Pathophysiological characteristics of myocardium injury model in type 2 diabetic rats

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.

Objective To study the levels of senlm uric acid(UA)in normal glucose(NC),impaired glucose regulation(IGR)and type 2 diabetes mellitus(T2DM),and investigate its relationship with insulin resistance and dyslipidemia.Method The levels of blood glucose,lipids,fasting insulin(HNS)and serum UA were measured in patients of 45 T2DM(T2DM group),20 IGR(IGR group)and 29 NC(NC group).Status of insulin resistance and insulin secretion function was evaluated by HOMA-IR and ISI.Results The levels of triglyceride(TG)and UA in T2DM group and IGR group were significantly higher than those in NC group[(3.34±8.77),(1.85±0.67),(1.26±0.38)mmoi/L and(316.71±96.20),(403.62±76.80),(325.45±94.43)mmol/L](P<0.01).HDL-C levels in T2DM group were significantly lower than those in IGR and NC group[(1.05±0.30),(1.07±0.21),(1.12±0.20)mmol/L](P<0.01).NO significant difference of FINS levels was found in the three groups.HOMA-IR level in T2DM and IGR group was higher than that in NC group(3.84,3.77,2.34)(P<0.01).ISI in T2DM and IGR group was lower than that in NC group(-4.52±0.79,-4.44±0.19,-4.03±0.58)(P<0.01).Correlation analysis indicated that the level of UA was positively related with BMI.TG and negatively related with HDL-C.Conclusion Increased UA in IGR indicates that hyperurieacidemia developes before DM. Key words: Uric acid; Diabetes mellitus; Impaired glucose regulation

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.

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.

Objective To investigate the correlation of intestinal flora diversity, inflammatory factors and insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). Methods Totally 80 elderly patients with T2DM were selected as the T2DM group, and 80 healthy subjects were enrolled as the control group. The Bacteroides, Prevotella, Lactobacillus, Bifidobacterium and Enterobacteriaceae were detected, and homeostasis model assessment-insulin resistance (HOMA-IR) was calculated in the two groups. The interleukin 6 (IL-6), IL-10, IL-22, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured and compared between them. Pearson correlation analysis was used to analyze the relationship of different intestinal flora with HOMA-IR and inflammatory factors in elderly T2DM patients. Results Compared to the control group, the amount of Bacteroides [(10.0 ± 0.5) logN/g vs. (8.1 ± 0.9) logN/g] and Enterobacteriaceae [(9.86 ± 0.27) logN/g vs. (7.05 ± 0.19) logN/g] was significantly higher (t = 3.162, 3.016; both P < 0.05), and the amount of Prevotella [(7.22 ± 0.27) logN/g vs. (9.35 ± 0.39) logN/g], Lactobacillus [(5.12 ± 0.25) logN/g vs. (7.67 ± 0.43) logN/g] and Bifidobacterium [(7.2 ± 0.4) logN/g vs. (11.0 ± 0.5) logN/g] was significantly lower in the T2DM group (t = 5.230, 4.163, 7.115; all P < 0.05). The levels of HOMA-IR [(6.4 ± 0.8) vs. (3.1 ± 0.4)], IL-6 [(154 ± 15) ng/L vs. (81 ± 10) ng/L], IL-22 [(628 ± 36) ng/L vs. (106 ± 11) ng/L], TNF-α [(208 ± 23) ng/L vs. (118 ± 11) ng/L] and IFN-γ [(136 ± 15) ng/L vs. (76 ± 13) ng/L] were significantly higher (t = 7.156, 3.167, 5.026, 3.557, 2.134; all P < 0.05), and the IL-10 level [(127.7 ± 18.7) ng/L vs. (376.8 ± 1.8) ng/L] was significantly lower in the T2DM group than in the control group (t = 2.272, P < 0.05). The correlation analysis showed that there were positive correlations between Prevotella, Enterobacteriaceae and HOMA-IR (r = 0.613, 0.437; both P < 0.05), and negative correlations between Bacteroides, Lacto-bacillus, Bifidobacterium and HOMA-IR (r = -0.617, -0.526, -0.575, -0.616; all P < 0.05). The Bacteroides, Prevotella, Lactobacillus and Bifidobacterium were negatively correlated to IL-6 (r = -0.617, -0.526, -0.575, -0.616; all P < 0.05), IL-22 (r = -0.636, -0.587, -0.621, -0.573; all P < 0.05), TNF-α (r = -0.593, -0.633, -0.476, -0.539; all P < 0.05) and IFN-γ (r = -0.475, -0.538, -0.602, -0.573; all P < 0.05), and positively correlated to IL-10 (r = 0.535, 0.623, 0.459, 0.506; all P < 0.05). Enterobacteriaceae was positively correlated to IL-6, IL-22, TNF-α and IFN-γ (r = 0.437, 0.599, 0.576, 0.518; all P < 0.05), and negatively correlated to IL-10 (r = -0.518, P < 0.05). Conclusion The association between intestinal flora and insulin resistance in elderly T2DM patients suggests that its mechanism may be related to the level of inflammatory factors. Key words: Aged; Diabetes mellitus, type 2; Intestinal flora; Inflammatory factors; Insulin resistance

