Aleksandra Araszkiewicz

Increased Accumulation of Skin Advanced Glycation End Products Is Associated with Microvascular Complications in Type 1 Diabetes

BACKGROUND Skin autofluorescence (AF) measured with an AF reader device is a noninvasive tool to measure the tissue accumulation of advanced glycation end products (AGEs). The aim of the study was to assess the association between AF and microvascular complications in type 1 diabetes mellitus (DM1). METHODS The study population consisted of 140 DM1 patients, 28 years old (interquartile range [IQR], 23-35), 76 of whom were women, with disease duration of 13 years (IQR, 8-19). We used the AGE Reader (DiagnOptics, Groningen, The Netherlands) to measure the AF phenomenon, which occurs because of fluorescent properties of AGEs. The patients were divided according to the presence or absence of diabetes-associated microvascular complications: retinopathy, nephropathy, and neuropathy and any microangiopathy. RESULTS The median AF was 2.0 (IQR, 1.7-2.4). In the univariate logistic regression AF was significantly associated with retinopathy (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.26-4.84, P = 0.008), nephropathy (OR 3.15, 95% CI 1.34-7.39, P = 0.008), neuropathy (OR 3.17, 95% CI 1.46-6.90, P = 0.003), and any microvascular complication (OR 2.94, 95% CI 1.46-5.92, P = 0.002). Multivariate logistic regression showed that skin AF was independently associated only with diabetic neuropathy (OR 2.98, 95% CI 0.99-8.90, P = 0.05). CONCLUSIONS The tissue accumulation of AGE is significantly associated with microvascular complications in DM1.

Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients with and without microangiopathy

Introduction The aim of the study was to assess carotid intima-media thickness (CIMT) as a subclinical marker of atherosclerosis and arterial stiffness in type 1 diabetic patients in relation to microangiopathy. Material and methods We included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years (interquartile range [IQR] 29-43), median disease duration 10 years (IQR: 9-14), mean ± standard deviation (SD) glycated haemoglobin (HbA1c) 8.4 ±1.4%. Fifty patients had at least one microangiopathic complication. Intima-media thickness (IMT) of the common carotid artery was measured using high resolution ultrasonography. Arterial stiffness was assessed using digital volume pulse analysis and tonometric measurement of wave reflection and central haemodynamics. Results Subjects with microangiopathy compared with those without had higher values of CIMT (median [IQR]: 0.53 mm [0.45-0.60 mm] vs 0.47 mm [0.34-0.52 mm], p = 0.002), higher central augmentation index (CAIx) (mean ± SD: 120.2 ±19.4% vs. 110.5 ±17.1%, p = 0.016) and higher peripheral augmentation index (PAIx) (65.7 ±18.1% vs. 57.2 ±14.9%, p = 0.023). In the logistic regression analysis, the duration of diabetes, systolic and diastolic blood pressure, postprandial glycaemia, HbA1c and triglycerides predicted the presence of diabetic microangiopathy independently of age and sex. The CIMT, CAIx and PAIx were associated with the presence of diabetic microangiopathy only in the univariate model. Conclusions In type 1 diabetic patients with microangiopathic complications, increased carotid IMT and arterial stiffness were observed. The study confirms the role of traditional risk factors for late diabetic complications, such as the duration of the disease and metabolic control in the development of microangiopathy.

Association Between IL-6 Concentration and Diabetes-Related Variables in DM1 Patients with and without Microvascular Complications

Interleukin 6 (IL-6) plays an important role in the initiation and acceleration of chronic inflammation and could contribute to development of microvascular complications in patients with type 1 diabetes (DM1). Therefore, this study was aimed to investigate the association between concentration of IL-6 in relation to glucose control, lipid profile, and body mass index (BMI) in 69 DM1 patients subdivided according to the absence or presence of microvascular complications. BMI, level of fasting plasma glucose (FPG), and concentrations of total cholesterol (TCH), LDL cholesterol (LDL-C), and IL-6 were higher in DM1 patients compared to the control group. In DM1 patients, IL-6 concentration was positively correlated with level of FPG, LDL-C, TCH concentrations, and BMI. These correlations were stronger in the subgroup of patients with microvascular complications. In addition, BMI independently influences IL-6 concentration in DM1 patients. In conclusion, elevated IL-6 concentration is associated with diabetes-related variables which could accelerate progression of microvascular complications in DM1 patients.

