Relationship between obesity, adipocytokines and inflammatory markers in type 2 diabetes: relevance for cardiovascular risk prevention.

This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF-α, IL-6 and hsCRP) as cardiovascular risk factors. A cross-sectional study comparing the basal levels of adipocytokines and inflammatory markers was done in 18 obese (BMI ≥ 30 kg/m²) (group A), 21 overweight (25 kg/m² ≤ BMI < 30 kg/m²) (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group D). The lowest levels of adiponectin and the highest levels of leptin, resistin, TNF-α, IL-6 and hsCRP were found in group A. Adiponectin levels were significantly lower, and resistin, TNF-α, and hsCRP levels were elevated in group C vs. D. However, leptin and IL-6 levels differed significantly between groups A and B, but not between groups C and D. Moreover, we found a significant negative correlation between adiponectin and TNF-α, but not with other markers, which was independent of the presence of obesity. In contrast, leptin and resistin correlated with the inflammatory markers, and this correlation was obesity-dependent. Our results suggest that obesity influences cardiovascular risk primarily through changes in leptin and resistin and less efficiently at the level of adiponectin.

Mortality after acute myocardial infarction: significance of cardiovascular diabetic autonomic neuropathy (CDAN).

UNLABELLED: The aim of this study was to compare intrahospital and long-term mortalities after more than 10 years of the follow up after the first acute myocardial infarction (AMI) with patients with and without CDAN and without diabetes mellitus (DM). METHODS: The study was based on 76 (43 men and 33 women) with DM type 2, CDAN was detected in 51 patients, and 374 (295 men and 79 women) without DM consecutively hospitalized with the first-ever AMI from January 1998. to December 2000. in Clinical Center of Montenegro Podgorica. Patients were followed until December 31. 2011. CDAN was searched for by standardized five tests evaluating heart rate and blood pressure variations. RESULTS: Intrahospital mortality was presented in 10.53% diabetic patients and 5.61% nondiabetic patients, this difference is significant (p = 0.048). Long-term mortality was presented at 24 (82.75%) patients with CDAN and 5 (17.25%) patients without CDAN (p = 0.029). Long-term mortality rate was significantly higher in diabetic patients 29 (42.64%) than in nondiabetic patients 102 (30.72%) (p = 0.012). CONCLUSION: Intrahospital mortality was significantly higher in diabetic than in nondiabetic patients. Identically the mortality after more than 10 years of the follow up after the first AMI was significantly higher in diabetic with, than in diabetic patients without CDAN, as in diabetic than in nondiabetic patients.

Psycho-social and clinical variables associated with depression in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2DM) doubles the odds of comorbid depression. Depression is a strong predictor of developing T2DM. The aim of the study was to compare depressed patients with T2DM to non-depressed ones with respect to demographic, psycho-social, clinical, anthropometric and metabolic characteristics; to examine the relationship between glycemic control and depression severity in depressed patients; to estimate the risk factors of depression. SUBJECTS AND METHODS: A group of depressed diabetic patients comprising those with a Major depressive episode, first or repeated (ICD-10; 1992) and endocrinologist-diagnosed T2DM, duration ≥5 years on oral, insulin therapy or both (N=46) and non-depressed ones (N=44) (90 in total) of both genders (<65 years) were included in this cross-sectional study. Laboratory and non-laboratory measures were performed.. The patient Health Questionnaire (PHQ-9) and a structured interview (MINI) were used to establish diagnosis, while the Beck Depression Inventory (BDI; cut off ≥16) was used to assess the severity ofdepression. Scaling of Life Events (SLE) for self-assessment of life events and Problem in Areas in Diabetes (PAID) for self-assessment of diabetes distress were also performed. RESULTS: Statistically significant higher rates of psychiatric heredity, neuropathy, higher level of diabetes related distress and a greater number of life events in depressed patients compared to non-depressed ones were found. There was a statistically significant positive correlation between BDI somatic subscore and the HbA1c level (r=0.343; p=0.020). The level of diabetes related distress (OR=1.084; p=0.000), total number of life events (OR=4.528; p=0.001) and neuropathy (OR=8.699; p=0.039) were statistically significant predictors of depression using logistic regression. CONCLUSIONS: The results obtained showed that depression in diabetic patients was predicted by both psychological (diabetes related distress, life events) and disease-specific variables (neuropathy). The severity of self-reported somatic depressive symptoms significantly correlated with the HbA1c level in depressed diabetic patients.