Objective To explore the clinical value of 3.0T magnetic resonance IDEAL-IQ technique in the quantitative evaluation of pancreatic fat deposition and iron deposition in patients with type 2 diabetes mellitus (T2DM) . Methods 3.0T MR examination (including IDEAL-IQ sequence) was performed on 32 newly diagnosed T2DM patients (T2DM group) and 15 healthy volunteers (control group). The fat content (FF) and iron content (R2* value) of the pancreas of each subject were measured by the IDEAL-IQ sequence. At the same time, fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured in both groups; and the steady-state model insulin secretion index (HOMA-β) and steady-state model insulin resistance index (HOMA-IR) were calculated. The differences in pancreatic fat fraction (FF), R2* value, FBG, FINS, HOMA-β, and HOMA-IR between the T2DM group and the control group were compared. The correlations between FF and R2* values of pancreas in the T2DM group with HOMA-β and HOMA-IR were analyzed; and the correlation between pancreatic FF and R2* values in the T2DM group was analyzed. Results There were statistical differences in FBG, FNIS, HOMA-β, and HOMA-IR between the T2DM group and the control group (all P<0.05). The FBG, FNIS, and HOMA-IR were higher and the HOMA-β was lower in the T2DM group than in the control group. The pancreatic fat content (FF) and R2* values in the T2DM group were positively correlated with HOMA-IR (r=0.469, P=0.008; r=0.423, P=0.003), and negatively correlated with HOMA-β (r =-0.595, P=0.001; r =-0.478, P=0.001). There was a moderate positive correlation between pancreatic fat content (FF value) and iron content (R2* value) in the T2DM group (r=0.508, P=0.001). Conclusion 3.0T MR IDEAI-IQ technology can quantitatively analyze the fat and iron deposition in pancreas of patients with T2DM, which has certain guiding value for the assessment of the conditions of T2DM and the choices of treatment plan. Key words: Type 2 diabetes mellitus; IDEAL-IQ; Pancreatic fat content; Pancreatic iron content

