Study on the expression of CD14 + CD16 + monocytes and VEGF in peripheral blood of patients with type 2 diabetes mellitus and diabetic macroangiopathy

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

The present study aimed to investigate the serum levels of adiponectin (APN) and adiponectin receptor 1 (AdipoR1) in patients with type 2 diabetes mellitus (T2DM) combined with macrovascular complications (MVC), as well as their correlation with clinical parameters. A total of 60 T2DM patients were divided into 2 groups according to the presence of MVC: T2DM + MVC group (n=30) and T2DM group (n=30). Additionally, 30 healthy people were selected as control group (NC group). Clinical data and biological parameters were detected and recorded. T test was performed to compare the differences between two groups, and the results were corrected using Bonferroni method. Meanwhile, the correlation analysis and multiple stepwise regression analysis were used to analyze the association of APN and AdipoR1 with clinical factors. The levels of APN and AdipoR1 were significantly decreased in T2DM group and T2DM + MVC group compared with NC group, with the lowest value in T2DM + MVC group (all P<0.01). Serum APN levels were positively correlated with FINS and TG (r = 0.412, 0.316, respectively; both P<0.05), and negatively correlated with SBP, DBP and LDL-C (r = -0.292, -0.383, -0.334, respectively; all P<0.05). Serum levels of AdipoR1 were positively correlated with APN (r = 0.726, P<0.01), and negatively correlated with BMI, SBP, DBP, FBG, TC and LDL-C (r = -0.440, -0.446, -0.374, -0.444, -0.344, -0.709, respectively; all P<0.01). Serum levels of APN and AdipoR1 are significantly lower in T2DM group and T2DM + MVC group, showing lowest value in T2DM + MVC group. APN and AdipoR1 levels may influence glucose and lipid metabolism in T2DM patients.

To investigate the correlation between the mild cognitive impairment (MCI) and serum level of adiponectin in elderly patients with Type II diabetes mellitus (T2DM), so as to provide evidence for early diagnosis of MCI and effective evaluation of the impairment of cognitive functions, thereby preventing the impairment of cognitive function as early as possible. Clinical data were collected from 260 T2DM patients (≥ 60 years old) in Endocrine Department and 120 healthy subjects (≥ 60 years old) who underwent physical examination in our hospital between June 2015 and June 2017. According to the evaluation results of MCI, these T2DM patients were further divided into the T2DM + MCI group (n = 138) and the T2DM + NMCI group (n = 122). General data, including gender, age, disease history and body mass index (BMI), and the laboratory indexes, including serum adiponectin, fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and blood fat, were collected for statistical analysis in T2DM + MCI group, T2DM + NMCI group and healthy control group. Comparisons among T2DM + MCI group, T2DM + NMCI group and healthy control group, showed that the serum level of adiponectin in T2DM + MCI group was significantly lower than those in remaining two groups (p < 0.01). Spearman correlation analysis revealed that score of Montreal Cognitive Assessment (MoCA) was positively correlated with the serum level of adiponectin (r = 0.446, p < 0.01). Multivariate linear regression analysis indicated that education (standard β = 0.325, p = 0.003), age (standard β = -0.236, p = 0.016), disease course of hypertension (standard β = -0.242, p = 0.006), disease course of diabetes mellitus (standard β = -0.377, p < 0.001) and the level of adiponectin were correlated with the cognitive impairment. The results of itemized assessment in MoCA scale showed that in T2DM + MCI group, the scores in visuospatial and executive abilities, attention, language and orientation were significantly lower than those in other two groups (p < 0.01). As for the delayed recall, the score in T2DM + MCI group was significantly lower than those in other two groups (p < 0.01), while the score in T2DM + NMCI group was lower than that in the healthy control group (p < 0.01); in terms of the naming ability and abstraction, no statistically significant differences were identified among three groups (p > 0.05). Age, poor education, disease course of hypertension, disease course of diabetes mellitus and a low level of adiponectin in serum are the risk factors in MCI of T2DM patients. Besides, the level of adiponectin in serum of T2DM patients is correlated with the development of MCI; elderly T2DM patients are afflicted by cognitive impairment, mainly in visuospatial and executive abilities, attention, language, delayed recall and orientation.

