Systemic Inflammation In Type Research Articles

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.3 years, 54.3% female) who were not shift-workers participated. The presence of diabetic retinopathy was determined. The standard deviation of sleep duration and sleep midpoint across all recorded nights were used to quantify sleep variability and regularity, respectively, assessed by 14-day actigraphy. The presence and severity of sleep apnea were assessed using an overnight home monitor. Low-density lipoprotein, haemoglobin A1C and high-sensitivity C-reactive protein were collected. Multiple regression analysis using natural-log-transformed values was performed to establish an independent association between sleep variability and high-sensitivity C-reactive protein. Twenty-two (62.9%) patients had diabetic retinopathy. The median (interquartile range) of high-sensitivity C-reactive protein was 2.4 (1.4, 4.6) mg L-1. Higher sleep variability was significantly associated with higher high-sensitivity C-reactive protein (r = 0.342, p = 0.044), as was haemoglobin A1C (r = 0.431, p = 0.010) and low-density lipoprotein (r = 0.379, p = 0.025), but not sleep regularity, sleep apnea severity or diabetic retinopathy. Multiple regression analysis showed that higher sleep variability (B = 0.907, p = 0.038) and higher HbA1c (B = 1.519, p = 0.035), but not low-density lipoprotein, contributed to higher high-sensitivity C-reactive protein. In conclusion, higher sleep variability in patients with type 2 diabetes who were not shift-workers was independently associated with higher systemic inflammation, conferring increased cardiovascular risk. Whether sleep interventions to reduce sleep variability can reduce systemic inflammation and improve cardiometabolic health should be investigated.

0828 Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes

Abstract Introduction Circadian misalignment increased systemic inflammation in sleep experiments and in those performing shift work. Milder degree of circadian misalignment such as day-to-day shift in sleep timing, i.e. sleep variability, was related to inflammation in population studies. Further, other sleep disturbances and glycemic control can contribute to inflammation. This pilot study explored if sleep variability was associated with inflammation in type 2 diabetes (T2D). Methods Subjects included 35 non-shift working T2D patients with and without diabetic retinopathy (DR) who were participating in a clinical study (NCT04547439). Sleep pattern was assessed by 14-day actigraphy, yielding sleep duration and efficiency. Standard deviation of sleep duration across the night was used to represent sleep variability. Sleep apnea severity was assessed by an overnight home monitor. Neuropathy pain, statin use, serum creatinine, low-density lipoprotein (LDL), HbA1C and by high-sensitivity c-reactive protein (hs-CRP) were collected. Spearman’s correlation analyses and multiple regression analysis (using natural-log transformed values) were performed to establish an independent association between sleep variability and hs-CRP. Results Mean (SD) age was 54.3 (6.4) years, 54.3% were female and 62.9% had DR. Median (interquartile range) of sleep variability was 69 (56,84) minutes. Median A1C was 7.5 (6.6, 8.7)% and hs-CRP was 2.4 (1.4, 4.6) mg/L. Higher hs-CRP was significantly associated with higher sleep variability (r=0.342, p=0.04), HbA1c (r=0.431, p=0.01) and LDL (r=0.379, p=0.03), but not with sleep duration, sleep efficiency, sleep apnea severity, DR status or other variables. Multiple regression analysis showed that higher sleep variability (B = 0.91, p=0.034) and higher HbA1c (B = 1.51, p=0.035), but not LDL, contributed to higher hs-CRP. Conclusion Higher sleep variability in non-shift working T2D patients was shown to be independently associated with higher systemic inflammation, conferring higher cardiovascular risk. This data supports the role of even a mild degree of circadian misalignment on systemic inflammation. Further investigations are needed to determine whether sleep intervention to increase sleep regularity can reduce systemic inflammation and improve cardiometabolic health. Support (if any) NEI R01EY029782 The University of Illinois Chicago Center for Clinical and Translational Science, which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002003.”