To investigate the characteristic of dynamic glucose level in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with newly diagnosed type 2 diabetes mellitus (T2DM) and to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the glucose level. A total of 65 cases of patients with T2DM who were newly diagnosed by oral glucose tolerance test (OGTT) were enrolled from April 2014 to April 2015 in Gansu Provincial Hospital, and divided into simple T2DM group (n=30) and OSAHS with T2DM group (n=35) according to aponea-hypopnea index (AHI) which was monitored by polysomnography (PSG). Their general clinical data were collected, and glucose level of different periods was monitored by continuous glucose moitoring system (CGMS). Changes of glucose level were compared between two groups before and after CPAP treatment. Age, gender proportion, BMI, smoking and drinking history, glycosylated hemoglobin (HbA1c) and blood lipid profile had no significantly difference between two groups. Longer neck circumstance and higher waist-hip ration (WHR), higher systolic blood pressure and diastolic blood pressure, higher fasting plasma glucose (FPG) [(9.4 ± 3.2) vs (7.3 ± 2.1) mmol/L, P=0.028] and fasting insulin (FINS) [(19.2 ± 8.7) vs (11.1 ± 4.7) mU/L, P=0.044] level, more serious homeostasis model assessment insulin resistance (HOMA-IR) were found in OSAHS patients with T2DM when compared to patients in simple T2DM group. The average dynamic glucose level of 24 hours, daytime, nocturnal and sleep time in OSAHS with T2DM group were higher than that in the simple T2DM group (all P<0.05). The alarming times when the average dynamic glucose level of nocturnal time was more than 0.1 mmol·L⁻¹·min⁻¹ in T2DM with OSAHS was more than that in control group (P=0.001). After treatment of CPAP, the level of AHI [(5.9 ± 3.6) vs (56.7 ± 11.4) times/h, P<0.001], average dynamic glucose level of 24 hours, day, nocturnal and sleep time were obviously decreased (all P<0.05); lowest saturation oxygen (LSpO₂) was significantly increased [(92.3 ± 3.7)% vs (81.5 ± 20.2)%, P<0.001]; the alarming times and HOMA-IR were obviously decreased (P=0.019, 0.043). According to multiple linear regression analysis, the AHI (β=0.736, P<0.001) in OSAHS with T2DM group was positively related to the average dynamic glucose level during sleep time, but the LSpO₂(β=-0.889, P<0.001) was negatively correlated. OSAHS patients with newly diagnosed T2DM have higher glucose level than that in simple T2DM patients, and CPAP therapy can obviously decrease the glucose level in newly diagnosed T2DM patients with OSAHS. AHI and LSpO₂may influence the average dynamic glucose level during sleep time.

Objective To explore the relationship between serum osteocalcin levels and glucolipid metabolism in elderly type 2 diabetic patients with non-alcoholic fatty liver disease(NAFLD). Methods Data collected from 97 patients with type 2 diabetes mellitus(T2DM)admitted to the Department of Geriatric Endocrinology of the First Affiliated Hospital of Zhengzhou University from June 2014 to April 2015 were retrospectively analyzed.Patients were divided into the T2DM group(type 2 diabetic patients without NAFLD, n=47)and the NAFLD group(T2DM patients with NAFLD, N=50). Healthy elderly subjects(n=30)from the same period served as the control group.Body mass index(BMI), osteocalcin, fasting blood glucose, fasting insulin, homeostasis model assessment for insulin secretion index(HOMA-β)and insulin resistance(HOMA-IR), glycosylated hemoglobin(HbA1c), total cholesterol, triglyceride, high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)were compared between the 3 groups. Results Levels of fasting blood glucose, fasting insulin, HbA1c, total cholesterol, triglyceride, LDL-C and HOMA-IR were higher, while levels of HDL-C, HOMA-β and osteocalcin were lower in the T2DM and NAFLD groups than in the control group(all P<0.05). Levels of BMI, fasting glucose, fasting insulin, HbA1c, total cholesterol, triglyceride, LDL-C and HOMA-IR were higher and levels of osteocalcin were lower in the T2DM group than in the NAFLD group(all P<0.05). Pearson correlation analysis showed that the osteocalcin level was negatively correlated with fasting blood glucose, HbA1C, HOMA-IR and BMI(r=-0.701, -0.442, -0.337 and -0.543, P<0.05 or P<0.01), and positively correlated with HOMA-β(r=0.341, P<0.05)in the NAFLD group. With serum osteocalcin as the dependent variable, multiple linear regression results showed that fasting blood glucose was an independent influencing factor for serum osteocalcin(β=-1.57, P<0.05)in the fatty liver group. Conclusions Serum osteocalcin levels significantly decrease in elderly T2DM patients with NAFLD, are closely correlated with glucolipid metabolism, and may have some important clinical significance in the prevention and treatment of NAFLD in elderly patients with type 2 diabetes. Key words: Osteocalcin; Diabetes Mellitus, Type 2; Fatty Liver

