Independent Risk Factor For Type Research Articles

Temporal changes in sleep duration, domain-specific sedentary behaviour and physical activity. A survey among 25 to 79 year-old Danish adults

Introduction: Recent evidence suggests that prolonged leisure time sedentary behaviour, including TV-viewing, is an independent risk factor for type 2 diabetes, cardiovascular disease and all cause mortality, irrespective of physical activity level. Monitoring sedentary behaviour as well as physical activity at population level is important in order to elucidate whether the two types of behaviour are in fact independent behaviours that should be addressed separately in public health recommendations.

Therapeutic Perspectives for Adiponectin: an Update

In obesity, the expansion of dysfunctional adipose tissue leads to augmented production of pro-inflammatory adipokines that mediate metabolic changes through their paracrine and/or endocrine actions. By contrast, the secretion and plasma concentration of adiponectin, an adipokine with cardiovascular protective, anti-diabetic and anti-inflammatory properties, are markedly decreased in obesity and its related pathologies. Epidemiological studies on different ethnic groups have identified hypoadiponectinemia as an independent risk factor for type 2 diabetes, hypertension, coronary heart disease and several types of cancers. In animals, replenishment of recombinant adiponectin or transgenic expression of adiponectin can reverse these obesity-related pathological conditions. Although there is currently no direct clinical evidence demonstrating that adiponectin is effective in treating obesity-related cardiometabolic diseases, therapeutic benefits of several anti-diabetic and cardiovascular drugs, such as the agonists of peroxisome proliferator-activated receptor (PPAR) γ and PPAR α and statins, are associated with increased plasma adiponectin in humans. In addition, a number of medicinal herbs and natural compounds with beneficial effects on cardiometabolic diseases, have been shown to increase adiponectin secretion in adipocytes. This review highlights recent advances on multiple beneficial effects of adiponectin and discusses the potential therapeutic interventions for obesity-related cardiometabolic syndromes by targeting adiponectin.

HIGH PREVALENCE OF TYPE-2 DIABETES IN CHINESE OIL WORKERS: INTERACTION BETWEEN SAA1 GENE AND WORK STRESS

ObjectivesSerum Amyloid A (SAA) was reported associated with insulin resistance and type-2 diabetes. The present study aimed to investigate the prevalence of type-2 diabetes and its association with SAA1 genetic...

Fatty liver: cause or consequence

Diabet. Med. 29, 1097 (2012) This year’s Dorothy Hodgkin Lecture (2012) at Diabetes UK was awarded to Christopher Byrne. In this months issue of Diabetic Medicine, he summarizes that lecture and proposes ‘that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and for increasing insulin resistance’ [1]. Non-alcoholic fatty liver disease is an established component of the metabolic syndrome and represents a spectrum of liver disease from uncomplicated fatty liver to end-stage liver disease. Non-alcoholic fatty liver disease has a prevalence of 17–33% in the general population and is as high as 70% in Type 2 diabetes. Increasing evidence implicates non-alcoholic fatty liver disease as an independent risk factor for Type 2 diabetes and cardiovascular disease. However, simply proving an association does not imply reverse causality. Last year, the recipient of the Dorothy Hodgkin Lecture was Naveed Sattar and his lecture was published earlier this year [2]. Indeed, Naveed contributed to the early evidence that that surrogates of liver fat (alanine aminotransferase; ALT) may predict new-onset diabetes based on data from the West of Scotland Coronary Prevention Study (WOSCOPS). He discussed the use of biomarkers for diabetes, including non-alcoholic fatty liver disease, in his lecture. He crystallizes the problem in the following sentences. ‘There remains debate in some quarters over whether excess liver fat is simply a consequence of peripheral insulin resistance driving hyperinsulinaemia, in turn driving de novo lipogenesis in the face of continued caloric excess, or whether excess calories, perhaps particularly excess carbohydrate, directly drive de novo hepatic lipogenesis, with subsequent deterioration in hepatic insulin resistance.’ In addition to the arguments presented by both Naveed Sattar and Chris Byrne, readers may be interested in an excellent recent review of mechanisms of insulin resistance and the role of ectopic lipid accumulation published in Cell this year by Samuel and Shulman [3]. If non-alcoholic fatty liver disease is an aetiological driver of insulin resistance and subsequent Type 2 diabetes and cardiovascular disease, then reversal of non-alcoholic fatty liver disease should lead to a decrease in risk of diabetes and cardiovascular disease. In table 2 of Christopher Byrne’s review, he lists potential treatments [1]. We eagerly await the results of randomized clinical trials that address this issue, including the WELCOME study (Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor therapy) that is testing the effects of high-dose purified n-3 long-chain fatty acids and is due for completion in 2012.