Allicin modulates the intestinal microbiota to attenuate blood glucose and systemic inflammation in type 2 diabetic rats

IntroductionAllicin is a wide spectrum prebiotic for human health, but whether it can attenuate blood in diabetes patients is rarely reported. In this study, we built a rat model and investigated the effect of allicin on diabetes mellitus type 2 (T2DM). We found that allicin could effectively reduce blood glucose levels, regulate intestinal microbiota, reduce lipid and body weight accumulation, and systemic inflammation in T2DM rats.MethodsThe rat model of type 2 diabetes was made by streptozotocin, and different doses of allicin were given orally by gavage. The intestinal contents of diabetes rats were sequenced and analyzed by 16S technology, and the clinical indicators of rats were detected for joint analysis.ResultsAllicin can improve the intestinal flora of type 2 diabetes rats, enrich beneficial metabolites, reduce blood glucose, improve blood lipids, reduce systemic inflammation, and improve type 2 diabetes.DiscussionIntestinal microbiome analysis showed that allicin gavage significantly regulated the structure and main components of the intestinal microbiota in T2DM rats. Allicin increased the abundance of probiotic microbes, such as Lactobacillus, Clostridium and Akkermansia, while it reduced pathogenic microbes, such as Enterobacter, Erysipelatoclostridium and Colidextribacter. Allicin gavage increased the abundance of intestinal short-chain fatty acids, such as acetic acid and propionic acid. Correlation analysis showed that the increased gut microbes by allicin gavage were significantly associated with health physiological parameters but negatively related to serum inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), and hypersensitive C-reactive protein (hs-CRP). In addition, our study also suggests that allicin may have prebiotic effects on chronic liver injury. This study shows that allicin can regulate various clinical symptoms of T2DM and is a potential therapeutic drug for T2DM.

Effect of Ziziphus jujube on cardiometabolic factors and systemic inflammation in type 2 diabetic patients: A randomized controlled trial

In the current study, we aimed to assess the effect of dried Ziziphus jujube on blood glucose, lipid profiles, anthropometric indices, and inflammatory factors in type 2 diabetic(T2D) patients. In this randomized controlled clinical trial, 48 patients, aged 30-65 years, were randomly assigned to two intervention(n=24) and control(n=24) groups. The subjects in the intervention group received 30g Ziziphus jujube daily for 12 weeks. At baseline and the end of the 12th week, 10ml of blood was taken from each patient after a 12- to 14-h overnight fasting. Plasma levels of fasting plasma glucose (FPG), triglycerides(TGs), total cholesterol(TC), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein-cholesterol(LDL-C), high-sensitivity C-reactive protein(hs-CRP), and interleukin-6(IL-6) were measured. Anthropometric indices were determined. Plasma FPG, TG, TC, and LDL-C decreased significantly up to-11.36%,-13.59%,-7.46%,-7.65% in the Ziziphus jujube group at the end of week 12 compared to baseline, respectively (P<0.05), and this reduction was significant in comparison with the control group (P<0.05). The plasma hs-CRP reduced significantly up to-24.46% in the Ziziphus jujube group at the end of week 12 compared to baseline (P<0.05), however, this reduction was not significant in comparison with the control group (P<0.05). Also, there were no significant differences between the two groups in mean changes of body mass index, plasma HDL-C, and IL-6. The current study showed that daily consumption of Ziziphus jujube may have beneficial effects on the lipid profiles and blood glucose levels in T2D. T his clinical trial was registered at the Iranian registry of clinical trials (IRCT registration number: IRCT20181210041913N1).

VitaminD affects the neutrophil-to-lymphocyte ratio in patients with type2 diabetes mellitus.