Objective To evaluate the effect of cinnamaldehyde (Cin) on glucose and lipids profiles in rats with type 2 diabetes mellitus (T2DM), subsequently to investigate its molecular mechanisms for reducing insulin resistance (IR). Methods Rat models of T2DM were established by combination of high–fat diet induction and intraperitoneal injection of low–dose streptozotocin. Rats were divided into the normal control group (NC), T2DM group, T2DM+ metformin (Met) group and T2DM + Cin group. After four weeks of treatment, blood was extracted for measurement of serum glucose, insulin and lipids. Western blot was used to detect the serum or tissue retinol–binding–protein 4(RBP4) and glucose transporter 4(GLUT4) protein levels. Immunohistochemistry was applied to detect the expression of insulin receptor substrate–1 (IRS–1) and phosphatidylinositol 3–kinase (PI3K) regulatory subunit p85 alpha (p85α) in gastrocnemius muscles. Results Cin displayed promising hypolipidemic, anti–hyperglycemic, and insulin sensitizing functions (FPG: (7.5±1.5) vs (22.7±4.0) mmol/L; TG: (0.77±0.15) vs(1.53±0.13)mmol/L; HOMA–IR: 8.0±3.0 vs 61.2±12.1, P<0.01) compared with the T2DM group. Serum RBP4 levels in Cin treated rats were markedly lowered, and the protein contents of tissue GLUT4 were significantly up–regulated. Also, Cin increased the expression of IRS–1 in gastrocnemius muscles of T2DM rats (0.52±0.05 vs 0.63±0.06, P<0.05), whereas notably decreased the expression of p85α (0.51±0.05 vs 0.43±0.04, P<0.05). Conclusion Cinnamaldehyde can improve glucose and lipids metabolism in type 2 diabetic rats and its pharmacological mechanisms are at least partially related with reducing serum RBP4 concentration, increasing IRS–1 and decreasing of p85α in gastrocnemius muscles. Key words: Cinnamaldehyde; Type 2 diabetes mellitus; Retinol binding protein 4; Phosphatidylinositol 3–kinase regulatory subunit p85α; Insulin receptor substrate–1