Hypertriglyceridemia (HTG) is an important feature of lipid metabolism abnormality in patients with type 2 diabetes mellitus (T2DM). Apolipoprotein A5 (apoA5) is positively correlated with triglycerides (TG) and insulin resistance (IR). However, its relationship with TG in humans is still controversial till now. Further, its exact mechanism in TG reducing also remains unclear. Meanwhile, adiponectin (APN) can also inhibit TG in humans. Whether there is any association between apoA5 and APN in TG inhibition remains to be explored. This study was taken to investigate the relationships among apoA5, TG, APN and IR in patients with impaired glucose regulation (IGR) and T2DM, the levels of apoA5, TG and APN in the plasma were detected in the current study. Thirty five patients with newly-diagnosed T2DM (T2DM group), 30 patients with IGR (IGR group), and 35 sex- and age-matched normal controls (NGT group) were studied. All the subjects underwent an intravenous glucose tolerance test (IVGTT). Fasting apoA5 and APN were detected by an enzyme linked immunosorbent assay (ELISA). Fasting free fatty acid was measured using colorimetry. Homeostasis model assessment of insulin resistance (HOMA-IR) was made. The plasmic apoA5 and APN levels in the T2DM and IGR groups were lower than that in the NGT group. Furthermore, the levels of apoA5 and APN in the T2DM group were lower than those in IGR group (P < 0.05). ApoA5 was negatively correlated with TG, FFA, 2hFFA, LDL-C, FPG, 2hPG, FINS, HOMA-IR, BMI, and WHR, but positively correlated with APN and HDL-C. The multiple linear regression analysis showed TG, APN, FFA, WHR and HOMA-IR were independent factors of apoA5. Down-regulated apoA5 and APN has a synergistic effect in the process from NGT to IGR and then to T2DM. They can increase FFA expression through participating in the occurrence and development of HTG and IR.

Serum levels of IL-32 in patients with type 2 diabetes mellitus and its relationship with TNF-α and IL-6

Background/AimDiabetic nephropathy (DN) is a common devastating complication in type 2 diabetes mellitus (T2DM). In order to investigate novel DN biomarkers, we evaluated serum levels of irisin, adiponectin, visfatin and interleukin 4 (IL-4) in patients with T2DM with normo-, micro- and macro-albuminuria and compared their means with non-diabetic controls.Patients and MethodsClinical data and routine laboratory parameters of metabolic and renal function status were determined in blood and urine samples obtained from 169 participants, divided into four groups according to the presence of diabetes and albuminuria using appropriate biochemical assays/calculations. Serum levels of irisin, adiponectin, visfatin and interleukin 4 (IL4) were assessed using enzyme-linked immunosorbent assay. Means of all tested parameters and biomarkers were compared using appropriate statistical methods. Logistic regression was used to determine albuminuria risk factors in T2DM as an indicator for DN.ResultsAll tested parameters differed significantly among T2DM groups and controls (p<0.001). Irisin, adiponectin, visfatin and IL4 significantly increased in T2DM patients with significant increasing albuminuria. Along with hemoglobin A1C, irisin was the most highly significant risk factor for development and progression of albuminuria (p<0.001). Adiponectin was also a significant independent risk factor (p=0.009), whilst visfatin and IL4 conferred no significant risk.ConclusionHigh irisin levels in normo-albuminuric patients indicates their potential to develop DN even prior to detectable albuminuria. Both irisin and adiponectin may be considered as potential biomarkers indicating risk for DN progression in T2DM that might be therapeutically targeted.

Hypomagnesaemia has been reported in type 2 diabetes mellitus (T2DM) and an association of low serum magnesium (Mg) with insulin resistance has been observed. In this cross-sectional study, 65 new T2DM patients and 65 healthy controls were investigated to assess the Mg status and see the association between Mg level and insulin resistance. Oral glucose tolerance test, HbA1c, serum Mg, and fasting insulin were measured and the level of insulin resistance was calculated by using the homeostasis model assessment for insulin resistance (HOMA-IR). Serum Mg level was similar in T2DM and control groups; a higher frequency of hypomagnesemia was observed in the T2DM than control group (26.2% vs. 12.3%) though it was not statistically significant (p= 0.074). Level of insulin resistance (HOMA-IR) was higher in the T2DM group and a higher frequency of subjects had insulin resistance in this group compared to controls. No significant differences in age, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fasting plasma glucose (FPG), HbA1c, fasting insulin level and HOMA-IR were observed between normomagnesaemic and hypomagnesaemic T2DM subjects. In the T2DM group, age, BMI, WC, WHR, FPG, fasting insulin and HOMA-IR correlated with serum Mg level though in the control group Mg had significant inverse correlations with BMI and fasting insulin. New T2DM subjects and healthy controls had similar Mg status although the frequency of hypomagnesemia was higher (not significant) in the T2DM group and serum Mg level had no correlation with glycemic status, fasting insulin and HOMA-IR in T2DM patients.