Aims/IntroductionChronic inflammation is an underlying feature of type 2 diabetes mellitus. Hypovitaminosis D is associated with type 2 diabetes mellitus, but whether it contributes to chronic inflammation is unclear. We examined the effects of vitamin D on various immune markers to evaluate its contribution to systemic inflammation in type 2 diabetes mellitus.Materials and MethodsWe retrospectively analyzed data from type 2 diabetes mellitus patients, people with prediabetes and control patients without diabetes (n = 9,746). Demographic and clinical variables were evaluated using descriptive statistics and generalized linear regression. A stratified analysis based on total serum vitamin D was also carried out.ResultsNeutrophil count was a significant predictor of 1,5‐anhydroglucitol and glycated hemoglobin (HbA1c) in patients with prediabetes (1,5‐anhydroglucitol: β = −0.719, P < 0.001 and HbA1c: β = −0.006, P = 0.002) and patients with diabetes (1,5‐anhydroglucitol: β = 0.207, P = 0.004 and HbA1c: β = −0.067, P = 0.010). Lymphocyte count was a significant predictor of HbA1c in patients without diabetes (β = 0.056, P < 0.001) and patients with prediabetes (β = 0.038, P < 0.001). The neutrophil‐to‐lymphocyte ratio (NLR) was a significant predictor of HbA1c in patients without diabetes (β = −0.001, P = 0.032). No immune markers differed significantly based on vitamin D level among patients without diabetes (P> 0.05 for all). Among patients with prediabetes, those who were vitamin D‐deficient had the highest NLR (P = 0.040). Among patients with diabetes, those who were vitamin D‐deficient had the highest neutrophil count (P = 0.001), lowest lymphocyte count (P = 0.016) and highest NLR (P < 0.001).ConclusionsThe NLR is strongly influenced by serum vitamin D level. Given the high prevalence of hypovitaminosis D and elevated NLR among chronic disease patients and the elderly, our results suggest that clinical interpretation of NLR as a predictive marker of type 2 diabetes mellitus‐related inflammation should consider vitamin D level, age and pre‐existing morbidity.

Treatment of periodontitis reduces systemic inflammation in type 2 diabetes.

To assess the impact of periodontal treatment on systemic inflammation in type 2 diabetes. Adults with type 2 diabetes (n=83) and without diabetes (controls, n=75) were recruited, and participants with periodontitis received periodontal treatment and 12months' follow-up. Biomarkers for periodontal inflammation (gingival crevicular fluid interleukin-6, tumour necrosis factor-α, interleukin-1β, interferon-γ, matrix metalloproteinase-8, matrix metalloproteinase-9, adiponectin) and serum markers of inflammation and diabetes control (glycated haemoglobin, high sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-α, interleukin-1β, interferon-γ, leptin, adiponectin) were measured. Structural equation modelling was used to evaluate periodontal treatment effects on oral and systemic inflammation. Periodontal treatment resulted in significant improvements in clinical status and reductions in gingival crevicular fluid biomarkers from baseline to month 12. Structural equation modelling identified that, at baseline, individuals with diabetes and periodontitis had significantly higher systemic inflammation than non-diabetic controls with periodontitis (Δ=0.20, p=.002), with no significant differences between groups for oral inflammation. There was a greater reduction in systemic inflammation following periodontal treatment in individuals with diabetes and periodontitis compared to those with periodontitis but not diabetes (Δ=-0.25, p=.01). Diabetes and periodontitis together appear to increase systemic inflammation, with evidence of reductions following periodontal treatment.

Glycoprotein A and B Height-to-Width Ratios as Obesity-Independent Novel Biomarkers of Low-Grade Chronic Inflammation in Women with Polycystic Ovary Syndrome (PCOS).

The polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women in reproductive age. Obesity and low-grade chronic inflammation are frequently associated with PCOS. Recently, proton nuclear magnetic resonance (1H-NMR)-derived glycoprotein profiles have emerged as potential biomarkers that reflect systemic inflammation in type 2 diabetes, obesity, and other pathological processes. The aim of this work is to study plasma glycoprotein profiles as metabolic/inflammatory biomarkers underlying PCOS and its association with inflammation and obesity. We used 1H-NMR spectroscopy to study five glycoprotein variables, namely GlycA, GlycB, and GlycF and the height-to-width (H/W) ratio of GlycA and GlycB, in 17 women with PCOS (9 non-obese and 8 obese), 17 control women (9 non-obese and 8 obese), and 19 healthy men (10 non-obese and 9 obese). H/W ratios of GlycA and GlycB, but not glycoprotein areas, were specifically associated with PCOS independently of obesity. When considered as a whole, obese subjects presented higher GlycA, GlycB, and GlycF areas and higher H/W GlycA and GlycB ratios than their non-obese counterparts. All glycoprotein variables were associated with hsCRP, IL-6, and TNF-α, showing different correlations among PCOS, women, and men. Our present exploratory results suggest that 1H-NMR-derived glycoprotein profiles might serve as novel diagnostic markers of low-grade chronic inflammation in women with PCOS.