The Vicious Cycle of Leptin-Insulin Resistance Predicts Impaired Glucose Metabolism in Obese Adults with Obstructive Sleep Apnea

le tt e r t o t H e e d it o r S is an overlooked area of metabolic processes and an important modulator of endocrine function. Despite a large body of evidence suggesting that obstructive sleep apnea (OSA) is an independent risk factor for type 2 diabetes, the underlying pathogenesis of impaired glucose metabolism (IGM) in OSA remains less well understood. The recent fi ndings of Papaioannou and colleagues showed no clinically signifi cant abnormalities of appetite regulating hormones in OSA that would suggest a cause for IGM.1 While the study provides an important insight into the phenotypic spectrum of OSA, it also raises questions related to possible yet unexplored more complex pathomechanisms linking appetite hormones with IGM in OSA. From a pathophysiological point of view, insulin resistance (IR) and beta-cell dysfunction both play a role in the development of IGM. While research has documented that OSA can contribute to IR independent of obesity, there is a paucity of information on leptin resistance-related IR in OSA that may potentially impair glucose homeostasis. Leptin is a wellknown adipose tissue-derived hormone that binds to receptors in the brain and inhibits expression of neuropeptide Y (NPY). Most obese humans produce large quantities of leptin but are insensitive to its effects. The suggested mechanisms underlying leptin resistance include defective leptin receptors and/or post-receptor signal transduction, reduced numbers of leptin receptors, interactions between leptin and plasma circulating factors, and other factors that override the leptin satiety signal. It is plausible that OSA-stress-related release of NPY from sympathetic nerves and activation of its Y2 receptors in the adipose tissue might stimulate fat angiogenesis and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity, while closing a vicious cycle of increasing leptin-insulin resistance. Considering different receptor-mediated effects of NPY, the plasma level of NPY might not necessarily be the best parameter to assess NPY effects in peripheral tissues. In our study,2 we demonstrated that OSA is associated with specifi c cytokines that refl ect link between OSA and glucose metabolism. Specifi cally, nocturnal oxyhemoglobin desaturations in OSA were closely associated with interleukin-6 (IL-6) production in obese women with IGM, but not in controls with normal glucose metabolism matched individually for sex, age, adiposity, and apnea-hypopnea index. Moreover, cross-sectional data from our study showed additional close associations of IL-6 with leptin-to-leptin receptor ratio and markers of adiposity only in IGM. These fi ndings support the role that IL-6 plays in obesity and extend it to possible pathophysiological processes linking obesity to IGM via leptin resistance and hypoxic stress in OSA. Further prospective studies are needed to explore the dynamic interactions among appetite regulating hormones, their receptors, and glucose homeostasis in OSA to develop novel interventions to prevent metabolic sequelae of OSA.

Evaluation of risk factors and effect of physical activity in caesarean section in nulliparous women

Objective: The aim of this study was to evaluate risk factors for caesarean section (CS) in nulliparous women and to determine the effect of physical activity on ease of labour. Methods: A prospective observational study, including 282 nulliparous women at 37–41 gestational weeks was conducted. Maternal demographic characteristics, obstetric history and Modified Grimby scale for evaluation of physical activity were noted. Patients were classified into spontaneous labour and induction group. Multiple logistic regression model was used to assess independent risk factors for type of delivery. Results: Caesarean rate was increasing with higher educational status (p < 0.001). Maternal height, maternal and paternal age were higher, whereas dilatation on admission was lower in CS group (p < 0.05). Maternal age, weight gain and CS rate were higher in induction group (p < 0.05). Fetal distress as a cause of CS was detected higher in induction group (p < 0.05). Physical activity has no significant effect on mode of delivery (p > 0.05). Maternal height (p = 0.011), and cervical dilatation on admission (p = 0.004) were identified as predictor factors for CS. Conclusion: Cervical dilatation is the most important negative predictive factor for CS, whereas, moderate physical activity has no effect on mode of delivery. Fetal distress was the most frequent cause of CS in induction group.

