Clinical and biological risk factors associated with inflammation in patients with type 2 diabetes mellitus.

BACKGROUND: Chronic inflammation has been associated with insulin resistance and related metabolic dysregulation, including type 2 diabetes mellitus (T2DM). Several non modifiable (i.e. genetic predisposition) and modifiable (i.e. sedentary lifestyle, energy-dense food) risk factors were suggested to explain the mechanisms involved in the development of inflammation, but are difficult to assess in clinical routine. The present study aimed to identify easy to asses clinical and biological risk factors associated with inflammation in patients with T2DM. METHODS: One hundred nine patients (51 men, 58 women), 28-60 years old, from seven primary healthcare centers in Gaza City, Palestine, took part to the cross-sectional study (November 2013-May 2014). Study participants had T2DM with no history of inflammatory diseases, cardiovascular diseases, medication and/or any health condition that might affect the inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP). Inflammation was defined for IL-6 ≥ 2 pg/mL and CRP ≥ 6 mg/L. Multivariable logistic regressions were used to identify the relationship between inflammation and clinical and biological risk factors. RESULTS: After adjustment for age and gender, inflammation seems to increase with increased body mass index (BMI) (OR: 1.427 [1.055-1.931]), increased fasting blood glucose (OR: 1.029 [1.007-1.052]) and decreased adiponectin values (OR: 0.571 [0.361-0.903]). There were also significant relationships between inflammation and BMI (OR: 1.432 [1.042-1.968]), fasting blood glucose (OR: 1.029 [1.006-1.052]) and adiponectin (OR: 0.569 [0.359-0.902]), after adjustment for smoking habits and physical activity. CONCLUSION: Managing obesity and associated complications (i.e. hyperglycemia, high adiponectin levels) might help decreasing inflammation in individuals with T2DM.

Is iron deficiency a risk factor for postpartum depression? A case-control study in the Gaza Strip, Palestine.

OBJECTIVE: This study aims to investigate the association between iron body status and postpartum depression (PPD) among mothers during the postpartum period. DESIGN: This is a case-control study. SETTING: Governmental primary health care centres in the Gaza Strip, Palestine. PARTICIPANTS: This study involved 300 mothers a month after delivery, with one 150 mothers that were recruited in the cases group who were diagnosed with PPD based on Edinburgh Postnatal Depression Scale (EPDS) ≥ 10. The control group included 150 mothers did not have PPD (EPDS < 10). Body iron status is represented by the index of sTfR/log ferritin. RESULTS: Among PPD mothers, 43·3 % had low ferritin level v. 15·3 % for controls (P < 0·001) and cases v. controls difference in mean Hb level was -0·61 (95 % CI -0·86, -0·35). The results of the multiple logistic regression reported that there is a statistically significant association between PPD and the body iron status existed, as mothers who suffered from iron deficiency (ID) were three times more likely to have PPD (ORadj 3·25; P = 0·015). Furthermore, the results of the final regression model showed that the other factors that can lead to PPD are absence of psychological guidance services (ORadj 8·54; P = 0·001), suffering from undesired feeling in the last pregnancy (ORadj 1·77; P = 0·034), in addition to having one of the mental health disorders in the last pregnancy (P = 0·001). CONCLUSION: Body iron status might be a risk factor for postpartum depression and other possibilities of reverse causality may worsen the condition.

Reply to Mrakic-Sposta et al. Comment on "Menzel et al. Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice-Which to Use Regarding Disease Outcomes? Antioxidants 2021, 10, 414".

We appreciate the commentary by Mrakic-Sposta et al [...].

Determination of risk factors associated with inflammation in hypertensive patients with type-2 diabetes mellitus in a Palestinian Diabetes Study.

