. ANOVA, Mann-Whitney U and Kruskal-Wallis statistical tests and binary logistic regression analysis were applied. No differences in anthropometric variables were observed between the four groups. The average weekly exercise hours have a higher value in CG without periodontitis. The number of leukocytes was higher in MIG, the number of monocytes was higher in CG and the number of teeth was lower in MIG with periodontitis. Adherence to the Mediterranean diet was higher in CG. Porphyromonas gingivalis and Tannerella forsythia were higher in CG with periodontitis and in MIG with and without periodontitis. At follow-up, the left ventricular ejection fraction (LVEF) data were better in the non-periodontitis group: 15 patients had Mayor Cardiovascular Adverse Events (MACE), 13 of them had periodontitis and 2 did not show periodontitis. Periodontitis, exercise, diet and smoking are risk factors related to MI. MACE presented in the 'MI follow-up' shows periodontitis, weight, exercise hours and dyslipidemia as risk factors. LVEF follow-up values are preserved in patients without periodontitis. Our data suggest that periodontitis can be considered a risk factor for MI and MACE in the studied population.

Molecular inflammation and oxidative stress are shared mechanisms involved in both myocardial infarction and periodontitis.

BACKGROUND AND OBJECTIVE: Our aims were to improve the understanding of the pathogenic relationship between cardiovascular diseases and periodontitis and to generate new perspectives in the prevention and treatment of acute myocardial infarction (AMI) and periodontitis. The present study evaluates possible differences in inflammation, oxidative stress, and autophagy markers among subject suffering AMI, periodontitis, or both, to explore possible common pathogenic mechanisms. MATERIAL AND METHODS: A total of 260 subjects were enrolled in the study: 106 subjects that survived to a first AMI (AMI group) and 154 subjects had no cardiac events in their clinical record (control group). A questionnaire was used to assess age, height, weight, blood pressure, and heart rate. The clinical probing depth, clinical attachment loss, number of remaining teeth, and average number of sites with bleeding on probing were assessed. Lipid peroxidation and protein levels of phosphorylated AMP-activated protein kinase (p-AMPK) and microtubule-associated proteins 1A/1B-light chain 3-II (LC3-II) were determined in isolated peripheral blood mononuclear cells by thiobarbituric acid reactive substances (TBARS) assay and Western blot, respectively. Plasma levels of interleukin-1ß were determined using a commercial ELISA kit. All the obtained variables were compared between subjects suffering an AMI with or without periodontitis and control subject periodontal healthy or with periodontitis. RESULTS: A higher proportion of subjects suffering AMI + periodontitis than only AMI (without periodontitis) was found. Higher levels of TBARS were found in subjects with periodontitis than in subjects without periodontitis in both AMI and control subjects. Positive correlations between IL-1ß levels and TBARS and between IL-1ß levels and LC3-II were found only in control subjects. CONCLUSION: Results from the present study are consistent with the suggestion of periodontitis as a potential risk factor for AMI. Periodontitis association with circulating lipid peroxides in both AMI and control subjects were found. The absence of differences in IL-1ß levels between AMI subjects (only AMI vs AMI + periodontitis) suggests that oxidative stress could be the main pathogenic link between AMI and periodontitis.

Screening for Gestational Diabetes Mellitus by Measuring Glycated Hemoglobin Can Reduce the Use of the Glucose Challenge Test.

BACKGROUND: Physiological changes during pregnancy, such as dilutional anemia and a reduced half-life of red blood cells, have prevented the use of glycated Hb (HbA1c) as a biomarker for gestational diabetes mellitus (GDM). Nevertheless, increasing evidence supports the use of HbA1c in GDM diagnostic strategies.We studied HbA1c as a biomarker of GDM and its possible use as a screening test to avoid the use of the glucose challenge test (GCT). METHODS: This case-control study involved 607 pregnant women between the 24th and 28th week of gestation. HbA1c level was determined, and GDM was diagnosed according to the National Diabetes Data Group criteria. The area under the ROC curve (AUC) was determined; two low and two high cut-off points were established to rule out GDM and classify high-risk pregnant women, respectively. For each cut-off, sensitivity (S), specificity (SP), and total number and percentage of GCTs avoided were determined. RESULTS: The AUC for HbA1c diagnostic performance was 0.68 (95% confidence interval 0.57-0.79). Using 4.6% HbA1c (27 mmol/mol) as the lower cut-off (S=100%), 14% of participants could avoid the GCT. Using 5.5% HbA1c (36 mmol/mol) as the upper cut-off (SP =94.5%), 6% of participants would be considered at high risk. CONCLUSIONS: HbA1c can be used as a screening test prior to the GCT, thereby reducing the need for the GCT among pregnant women at a low risk of GDM.