Effect of dipeptidyl-peptidase-4 inhibitors on C-reactive protein in patients with type 2 diabetes: a systematic review and meta-analysis

BackgroundDipeptidyl peptidase-4 inhibitors (DPP-4i) are emerging glucose-lowering agents through interacting with DPP-4 substrate, impact of which on systemic inflammation in type 2 diabetes mellitus (T2DM) remains unknown. This study aimed to evaluate the effect of DPP-4i on modulating serum levels of C-reactive protein (CRP) in T2DM.MethodsPubMed, Cochrane library and Embase databases were searched. Randomized controlled trials (RCTs) with comparators were selected. A random-effects model was used for quantitative data analysis. Heterogeneity was evaluated with I2 index. Sensitivity analysis was performed using the one-study remove approach.ResultsSixteen trials with 1607 patients with T2DM were included. Pooled analysis of DPP-4i demonstrated a significant decrease in serum CRP concentrations (− 0.86 mg/L, 95% CI, − 1.36 to − 0.36). No significant difference was found between DPP-4i and active comparators on serum CRP concentrations (0.64 mg/L, 95% CI, − 0.10 to 1.37). Pooled analysis proved to be stable and credible by sensitivity analysis. In subgroup analysis, changes in serum concentrations of CRP were significantly associated with short diabetes duration (− 0.23 mg/L, 95% CI, − 0.41 to − 0.05).ConclusionsDDP-4i effectively reduced serum CRP levels and showed no stronger effect than traditional oral antidiabetic agents.International Prospective Register for Systematic Review (PROSPERO) number: CRD42017076838.

Study of Pulmonary function tests in Type 2 Diabetes Mellitus and their correlation with glycemic control and systemic inflammation.

Background - Reduced lung function in diabetes has been described for long but its clinical importance is not yet clear. Also, limited literature is available regarding its association with sugar control, and its correlation with inflammatory markers. Thus, we aimed to study the pulmonary function test abnormalities and systemic inflammation in type 2 diabetes mellitus. Methods 100 patients of type 2 diabetes were divided into two groups depending on control of diabetes (group A-HbA1C≤7% and group B-HbA1C >7%). All the subjects selected underwent detailed evaluation including testing for HbA1C, HsCRP (high-sensitivity C-reactive protein), serum ferritin and serum fibrinogen, along with pulmonary function testing. Results Percentage predicted FVC (forced vital capacity), FEV1 (forced expiratory volume in 1 second) and SVC (slow vital capacity) were significantly reduced, while mean values of inflammatory markers [fibrinogen (p <0.001) and hsCRP (p 0.002)] were significantly higher in uncontrolled diabetes group. There was a significant negative correlation between FEV1 (r = -0.739, p<0.001), FVC ( r = -0.370, p<0.001), SVC (r = -0.635, p< 0.001) with HbA1C. HbA1C had a positive correlation with hsCRP (r = -0.308, p 0.002) and fibrinogen (r = 0.388 ,p 0.001). Conclusion Pulmonary functions were decreased and inflammatory markers like hsCRP, fibrinogen, and ferritin significantly increased in uncontrolled diabetics. Also, a potential association was seen between higher values of inflammatory markers like hsCRP and fibrinogen and decrease in lung function. This information, requiring confirmation with larger multicentre studies, remains important because of potential epidemiological, clinical and therapeutic implications.

Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1β and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) μmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.

Association between adherence to dietary recommendations and high-sensitivity C-reactive protein level in type 1 diabetes.