Changes of adiponectin and inflammatory cytokines after periodontal intervention in type 2 diabetes patients with periodontitis

Objective To investigate the expression and clinical significance of serum microRNA(miRNA) in Uygur patients with diabetic kidney disease(DKD). Methods A total of 50 Uygur patients with type 2 diabetes mellitus(T2DM) were collected from March 2015 to December 2015 in the Department of Endocrinology and Physical Examination Center of the First Affiliated Hospital, Xinjiang Medical University. Patients were divided into 2 groups: T2DM group[24 h microalbunminuria(MAU)<30 mg/24 h, n=25]and DKD group (MAU≥30 mg/24 h, n=25). Another 25 Uygur healthy volunteers were included as control group(n=25).The level of serum miRNAs were measured by real-time polymerase chain reaction, and the associations between miRNAs with clinical parameters in diabetic nephropathy were analyzed. Results The expression of miR-21, miR-187, miR-451 were decreased in T2DM group(0.7±0.4, 0.8±0.4, 0.7±0.4) and DKD group(0.7±0.4, 0.8±0.3, 0.8±0.6)compared with those in control group(1.5±0.9, 1.2±0.7, 1.7±1.0, t=2.29-3.99, all P<0.05). The miR-145 level was significantly decreased in DKD group compared with that in T2DM group or control group (0.6±0.3 vs 0.9±0.4, 0.6±0.3 vs 1.1±0.6, t=2.50, 3.06, all P<0.05) . The level of serum miR-21, miR-187, miR-145, or miR-451 was positively correlated with eGFR (r=0.365-0.743) , but inversely correlated with SCr and UAER (r=-0.545--0.223,all P<0.05) . The level of serum adiponectin was decreased in T2DM group and DKD group compared with that in control group. However, the adiponectin level was higher in DKD group than in T2DM group (t=-2.11-4.18, all P<0.05). miR-21, miR-187, miR-145, and miR-451 were significantly correlated with adiponectin level (r=0.281-0.671, all P<0.05) . Conclusion miR-21, miR-187, miR-145 and miR-451 may be involved in the pathogenesis of DKD, and may be potential diagnostic biomarkers of DKD. Key words: Diabetic kidney disease; MicroRNA; Adiponectin; Glomerular filtration rate

Meteorin-like (Metrnl) is a newly discovered adipokine with favorable effect on insulin sensitivity. Previous studies have reported lower levels of Metrnl in obese patients. However, there is conflicting data regarding its circulating levels in type 2 diabetes mellitus (T2DM) and there is no data in patients with coronary artery disease (CAD). The aim of the present study was to evaluate the Metrnl serum level in patients with T2DM and CAD, and also to evaluate the serum levels of Metrnl with serum levels of adiponectin, IL-6 and TNF-α in patients. This study was conducted on 66 patients with CAD, 63 T2DM patients and 41 controls. The serum levels of Metrnl, adiponectin, IL-6 and TNF-α were measured using ELISA techniques. The serum levels of Metrnl were found to be lower in CAD (75.18 ± 28.48 pg/mL) and T2DM patients (73.89 ± 33.60 pg/mL) compared to the control group (95.33 ± 32.56 pg/mL) (p < 0.005 and p<0.003, respectively). Additionally, adiponectin decreased in CAD and T2DM patients as compared to the control group, while IL-6 and TNF-α were higher in CAD and T2DM patients. Metrnl showed independent association with the risk of CAD and T2DM presence. Furthermore, Metrnl illustrated a negative correlation with IL-6 and TNF-α in both CAD patients and also with BMI, insulin resistance, IL-6 and TNF-α in T2DM patients. Metrnl showed an association with CAD and T2DM presence and with components of their pathogenesis such as inflammation and insulin resistance. These results suggested a possible interaction between Metrnl and the pathogenesis of CAD and T2DM, however more studies are needed to prove this concept.

