Dariusz Naskręt

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.

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.

Albuminuria and VEGF as early markers of cardiovascular disturbances in young type 1 diabetic patients

AIMS The aim of the study was to assess myocardial perfusion by means of non-invasive diagnostic methods and measurement of the plasma concentration of vascular endothelial growth factor (VEGF) in patients with long-lasting type 1 diabetes. METHODS AND RESULTS The study was performed on 41 Type 1 diabetic patients (23 females, 18 males), aged 30±7.6 with a duration of disease 15.2±5.5years. 17 patients exhibited microalbuminuria (10 females, 7 males) and 24 subjects were without microalbuminuria (13 females, 11 males). The methods used included a 24-h ECG tape, an exercise treadmill test, echocardiological evaluation with dobutamine and atropine challenge and single photon emission computer tomography (SPECT) at rest, and after dipyridamol induction of ischemia. All the exercise and stress echocardiography tests were negative. There were significant differences between microalbuminuric and normoalbuminuric subjects in the duration of their exercise tests (586.9±110.5 vs. 664.9±133.2s, p=0.027), performed work (11.4±1.6.vs. 12.6±1.8 METs, p=0.045), achieved pulse limit (89.1±3.6 vs. 92.6±5.2%, p=0.037), rest ejection fraction (55.8±8.7 vs. 62.0±4.4%, p=0.040), abnormal changes in SPECT (53 vs. 21%, p=0.047) and VEGF concentration (101.5±7.8 vs. 75.15±16.5pg/ml, p<0.05). The presence of retinopathy increased 12-fold the probability of significant changes in the SPECT (OR 12.1, 95% CI 1.38-105.64, p=0.02) and nephropathy (OR 4.27; 95%CI 1.09-16.83, p=0.03). CONCLUSION Asymptomatic patients with long lasting type 1 diabetes may have disturbances in myocardial perfusion, especially these with microalbuminuria.

Influence of remission and its duration on development of early microvascular complications in young adults with type 1 diabetes

INTRODUCTION Prevalence of partial remission ranges between 20% and 80% in the initial course of type 1 diabetes. In this phase of the disease, a substantial insulin secretion contributes to good metabolic control. The aim of the study was to determine the association between presence of partial remission and occurrence of microangiopathy complications in type 1 diabetes. MATERIAL AND METHODS Ninety-eight consecutive patients with newly diagnosed type 1 diabetes were asked to participate in a cohort study. Partial remission was defined as the time in which all of the following criteria were met: HbA1c below 6.5% (48mmol/mol), daily insulin requirement below 0.3 U/kg body weight and serum Cpeptide concentration above 0.5ng/ml. Patients were divided into those who were in remission at any time during follow-up (remitters) and non-remitters. After 7years of follow-up, the occurrence of microangiopathy complications was analyzed. In statistical analysis, Mann-Whitney test, chi(2) test and Fisher test were used for analysis between groups. We applied a Coxs multivariate regression model and univariate regression method. P<0.05 was considered statistically significant. RESULTS In univariate logistic regression, a significant association was found between absence of remission and occurrence of at least one microvascular complication. In the Cox proportional hazards regression model that included clinically significant parameters at diagnosis (presence of ketoacidosis, cigarette smoking and HbA1c value) as covariates, absence of remission was associated with occurrence of chronic complications of diabetes at 7years [HR: 3.65 (95% CI 1.23-4.56), p=0.04]. In non-remitters, higher incidence of at least one microvascular complication (46.4% vs. 7.6%), higher incidence of retinopathy (42.8% vs. 5.7%), and neuropathy (21.4% vs. 1.9%) was found. CONCLUSIONS Occurrence of partial remission of diabetes is associated with a reduced risk of chronic microvascular complications at 7-year follow-up.

Baseline diabetic knowledge after 5-day teaching program is an independent predictor of subclinical macroangiopathy in patients with type 1 diabetes (Poznan Prospective Study).