Inflammation plays an important role in the pathogenesis of cardiovascular diseases. Diet, as a modifiable risk factor, may in turn impact systemic inflammation. We therefore assessed whether adherence to the dietary recommendations is associated with high-sensitivity C-reactive protein (hs-CRP) concentrations in type 1 diabetes. Cross-sectional data from 677 FinnDiane study participants (48% men, mean±standard deviation age 46±13years) were included. Dietary intake was assessed with a self-administered questionnaire. A diet score, with higher values denoting better adherence to the recommendations, was calculated. Serum hs-CRP concentration was measured, and individuals with hs-CRP <1.0mg/l, and hs-CRP >3.0 but ≤10.0mg/l were compared. Men and women with high hs-CRP had higher BMI, waist circumference, and triglyceride concentration, but lower HDL-cholesterol concentration. Adjusted for BMI, mean diet score was higher in the low hs-CRP group, both in men (10.8±3.6 vs. 9.9±3.8, p=0.023) and women (12.7±3.4 vs. 11.6±3.5, p=0.021). After further adjustments with potential confounding factors, the difference remained significant only in men. A diet that more closely adheres to the dietary recommendations is associated with lower hs-CRP in men. A prudent diet may help reduce systemic inflammation in type 1 diabetes.

Role of T Lymphocytes in Type 2 Diabetes and Diabetes-Associated Inflammation.

Although a critical role of adaptive immune system has been confirmed in driving local and systemic inflammation in type 2 diabetes and promoting insulin resistance, the underlying mechanism is not completely understood. Inflammatory regulation has been focused on innate immunity especially macrophage for a long time, while increasing evidence suggests T cells are crucial for the development of metabolic inflammation and insulin resistance since 2009. There was growing evidence supporting the critical implication of T cells in the pathogenesis of type 2 diabetes. We will discuss the available effect of T cells subsets in adaptive immune system associated with the procession of T2DM, which may unveil several potential strategies that could provide successful therapies in the future.

Altered levels of serum Copper, Magnesium as a marker of oxidative stress in Predicting Systemic Inflammation in Type 2 Diabetes

Introduction: Diabetes Mellitus is a metabolic disease characterized by hyperglycemia due to defective insulin secretion or action. Trace elements like Copper(Cu) and magnesium (Mg) have been found to be altered in diabetes mellitus and induce reactive oxygen species which has got role in progression of disease. Malondialdehyde (MDA) is a surrogate marker of oxidative stress in type 2 diabetes mellitus. Aims And Objectives: Propose of the study was to estimate serum magnesium (Mg), copper and MDA levels in type 2 diabetes mellitus patients and to compare with that of healthy individuals, also to identify the interrelationship among these and copper &magnesium can be used as an alternate marker of oxidative stress when MDA not available. Materials And Methods:The study included 75 control healthy individuals without Type2 DM and 75 Cases with type 2 DM. Serum concentrations of Glucose, Total Cholesterol, Triglycerides, LDL-C, HDL-C, HbA1c, Magnesium, Copper and MDA was measured. Student's t-test, Pearson correlations tests were used for statistical analysis. Results And Observations: The serum copper level was found to be significantly increased in type 2 DM with HbA1C >7% (157.32±16.89) when compared to control (106.24±25.99). The serum Mg level was found to be significantly decreased (1.62±0.29) (p 7 when compared to control (1.82±0.18). We found a significant increased level of serum Total Cholesterol and LDL-c and Triglycerides and decreased HDL-c in type 2 DM subjects with (p 7% when compared to control. MDA (4.62+1.17nmol/L) in type 2 DM patients when compared to controls(1.4+0.8 nmol/L)( p< 0.0001). Overall, mean serum MDA level in the study group was significantly higher than in the controls. Conclusion: Patients with DM had altered metabolism of Cu (hypercuprimiea) and Mg (hypomagnesaemia). As Cu and Mg has got role in metal induced free radical formation which leads to oxidative stress we compared with novel oxidative marker MDA and concluded that these two trace elements can be used as marker of oxidative stress, which can predict systemic inflammation in type 2 DM to prevent well know complication in advance

Pharmacological treatment and impairment of pulmonary function in patients with type 2 diabetes: a cross-sectional study.