OBJECTIVE: To determine the risk factors associated with inflammation in hypertensive patients with type-2 diabetes mellitus. METHODS: A total of 164 hypertensive patients with type 2 diabetes patients aged 38-60 years were selected from 7 primary healthcare centers in Gaza city, Palestine. Interview questionnaire were employed to collect data related to age, gender, smoking habits, and physical activity pattern. Laboratory biochemical tests included fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), interleukin 6 (IL-6), high sensitive C reactive protein (hs-CRP), and adiponectin were estimated in all patients. RESULTS: The study involved 118 (72%) women and 46 (28%) men; the mean of age was 53.7 ± 0.46 years. A tertile of inflammation feature with hs-CRP was developed. The highest tertile of hs-CRP was significantly associated with women, higher obesity indices, metabolic dysregulation involving lipid profile markers, FBG and blood pressure, IL-6, and lower adiponectin. After adjusting for age, gender, smoking habits, and physical activity; the risk factor of high level of hs-CRP were the increased body mass index [OR: 1.17, p = .018], IL-6 [OR: 2.22, p = .025] and FBG [OR: 1.01, p = .007], as well as reduced adiponectin [OR: 0.81, p = .002]. CONCLUSION: The inflammation state was affected by obesity and had been related to altered adipokines levels of IL-6 and adiponectin, as well as affected by the glycemic control, as evidenced by higher serum level of FBG.

Vitamin C deficiency and risk of metabolic complications among adults with chronic respiratory diseases: A case-control study.

BACKGROUND: Chronic respiratory disease (CRD) is an airflow limitation that represents a wide array of serious diseases. The aim of this study is to examine the influence of vitamin C deficiency on metabolic health-related quality in individuals with and without chronic respiratory disease in the Gaza Strip. METHODS: A matched case-control study including 52 cases of CRD and 52 controls of healthy participants were matched by age, sex, body mass index (BMI) and waist circumferences (WC). The study was conducted at the Ministry of Health secondary health-care centers in Gaza strip, Palestine. The biochemical data included Protein Carbonyl (PC), high sensitivity C reactive protein (CRP), vitamin C, fasting blood glucose (FBG) and markers of the lipid profile. RESULTS: By the qualitative estimation of vitamin C consumption, there was a significantly lower consumption of foods that are rich in vitamin C by CRD patients than the matched controls. By comparing the results between both groups, CRD patients had significantly lower plasma concentrations of vitamins C than the control group (18.43 ± 11.93 µgm/ml vs. 24.06 ± 11.19 µgm/ml, P = 0.025), but significantly higher in PC (3.86 ± 4.21 µgm/ml vs. 2.11 ± 0.97 µgm/ml, P = 0.005), CRP (5.98 ± 8.84 mg/l vs. 1.87 ± 1.96 mg/l, P = 0.001), and FBG (102.46 ± 15.09 mg/dl vs. 95.92 ± 10.88 mg/dl, P = 0.017). The results revealed that CRD patients had significantly lower blood oxygen saturation than the control group (96.36 ± 3.81 vs. 98.51 ± 0.75, P < 0.001), whereas no significant differences were observed regarding the lipid profiles markers. CONCLUSION: CRD patients have lower levels of vitamin C in their plasma and their diet than do healthy matched people; they also have higher oxidative stress and inflammatory markers than healthy people, which are risk factors for predicting metabolic complications.

Common and Novel Markers for Measuring Inflammation and Oxidative Stress Ex Vivo in Research and Clinical Practice-Which to Use Regarding Disease Outcomes?

Many chronic conditions such as cancer, chronic obstructive pulmonary disease, type-2 diabetes, obesity, peripheral/coronary artery disease and auto-immune diseases are associated with low-grade inflammation. Closely related to inflammation is oxidative stress (OS), which can be either causal or secondary to inflammation. While a low level of OS is physiological, chronically increased OS is deleterious. Therefore, valid biomarkers of these signalling pathways may enable detection and following progression of OS/inflammation as well as to evaluate treatment efficacy. Such biomarkers should be stable and obtainable through non-invasive methods and their determination should be affordable and easy. The most frequently used inflammatory markers include acute-phase proteins, essentially CRP, serum amyloid A, fibrinogen and procalcitonin, and cytokines, predominantly TNFα, interleukins 1ß, 6, 8, 10 and 12 and their receptors and IFNγ. Some cytokines appear to be disease-specific. Conversely, OS-being ubiquitous-and its biomarkers appear less disease or tissue-specific. These include lipid peroxidation products, e.g., F2-isoprostanes and malondialdehyde, DNA breakdown products (e.g., 8-OH-dG), protein adducts (e.g., carbonylated proteins), or antioxidant status. More novel markers include also -omics related ones, as well as non-invasive, questionnaire-based measures, such as the dietary inflammatory-index (DII), but their link to biological responses may be variable. Nevertheless, many of these markers have been clearly related to a number of diseases. However, their use in clinical practice is often limited, due to lacking analytical or clinical validation, or technical challenges. In this review, we strive to highlight frequently employed and useful markers of inflammation-related OS, including novel promising markers.

