Anna Borkowska

Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment

Objective The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI). Methods 276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected. Results In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors. Conclusions We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators.

Role of adipocytokines and its correlation with endocrine pancreatic function in patients with pancreatic cancer.

INTRODUCTION Some authors suggest that adipocytokines contribute to the induction of pancreatic carcinogenesis as well as the development of endocrine insufficiency. AIMS We evaluate the circulating concentrations of leptin, resistin and visfatin in patients with newly diagnosed pancreatic cancer (PC) and relationship between serum adipocytokines level and clinicopathological features of PC. Moreover the usefulness of those adipocytokines as possible biomarkers of endocrine pancreatic function in PC has been assessed. METHODS The pilot study group consisted of 45 individuals (mean age 65.6 ± 11.5 years, BMI 21.8 ± 3.4 kg/m(2)) with newly diagnosed PC (within last 1-3 months) and 13 healthy individuals with age, gender and BMI matched to the study group. Among PC patients 18 (40%) had recently diagnosed diabetes. Fasting plasma leptin, resistin, visfatin concentrations were determined with ELISA (R&D Systems, Phoenix Pharmaceuticals) and insulin by RIA (DakoCytomation). RESULTS Patients with PC as compared to controls had significantly lower plasma leptin (40.6 ± 21.3 vs 63.2 ± 16.3 pg/mL; p < 0,0008). In contrast PC patients showed more than six fold higher level of resistin (126.2 ± 143.2 vs 18.9 ± 7.2 ng/mL; p < 0.009) than controls. The median plasma visfatin was 2.8 ± 1.8 ng/mL, which was not significantly different from the controls (3.8 ± 1.1 ng/mL). When PC patients with and without diabetes were considered separately, plasma leptin concentrations among nondiabetic patients were slightly, but not significantly higher (44.6 ± 21.0) as compared to diabetics (34.5 ± 20.7). Moreover there was no difference between visfatin and resistin level in PC, among patients with and without diabetes. No significant differences between serum level of leptin, visfatin and resistin and age, gender, BMI, smoking status, tumor localization, distant metastases and pain has been found. CONCLUSION The results of this study confirm previous findings that patients with newly diagnosed pancreatic cancer are characterized with lower level of leptin. This pilot study showed significantly higher resistin concentrations in patients with PC in comparison to healthy controls, which may be helpful in PC early diagnosis. Changes in leptin and resistin level in PC are not likely related to endocrine disorders.

C-Reactive Protein, Advanced Glycation End Products, and Their Receptor in Type 2 Diabetic, Elderly Patients with Mild Cognitive Impairment

Objective The aim of the study was to evaluate serum levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), and C-reactive protein (CRP) in elderly patients with type 2 diabetes mellitus with and without mild cognitive impairment (MCI) and to determine the predictors (including AGEs, RAGE, and CRP levels) of having MCI in elderly patients with type 2 diabetes. Methods Two hundred seventy-six diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. Results Serum AGEs, RAGE, and CRP levels were significantly increased in MCI patients compared to controls. In group of patients with MCI, serum RAGE level was positively correlated with AGEs level and with CRP level. RAGE, AGEs, and CRP concentrations were positively correlated with HbA1c levels and negatively correlated with MoCA score. The univariate logistic regression models revealed that variables, which increased the likelihood of diagnosis of MCI in elderly patients with type 2 diabetes were higher levels of HbA1c, RAGE, AGEs, CRP, TG, lower level of HDL cholesterol, previous CVD, HA, or use of HA drugs, hyperlipidemia, retinopathy, nephropathy, increased number of co-morbidities, older age, and less years of formal education. HA or use of HA drugs, previous CVD, higher level of RAGE and CRP, older age and less years of formal education are the factors increasing the likelihood of having MCI in elderly patients with type 2 diabetes in multivariable model. Conclusion In summary, serum AGEs, RAGE, and CRP are increased in the circulation of MCI elderly diabetic patients compared to controls. A larger population-based prospective study needs to be performed to further confirm the relationship between AGEs, RAGE, and the cognitive decline or progress to dementia.

Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment

The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

Plasma levels of thrombomodulin, plasminogen activator inhibitor-1 and fibrinogen in elderly, diabetic patients with depressive symptoms

BackgroundDiabetes, depression and aging have been associated with pro-inflammatory and prothrombotic state.AimThe aim of the study was to determine the plasma levels of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in elderly diabetic patients with and without depressive symptoms and to examine factors (including thrombomodulin, PAI-1, fibrinogen levels) associated with depressive symptoms in elderly patients with type 2 diabetes (T2DM).MethodsA total of 276 T2DM elders were evaluated: 82 subjects with depressive symptoms and 194 controls. Data were collected concerning biochemical parameters and biomarkers.ResultsPlasma thrombomodulin, PAI-1 and fibrinogen were elevated in patients with depressive symptoms compared to controls. Thrombomodulin level was correlated with fibrinogen and PAI-1 levels. All parameters were correlated with the Geriatric Depression Scale-30 score. The univariate logistic regression models revealed that variables which increased the likelihood of diagnosis of depressive symptoms in elderly patients with T2DM were: female sex, smoking habit, longer duration of T2DM, hyperlipidemia, neuropathy, increased number of co-morbidities, higher BMI, and higher levels of total and LDL cholesterol, thrombomodulin, PAI-1 and fibrinogen. In addition, the multivariable analysis indicated that female sex, smoking habit, increased number of co-morbidities, higher BMI, and higher levels of LDL cholesterol and thrombomodulin are the predisposing factors for depressive symptoms.ConclusionsElderly diabetic patients with depressive symptoms have higher levels of thrombomodulin, PAI-1 and fibrinogen. Further prospective larger studies are needed to provide potential directions for the research, treatment and prevention of co-morbid depression and diabetes.

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma

AIM To estimate the levels of serum cytokines in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) patients in order to evaluate their usefulness as possible biomarkers. METHODS The study included 167 Caucasian patients: 74 with PDAC (28 men and 42 women, aged 30-88 years), 78 with CP (50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor (TGF)-β1, HA and s-Fr were measured in patients with CP (n = 78), PDAC (n = 74) and healthy controls (n = 15) using ELISA (Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification. RESULTS Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level (1066 ± 582 and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr (2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA (199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course (2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group (986 vs 839, P = 0.043). CONCLUSION Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.

Serum Soluble Adhesion Molecules and Markers of Systemic Inflammation in Elderly Diabetic Patients with Mild Cognitive Impairment and Depressive Symptoms.

The aim of the study was to determine the serum levels of soluble adhesion molecules and hs-CRP in elderly diabetics with mild cognitive impairment (MCI) alone or with depressive symptoms. Methods. 219 diabetics elders were screened for psychiatric disorders and divided: group 1, MCI without depressive mood; group 2, MCI with depressive mood; group 3, controls. Data of biochemical parameters and biomarkers were collected. Results. In groups 1 and 2 levels of all biomarkers were significantly higher as compared to controls. The highest level of hs-CRP and sICAM-1 was detected in group 2. SVCAM-1 and sE-selectin levels were also the highest in group 2; however they did not significantly differ as compared to group 1. MoCA score was negatively correlated with all biomarkers in group 1. The logistic regression model showed that variables which increased the likelihood of having depressive syndrome in MCI patients were older age, stroke, neuropathy, increased number of comorbidities, and higher sICAM-1 level. Conclusions. We first demonstrated that elderly diabetic patients with MCI, particularly those with depressive mood have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation. Coexisting depressive syndrome in patients with MCI through common inflammatory pathways may result in augmentation of psychiatric disorders.

Ghrelin Levels in Elderly, Diabetic Patients with Mild Cognitive Impairment

Objective: The etiology of cognitive impairment in diabetes is unknown, but probably associated with many factors. One of the recent hypotheses suggests that ghrelin could be involved in cognitive impairment in diabetic patients. It has been reported that ghrelin signaling occurs in the hippocampus and improves memory and spatial learning. The aim of this study was to evaluate serum levels of ghrelin in elderly, diabetic patients with and without mild cognitive impairment (MCI) and to determine the predictors of having MCI in elderly diabetics. Methods: The cross-sectional study was conduct among 276 elderly subjects with type 2 diabetes. 87 patients with MCI and 189 controls were selected according to the criteria proposed by the MCI Working Group of the European Consortium on Alzheimer’s Disease (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. The serum levels of ghrelin were assessed using ELISA kit. Results: Serum levels of ghrelin were significantly lower in patients with MCI compared to controls. In MCI patients serum ghrelin levels were positively correlated with MoCA score and negatively correlated with HbA1c and BMI. The logistic regression models revealed that variables which increased the likelihood of diagnosis of MCI in elderly diabetic patients were: lower levels of ghrelin, higher levels of HbA1c, hypertension, previous cardiovascular disease, increased number of co-morbidities, and less years of formal education. Conclusion: In summary, serum levels of ghrelin were decreased in MCI elderly diabetic patients compared to controls and associated with poor MoCA score. The results indicated that lower ghrelin levels may be a risk factor for a cognitive impairment in diabetic, elderly patients. Further prospective larger studies are needed to confirm the role of this marker in the progression to dementia.