Coexistence of anti-Jo1 and anti-signal recognition particle antibodies in a polymyositis patient. / Coexistencia de anticuerpos anti-histidil-tRNA-sintetasa y anti-partícula de reconocimiento de la señal en un paciente con polimiositis.

Idiopathic inflammatory myopathies are a heterogeneous group of potentially treatable myopathies. They are classified, on the basis of clinical and histopathological features, into four subtypes: dermatomyositis, polymyositis, necrotizing autoimmune myositis and inclusion-body myositis. Myositis-associated antibodies and myositis-specific autoantibodies are frequently found in patients with idiopathic inflammatory myopathies, and are useful in the diagnosis and classification. Anti-histidyl transfer RNA synthetase antibody is the most widely prevalent and is highly specific for polymyositis. Signal recognition particle antibody is also a specific autoantibody for polymyositis, but it is infrequent and rarely found in patients having other myositis-specific autoantibodies. We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyze the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis.

Predictive value of the kinetics of procalcitonin and C-reactive protein for early clinical stability in patients with bloodstream infections due to Gram-negative bacteria.

OBJECTIVE: To investigate whether the magnitude of the change in procalcitonin (PCT) and C-reactive protein (CRP) levels between day 1 and day 2 after the blood culture date is associated with early clinical stability (ECS) on day 3 in patients with bacteremia due to Gram-negative bacteria (GNB). MATERIALS/METHODS: A prospective cohort study carried out in a 950-bed tertiary hospital in Spain between March 2013 and May 2014. Patients with GNB bacteremia were included. Changes in PCT and CRP kinetics from day 1 to day 2 (∆%PCT, ∆%CRP) were expressed as percentage of decline in blood levels. Logistic regression was used to identify predictors of ECS. Classification and regression tree analysis was performed to identify breakpoints. The discriminatory power of ∆%CRP and ∆%PCT as predictors of ECS was assessed by the area under the ROC (AUROC). RESULTS: 71 patients were included, and 53 (74.56%) reached ECS. Multivariate analyses showed that SOFA score on day 1, ∆%PCT, and ∆%CRP were associated with ECS after controlling for confounders. ∆%PCT ≥ 30% (decline) and ∆%CRP ≥ 10% (decline) predicted ECS only among patients with SOFA≤3 on day 1 (n = 54; 43 reached ECS). In these patients, the AUROCs for the prediction of ECS were 0.96 (95% CI: 0.90-1) for ∆%CRP and 0.96 (95% CI: 0.90-1) for ∆%PCT, respectively. CONCLUSIONS: In the subgroup of patients with a SOFA score on day 1 ≤3, a ≥30% decline in PCT or a ≥10% decline in CRP between day 1 and day 2 was a very good predictor of ECS (which in turn was associated with a lower 30-day mortality and a greater clinical cure on day 14). Patients who do not achieve this decrease may need more intensive workup. In this subgroup (with a SOFA on day 1 ≤3), CRP may be preferred due to its lower cost.

Fasting Glycemia as Screening Tool to Rule-Out Gestational Diabetes in Low-Risk Population.

BACKGROUND: The use of a glucose challenge test as the universal screening for gestational diabetes is common in many countries. This test represents significant costs for laboratories and inconveniences for the patients, who have to wait for one hour and, very often, feel discomfort and nausea. In this work we propose the use of fasting glycemia, in a population with low prevalence of gestational diabetes as a pre-screening test that would avoid the oral glucose overload in those pregnant women with low risk of gestational diabetes. METHODS: The study was done with the fasting glucose levels of 6,573 pregnant women who underwent a two steps strategy to screen for gestational diabetes, a first step consisting of a 50 g glucose challenge test, followed when glycemia ≥ 140 mg/dL by a 100 g Oral Glucose Tolerance Test, based on recommendations made by National Diabetes Data Group. RESULTS: The ROC curve for fasting glucose was calculated, and we obtained an AUC = 0.633 (0.569 - 0.696). The sensitivity, specificity, and predictive values were established for different thresholds. CONCLUSIONS: We proposed that women with fasting glycemia ≤ 62 mg/dL, (S = 91.3%, NPV = 98.79% and LR- = 0.87) are in low risk of suffering gestational diabetes, which means that 10% of our population would not undergo the glucose challenge test.