Melissopalynological Study, Phenolic Compounds, and Antioxidant Properties of Heterotrigona itama Honey from Johor, Malaysia.

Six honey samples produced by the stingless bee Heterotrigona itama were analyzed for their plant sources, phenolic compositions, and antioxidant activities. The honey samples were acetolyzed and identified microscopically, and the phenolic compounds were identified by using HPLC-DAD. The antioxidant activities were evaluated using three different assays (FRAP, DPPH, and ABTS) by spectrophotometry. The melissopalynological analysis showed that 26 pollen types from 14 plant families were identified in the honey. Cocos nucifera and Rhizophora mucronata presented as predominant pollen. A total of 6 phenolic acids such as catechin, chlorogenic acid, epicatechin, protocatechuic acid, p-coumaric acid, and rutin were identified. Rhizophora mucronata honey possessed the highest antioxidant activity in all assays. The result showed the influence of plant sources on the phenolic compounds and the antioxidant properties of stingless bee honey. These findings could be significant contributions for the sustainability of stingless bee industry as well as to promote Malaysian stingless bee honey worldwide.

Obesity, Hypertension, and Type-2 Diabetes Mellitus: The Interrelationships and the Determinants among Adults in Gaza City, Palestine.

OBJECTIVES: To describe the distribution of social factors, lifestyle habits and anthropometric measurements according to hypertension and Type-2 diabetes. METHODS: A cross-sectional study was conducted in Gaza City, Palestine that included 379 patients (20-60 years) who had hypertension and/or diabetes. Three groups of patients were involved; 106 hypertensive (HT), 109 diabetic (T2DM) and 164 hypertensive diabetics (HT + T2DM). RESULTS: The HT + T2DM group were older and had a higher body mass index compared to HT and T2DM groups. There were 62.3% patients who were female, 49.2% were highly educated HT patients, and 49.3% patients had a low level of education and were HT + T2DM. There were 55.8% patients who lived in large families. Patients who were passive smokers or never smoked before were mostly HT + T2DM, while active smokers and past smokers had T2DM. There were 48.2% patients who were highly physically active who had HT, 40.9% whom were moderately active had T2DM, and 53.8% of patients who had a low level of activity were HT + T2DM. Multivariate linear regression showed that having a diseased mother, living in a large family, being a past or passive smoker, or never having smoked, having a low or moderate level of activity, and having HT or HT + T2DM, were significantly associated with an increased body mass index. CONCLUSION: Parental health/disease conditions and environmental factors (social network and lifestyle habits) played the greatest role in the development of obesity and disease.

Obesity and inflammation: the linking mechanism and the complications.

Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

Obesity, cardiovascular disease, and role of vitamin C on inflammation: a review of facts and underlying mechanisms.

Obesity means the accumulation of excessive fat that may interfere with the maintenance of optimal state of health. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type-2 diabetes mellitus, and dyslipidemia, but there are evidences for other mediators such as chronic inflammation, oxidative stress, and thrombosis. The decreased levels of antioxidants factors and nitric oxide predispose to further cardiovascular adverse events. To reduce the risks, antioxidants can help by neutralizing the free radicals and protecting from damage by donating electrons. Having the capacity, vitamin C protects from oxidative stress, prevention of non-enzymatic glycosylation of proteins, and enhances arterial dilation through its effect on nitric oxide release. It also decreases lipid peroxidation, and alleviates inflammation. The anti-inflammatory property of vitamin C could be attributed to ability to modulate the NF-kB DNA binding activity and down-regulation in the hepatic mRNA expression for the interleukins and tumor factors.