Levels of fetuin‐A relate to the levels of bone turnover biomarkers in male and female patients with type 2 diabetes

To evaluate the relationship of plasma fetuin-A levels with markers of bone turnover in male and female type 2 diabetic subjects. Fetuin-A, which is a serum protein produced by the liver and promotes bone mineralization, is an independent risk factor for type 2 diabetes, whilst type 2 diabetes is associated with an increased incidence of osteoporosis or fractures. It is not known how fetuin-A levels relate to parameters of bone metabolism in type 2 diabetes. Eighty patients with type 2 diabetes [40 men and 40 women matched for age, body mass index (BMI) and time since diagnosis of diabetes] were studied. Fetuin-A together with metabolic parameters and levels of serum carboxy-terminal telopeptide of type 1 collagen (C-telopeptide), osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (ALP) and sex hormones was determined in all participants. Fetuin-A levels did not differ significantly between male and female diabetic subjects. In a model adjusted for age, BMI, fatty liver index (FLI), time since diagnosis of diabetes, HbA(1c) , antidiabetic and lipid-lowering drug therapies, smoking, total serum protein, creatinine, gamma glutamyl-transferase, parathyroid hormone, C-reactive protein, glomerular filtration rate, and presence of micro-, cardio-, and peripheral vascular diabetic complications, fetuin-A showed a significant positive association with levels of bone ALP (r = 0·71, P = 0·006) in men. In women, fetuin-A was significantly negatively associated with C-telopeptide (r = -0·60, P = 0·03) levels. Results suggest an independent association of fetuin-A levels with markers of bone turnover in male and female patients with type 2 diabetes. More studies are needed to determine whether fetuin-A could serve as a new marker for fracture risk or osteoporosis in type 2 diabetes and to explore its potential sexually dimorphic effects.

Pathophysiological Insights into Cardiovascular Health in Metabolic Syndrome

Pathophysiological Insights into Cardiovascular Health in Metabolic Syndrome

The growth arrest-specific 6 (Gas6) gene polymorphism c.834+7G>A is associated with type 2 diabetes

AimsThe plasma protein growth arrest-specific 6 (Gas6) is important to the inflammatory process and involved in the development of diabetic renal and vascular complications. Recently, Gas6 protein also represents a novel independent risk factor of type 2 diabetes. We further investigated the association of c.843+7G>A Gas6 polymorphism and type 2 diabetes. MethodsA total of 278 adults, including 96 with normal glucose tolerance (NGT), 82 with impaired glucose tolerance (IGT), and 100 with type 2 diabetes were recruited. All subjects were genotyped for c.843+7G>A Gas6 polymorphism. ResultsPlasma Gas6 concentrations were significantly lower among patients with type 2 diabetes compared to subjects with IGT and NGT. Subjects with Gas6 c.843+7AA genotype had higher Gas6 levels and lower glucose values than GG genotype. The AA genotype and A allele were less frequent in patients with type 2 diabetes compared with NGT subjects. In univariate analysis, the AA genotype was found to be associated with a decreased risk for type 2 diabetes. Moreover, the association was even stronger after adjustment for established diabetes risk factors. ConclusionsThe Gas6 c.843+7AA genotype and A allele are less prevalent in type 2 diabetes, which may have a protective role for type 2 diabetes.

Telomere Dysfunction–Related Serological Markers Are Associated With Type 2 Diabetes

OBJECTIVERecent studies have identified a set of serological markers for telomere dysfunction and DNA damage. The relevance of these serological markers in type 2 diabetes remains elusive. We investigated the association of serological markers (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase) with leukocyte telomere length, a functional variant of uncoupling protein-2 (UCP2), and susceptibility of type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 930 patients and 867 control subjects were recruited to examine the association between leukocyte telomere length, UCP2 variant (−886G>A), recently identified serological markers, and type 2 diabetes. Telomere length was determined by a quantitative real-time PCR–based assay. EF-1α, stathmin, and C-reactive proteins were measured by enzyme-linked immunosorbent assays. N-acetyl-glucosaminidase was measured by an enzyme activity assay. The UCP2 variant was determined by PCR and restriction enzyme digestion.RESULTSThe average telomere length of type 2 diabetic patients was significantly shorter than that of control subjects. Serological N-acetyl-glucosaminidase correlates with both age and telomere length and was significantly higher in patients than in control subjects. Neither EF-1α nor stathmin showed significant difference between patients and control subjects. The UCP2–886G>A variant correlated with type 2 diabetes status but did not correlate with telomere length or the serological markers. Multivariate analysis showed that higher serological N-acetyl-glucosaminidase, shorter telomeres, and the UCP2–886G>A variant are independent risk factors for type 2 diabetes.CONCLUSIONSSerological N-acetyl-glucosaminidase, telomere length, and the UCP2–886G>A variant are independent risk factors for type 2 diabetes. Serological N-acetyl-glucosaminidase correlates with telomere length but not with the UCP2–886G>A variant.