PURPOSE The cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (DM1). Carotid intima-media thickness (IMT) has been approved as a marker of subclinical atherosclerosis. The aim of this prospective study was to evaluate the relationship between baseline diabetic knowledge after five-day teaching program and IMT in patients with (DM1) treated with intensive functional insulin therapy (IFIT) from the onset of the disease. MATERIAL/METHODS The analysis included 79 subjects aged 23.4 ± 5.1 years with newly diagnosed DM1, participating in Poznan Prospective Study (PoProStu). The patients attended a five-day structured training program in IFIT at diagnosis, followed by a test consisting of 20 questions. After follow-up period of 11 years we evaluated the presence of microangiopathy and subclinical macroangiopathy. IMT of the right common carotid artery was determined using high resolution ultrasonography and calculated automatically with the Carotid Analyzer for Research program. RESULTS After 11-year follow-up median intima-media thickness was 560 (IQR: 520-630) μm. We found a negative correlation between diabetes knowledge at baseline and IMT at the end of follow-up (r=-0.27, p=0.017). In multivariate linear regression model baseline diabetic knowledge test result was associated with IMT at follow-up, independently from sex, age, smoking status, presence of hypertension and diabetic kidney disease (all at follow-up) and from mean follow-up LDL-cholesterol concentrations and HbA1c results (β=-8, 95% CI -16, -1, p=0.037). CONCLUSIONS Baseline diabetic knowledge after 5-day teaching program is an independent predictor of subclinical macroangiopathy in patients with DM1.

High-intensity Exercise in Men with Type 1 Diabetes and Mode of Insulin Therapy

The purpose of this study was to evaluate the impact of high intensity exercise on glucose levels and risk of metabolic decompensation in males with type 1 diabetes (T1D), depending on the method of insulin administration. The study comprised 29 males (aged 25.3±5.1 years; duration of diabetes 10.3±3.2 years) treated with continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI). Treadmill exercise test was performed twice in each patient until subjective exhaustion as maximum according to the Borg scale. All the patients achieved ≥85% of the maximal heart rate. Distance during the test was 4 500±1 400 m and 4 473±1 559 m in the MDI and CSII groups, respectively, which was achieved in 31±8 min. During the test and in the 6 h after, no clinically significant episodes of hypoglycemia occurred. Mean glucose levels did not exceed 10 mmol/L in most patients. The risk of the composite endpoint (hypoglycemia<3.8 mmol/L, hyperglycemia≥16.6 mmol/L, ketones≥0.6 mmol/L, and lactate>2.2 mmol/L) was higher in patients treated with MDI than CSII (OR3.75, 95%CI:1.22-11.52, p=0.02). In conclusion, planned high intensity physical effort in men with well-controlled T1D is metabolically safe. CSII shows greater metabolic advantage over MDI during and after high intensity exercise in men with T1D.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity

Abstract To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = –0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: –0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

Higher concentrations of osteoprotegerin in type 1 diabetic patients are related to retinopathy: Results from the Poznań Prospective Study

BACKGROUND Osteoprotegerin (OPG) is an arterial calcification marker which has been associated with vascular damage. Elevated OPG concentrations associated with low-grade inflammatory processes are found in diabetic subjects. OBJECTIVES The aim of the study was to assess concentrations of OPG in relation to the presence of diabetic complications in patients with diabetes type 1 (DM 1) participating in the Poznań Prospective Study (PoProStu). MATERIAL AND METHODS The study included 74 patients with DM1 (48 men) with a median age of 39 years (interquartile range [IQR]: 34-43) and a median 15-year history (IQR: 14-16) of diabetes, who were participants in the PoProStu. Serum OPG concentration was measured using the ELISA method, and serum concentration of C-reactive protein was measured with a high sensitivity test (hsCRP). The visceral adipose index (VAI) was used to determine indirect markers of insulin resistance (IR). The prevalence of microangiopathic diabetes complications was assessed. RESULTS Retinopathy was diagnosed in 28 patients (38%), diabetic kidney disease (DKD) in 28 (38%) patients, and neuropathy in 17 (23%) patients. The median OPG level was 43.8 (28.0-74.0) pg/mL. Patients with retinopathy had higher levels of OPG than those without retinopathy: 47.5 (35.0-88.0) vs 35.4 (24.7-69.4) pg/mL (p = 0.04). Positive correlations were observed between OPG concentration and hsCRP (Rs = 0.53; p < 0.001), HbA1c level (Rs = 0.36; p = 0.002), VAI (Rs = 0.23; p = 0.04) and waist circumference (Rs = 0.24; p = 0.04). CONCLUSIONS Higher concentrations of osteoprotegerin in DM1 patients are related to the presence of retinopathy. The study results indicate that OPG might play a role in the pathogenesis of vascular complications in association with hyperglycemia and low-grade inflammatory processes.