Glucose variability and glycated hemoglobin HbA1c in type 1 and type 2 diabetes

Introduction. The ultimate goal of diabetes therapy is to prevent chronic complications of the disease. HbA 1c level is closely related to the risk of development of micro- and macrovascular complications, however blood glucose variability (BGV) has emerged recently as yet another possible risk factor for vascular, particularly endothelial damage in diabetes. Continuous glucose monitoring systems (CGMS) are currently used for the BGV assessment, however due to their costs they are rarely utilised in daily clinical practice. The aim of the study was to assess BGV and its relationship with HbA 1c in patients with well (HbA 1c ∼7%) and poorly (HbA 1c ∼10%) controlled type 1 and type 2 diabetes. Material and methods. 131 patients subdivided in 4 groups according to diabetes type and level of metabolic control were enrolled into the study. All patients underwent continuous glucose monitoring with the use of iPRO2 system (Medtronic). Results. BGV was lower in type 2 than in type 1 diabetes patients. There was no statistically significant relationship between BGV and HbA 1c in well or poorly controlled patients with type 1 or type 2 diabetes. However, well controlled type 1 diabetes patients presented with greater degree of BGV than poorly controlled type 1 diabetes subjects. Conclusions. HbA 1c does not reflect blood glucose variability as assessed with CGMS in type 1 or type 2 diabetes subjects. BGV is significantly greater in type 1 diabetes than in type 2 diabetes, therefore the use CGMS might be of particular benefit for the former group of patients, especially those with good glycemic control.

Time of onset of coronary artery disease in diabetic patients depends on genetic polymorphism in region 9p21 but not in 1p25

Introduction. Type 2 diabetes (T2DM) is an important risk factor for development of coronary artery disease (CAD) and its complications. Recent genetic studies revealed possible association between those two conditions on the genome level. In our study we analysed whether polymorphisms in loci 1q25 and 9p21, previously characterized as risk factors of CVD, have an influence on early-onset CAD in T2DM patients. Materials and methods. Our case-control study included 338 patients suffering from T2DM and CAD. For the study purpose the cohort was divided into two groups based on the age of CAD onset: case group with earlyonset CAD (< 55 for males and < 65 years for females, n = 180) and control group (≥ 55 and ≥ 65 years respectively, n = 158). Epidemiological data was taken from medical history and retrospective questionnaire; blood samples were collected. The rs2383206, rs1333049 and rs10911021 were genotyped using method of fluorescently labelled allele specific oligonucleotides. Results. Statistical analysis did not reveal any significant differences between two groups in the mean duration of diabetes, metabolic parameters (weight, waist circum- ference, frequency of obesity according to BMI, mean blood pressure or lipids levels) and smoking history. There were statistical differences between groups in family incidence of CAD (70.0% patients in cases vs. 45.6% in controls; p < 0.005), hypertension (77.1% vs. 47.8%; p < 0.005) and obesity (61.2% vs. 49.0%; p < 0.05). Genetic analysis revealed that frequency of the G allele of rs2383206 in 9p21 region was significantly higher in cases than in controls (62.4% vs 44.0% p < 0.00001). Homozygotes GG were 39.4% of cases and 18.8% in controls (p = 0.0001). The OR for increased risk of early CAD in GG homozygotes was 2.81, 95% CI: 2.39–3.24, after adjustment for conventional risk factors it was reduced to 2.58. There was statistically significantly higher frequency of GG homozygotes among patients with poor glycaemic control (HbA1c ≥ 7%; 41.3% vs. 15.9; p = 0.0011) and non-obese subjects (BMI < 30 kg/m2; 39.7% vs. 18.2%, p = 0.0002). Similar association between genotype and risk of early CAD was found for another polymorphism rs1333049 in 9p21 region. Frequency of allele C was significantly higher in cases than in controls (56.3% vs 43.4, p = 0.0036) and homozygotes CC were 31.6% in cases and 17.4% in controls (p = 0.0083). OR for this association was 2.2 (95% CI: 1.83–2.56); after adjustments 1.96. We didn’t find any association between genotypes distribution of rs10911021 and early onset of CAD. Conclusions. Our findings clearly suggest that polymorphisms in 9p21 region have an influence on development of early-onset CAD in T2DM, especially in non-obese patients and subjects with poor glycaemic control. (Clin Diabet 2016; 5, 1: 7–14)