Slobodan Antic

Effects of Aerobic Exercise on Microalbuminuria and Enzymuria in Type 2 Diabetic Patients

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-β-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 ± 7.3 years, with a mean BMI of 30.8 ± 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.

Oxidative stress parameters as possible urine markers in patients with diabetic nephropathy

OBJECTIVE Reactive oxygen species play a crucial role in the pathogenesis of diabetic nephropathy (DN). The present study was performed to assess oxidative stress parameters-thiobarbituric acid reactive substances (TBARS), reactive carbonyl derivates (RCDs), and total sulfhydryl groups (TSHGs)-in serum and urine of patients with DN. METHODS All parameters were determined in patients with type 2 and type 1 diabetes mellitus and microalbuminuria (DMT2-MIA, DMT1-MIA, respectively) and patients with type 2 diabetes mellitus and macroalbuminuria (DMT2-MAA) compared to healthy controls. RESULTS Serum and urine TBARS levels were higher in all patients with DN and microalbiminuria compared to the control group. RCD levels significantly increased in serum of patients with DMT2 relative to the controls as well as in urine of patients with DMT2-MAA and DMT1-MIA. In all groups of patients, TSHGs decreased in serum but not in urine of patients with DMT2-MAA. CONCLUSION Urine TBARS, RCDs, and TSHGs could be proposed as possible markers for oxidative damage of kidney in DN.

Monotherapy with metformin: does it improve hypoxia in type 2 diabetic patients?

Abstract Metformin reduces blood glucose levels predominantly by inhibiting hepatic gluconeogenesis, although it also may enhance insulin receptor number or activity. The full effects of metformin are still poorly understood. In this study the effects of metformin on plasma xanthine oxidase (XO) activity, thiobarbituric acid-reactive substance (TBARS), lactate and fructosamine concentration as well as erythrocyte antioxidant enzyme activities were investigated in 46 patients with type 2 diabetes mellitus. All parameters were measured simultaneously just before metformin therapy (T0), 1 month (T1) and 2 months (T2) later. Results were compared with placebo and control group. We noted significant decrease in XO activity and in TBARS concentration (p<0.001) during monotherapy with metformin vs. placebo and T0 group. A significant correlation was observed between the activity of XO and the concentration of fructosamine (p<0.001). Erythrocyte glutathione peroxidase showed significantly lower activity in T2 group in comparison with T0 group (p<0.01). It is known that diabetic patients produce more TBARS as a result of enhanced free radical generation the source of which may also be the large amounts of XO produced following the conversion of xanthine dehydrogenase in hypoxic diabetic tissues. Thus, our results indirectly suggest that metformin can reduce toxic tissue damage through the inhibition on XO activity.

Reversal of increased lymphocyte PC-1 activity in patients with Type 2 diabetes treated with metformin

The plasma cell differentiation antigen (PC‐1) is an inhibitor of insulin receptor tyrosine kinase activity, and has been implicated in the pathogenesis of insulin resistance in Type 2 diabetes. Metformin increases peripheral insulin sensitivity and, therefore, we have studied the effect of metformin treatment on lymphocyte PC‐1 (ecto‐alkaline phosphodiesterase I, APD) in patients with Type 2 diabetes.

Effects of regular exercise on cardiovascular risk factors profile and oxidative stress in obese type 2 diabetic patients in regard to SCORE risk.

Aim — The aim of the present study was to investigate not only the effects of aerobic exercise on overall cardiovascular risk factors profile and oxidative stress in obese, type 2 diabetic patients, but to elucidate if those effects depended on the previously estimated Systematic Coronary Risk Evaluation (SCORE) risk. Subjects and methods — Changes in several well-established cardiovascular risk factors and oxidative stress-defense parameters were measured in a total of 30 previously sedentary, obese type 2 diabetic patients, including 16 low-risk (SCORE < 5%, aged 48.8 ± 6.0 years, with a mean BMI of 33.28 ± 2.94 kg/m2) and 14 high-risk (SCORE ≥ 5%, aged 56.3 ± 6.9 years, with a mean BMI of 31.40 ± 1.13 kg/m2) patients, in regard to the SCORE model, during six months of regular aerobic exercise, performed under supervision. Results — Significant improvement was observed in the majority of cardiovascular risk factors, including body mass index, waist circumference, blood pressure, glycaemia, glycated haemoglobin, median blood glucose and lipid profile parameters in both diabetic subgroups during the exercise programme. However, the benefits of exercise on the majority of examined parameters became more evident in the low-risk subgroup, compared to the high-risk subgroup from baseline to 3 months. Regular exercise markedly reduced oxidative stress in both subgroups as well, as demonstrated for glutathione, plasma malondialdehyde, sulphydryl groups and catalase. Conclusion — Regular aerobic exercise, performed under supervision, has many beneficial effects in improving overall cardiovascular risk factors profile and reducing oxidative stress in both low-risk and high-risk (according to SCORE model), previously sedentary and obese type 2 diabetic patients.