Comparison of Citrate Buffer with Sodium Fluoride as Additives in Determining Glycemia.

BACKGROUND: The objectives of this study are to compare the effect of sodium fluoride and citrate on the stability of glucose in samples maintained at room temperature up to three hours, and to assess the clinical impact in the O'Sullivan test results after changing the additives in the collecting tubes. METHODS: The selected population was pregnant women between the 24th and 28th week of gestation, who were at the health center to undergo the O'Sullivan test as part of the screening program for GDM (gestacional diabetes mellitus). Two blood samples were extracted from each patient: one using a tube with citrate and sodium fluoride buffer (tubes Vacuette Glucomedics citrate, 2 mL, Ref 454347) (tube C) and another containing just sodium fluoride (BD Vacationer tubes FX fluoride, 2 mL, Ref 368920) (tube F). The statistical treatment of the data was performed using SPSS version 24 and Method validator. Finally, we assessed the real clinical impact of replacing tubes C for tubes F in the classification of pregnant women. To do so, we collected the results of O'Sullivan tests conducted in our hospital during a year, all of them done in tubes F, and we applied the mean difference calculated in T = 1 to estimate the number of pregnant women that should be reclassified. RESULTS: The average glycaemia in tubes C are significantly greater than average glycaemia in tubes F (p < 0.05) at all time points. The clinical impact assessment was done over the 6,526 O'Sullivan test results with a prevalence of positive tests of 21.35%. The prevalence using tubes C instead of tubes F estimated with mean differences previously calculated is 33.45%. CONCLUSIONS: The glucose concentrations in tubes F stored at room temperature up to 3 hours were significantly lower (p < 0.05) than those measured in tubes C stored under the same conditions. We observed that it is in the first minutes after extraction, while the samples are collected and aliquots done, that the glucose consumption occurs in tubes F, but not in tubes C. There is a need to change the preanalytical conditions to prevent any loss of glucose. This will enable more accurate diagnosis and management of diabetes mellitus.

Role of leptin as a link between metabolism and the immune system.

Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology.

Zenit RA evaluation, a solid-phase chemiluminescence immunoassay for detection of anti-cellular antibodies.

AIM: The objective was to compare Zenit RA chemiluminescent immunoassay (CLIA) from Menarini Diagnostics and ELISA from INOVA Diagnostics for the presence of specific anti-Ro/SS-A, anti-La/SS-B, anti-U1snRNP, anti-Sm, anti-Scl-70, anti-Jo-1 antibodies. Results/methodology: We studied 501 samples (178 connective autoimmune disease, 150 other autoimmune or inflammatory disease and 173 other disease or healthy). All samples were analyzed using CLIA and ELISA. The Kappa agreement was excellent for anti-SSA/Ro (0.864), good for anti-SSB/La (0.735), anti-Scl-70 (0.685) and ENA-screening (0.778), moderate for anti-RNP (0.563) and bad for anti-Sm (0.266) and anti-Jo-1 (0.243). Different combination of cut-off improved the specificity and agreement. CONCLUSION: Zenit RA CLIA for detecting autoantibodies, provides a simple, useful and accurate tool.

Evaluation of Bio-Rad D-100 HbA1c analyzer against Tosoh G8 and Menarini HA-8180V.