Objective To investigate the risk factors of type 2 diabetes mellitus(T2DM) in patients with nonalcoholic fatty liver disease (NAFLD) and correlations with carotid atherosclerosis.Methods The clinical data of 51 cases of N AFLD with T2DM (NAFLD with T2DM group),43 cases of NAFLD(NAFLD group) and 45 healthy objects (control group) were collected.The clinical biochemical features,carotid intima-media thickness (IMT) were observed.Results The BMI and smoking rate in NAFLD with T2DM group and NAFLD group were significandy higher than those in control group [(27.25 ±3.16),(26.31 ± 2.63) kg/m2 vs.(23.12 ±3.44) kg/m2,43.1％(22/51),37.2％(16/43) vs.13.3％(6/45)](P＜0.05).The ratio of family history of T2DM in NAFLD with T2DM group was significantly higher than that in NAFLD group and control group[66.7％(34/51)vs.32.6％(14/43),8.9％(4/45)](P ＜ 0.05).Compared with control group,the level of total cholesterol (TC),trigalloyl glycerol (TG),low density lipoprotein cholesterol (LDL-C),alanine transaminase(ALT),aspartic transaminase(AST),IMT in NAFLD with T2DM group and NAFLD group were significantly higher [(5.39 ± 0.85),(5.12 ± 0.77) mmol/L vs.(4.11 ± 0.64) mmol/L,(2.77 ± 1.11),(2.32 + 1.04) mmol/L vs.(1.21 ± 0.52) mmol/L,(2.98 ±0.93),(2.76 +0.78) mmol/L vs.(2.15 ±0.57) mtmol/L,(48.4 ± 18.9),(43.3 ± 16.5) U/L vs.(21.4 ± 13.6) U/L,(46.2 ± 16.7),(42.1 ± 17.5) U/L vs.(20.5 ± 12.6) U/L,(1.95 ±0.93),(1.26±0.51) mmvs.(0.71 ±0.22) mm](P＜ 0.05),while the level of high density lipoprotein cholesterol (HDL-C) was significantly lower [(1.01 ± 0.35),(1.13 + 0.22) mmol/L vs.(1.31 ± 0.26) mmol/L] (P ＜ 0.05).The level of above mentioned index,there were no significant difference between NAFLD with T2DM group and NAFLD group (P ＞ 0.05).The level of fasting blood glucose (FBG),2-hour postprandial blood glucose (2 h PBG),glycosylated hemoglobin (HbA1c),fasting insulin (FINS),2-hour postprandial insulin (2 h PINS) and insulin resistance index of HOMA (HOMA-IR) in NAFLD with T2DM group were significantly higher than those in NAFLD group and control group [(8.15 ± 1.48) mmol/L vs.(5.10 ± 1.32),(5.62 ± 0.88) mmol/L,(13.67 ± 1.59) mmol/L vs.(7.31 ± 1.25),(8.64± 1.35) mmol/L,(7.03 ±0.84)％ vs.(5.16 ±0.72)％,(5.53 ±0.61)％,(13.32 ±4.55) mU/L vs.(6.06 ±3.11),(9.13 ±4.37) mU/L,(106.37 ±21.45) mU/L vs.(33.21 ± 18.87),(46.34 ± 16.39) mU/L,3.88 + 2.14 vs.1.13 ± 0.36,2.23 ± 1.15] (P ＜ 0.05).Carotid IMT,the incidence of carotid plaque and Crouse scores of plaque in NAFLD with T2DM group were significandy higher than those in NAFLD group [(1.95 ±0.93) mm vs.(1.26 ±0.51) mm,64.7％(33/51) vs.30.2％(13/43),(3.11 ±0.57) nn vs.(1.35 ± 0.49) mm] (P ＜ 0.05).The regression analysis showed that family history of T2DM,FBG,2 h PBG,FINS,2 h PINS were independently associated with T2DM.Conclusions Family history of T2DM,FBG,2 h PBG,FINS,2 h PINS are the main risk factors for the onset of T2DM in NAFLD.The risk of carotid atherosclerosis is increased in patients of NAFLD with T2DM. Key words: Fatty liver disease, nonalcoholic; Diabetes mellitus,type 2; Carotid artery disease; Risk factors

Background: Type 2 Diabetes Mellitus (T2DM) is a common problem that is accompanied by disturbed metabolic homeostasis, oxidative stress and increase in proinflammatory cytokines.On the other hand, normal body metabolism is essential for the testicular function.Also, nesfatin-1 is a peptide hormone produced by numerous tissues, including the testes and shared in regulation of metabolic homeostasis and had antioxidant and anti-inflammatory properties.Aim: To investigate the effects of T2DM on testicular functions and the effects of exogenous treatment with nesfatin-1 on modulation of those effects, and, to declare the possible involved mechanisms.Material and Methods: 24-healthy adult male albino rats with a weight of 180-200gm, were divided into three groups of 8 rats each; control, type 2 diabetic (T2DM) and nesfatin-1 treated type 2 diabetic (T2DM + Nesfatin) groups.The control group received a standard diet, while, the diabetic groups (T2DM and T2DM + Nesfatin) received a High Fat Diet (HFD).Five weeks after beginning HFD, rats were fasted for 12h and received streptozotocin, in a dose of 35mg/kg, dissolved in 0. 1M sodium citrate buffer (pH 4.5) intraperitoneally (i.p.).Then, rats of the control and T2DM groups received normal saline i.p. in a dose of 1ml/kg/day for more 4 weeks and they continued to be fed with their corresponding diet, while, those of T2DM + Nesfatin group were treated with nesfatin-1 in a dose of 2 µ g/kg/day i.p. for more 4 weeks and they continued to be fed with HFD.The serum levels of testosterone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), tumor necrosis factor alpha (TNF α ) and interleukin-1 beta (IL-1 β ) were measured in the studied groups.Also, epididymal sperm motility and count, testicular histopathology and antioxidant enzymes Superoxide Dismutase (SOD) and catalase (CAT) activities were examined.Results: A significant (p<0.001)increase in the final Body Mass Index (BMI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index, serum levels of glucose, insulin, Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDL), TNFα and IL-1 β was found in the T2DM group in comparison to the control group.On the other hand, a significant (p<0.001)decrease in serum levels of High Density Lipoprotein (HDL), FSH, LH, and testosterone was