There is no clear relationship between type 2 diabetes mellitus and lung function decline; it is also unclear whether the type of treatment can modify spirometric variables and levels of inflammatory biomarkers. To compare pulmonary function in patients with type 2 diabetes treated with an insulin-sensitizing agent (metformin) and in those treated with secretagogues, as well as combined with insulin, and to evaluate differences in inflammatory biomarkers between treatment groups. We conducted a cross-sectional analytic study in 196 diabetic patients with type 2 diabetic mellitus. Spirometric variables and levels of inflammatory biomarkers (ferritin, fibrinogen, C-reactive protein, interleukin 6, tumor necrosis factor-alpha), were obtained. Residual values (observed minus expected) for forced vital capacity and for forced expiratory volume were calculated and compared between treatment types. Differences in median levels of biomarkers were also compared. After adjustment by known determinants of lung function, and by the control and duration of type 2 diabetes, patients treated with the insulin-sensitizing agent had statistically significant lower differences against expected values for forced vital capacity compared with secretagogues (-212.1 ml vs 270.2 ml, p=0.039), as well as for forced expiratory volume, but without statistical significance (-133.2 mL vs -174.8 mL, p>0.05). In the group of patients treated with the insulin-sensitizing agent, ferritin and tumor necrosis factor-alpha levels were lower (p<0.01). This study supports the hypothesis that insulin-sensitizing agents appear to be associated with less deterioration of lung function and less systemic inflammation in type 2 diabetes. The present study serves to formulate new hypothesis and research projects.

Lipid accumulation product is associated with insulin resistance, lipid peroxidation, and systemic inflammation in type 2 diabetic patients.

BackgroundLipid accumulation product (LAP) is a novel biomarker of central lipid accumulation related to risk of diabetes and cardiovascular disease. In this study, we assessed the association of LAP with glucose homeostasis, lipid and lipid peroxidation, and subclinical systemic inflammation in diabetic patients.MethodsThirty-nine male and 47 female type 2 diabetic patients were assessed for anthropometrics and biochemical measurements. LAP was calculated as [waist circumference (cm)-65]×[triglycerides (mmol/L)] in men, and [waist circumference (cm)-58]×[triglycerides (mmol/L)] in women. Associations of LAP with fasting glucose, insulin, insulin resistance index, lipid and lipoprotein levels, malondialdehyde, and high-sensitive C-reactive protein (hs-CRP) were assessed.ResultsMean age and LAP index were 53.6±9.6 and 51.9±31.2 years, respectively. After adjustments for age, sex and body mass index status, a significant positive correlation was observed between LAP index and fasting glucose (r=0.39, P<0.001), and homeostasis model assessment of insulin resistance (r=0.31, P<0.05). After additional adjustment for fasting glucose levels, antidiabetic and antilipidemic drugs, the LAP index was also correlated to total cholesterol (r=0.45, P<0.001), high density lipoprotein cholesterol (HDL-C) levels (r=-0.29, P<0.05), triglycerides to HDL-C ratio (r=0.89, P<0.001), malondialdehyde (r=0.65, P<0.001), and hs-CRP levels (r=0.27, P<0.05).ConclusionHigher central lipid accumulation in diabetic patients was related to higher insulin resistance, oxidative stress and systemic inflammation.

Adipose tissue macrophages in the development of obesity-induced inflammation, insulin resistance and type 2 Diabetes

It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and type 2 diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in type 2 diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of type 2 diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesity-induced inflammation and the roles ATMs play in this process.

Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes

OBJECTIVEEvaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, known to have different efficacy on mean amplitude of glycemic excursions (MAGE), on oxidative stress, and on systemic inflammatory markers in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA prospective, randomized, open-label PROBE design (parallel group with a blinded end point) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin. The study assigned 45 patients to receive sitagliptin (100 mg once daily; sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice daily; vildagliptin group) for 12 weeks. MAGE, evaluated during 48 h of continuous subcutaneous glucose monitoring, allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients. Assessment of oxidative stress (nitrotyrosine) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients.RESULTSHbA1c, fasting and postprandial glucose, MAGE, and inflammatory and oxidative stress markers were similar between the groups at baseline. After 12 weeks, MAGE (P < 0.01) was lower in the vildagliptin group than in the sitagliptin group. After treatment, HbA1c and postprandial glucose evidenced similar changes between the groups (P = NS). Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine (P < 0.01), IL-6 (P < 0.05), and IL-18 (P < 0.05) than sitagliptin treatment. Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA1c.CONCLUSIONSMAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients. These effects were greater in the vildagliptin group than in the sitagliptin group.