PurposeType 2 diabetes mellitus (T2DM), a metabolic disorder, remains associated with a physiological impairment affecting large populations worldwide. Onset of T2DM is multifactorial where obesity and abnormal basal metabolic rate are considered most critical. Of people diagnosed with T2DM, about 80% are also obese. It is also reported that obese individuals have an increased odds of developing depression, whereas T2DM is estimated to increase the incidence by two-fold. The preponderance of research data demonstrates that T2DM alters the serum level of cortisol and adiponectin which are known to be associated with neuronal physiology. The study explored, how a metabolic disorder like T2DM is linked with the altered plasma level of cortisol and adiponectin, the risk factors for stress and depression.Patients and MethodsA cross-sectional population study was conducted in T2DM patients using a bimodal approach. First approach used questionnaires, (1) Patient Health Questionnaire (PHQ-9) and (2) Stress Coping Inventory Questionnaire (SCQ) to assess signs and symptoms of depression and stress, respectively, in T2DM patients. In the second approach, robust biochemical analysis was conducted for serum adiponectin and cortisol levels.ResultsAn association of T2DM in stress and depression was evaluated in 158 subjects (105 T2DM obese patients and 53 healthy controls). A lower PHQ-9 score and adiponectin levels were seen in T2DM obese patients compared to healthy controls (p<0.05). Further, results also depicted a lower adiponectin levels in T2DM obese patients with depression compared to T2DM obese patients without depression (p<0.05). The study did not find a significant difference in cortisol serum levels among the T2DM and control groups. However, a higher level of serum cortisol was reported in T2DM obese patients with depression over those T2DM obese patients who lacked depression (p<0.05).ConclusionThe findings suggest that T2DM obese patients might have a higher risk of developing stress and depression. Further, biochemical parameters, adiponectin and cortisol, might be the potential biomarkers for T2DM and may help in early diagnosis of these comorbid conditions.

Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be concluded that ALR levels are affected by use of antidiabetic drugs among which glimepiride shows more effect on adiponectin and resistin levels, while leptin gets affected more by metformin. It can also be proposed that ALR levels are not affected by diabetes only, suggesting that their alterations in T2DM may be due to obesity as we observed more ALR changes in obese cases when compared to T2DM cases, and so there might be an important link between adiposity and insulin resistance.

This study aimed to explore the risk factors attributed to osteoporosis in newly type 2 diabetes mellitus (T2DM) patients. This study aimed to recruit 244 T2DM patients and 218 non-diabetic controls. We collected demographic characteristics, medical history, bone mineral density and biomarkers including bone specific alkaline phosphatase (BALP), osteocalcin, N-terminal peptide of type I procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRCAP-5b), β-Cross Laps of type I collagen-containing cross-linked C-telopeptide (β-CTX), 25-hydroxyvitamin D, parathyroid hormone were recorded or detected. Bone mineral density (BMD) was our primary outcome. Based on the result of BMD, we divided both the control group and T2DM group into three subgroups: normal bone mass, osteopenia and osteoporosis. In control group, we found age, sex, menopausal status, BMI, P1NP, BALP, TRACP-5b, osteocalcin, and corrected serum calcium are differential among three subgroups. In T2DM group, we found age, sex, menopausal status, drinking status, BMI, HbA1c, TRACP-5b and OC were differential among three subgroups. In T2DM and control groups, age, female, postmenopausal status, BALP, TRACP-5b and osteocalcin were positively correlated while BMI was negatively correlated with osteoporosis. In control group, β-CTX was positively correlated with osteoporosis. In T2DM group, HbA1c and corrected serum calcium concentration were positively correlated with osteoporosis. After further adjustment of age, BMI in male, TRACP-5b was positively correlated with the risk of osteoporosis in newly diagnosed T2DM. After adjusted of age, BMI and menopausal status in female, OC was positively correlated with the risk of osteoporosis in newly diagnosed T2DM and controls. In female T2DM, BALP and P1NP were positively correlated with the risk of osteoporosis. In conclusion, age, BMI and menopausal status are common risk factors for osteoporosis in diabetic and non-diabetic patients, however TRACP-5b, BALP and osteocalcin are special risk factors for osteoporosis in newly diagnosed T2DM patients but not non-diabetic patients, which may be applied to identify osteoporosis risk in T2DM patients, but this result needs to be proven with fracture data.

The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients. A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis. The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels. The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.