Objective To explore the effects of growth differentiation factor 11 (GDF11) on endothelium-dependent vasodilation function of aorta in apolipoprotein E-Null (ApoE-/-) diabetic mice and to investigate the mechanisms. Methods Ten of the 40 healthy male ApoE-/- mice at 4-week age were selected as normal control group according to random number method and received basic diet, whereas the other 30 mice were fed with high-fat diet for 4 weeks and then treated with streptozotocin intraperitoneal injection (50 mg/kg) for 5 days to induce type 2 diabetes mellitus (T2DM). Diabetes was successfully induced in twenty mice which were then randomly divided into GDF11 group (0.1 mg·kg-1·d-1 intraperitoneal injection, n=10) and T2DM control group (T2DM group, equivalent phosphate buffered saline, n=10) according to random number method. After 4 weeks of intervention, fasting plasma glucose, fasting plasma insulin, HbA1c and serum GDF11 were measured respectively. Homeostasis model assessment-insulin sensitive index (HOMA-ISI) was calculated. The relaxation response and nitric oxide levels were detected in isolated aorta of mice. Acetylcholine (Ach)-induced endothelium-dependent vasodilation and sodium nitroprusside (SNP) -induced endothelium-independent vasodilation were measured in aortas for estimating endothelial function. Endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS) and Smad2/3, phosphorylated Smad2/3 (P-Smad2/3) were measured by Western blotting in isolated aorta of mice. Results Compared with NC group, fasting plasma glucose, fasting plasma insulin, and HbA1c were significantly increased, meanwhile HOMA-ISI, serum GDF11 concentration and Ach-dependent relaxation response were significantly reduced in T2DM group; compared with T2DM group, all markers mentioned above were improved in GDF11 group (F=70.923-675.430, all P 0.05). Compared with NC group, nitric oxide, P-eNOS, P-Smad2/3 were significantly decreased in T2DM group, but indexes mentioned above were all increased in GDF11 group (F=40.120-148.060, all P<0.01). Conclusion GDF11 improves endothelium-dependent vasodilation function in ApoE-/- diabetic mice by enhancing nitric oxide synthesis and Smad2/3 signaling pathways. Key words: Growth differentiation factor 11; Type 2 diabetes mellitus; Endothelium-dependent vasodilation; Nitric oxide

Glymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance. In our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates. In the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = -1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = -1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = -0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = -0.35, p < 0.005). The ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.