Insulin Resistance is Associated with Microangiopathy in Type 1 Diabetic Patients Treated with Intensive Insulin Therapy from the Onset of Disease

AIM The aim of the study was to evaluate the relationship between indirect parameters of insulin resistance (IR) and risk of microangiopathy in patients with type 1 diabetes (DM1), treated from the initial diagnosis with intensive insulin therapy. METHODS The study group consisted of 81 patients with DM1 (51 men, 30 women), aged 34±6.4, and who were observed for 10±1.5 years. Indirect parameters of IR were evaluated: waist circumference, waist to hip ratio (WHR), body mass index (BMI), daily insulin requirement, gain of weight from the beginning of the disease, lipid profile, estimated glucose disposal rate (eGDR), inflammatory markers and features of metabolic syndrome. Patients were divided into two groups depending on the presence or absence of microangiopathy. RESULTS In the group with microangiopathy (n=36) in comparison with patients without complications (n=45) we found: larger waist circumference (88.9±11.7 vs. 83.7±10.2 cm; p=0.036), higher weight before diabetes (77.3±17.0 vs. 67.0±12.5 kg; p=0.008), higher WHR (0.90±0.08 vs. 0.86±0.08; p=0.048), higher level of triglycerides (1.3±0.8 vs. 0.9±0.3 mmol/l; p=0.002) and lower eGDR (7.2±2.4 vs. 8.8±1.9 mg/kg/min; p=0.0019). In patients with microangiopathy, features of metabolic syndrome were found more often (12 (33.3%) vs. 4 (8.9%); p=0.006). A significant relationship, adjusted for sex, age and duration of diabetes, between eGDR and microangiopathy was revealed (OR 0.65 (95%CI 0.49-0.86); p=0.0037). CONCLUSION The results show that in patients with DM1, treated from the initial diagnosis with intensive insulin therapy, there is an independent relationship between IR and the diabetic microangiopathy.

Knowledge after five-day teaching program in intensive insulin therapy performed at the onset of type 1 diabetes influence the development of late diabetic complications

We evaluated the influence of baseline diabetic knowledge on clinical course of type 1 diabetes treated with intensive functional insulin therapy (IFIT) from the onset of the disease. 86 subjects with newly diagnosed type 1 diabetes, aged 23.4+/-5.1 attended a five-day structured training program in IFIT at baseline, followed by a test consisting of 20 questions. Patients were divided into subgroups according to test results: group A>16, group B 12-16 and group C<12 scores. At follow-up (7.1+/-1.5 years) metabolic control and development of microangiopathy were assessed. Patients with low knowledge at baseline had higher HbA1c levels than subjects with higher knowledge (group C: 9.2+/-1.9 vs. group A: 7.7+/-1.5%, p<0.05 and vs. group B: 7.8+/-1.6%, p<0.05), higher BMI (group C: 23.9+/-3.2 vs. group A: 21.8+/-3.1 kg/m(2), p<0.05) and lower HDL-cholesterol level (group C: 1.8+/-0.5 vs. group A: 2.0+/-0.3 mmol/l, p<0.05). Patients with retinopathy and albuminuria at follow-up had lower level of diabetic knowledge at baseline (respectively: 12.5+/-3.6 vs. 14.2+/-3.3 scores, p<0.05; and 12.6+/-2.9 vs. 14.1+/-3.5 scores, p<0.05). The development of microangiopathy was associated with lower diabetic knowledge (RR=3.71; 95%CI: 1.15-12.01, p=0.02 for retinopathy and RR=4.33; 95%CI: 0.98-19.10, p=0.04 for microalbuminuria). The higher diabetic knowledge at baseline the better metabolic control and lower risk of microangiopathy in the future.

The evaluation of IL-12 concentration, PAF-AH, and PLA2 activity in patients with type 1 diabetes treated with intensive insulin therapy

OBJECTIVES The aim of the study was to evaluate the concentration of interleukin 12 (IL-12), the activity of phospholipase A(2) (PLA(2)), and platelet-activating factor acetylhydrolase (PAF-AH) in type 1 diabetes (DM1) patients treated with intensive insulin therapy. DESIGN AND METHODS Studied parameters were measured in 81 patients, who were subdivided according to the HbA(1)c value, hsCRP concentration, and presence or absence of late complications. RESULTS PAF-AH activity was higher in the DM1 patients versus the control group (P=0.042). IL-12 concentration was the highest in subgroup with > or =3 mg/L hsCRP (P<0.05). Negative correlations were found for the IL-12 and age of patients and for apo A-I in the subgroup with poor metabolic control. In addition, positive correlation for hsCRP and PAF-AH activity in the subgroup with > or =3 mg/L CRP (P<0.05) was also found. CONCLUSIONS PAF-AH and IL-12 appear to be implicated in the development of a chronic inflammation in DM1. In addition, our results emphasize a protective role of apo A-I against an increase in IL-12 production.

Higher risk of microvascular complications in smokers with type 1 diabetes despite intensive insulin therapy.