Epidemiological survey on the prevalence of periodontitis and diabetes mellitus in Uyghur adults from rural Hotan area in Xinjiang.

Background and Aims. This study was designed to explore the relationship between periodontitis and diabetes mellitus (DM) in Uygur adults from Xinjiang. Methods and Results. Data were obtained using questionnaire and oral examination. Participants (48.87 ±13.72 yr) were categorized into periodontitis and non-periodontitis groups in accordance with the chronic periodontitis diagnostic criteria. Based on gum inflammation, bleeding on probing, periodontal pocket depth and attachment loss, patients were further divided into mild, moderate and severe periodontitis groups. Among 962 subjects, 453 (47.1%) suffered from chronic periodontitis with a prevalence of type 2 DM and impaired fasting glucose of 9.5% and 11.4%, respectively. In the periodontitis group, the prevalence of type 2 DM was 75.6% compared with 22.4% in the non-periodontitis group. Likewise, the prevalence of impaired fasting glucose was 71.3% and 28.7% in periodontitis and non-periodontitis groups, respectively. The univariate logistic regression analysis revealed moderate and severe periodontitis as risk factors for DM (OR = 3.4, OR = 2.9). Multivariate logistic regression analysis showed that moderate periodontitis is independently associated with DM (OR = 4). Conclusions. Our data revealed that prevalence of DM is overtly higher in periodontitis patients than in individuals without periodontitis. Furthermore, moderate periodontitis is considered an independent risk factor for type 2 DM.

Risk Factors for Type 1 Diabetes Mellitus among Children and Adolescents in Basrah

Environmental factors play an important role in the pathogenesis of type 1 diabetes mellitus, many of these factors have been uncovered despite much research. A case-control study was carried out to determine the potential maternal, neonatal and early childhood risk factors for type 1 diabetes mellitus in children and adolescents in Basrah. A total of 96 diabetic patients who have been admitted to the pediatric wards at 3 main hospitals in Basrah, and those who have visited primary health care centers over the period from the 4(th) of November 2006 to the end of May 2007 were recruited. In addition, 299 non-diabetic children were included, their age ranged from 18 months to 17 years. Family history of type 1 diabetes mellitus and thyroid diseases in first and second degree relatives was found to be an independent risk factor for type 1 diabetes mellitus, (p<0.001). Regarding maternal habits and illnesses during pregnancy, the study has revealed that tea drinking during pregnancy is a risk factor for type 1 diabetes mellitus in their offspring, (p<0.05). In addition, maternal pre-eclampsia and infections were found to be significant risk factor for type 1 diabetes mellitus, (p<0.001). Neonatal infections, eczema and rhinitis during infancy were also significantly associated with development of type 1 diabetes mellitus. Moreover, the results revealed that duration of <6 months breast feeding is an important trigger of type 1 diabetes mellitus. Exposure to environmental risk factors during pregnancy (tea drinking, pre-eclampsia, and infectious diseases), neonatal period (respiratory distress, jaundice and infections) and early infancy are thought to play an important role in triggering the immune process leading to B-cell destruction and the development of type 1 diabetes mellitus.

High-Normal HbA1c Is a Strong Predictor of Type 2 Diabetes in the General Population

OBJECTIVEGlycosylated hemoglobin (HbA1c) recently has been recommended for the diagnosis of diabetes by the American Diabetes Association, but its value in the prediction of type 2 diabetes is poorly understood. In this study we evaluated how high-normal HbA1c levels predict type 2 diabetes.RESEARCH DESIGN AND METHODSWe measured HbA1c in 919 Caucasian subjects, aged 40–79 years, and recorded new cases of type 2 diabetes in the following 15 years. Diabetes was diagnosed with HbA1c.RESULTSSubjects were stratified according to baseline HbA1c (<5.0, 5.00–5.49 [reference], 5.50–5.99, and 6.00–6.49%). Sex- and age-adjusted hazard ratios (95% CI) for type 2 diabetes were 1.11 (0.30–4.41), 1.00, 3.79 (1.79–8.06), and 12.50 (5.51–28.34), respectively. Results did not change after adjusting for several putative confounding factors and were confirmed when models with updated variables were used.CONCLUSIONSHbA1c is an independent risk factor for type 2 diabetes. Subjects with high-normal levels of HbA1c deserve particular attention because they have a strong risk of developing diabetes.

Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans

Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment.

Clinical significance of D-dimer in rapid screening for acute aortic dissection

Objective To investigate clinical significance of D-dimer and other easily-obtained laboratory parameters in rapid screening for acute aortic dissection ( AAD). Methods Data of general health, clinical symptoms, white blood cell (WBC) count, serum levels of C-reactive protein (CRP),cardiac troponin Ⅰ (cTn Ⅰ ) and D-dimer in patients with confirmed AAD and acute coronary syndrome (ACS) were retrospectively analyzed. Significance of varied parameters in clinical diagnosis for AAD was evaluated by logistic regression model and their diagnostic values were evaluated by receiver operating characteristics (ROC) curve. Results Serum level of D-dimer increased significantly in patients with type Ⅰ AAD, as compared with that in those with type Ⅱ and type Ⅲ (P = 0. 111 and 0. 002, respectively). D-dimer, WBC and CRP all were independent risk factors for type Ⅰ AAD by logistic regression model fitted,with the largest effect of D-dimer. Analysis by ROC curve with sensitivities and specificities of serum levels of D-dimer and CRP, and WBC count also showed the same results. Conclusions Determination of serum level of D-dimer had significantly diagnostic value for AAD, and can be sued as rapid screening for it if combined with determinations of WBC and CRP. Key words: Aortic diseases ; Diagnosis ; D-dimer ;

Chronic Ethanol Consumption-induced Pancreatic β-Cell Dysfunction and Apoptosis through Glucokinase Nitration and Its Down-regulation

Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of chronic ethanol consumption on pancreatic β-cell dysfunction and whether generated peroxynitrite participates in the impaired glucose homeostasis. Here we show that chronic ethanol feeding decreases the ability of pancreatic β-cells to mediate insulin secretion and ATP production in coordination with the decrease of glucokinase, Glut2, and insulin expression. Specific blockade of ATF3 using siRNA or C-terminally deleted ATF3(ΔC) attenuated ethanol-induced pancreatic β-cell apoptosis or dysfunction and restored the down-regulation of glucokinase (GCK), insulin, and pancreatic duodenal homeobox-1 induced by ethanol. GCK inactivation and down-regulation were predominantly mediated by ethanol metabolism-generated peroxynitrite, which were suppressed by the peroxynitrite scavengers N(γ)-monomethyl-L-arginine, uric acid, and deferoxamine but not by the S-nitrosylation inhibitor DTT, indicating that tyrosine nitration is the predominant modification associated with GCK down-regulation and inactivation rather than S-nitrosylation of cysteine. Tyrosine nitration of GCK prevented its association with pBad, and GCK translocation into the mitochondria results in subsequent proteasomal degradation of GCK following ubiquitination. This study identified a novel and efficient pathway by which chronic ethanol consumption may induce GCK down-regulation and inactivation by inducing tyrosine nitration of GCK, resulting in pancreatic β-cell apoptosis and dysfunction. Peroxynitrite-induced ATF3 may also serve as a potent upstream regulator of GCK down-regulation and β-cell apoptosis.

Plasma Protein Growth Arrest–Specific 6 Levels Are Associated With Altered Glucose Tolerance, Inflammation, and Endothelial Dysfunction

OBJECTIVEPlasma protein growth arrest–specific 6 (Gas6) is important to the inflammatory process and is involved in the development of diabetic renal and vascular complications. We set out to determine whether plasma Gas6 levels are associated with altered glucose tolerance, insulin sensitivity, inflammation, and endothelial dysfunction.RESEARCH DESIGN AND METHODSA total of 278 adults, including 96 with normal glucose tolerance (NGT), 82 with impaired glucose tolerance (IGT), and 100 with type 2 diabetes were recruited. Plasma Gas6 concentration and biochemical, proinflammatory, and endothelial variables were determined. Insulin sensitivity was examined by homeostasis model assessment.RESULTSPlasma Gas6 concentration was significantly lower among patients with type 2 diabetes compared with subjects with NGT (P < 0.001). The plasma Gas6 value was inversely correlated with fasting glucose, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular cell adhesion molecule (VCAM)-1. In multivariate logistic regression analysis, after adjustment for established diabetes risk factors, higher plasma Gas6 concentrations were significantly associated with a decreased risk of type 2 diabetes. Moreover, the association became slightly stronger after further adjustment for TNF-α, IL-6, high-sensitive C-reactive protein, E-selectin, intercellular adhesion molecule-1, and VCAM-1.CONCLUSIONSPlasma Gas6 is associated with altered glucose tolerance, inflammation, and endothelial dysfunction. It also may represent a novel independent risk factor of type 2 diabetes and a potential surrogate marker of inflammation and endothelial dysfunction.