Objective To investigate the correlation between plasma 25-hydroxyvitamin D(25-OHVD)levels and the CD4+ /CD8+ ratio in elderly men in different states of glucose metabolism. Methods Clinical data of 206 elderly male patients at the geriatrics department of our hospital from April 2011 to August 2017 were collected and retrospectively analyzed.There were 85 patients with type 2 diabetes mellitus(T2DM), 39 patients with impaired glucose tolerance(IGT)and 82 patients with normal glucose tolerance(NGT). Locally weighted regression and multivariate generalized linear regression models were used to analyze the correlation between plasma 25-OHVD levels and the CD4+ /CD8+ ratio. Results There were significant differences in two-hour postprandial blood glucose and homeostasis model assessment of insulin resistance(HOMA-IR)between the NGT, IGT and T2DM groups(6.5 mmol/L, 9.2 mmol/L vs.11.0 mmol/L, 11.92±10.57, 16.46±10.89 vs.32.67±7.39, respectively, P 0.05). The CD4+ /CD8+ ratios in the T2DM and IGT groups were not significantly different from each other(1.4 vs.1.6, P>0.05), but were lower than that in the NGT group(2.7, P<0.01). After adjusting for the influence of related confounders, CD4+ /CD8+ increased by 0.4 on average with each standard deviation(7.62 μg/L)increase of 25-OHVD.Compared with 25-OHVD patients in the first quartile, CD4+ /CD8+ in the second, third and fourth quartile increased by 0.7, 0.9 and 1.1 respectively on average, showing a significant positive correlation and a significant linear trend in the level of 25-OHVD and the CD4+ /CD8+ ratio(P<0.01). Conclusions With the aggravation of glucose tolerance, plasma 25-OHVD levels and the CD4+ /CD8+ ratio decrease by varying degrees in elderly men.The deficiency of plasma 25-OHVD may be an independent risk factor for a low CD4+ /CD8+ ratio. Key words: Diabetes mellitus, type 2; 25-hydroxyvitamin D2; CD4-CD8 ratio

This study utilized artificial intelligence (AI) to quantify coronary computed tomography angiography (CCTA) images, aiming to compare plaque characteristics and CT-derived fractional flow reserve (FFR-CT) in type 2 diabetes mellitus (T2DM) patients with or without hypertension (HTN). A retrospective analysis was conducted on 1,151 patients with suspected coronary artery disease who underwent CCTA at a single center. Patients were grouped into T2DM (n = 133), HTN (n = 442), T2DM (HTN+) (n = 256), and control (n = 320). AI assessed various CCTA parameters, including plaque components, high-risk plaques (HRPs), FFR-CT, severity of coronary stenosis using Coronary Artery Disease Reporting and Data System 2.0 (CAD-RADS 2.0), segment involvement score (SIS), and segment stenosis score (SSS). Statistical analysis compared these parameters among groups. The T2DM (HTN+) group had the highest plaque volume and length, SIS, SSS, and CAD-RADS 2.0 classification. In the T2DM group, 54.0% of the plaque volume was noncalcified and 46.0% was calcified, while in the HTN group, these values were 24.0 and 76.0%, respectively. The T2DM (HTN+) group had more calcified plaques (35.7% noncalcified, 64.3% calcified) than the T2DM group. The average necrotic core volume was 4.25 mm3 in the T2DM group and 5.23 mm3 in the T2DM (HTN+) group, with no significant difference (p > 0.05). HRPs were more prevalent in both T2DM and T2DM (HTN+) compared to HTN and control groups (p < 0.05). The T2DM (HTN+) group had a higher likelihood (26.1%) of FFR-CT ≤0.75 compared to the T2DM group (13.8%). FFR-CT ≤0.75 correlated with CAD-RADS 2.0 (OR = 7.986, 95% CI = 5.466-11.667, cutoff = 3, p < 0.001) and noncalcified plaque volume (OR = 1.006, 95% CI = 1.003-1.009, cutoff = 29.65 mm3, p < 0.001). HRPs were associated with HbA1c levels (OR = 1.631, 95% CI = 1.387-1.918). AI analysis of CCTA identifies patterns in quantitative plaque characteristics and FFR-CT values. Comorbid HTN exacerbates partially calcified plaques, leading to more severe coronary artery stenosis in patients with T2DM. T2DM is associated with partially noncalcified plaques, whereas HTN is linked to partially calcified plaques.