OBJECTIVES: To evaluate the Bio-Rad D-100®, an HPLC analyzer for glycated hemoglobin (HbA1c) determination, and to compare its performance with the Menarini HA-8180V® and Sysmex G8®. METHODS: Method comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP9-A2 guidelines. We selected 100 samples from the routine laboratory workload and analyzed them in duplicate with the three analyzers. The imprecision study was performed according to CLSI EP5-A2 guidelines for both inter-assay and intra-assay variability. Bias was assessed with external quality control material. To establish linearity, CLSI EP6-A protocol was followed. RESULTS: Method comparison (95% confidence intervals in parentheses): D-100 vs G8: Passing-Bablok regression; y=0.973(0.963-0.983)×-0.07(-0.07-0.069); r=0.9989. Bland-Altman mean difference: -0.229%HbA1c (-0.256: -0.202); Relative bias plot: D-100/G8 vs D100-G8 mean ratio=0.971(0.967-0.975). D-100 vs HA-8180V: Passing-Bablok regression; y=0.944(0.932-0.958)×-0.078(0.024-0.173); r=0.9989. Bland-Altman mean difference: -0.363%HbA1c (-0.401: -0.325); Relative bias plot D-100/HA-8180V vs D100-HA-8180V mean ratio=0.955(0.952-0.958). Inter-assay coefficient of variation (CV): 0.81%. Intra-assay CV: 1.04% (low level), and 0.78% (high level). Bias against target value=2.332%. Linearity: r2=0.998 in the concentration range 4.4-13.9%HbA1c. Carry-over: 0.0024%. CONCLUSIONS: The Bio-Rad D-100 shows good correlation with G8 and HA-8180V. There is a small proportional systematic difference (2.7% and 5.6%, respectively) in both comparisons. Inter and intra-assay CVs are both lower than the lowest CV obtained in studies performed with D-100 and other instruments.

Evaluation of a HbA1c point-of-care analyzer.

OBJECTIVES: A better glycemic monitoring of diabetic patients and avoiding complications of poorly controlled diabetes could be possible with point-of-care testing technology (POCT) for HbA1c determination. B-Analyst® was studied to check whether it complied with the quality requirements for this purpose. DESIGN AND METHODS: We evaluated the B-Analyst® (Menarini Diagnostics), which is based in the principle of latex agglutination immunoturbidimetry, to assess the validity of the technique of HbA1c. We carried out the method comparison with the HA-8180® (Menarini Diagnostics) as a reference method [High Performance Liquid Chromatography (HPLC)]. We assessed the analytical quality of the B-Analyst® studying the accuracy: inter-assay variability and intra-assay study. Furthermore, possible interferences by hemoglobinopathies were studied. RESULTS: Regression analysis of the data for the method comparison between HA-8180® and B-Analyst® showed a slope of 1.0085 and an intercept of 0.1208. The Pearson's correlation coefficient was 0.9958 (p<0.0001). Bias study showed a mean difference from B-Analyst® with respect to HA-8180® of 0.1872 with a 95% confidence interval. The standard error of the estimate (Syx) was 0.2091. The concordance correlation coefficient to assess accuracy was 0.9922 (0.9891-0.9945). The CV for the inter-assay study was 1.4%. For the intra-assay study we analyzed 3 samples with different HbA1c % whose CV were 1.03% [4.7% HbA1c (28 mmol/mol)], 0.46% [6.4% HbA1c (46 mmol/mol)] and 0.78% [8.1% HbA1c (65 mmol/mol)]. CONCLUSION: The B-Analyst® evaluated not only showed good correlation with HA-8180®, but also it presented a great accuracy both in the inter-assay and in the intra-assay studies. The B-Analyst® complies with quality specifications required for monitoring of diabetic patients.

Relation of periodontitis and metabolic syndrome with gestational glucose metabolism disorder.

BACKGROUND: Gestational diabetes mellitus (GDM) and metabolic syndrome have been related to periodontitis. This study's objective is to establish the relationship between them in pregnant women affected by gestational glucose metabolism disorder. METHODS: In 188 pregnant women with positive O'Sullivan test (POT) results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The mother's periodontal parameters, age, prepregnancy weight and height and body mass index (BMI), blood pressure, gestational age, and birth weight were recorded at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein, triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein, high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL) cholesterol levels. RESULTS: Prepregnancy weight, prepregnancy BMI, systolic and diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in GDM compared with POT (P <0.05). VLDL cholesterol, triglycerides, and 2-hour OGTT were higher in patients with periodontitis than in patients without periodontitis (P <0.05). HbA1c, triglycerides, and 1- and 2-hour OGTT were positively related with probing depth and clinical attachment level; blood glucose was related only to bleeding on probing (P <0.05). HbA1c, basal OGTT, and 1- and 2-hour OGTT were positively related to prepregnancy BMI and blood pressure; HDL cholesterol was negatively related to prepregnancy BMI; C-reactive protein was positively related to prepregnancy BMI and diastolic blood pressure (P <0.05). CONCLUSION: These data support the relationships among periodontal disease and some biochemical parameters such as lipid and glucose data in pregnancy, and also among metabolic syndrome and biochemical parameters.