PTPN22 1858T allele is associated with younger age at onset of type 1 diabetes and is not related to subsequent thyroid autoimmunity

To evaluate the prevalence of PTPN22 C1858T polymorphism in young type 1 diabetes patients with or without autoimmune thyroiditis. Genotyping was performed in 209 controls and 243 patients diagnosed with diabetes at median age of 8.6 years. Diabetes-related autoimmunity was assessed at diagnosis of the disease, while thyroid-related autoimmunity was determined at diabetes onset and at annual intervals up to 15 years of follow-up. The 1858T allele frequency was 15.2% in patients and 10.5% in controls (odds ratio 1.53, p = 0.037). 1858T positive patients were significantly younger at diagnosis of diabetes than those without this allele ( p = 0.003). No association was found between C1858T polymorphism and diabetes-related autoimmunity ( p = 0.173) or thyroid autoimmune disease ( p = 0.321), respectively. We conclude that PTPN22 1858T allele is an independent risk factor for type 1 diabetes and associated with younger age at the onset of the disease. However, no association with concomitant thyroid autoimmunity was found.

Continuous Positive Airway Pressure Treatment in Patients with Sleep Apnoea: Does it Really Improve Glucose Metabolism?

Obstructive Sleep Apnoea Syndrome (OSAS) is a common disorder, characterised by repetitive episodes of partial or complete obstruction of the upper airway during sleep and associated with increasing respiratory efforts. These perturbations lead, in turn, to oxyhaemoglobin desaturation, sleep fragmentation, and daytime symptoms, mainly excessive sleepiness. Accumulating evidence suggests that intermittent hypoxia and oxyhaemoglobin desaturation may result, independently of obesity, in impaired glucose metabolism, as well as insulin resistance even in non-diabetic patients with OSAS. Additionally, OSAS has been proposed as an independent risk factor for type 2 diabetes mellitus. Continuous Positive Airway Pressure (CPAP) is the treatment of choice for OSAS, since it eliminates upper airway collapse during sleep and also improves sleep fragmentation, daytime symptoms and quality of life. Moreover, it has been proposed that the amelioration of breathing disturbances during sleep can improve several markers of glucose metabolism and insulin resistance, such as glycated haemoglobin, fasting glucose, insulin, and insulin resistance. Indeed, some studies have reported improvements in these parameters especially in compliant patients. However, other works failed to confirm this beneficial effect. The present article reviews the issue whether CPAP treatment exerts a beneficial effect on glucose metabolism and insulin resistance.

Diastolic function is strongly and independently associated with cardiorespiratory fitness in central obesity

Cardiorespiratory fitness [maximal O2 consumption (VO2max)] is an independent risk factor for type 2 diabetes; but in individuals at risk, factors influencing VO2max are poorly understood. We tested the hypothesis that VO2max is associated with diastolic function [subendocardial variability ratio (SEVR), %], as diastolic function influences myocardial perfusion. We studied 47 men and women with central obesity without diabetes. We measured fitness (VO2max) by treadmill testing and diastolic function (SEVR%) by pulse-wave analysis. We measured other factors influencing this relationship: insulin sensitivity [whole body glucose uptake-to-insulin concentration ratio (M/I)] by hyperinsulinemic euglycemic clamp, fatness by MR imaging and dual-energy X-ray absorptiometry, physical activity energy expenditure (metabolic equivalents of tasks) by the Sensewear Pro2 device, and muscle microvascular exchange capacity (capillary filtration coefficient) by venous plethysmography. Mean age of the subjects was 51+/-9 (SD) yr. VO2max was associated with SEVR% (r=0.50, P=0.001), fatness (r=-0.39, P=0.008), and HbA1c (r=-0.35, P=0.018), but not with whole body glucose uptake-to-insulin concentration ratio, metabolic equivalents of tasks, or capillary filtration coefficient. In regression modeling with age, sex, fatness, and SEVR% as explanatory variables, only age, sex, and SEVR% were independently associated with VO2max (SEVR%--standardized B coefficient=0.37, 95% confidence interval=0.003-0.18, P=0.007). This model identified 46% of the variance in VO2max (R2=0.46, P=0.0001). There was a strong, independent association between VO2max and a measure of diastolic function in sedentary individuals with central obesity.