Gene-environment Interaction: The Causes of High Obesity Incidence.

Urbanization has provided experimental settings for testing the interactive relationship between genetic background and changes in lifestyle and dietary patterns. The concept of gene-environment interaction was described by epidemic of obesity along with urbanization. Genome-wide association has identified several genes such as melanocortin-4 receptor that associates with environmental influences of obesity. Gene environment (GxE) interaction refers to modification by an environmental factor of the effect of a genetic variant on a phenotypic trait. GxE interactions can serve to modulate the adverse effects of a risk allele, or can exacerbate the genotype-phenotype relationship and increase risk.

Obesity can predict and promote systemic inflammation in healthy adults.

BACKGROUND: To find out the differences on biomedical data between obese and non-obese participants, and to identify risk factors associated with systemic inflammation in healthy Palestinian adults. METHODOLOGY: A cross-sectional study involved 105 apparently healthy adults. Interview questionnaire was used to collect personal information. Participants were excluded if they suffered from acute or chronic inflammatory diseases, or continued using medicines, which might affect the biomedical results. RESULTS: In association with increased Body Mass Index (BMI), the obese group displayed significant higher markers including: interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), total cholesterol (TC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Obese group in association with increased waist circumference (WC) was higher significantly in inflammatory markers (IL-6, hs-CRP), lipid profile (TC) and triglyceride (TG), and blood pressure (SBP, DBP). A tertile of a feature of systemic inflammation (hs-CRP) was created, by Ordinal Logistic Regression, after adjusting for the age, gender, smoking habits, physical activity pattern, father and mother's health history; risk factors were the increased BMI [OR: 1.24] (95% CI: 1.005-1.548, P=0.050), IL-6 [OR: 3.35] (95% CI: 1.341-8.398, P=0.010), DBP [OR: 1.19] (95% CI: 1.034-1.367, P=0.015), and reduced Adiponectin [OR: 0.59] (95% CI: 0.435-0.820, P=0.001). Finally, BMI correlated with IL-6 and hs-CRP (r=0.326, P=0.005; r=0.347, P<0.001; respectively), and hs-CRP correlated with IL-6 (r=0.303, P=0.010), and inversely with Adiponectin (r=-0.342, P=0.001). CONCLUSION: The increased level of IL-6 and reduced Adiponectin, which strongly associated with obesity, indicated that having high BMI is a useful marker in association with IL-6 and further developed systemic inflammation.

Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial.

BACKGROUND: Obesity is a degree of excess weight that predisposes people to metabolic syndromes via an inflammatory mechanism. Hypertensive and diabetic people have higher risks of developing systemic inflammation. Long chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs) can reduce the cardiovascular events and help against inflammation. OBJECTIVE: To identify the effects of LC ω-3 PUFAs on reducing the levels of inflammatory markers on hypertensive and/or diabetic obese adults. MATERIALS AND METHODS: Sixty-four patients, who were hypertensive and/or diabetic obese with high levels of inflammatory markers, from primary healthcare centers of Gaza City, Palestine, enrolled in two groups of an open-label, parallel, randomized, controlled trial for 8 weeks. Thirty-three patients were in the control group, and 31 patients were in the experimental group. The experimental group was treated with a daily dose of 300 mg eicosapentaenoic acid and 200 mg of docosahexaenoic acid. RESULTS: Treatment with LC ω-3 PUFAs significantly reduced the level of high sensitivity C reactive protein (hs-CRP) [14.78±10.7 to 8.49±6.69 mg/L, p<0.001], fasting blood glucose (FBG) [178.13±58.54 to 157.32±59.77 mg/dL, p=0.024], and triglyceride (TG) [209.23±108.3 to 167.0±79.9 mg/dL, p<0.05] after 8 weeks of treatment, whereas no significant changes appeared in interleukin 6 (IL-6) and total cholesterol (TC). In the control group, significant reduction was detected for FBG [187.15±64.8 to 161.91±37.9 mg/dL, p<0.05] and TG [202.91±107.0 to 183.45±95.82 mg/dL, p<0.05], and no changes for hs-CRP, IL-6, or TC. By comparing the experimental group with the changes of control group at the endpoint, LC ω-3 PUFAs did not reach the clinical significance in treating effectiveness for any of the clinical variables. CONCLUSION: LC ω-3 PUFAs have recommended effects on health; the obtained results can improve the role of LC ω-3 PUFAs as a protective factor on inflammation and metabolic dysregulation. The time allowed or the dose used could be insufficient to achieve full treatment affectivity.