Effective treatment of pulmonary tuberculosis restores plasma leptin levels.

An impaired immune response in tuberculosis patients seems to be related to weight loss that coexists with an immunoendocrine imbalance. Thus, wasting is well-recognised as a prominent feature of tuberculosis (TB), which may not be reversed even after six months of treatment. Adipokines may play a role in the immune response to M. tuberculosis, and TB may impair the expression of inflammatory adipokines, such as leptin. We aimed to study patients with pulmonary TB before and six months after treatment, by measuring plasma leptin, soluble leptin receptor and adiponectin, weight and body mass index. Nineteen patients with a diagnosis of pulmonary TB were included in the study. Blood samples were obtained before and six months after treatment, to measure plasma adipokine levels. We found an increase in plasma leptin levels after treatment (p<0.05). Even though BMI also increased, the extent was not enough to account for the changes in the leptin levels. On the other hand, plasma soluble leptin receptor and adiponectin levels did not change significantly after treatment. In conclusion, these results suggest that active TB infection may affect the expression of leptin, in addition to the wasting that may occur in these patients, and that effective TB treatment increases circulating leptin levels, probably restoring normal immunological competence.

Evaluation of two HbA1c point-of-care analyzers.

BACKGROUND: Measurement of HbA1c is the most important parameter to assess glycemic control in diabetic patients. Different point-of-care devices for HbA1c are available. The aim of this study was to evaluate two point-of-care testing (POCT) analyzers (DCA Vantage from Siemens and Afinion from Axis-Shield). We studied the bias and precision as well as interference from carbamylated hemoglobin. METHODS: Bias of the POCT analyzers was obtained by measuring 53 blood samples from diabetic patients with a wide range of HbA1c, 4%-14% (20-130 mmol/mol), and comparing the results with those obtained by the laboratory method: HPLC HA 8160 Menarini. Precision was performed by 20 successive determinations of two samples with low 4.2% (22 mmol/mol) and high 9.5% (80 mmol/mol) HbA1c values. The possible interference from carbamylated hemoglobin was studied using 25 samples from patients with chronic renal failure. RESULTS: The means of the differences between measurements performed by each POCT analyzer and the laboratory method (95% confidence interval) were: 0.28% (p<0.005) (0.10-0.44) for DCA and 0.27% (p<0.001) (0.19-0.35) for Afinion. Correlation coefficients were: r=0.973 for DCA, and r=0.991 for Afinion. The mean bias observed by using samples from chronic renal failure patients were 0.2 (range -0.4, 0.4) for DCA and 0.2 (-0.2, 0.5) for Afinion. Imprecision results were: CV=3.1% (high HbA1c) and 2.97% (low HbA1c) for DCA, CV=1.95% (high HbA1c) and 2.66% (low HbA1c) for Afinion. CONCLUSIONS: Both POCT analyzers for HbA1c show good correlation with the laboratory method and acceptable precision.

Glycated hemoglobin vs. the oral glucose tolerance test for the exclusion of impaired glucose tolerance in high-risk individuals.

BACKGROUND: The aim of this study was to compare the use of glycated hemoglobin (HbA(1c)) and the oral glucose tolerance test (OGTT) in the diagnosis of impaired glucose tolerance in high-risk individuals. METHODS: A total of 713 patients with at least two risk factors for the development of type 2 diabetes were enrolled in the study. Fasting glucose and HbA(1c) were measured in all individuals. Patients whose fasting glucose concentrations were below 7.0 mmol/L underwent an OGTT. RESULTS: From the 713 patients, 234 were euglycemic, 200 had impaired fasting glucose, 118 presented with impaired glucose tolerance and 161 met the diagnostic criteria for type 2 diabetes. OGTT was performed in a total of 596 patients (83.6%). Statistically significant differences were observed for HbA(1c) concentrations in all groups. Receiver operating characteristic curve analysis was performed to assess the capability of HbA(1c) to discriminate between normal glucose tolerance and impaired glucose tolerance. An HbA(1c) value of 36 mmol/mol (5.4%) gave an optimal sensitivity of 85% and a specificity of 73%, and a negative predictive value of 97% for identifying patients with impaired glucose tolerance. CONCLUSIONS: HbA(1c) can be used to rule out patients at high-risk of developing type 2 diabetes.

Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells.

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin's role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT(1) receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT(1) antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT(1) cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.

Role of leptin in the activation of immune cells.

Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.