[Vascular inflammation: effect of proatherogenic dyslipidemic trio or quartet].

Atherosclerosis is a vascular inflammatory disease resulting from lipid deposition within vascular wall and changes in structure and function of the vascular wall. Atherosclerosis is accelerated when total and LDL cholesterol are elevated and/or HDL is low. Free radical production is increased in hypercholesterolemia leading to oxidative transformation of both parts of LDL particles, protein and lipid part. Small, dense LDL particles have extreme atherogenic potential; they can be easily oxidized and strongly maintain vascular inflammation. Oxidized LDL particles (oxLDL) support further free radical production. OxLDL are removed by macrophages into sub epithelial space. During that process macrophages produce inflammatory cytokines and induce the production of adhesion molecules, which further cause adherences of new macrophages and further support inflammation. OxLDL also induce sinthesis of endothelial growth factor receptors, which enable transduction of different signals important for: vascular remodeling, cellular migration, mitosis and NF-kappaB activation and increased metalloproteinase activity. HDL particles have an important role in the reverse cholesterol path and protective effects in vascular inflammation and atherogenesis. The ratio of apoprotein AI and AII, amount of CETP, LCAT and paraoxsonase, determine the function of HDL particles. Increased levels of triglycerides in the morning and especially postprandial levels are an independent risk factor for coronary heart disease, and heighten the risk when associated with other lipid disturbances. An increased triglyceride level is associated with the increased PAI I and reduced fibrinolisis. The ratio of total cholesterol/HDL cholesterol, as well as the levels of markers of inflammation such as CRP or IL-6, have great predictive value for the development of ischemic heart disease and cardiovascular diseases.

[Analysis of the effect of diabetes type 2 duration on beta cell secretory function and insulin resistance].

Diabetes type 2 is a chronic metabolic disorder. Pathogenesis of diabetes type 2 results from the impaired insulin secretion, impaired insulin action and increased endogenous glucose production. Diabetes evolves through several phases characterized by qualitative and quantitative changes of beta cell secretory function. The aim of our study was to analyze the impact of diabetes duration on beta cell secretory function and insulin resistance. The results indicated significant negative correlation of diabetes duration and fasting insulinemia, as well as beta cell secretory function assessed by HOMA beta index. Our study also found significant negative correlation of diabetes duration and insulin resistance assessed by HOMA IR index. Significant positive correlation was established between beta cell secretory capacity (fasting insulinemia and HOMA beta) and insulin resistance assessed by HOMA IR index, independently of diabetes duration. These results indicate that: beta cell secretory capacity, assessed by HOMA beta index, significantly decreases with diabetes duration. In parallel with decrease of fasting insulinemia, reduction of insulin resistance assessed by HOMA IR index was found as well.

[Oxidized LDL and lipids as risk factors for ischemic heart disease in type 2 diabetes].