Atherosclerotic cardiovascular disease: a review of initiators and protective factors.

Atherosclerotic cardiovascular disease (CVD) is a collective term comprising of a group of disorders of the heart and blood vessels. These diseases are the largest cause of morbidity and premature death worldwide. Coronary heart disease and cerebrovascular disease (stroke) are the most frequently occurring diseases. The two major initiators involved in the development of atherosclerotic CVD are vascular production of reactive oxygen species (ROS) and lipid oxidation. In atherosclerosis development, ROS is associated with rapid loss of anti-inflammatory and anti-atherogenic activities of the endothelium-derived nitric oxide (NO(·)) resulting in endothelial dysfunction. In part involving activation of the transcription factor NF-κB, ROS have been involved in signaling cascades leading to vascular pro-inflammatory and pro-thrombotic gene expression. ROS is also a potent activator of matrix metalloproteinases (MMPs), which indicate plaque destabilization and rupture. The second initiator involved in atherosclerotic CVD is the oxidation of low-density lipoproteins (LDL). Oxidation of LDL in vessel wall leads to an inflammatory cascade that activates atherogenic pathway leading to foam cell formation. The accumulation of foam cells leads to fatty streak formation, which is the earliest visible atherosclerotic lesion. In contrast, the cardiac sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and hepatic apolipoprotein E (apoE) expression can improve cardiovascular function. SERCA2a regulates the cardiac contractile function by lowering cytoplasmic calcium levels during relaxation, and affecting NO(·) action in vascular cells, while apoE is a critical ligand in the plasma clearance of triglyceride- and cholesterol-rich lipoproteins.

Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial.

BACKGROUND: Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity. REGISTRATION NUMBER: FPSK_Mac [13]04. OBJECTIVE: The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults. SUBJECTS AND METHODS: Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day. RESULTS: In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found. CONCLUSION: Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.

Role of fish oil in human health and possible mechanism to reduce the inflammation.

The roles of Omega-3 FAs are inflammation antagonists, while Omega-6 FAs are precursors for inflammation. The plant form of Omega-3 FAs is the short-chain α-linolenic acid, and the marine forms are the long-chain fatty acids: docosahexaenoic acid and eicosapentaenoic acid. Omega-3 FAs have unlimited usages, and they are considered as omnipotent since they may benefit heart health, improve brain function, reduce cancer risks and improve people's moods. Omega-3 FAs also have several important biological effects on a range of cellular functions that may decrease the onset of heart diseases and reduce mortality among patients with coronary heart disease, possibly by stabilizing the heart's rhythm and by reducing blood clotting. Some review studies have described the beneficial roles of Omega-3 FAs in cardiovascular diseases (CVDs), cancer, diabetes, and other conditions, including inflammation. Studies of the effect of Omega-3 FAs gathered from studies in diseased and healthy population. CVDs including atherosclerosis, coronary heart diseases, hypertension, and metabolic syndrome were the major fields of investigation. In studies of obesity, as the central obesity increased, the level of adipocyte synthesis of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were increased and the level of anti-inflammatory adiponectin was decreased indicating a state of inflammation. The level of C reactive protein (CRP) synthesized from hepatocyte is increased by the influence of IL-6. CRP can be considered as a marker of systemic inflammation associated with increased risks of CVDs. In molecular studies, Omega-3 FAs have direct effects on reducing the inflammatory state by reducing IL-6, TNF-α, CRP and many other factors. While the appropriate dosage along with the administrative duration is not known, the scientific evidence-based recommendations for daily intake are not modified.