Effect of Simvastatin and Fenofibrate on Cytokine Release and Systemic Inflammation in Type 2 Diabetes Mellitus With Mixed Dyslipidemia

The aim of our study was to compare the effect of simvastatin and fenofibrate treatment on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetes and to assess whether their coadministration is superior to treatment with only 1 of these drugs. One hundred ninety-six adult patients with recently diagnosed and previously untreated type 2 diabetes and mixed dyslipidemia, complying throughout the study with lifestyle intervention and treated with metformin, were randomized in a double-blind fashion to receive simvastatin (40 mg), fenofibrate (200 mg), simvastatin plus fenofibrate, or placebo for 90 days. Main outcome measurements were monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein. One hundred ninety patients completed the study. Simvastatin and fenofibrate decreased monocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 and lymphocyte release of interleukin-2, interferon-γ, and tumor necrosis factor-α, which was accompanied by a decrease in plasma C-reactive protein levels. Anti-inflammatory effects of fenofibrate partly correlated with the improvement in insulin sensitivity. Lymphocyte-suppressing, but not monocyte-suppressing, effect was stronger if these 2 agents were administered together. In conclusion, simvastatin and fenofibrate exhibit a similar effect on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetic subjects with mixed dyslipidemia. This effect may be clinically relevant in the prevention of vascular complications in metformin- and diet-treated subjects with newly diagnosed diabetic dyslipidemia.

The Role of Visfatin in Diabetic Nephropathy

As a result of the energy overload in obesity, insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and atherosclerosis develop, which together comprise the metabolic syndrome. Although the kidney becomes a victim of hyperglycemia in diabetes mellitus, recent work has shown that the abnormalities of lipid and glucose metabolism in the kidney are similarly important to those in adipose tissue. Interestingly, obesity triggers the release of adipokines such as leptin, resistin, and visfatin, and these can then be associated with the progression of diabetic nephropathy and other vascular complications. These adipokines, which are also synthesized in the kidney, appear to have an important role in renal injury associated with insulin resistance. Our studies found that visfatin is not only a surrogate marker of systemic inflammation in type 2 diabetic patients but is also up-regulated in diabetic kidney through the uptake of glucose into renal cells, which leads to the activation of the intracellular insulin signaling pathway and pro-inflammatory mechanisms. However, we also observed a beneficial effect of visfatin administration to type 2 diabetic mice. Visfatin injection improved diabetic nephropathy in vivo, in contrast to our previous in vitro study of cultured renal mesangial cells. These results suggest the possibility of multiple cross-talk between adipose tissue and kidney in the metabolic syndrome, particularly in diabetic nephropathy. Further study should be undertaken to understand the role of adipose tissue and kidney as major organs in the metabolic syndrome.

C-reactive protein mediates the association of liver fat and carotid intima–media thickness in healthy men and men with the metabolic syndrome and/or uncomplicated type 2 diabetes

We investigated whether the relation between liver fat and subclinical atherosclerosis is mediated by low-grade systemic inflammation in type 2 diabetes (T2DM) and the metabolic syndrome (MetS). In 16 T2DM, 36 MetS, and 21 age-matched healthy men, liver fat was quantified by 1H-MRS. Carotid intima–media thickness (cIMT) was measured by ultrasound. Differences between controls, MetS and T2DM or between high versus low liver fat content were calculated. Furthermore, the association of liver fat content, cIMT and CRP was assessed. Liver fat percentage was highest in T2DM, as compared to MetS and controls [17.5% (8.0–27.6), 8.2% (4.2–14.2) and 5.3% (2.3–7.4), respectively; P < 0.001]. Subjects with high-liver fat content had increased cIMT and CRP (all P < 0.02). Liver fat content was positively associated with cIMT ( r = 0.37; P = 0.003). The association of liver fat content and cIMT disappeared after adjustment for CRP. The association between liver fat content and subclinical atherosclerosis seems mediated by low-grade inflammation, possibly due to increased hepatic production. Lowering of liver fat content may decrease CVD risk by concomitantly reducing the pro-inflammatory state in high-risk populations.