Subclinical hypothyroidism: association with cardiovascular risk factors and components of metabolic syndrome

The aim of this cross-sectional study was to evaluate the cardiovascular risk in patients with subclinical hypothyroidism (SH) and metabolic syndrome (MetS) components. The study included 60 patients with SH and a control group of 60 healthy volunteers, gender and age matched, with normal thyroid-stimulating hormone (TSH) and free thyroxin (FT4) concentration. The following measurements were made in all participants: TSH, FT4, thyroid peroxidase antibodies, anti-thyroglobulin antibodies, body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose, total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), TC/HDL cholesterol and LDL/HDL cholesterol ratio, basal insulin level and homeostatic model assessment insulin resistance (HOMA-IR) index. MetS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The results showed that the following indices were statistically significantly higher in the SH group: BMI (p < 0.05), diastolic blood pressure (p < 0.001), TC (p < 0.05), TG (p < 0.05) and basal insulin level (p < 0.05). Although MetS parameters were present in a higher per cent in the SH group, there was a significantly higher number of patients with hypertension and decreased HDL cholesterol (p < 0.05). More frequently, MetS was diagnosed in SH patients (46.67%) than in the control group (33.33%), although the difference was not statistically significant. These results indicated that the traditional cardiovascular risk factors were more frequently present in SH patients as compared to euthyroid participants. Our results did not confirm significantly higher presence of MetS in SH patients in comparison with euthyroid respondents.

Low-level lasers as an adjunct in periodontal therapy in patients with diabetes mellitus.

BACKGROUND Diabetes mellitus (DM) increases the risk of periodontitis, and severe periodontitis often coexists with severe DM. The proposed dual pathway of tissue destruction suggests that control of chronic periodontal infection and gingival inflammation is essential for achieving long-term control of DM. The purpose this study is to evaluate the effects of low-level laser therapy (LLLT) by exfoliative cytology in patients with DM and gingival inflammation. SUBJECTS AND METHODS Three hundred patients were divided in three equal groups: Group 1 consisted of patients with periodontitis and type 1 DM, Group 2 of patients with periodontitis and type 2 DM, and Group 3 of patients with periodontitis (control group). After oral examination, smears were taken from gingival tissue, and afterward all of the patients received oral hygiene instructions, removal of dental plaque, and full-mouth scaling and root planing. A split-mouth design was applied; on the right side of jaws GaAlAs LLLT (670 nm, 5 mW, 14 min/day) (model Mils 94; Optica Laser, Sofia, Bulgaria) was applied for five consecutive days. After the therapy was completed, smears from both sides of jaws were taken. The morphometric analysis was done using the National Institutes of Health Image software program and a model NU2 microscope (Carl Zeiss, Jena, Germany). RESULTS Investigated parameters were significantly lower after therapy compared with values before therapy. After therapy on the side subjected to LLLT, there was no significantly difference between patients with DM and the control group. CONCLUSIONS It can be concluded that LLLT as an adjunct in periodontal therapy reduces gingival inflammation in patients with DM and periodontitis.

Radionuclide Staging of Renal Function in Type 1 Diabetes Mellitus

Aim. The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-β-D-glucosaminidase (NAGA) excretion rates. Patients and methods. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m (99mTc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m (99mTc-DMSA). Additionally, 99mTc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. Results. 99mTc-DTPA clearance and 99mTc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between 99mTc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with 99mTc-DTPA clearance rate (r = −0.485, p = 0.0004) and 99mTc-DMSA tubular fixation (r = −0.526, p = 0.0002). Conclusions. The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.

PC-1 (ENPP1) K121Q polymorphism in overweight and obese type 2 diabetic coronary heart disease patients.

Aim — The aim of the present study was to investigate the prevalence of the PC-1 121Q allele and to test its association to cardiovascular risk factors in type 2 diabetes mellitus (DM) patients. Methods — A total of 103 unrelated Caucasians from Serbia, including 71 DM patients without CHD (aged 59.4±8.9years, with a mean body mass index (BMI) of 33.3±4.8kg/m2) and 32 DM patients who suffered from coronary heart disease (DM+CHD) (aged 59.3±8.0years, with a mean BMI of 30.37±3.71kg/m2), were genotyped for PC-1 K121Q using a mutagenic separated PCR assay. Results — The prevalence of the PC-1 121Q allele was significantly higher in DM+CHD, compared to DM (P<0.001) and control (P<0.001) groups, since it was found in 10 (14%) DM patients, 13 (41%) DM+CHD patients and 10 (17%) control subjects.When the association of PC-1 121Q allele and the risk of suffering from CHD were assessed within the DM group in a binary logistic regression model adjusting for age and sex, PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P=0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. Conclusion — The prevalence of the PC-1 121Q allele was significantly higher in type 2 diabetic patients who suffered from CHD, compared to type 2 diabetic patients without CHD. However, after a binary logistic regression model analysis, adjusting for age and sex., PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P=0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. Since these data were cross-sectional, the potential patient selection and survival bias, as well as community underdiagnosis of DM and CHD, could most likely substantially underestimate the genetic influence.

Anxiety levels related to the type of therapy for cervical cancer

The aim of this study was to examine the effect of treatment type on anxiety in patients with cervical cancer. Subjects and methods: This prospective study was conducted in 60 patients with cervical cancer treated by radiotherapy. The study was done before treatment, and 3 and 6 months after initial testing. For assessment of anxiety the Hamilton Anxiety Scale (HAM-A) was used.: At baseline, the values of the scale of anxiety in patients who were treated surgically were significantly higher than in patients who had been treated by radiotherapy, but the intensity of anxiety gradually decreased in both groups. In this study, pain and irregular menstrual bleeding were the most important risk factors for the development of anxiety.: Routine assessment should be introduced in clinical practice for the detection and monitoring of anxiety in all patients with cervical cancer, and a psychiatrist should be included in the multidisciplinary team for their treatment.