BACKGROUND: [corrected] Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). Factors that contribute to endothelial cell dysfunction associated with the initiation of atherosclerosis include oxidative stress. The aim of this study was to investigate the relationship between lipid profile and oxidative stress in type 2 diabetics with and without ischemic heart disease (IHD). METHODS: We studied 80 patients with T2D, 40 with IHD (group A1) and 40 without IHD (group A2). We also studied 51 non-diabetics, 31 with IHD (group B1), and 20 without IHD (group B2 control group). Lipid profile was estimated by the total cholesterol, HDL cholesterol, LDL cholesterol, the level of triglyceride (Tg), lipoproteina a (Lp a), Apo A I, A II, B 100 and E. To evaluate the oxidative status we measured circulating oxidized LDL (ox LDL), erythrocyte antioxidative enzyme activity: superoxide dismutase (E-SOD), glutathione peroxidase (E-GPX), as well as the total antioxidative serum activity (TAS). Inflammatory reaction was estimated by C-reactive protein (CRP) and fibrinogen. RESULTS: No significant difference was found in the lipid profile in groups A1, A2 and B1, but the group B2 had the lowest one. Lp a level was significantly higher in group B1 comparing to other groups (p < 0.05). There was no significant difference in the level of ox LDL between the groups. In diabetics, ox LDL positively correlated with the total cholesterol, LDL cholesterol, non HDL cholesterol, Apo B 100 and the relations between LDL/HDL and Tg/HDL (p < 0.001), as well as with Tg and fibrinogen (p < 0.05). In group B1, ox LDL positively correlated with total cholesterol, Tg (p < 0.01), LDL, and non HDL cholesterol (p < 0.05) and significantly with Apo B 100 (p < 0.001). There was no significant difference in the antioxidant enzyme activities between the groups of diabetics (A1 and A2), but fibrinogen was higher in the group with IHD (group A1, p < 0.05). Group B1 had lower E-SOD activity than the groups A1 and A2 (p < 0.05), but CRP was higher (p < 0.05). There were no significant correlations between oxLDL and CRP in groups A1 and A2, but it was statistically significant in the group B1 (p < 0.05). CONCLUSION: In this study we demonstrated the increased oxidative stress in diabetics compared to non-diabetics regardless of the presence of IHD. Fibrinogen, but not CRP, was higher in diabetics with IHD, compared to diabetics without IHD. The increased oxidative stress, the reduced antioxidative activity E-SOD, and the higher level of CRP were found in non-diabetics with IHD compared to non-diabetics without IHD.

[Relationship between low glomerular filtration rate, hypertension, and microalbuminuria in type 1 diabetes mellitus].

AIM: To investigate the influence of low glomerular filtration rate, as well as of systolic and diastolic hypertension, on microalbuminuria in patients with type 1 diabetes mellitus. METHODS: Twenty seven patients with type 1 diabetes mellitus (18 males, 9 females) were studied. All of the patients were below 50 years of age. In 93% of the cases, the duration of diabetes was less than 15 years. GFR was determined, after intravenous injection in the lying position, by using a 99m-Tc-DTPA, while microalbuminuria was calculated for the 24-hour urine using the nephelometric immunoassay (30-300 mg/24 h). The patients were divided into 3 groups according to the value of GFR. The values ranged from 90 to 125 ml/min/1.73 m2 were considered normal (in 63% of the patients in group 1), those above that range were considered as hyperfiltration (in 22.2% of the patients in group 2), while those below that range were considered as hypofiltration (in 13.8% of the patient in group 3). RESULTS: Data analyzed with the one-way ANOVA, indicated a significant statistical difference between the 3 groups in the duration of diabetes (p < 0.05), micro-albuminuria (p < 0.01), systolic BP (p < 0.01), diastolic BP (p < 0.05), fructosamine (p = 0.50), urea (p < 0.05), creatinine (p = 0.05), and uric acid (p < 0.05). Microalbuminuria correlated with the age of patients (p <0.05) (Spearman's rho), diabetes mellitus duration (p < 0.01), systolic BP (p < 0.05), diastolic BP (p < 0.05), LDL-cholesterol (p < 0.05). There was no statistically significant correlation between GFR and the other parameters. Hypertension, microalbuminuria, and the duration of diabetes correlated positively with the reduction of GFR, revealing the most frequent reduction of GFR in the patients with more than 15-year duration of diabetes. CONCLUSIONS: Hypertension and low GFR were associated with microalbuminuria in type 1 diabetes, while the duration of diabetes was shown to be the independent risk factor for the development of microalbuminuria.

[Effect of glycemic control on microalbuminuria and arterial blood pressure in patients with type 1 diabetes].