AIM The aim of the study was to evaluate the relationship between smoking status and the incidence of microvascular complications in patients with type 1 diabetes (DM1), treated with intensive functional insulin therapy (IFIT) from the onset of the disease. METHODS 81 participants (51 men, 30 women) of Poznan Prospective Study (PoProStu) with mean age of 34.0 ± 6.4 years were included in this analysis. Patients were observed for 10.0 ± 1.5 years. Evaluation of microvascular complications of diabetes, such as retinopathy, diabetic kidney disease and neuropathy was performed. Patients were divided into two groups depending on the smoking status: smokers and non-smokers. RESULTS In the group of smokers (n=36) in comparison with patients who had never smoked (n=45) any microangiopathy (58.3% vs 33.3%, p=0.02), retinopathy (44.4% vs 20%, p=0.02), diabetic kidney disease (47.2% vs 24.4%, p=0.03) and neuropathy (25% vs 4.4%, p=0.02) were found more often. A significant relationship, adjusted for age, sex, duration of diabetes, presence of hypertension and HbA1c between smoking and neuropathy and retinopathy was revealed [OR 10.16 (95%CI 1.59-64.95); p=0.01 and OR 3.50 (95%CI 1.01-12.12); p=0.04, respectively]. CONCLUSION The results show that in patients with DM1, there is a strong relationship between smoking and the diabetic microvascular complications, especially with neuropathy, despite treatment from the initial diagnosis with intensive insulin therapy.

Carotid intima-media thickness and arterial stiffness in type 1 diabetic patients are dependent on age and mean blood pressure.

AIM The aim of the study was to assess the factors that influence carotid intima-media thickness (CIMT) and arterial stiffness in type 1 diabetic patients. MATERIAL AND METHODS We included 87 type 1 diabetic patients (44 women, 43 men), median age 34 years, disease duration 10 years, HbA1c 8.2%. CIMT was measured using high resolution ultrasonography. Arterial stiffness was assessed with the use of digital volume pulse analysis and tonometric measurement of wave reflection and central haemodynamics. Serum C-reactive protein (hsCRP), matrix metalloproteinase-9 (MMP-9), soluble intracellular adhesion molecule-1 (sICAM-1) and myeloperoxidase (MPO) concentrations were also measured. RESULTS CIMT and arterial stiffness correlated with age, duration of diabetes, systolic and diastolic blood pressure, GFR-glomerular filtration rate and sICAM-1. Multiple regression analysis identified only age as significant determinant of CIMT. Age, mean blood pressure and GFR, but not duration of diabetes were significant determinants of arterial stiffness. CONCLUSIONS In type 1 diabetic patients both CIMT and arterial stiffness were related to age, blood pressure, kidney function and sICAM-1 serum concentration.

Does oxidized LDL contribute to atherosclerotic plaque formation and microvascular complications in patients with type 1 diabetes

OBJECTIVE The aim of the study was to investigate whether changes in the level of oxidized LDL (oxLDL) over 2-years contribute to the development of subclinical macroangiopathy and/or microvascular complications in patients with DM1. DESIGN AND METHODS Basic clinical and biochemical parameters and oxLDL level were measured in 70 patients at baseline and after 2 years of the study. In addition, an ultrasonographic study was performed to assess the carotid intima media thickness (IMT). RESULTS Patients did not differ according to basic clinical and biochemical parameters at the beginning and after 2 years of the study. IMT increased (p=0.000001) whereas oxLDL level decreased (p=0.00001) in DM1 patients during 2 years. Multivariate regression analysis showed that oxLDL independently influences IMT in DM1 patients (β=0.454, R2=0.35). Further, positive correlations between oxLDL value and LDL-C concentration (r=0.585, p<0.05, n=70) and between oxLDL level and apo-B concentration have been established (r=0.610, p<0.05, n=70). Moreover, patients with chronic microvascular complications showed a higher value of IMT in comparison with patients without them (p=0.003). CONCLUSION Our results provide the evidence that oxLDL accelerates atherosclerotic plaque formation and may contribute to the development of microvascular complications in DM1.

The relationship between concentrations of magnesium and oxidized low density lipoprotein and the activity of platelet activating factor acetylhydrolase in the serum of patients with type 1 diabetes

The study was aimed at comparing the concentration of metabolic parameters, the serum concentration of oxidized low density lipoproteins (oxLDL) and the activity of platelet activating factor acetylhydrolase (PAF-AH) in the relation to the serum concentration of magnesium (Mg) in patients with type 1 diabetes (DM1). DM1 patients (n=78) were divided into 2 groups: patients with low serum Mg concentration (<0.7 mmol/L, group 1, n=34) and patients with reference levels of Mg (>or=0.7 mmol/L, group 2, n=44). A control group (n=24) of healthy subjects was also recruited. Our results showed that DM1 patients had lower serum Mg concentrations than the control group. It was found that parameters of poor metabolic control and lipid profile are not related to the serum Mg concentration in DM1 patients. However, both the Mg concentration and the PAF-AH activity are independently related to the serum oxLDL concentration. In group 1 the oxLDL concentration and the PAF-AH activity were higher than in group 2, and the control group. Two groups of DM1 patients did not show any differences with regard to the metabolic control. Therefore, the oxidative modification of LDL and the higher activity of PAF-AH are related with the low Mg status; however, no relation has been observed between these parameters and the poor metabolic control in DM1 patients.