INTRODUCTION: Diabetic nephropathy is the leading cause of hypertension in type 1 diabetes. Microalbuminuria is usually the first manifestation of renal disease and antedate hypertension. The aim of this study was to investigate relationships between glycemic control, hypertension and microalbuminuria in type 1 diabetics. MATERIAL AND METHODS: We studied 27 type 1 diabetics, 18 male and 9 female, aged 18-50 years, with a duration of diabetes <20 years. Glycemic control was assessed using glycosylated hemoglobin (HbA1c) measurements, fructosamine and lipid analysis. 24-h urinary albumin excretion rate was evaluated by radioimmunoassay. Patients with persistent urinary albumin excretion rate 30-300 mg/24 h were defined as microalbuminuric (Group A--41% patients) and lower than that, as normoalbuminuric (Group B--59%). We examined them twice: first in poor glycemic control and then in good glycemic control. RESULTS: We found significant differences (Student's t-test) between groups in regard to microalbuminuria (p <0.01), diabetes duration (p=0.05), systolic blood pressure (BP) and diastolic BP (p<0.05). Systolic BP (p<0.01), diastolic BP (p<0.01) and microalbuminuria (p=0.05) positively correlated (Spearman's rho) with poor glycemic control in Group A. In both groups there was a significant improvement in glycemic control and regression in systolic and diastolic BP (p<0.01), but only Group B showed significant reduction in urinary albumnin excretion rate (p<0.01). DISCUSSION AND CONCLUSION: In this study, type 1 diabetics showed regression in systolic and diastolic hypertension with improvements of glycemic control regardless of presence of microalbuminuria, but only normoalbuminuric showed significant reduction in urinary albumin excretion rate.

[The prevalence of hypertension and microalbuminuria in diabetes mellitus type 1 and type 2].

INTRODUCTION: The prevalence of hypertension is two times higher in diabetics than in non-diabetics. In type 1 diabetes mellitus (T1DM), the incidence of hypertension is similar to the incidence of nephropathy. In obese patients with type 2 DM (T2DM) there can be associated complications of hyperinsulinaemia, dyslipidaemia, and hypertension, which can lead to coronary artery disease and stroke. These associated complications are the result of a genetic defect that produces insulin resistance--Syndrome X. Increased microalbuminuria correlates with increased levels of blood pressure (BP) and increased LDL cholesterol, and this is why microalbuminuria is associated with an increase in cardiovascular deaths in diabetics, even in the absence of renal failure. AIM: The aim of this study was to research the influence of a patient's age, diabetes duration, and obesity on the frequency of hypertension and its association with microalbuminuria in T1 DM and T2DM. METHOD: 168 hospitalised patients with DM (79 T1DM, 89 T2DM) were analysed. The main outcome measures were: 24-hour urinary albumin excretion rate by radioimmunoassay (MA = 30-300 mg/24h), arterial hypertension (systolic BP > or = 140 mm Hg and/or diastolic BP > or = 90 mm Hg), and body mass index (BMI). RESULTS: Microalbuminuria was detected in 42% of patients with T1DM and 47% of patients with T2DM. 34% of T1DM patients and 78% of T2DM patients were hypertensive. Patients were divided into four groups, according to the presence of hypertension and microalbuminuria: Group I--patients with hypertension and MA, Group II--patients with hypertension but without MA, Group III--patients without hypertension and MA, Group IV--patients without hypertension but with MA. 44% of T1DM patients were without hypertension and microalbuminuria, while the most frequent T2DM patients were those with hypertension (37% with and 41% without microalbuminuria). A significant correlation between BMI and diastolic BP in both types of DM (p < 0.01 for T1DM, and p < 0.05 for T2DM) was discovered. T2DM hypertensive patients were obese and there was a significant correlation between a patient's systolic BP and his or her age (p < 0.05). CONCLUSION: These results suggest that hypertension can be prevented in patients with T2DM with weight reduction. There was a significant association between hypertension and microalbuminuria, especially in T1DM patients. Tight control of blood pressure is essential for the reduction of microalbuminuria as well as further micro- and macro-vascular diabetic complications.