Helicobacter pylori infection is associated with increased accumulation of advanced glycation end products in the skin in patients with type 1 diabetes: A preliminary study.

BACKGROUND: Helicobacter pylori infection (HPI) is more frequently diagnosed in patients with diabetes. Insulin resistance in patients with type 1 diabetes (DMT1) is associated with the accumulation of advanced glycation end products (AGEs) in the skin and progression of chronic complications. OBJECTIVES: Assessment of the relationship between the incidence of HPI and skin AGEs in patients with DMT1. MATERIAL AND METHODS: The study included 103 Caucasian patients with a DMT1 duration >5 years. A fast qualitative test was performed to detect the HP antigen in fecal samples (Hedrex). The content of AGEs in the skin was estimated using an AGE Reader device (DiagnOptics). RESULTS: The HP-positive (n = 31) and HP-negative (n = 72) groups did not differ in terms of age, gender, duration of diabetes, fat content, body mass index (BMI) and lipid profile, metabolic control, and inflammatory response markers. The studied groups differed in the amount of AGEs in the skin. The relationship between HPI and increased AGEs in the skin was confirmed in a multifactor regression model taking into account age, gender, DMT1 duration, glycated hemoglobin A1c (HbA1c), BMI, low-density lipoprotein cholesterol (LDL-C) and the presence of hypertension, and tobacco use. The studied groups also differed in serum levels of vitamin D. CONCLUSIONS: Increased accumulation of AGEs in the skin of patients with DMT1 with coexisting HPI suggests that eradication of HP may significantly improve DMT1 outcomes.

Influence of resistant starch resulting from the cooling of rice on postprandial glycemia in type 1 diabetes.

INTRODUCTION: Carbohydrates are one of the macronutrients which have the most substantial influence on glycemic response. The cooling of rice after cooking causes retrogradation of starch, which becomes a non-absorbable product in the human digestive tract. AIM OF THE STUDY: This study aimed to assess whether cooling of rice affects postprandial glycemia in subjects with type 1 diabetes. MATERIALS AND METHODS: The study included 32 patients with type 1 diabetes. Each participant of the study consumed two standardized test meals consisting of long-grain white rice. One of the test meals was served immediately after preparation, and another was cooled for 24 h at 4 °C after preparation and reheated before being served. Postprandial glycemia was measured for 3 h using the FreeStyle Libre flash glucose monitoring system for each patient. RESULTS: After consumption of the test meal containing rice subjected to the cooling process when compared to fresh rice, a significantly lower value of maximum glycemia (11 vs. 9.9 mmol/L, p = 0.0056), maximum glycemic increase (2.7 vs. 3.9 mmol/L, p < 0.0001), areas under the glycemic curve (135 vs. 336 mmol/L * 180 min, p < 0.0001) and significantly shorter time to peak (35 vs. 45 min, p = 0.031) was observed. There was a significantly higher number of hypoglycemic episodes among the patients after consuming test meals with cooled rice compared to fresh ones during 180 min of observation (12(38) vs. 3(9), p = 0.0039). CONCLUSIONS: Consumption of rice subjected to the cooling process results in a lower increase of postprandial blood glucose in subjects with type 1 diabetes. At the same time it increases the risk of postprandial hypoglycemia using a standard insulin dose.

Clinical Remission of Type 1 Diabetes Predicts Higher Insulin Sensitivity at 7 Years from Diagnosis of the Disease.

Background: Clinical remission of type 1 diabetes is not only associated with regeneration of beta cells and preserved insulin secretion but also with increased insulin sensitivity. The aim of the study was to determine the association between presence of remission in the first year of type 1 diabetes and insulin resistance at 7 years from diagnosis of the disease. Material and Methods: A total of 108 consecutive patients with newly diagnosed type 1 diabetes were followed prospectively. During the follow-up time, the onset and duration of clinical remission were registered. Seventy-four patients were included in the final analysis. Insulin sensitivity was assessed by the glucose disposal rate (GDR), determined using the hyperinsulinemic-euglycemic clamp, performed at 7 years from diagnosis of diabetes. Patients were divided into groups with GDR <4.5 mg/(kg·min) (G1-lower insulin sensitivity group) and GDR ≥4.5 mg/(kg·min) (G2-higher insulin sensitivity group). Results: Higher insulin sensitivity was observed in the remission group [GDR 6.2 interquartile range (IQR) 4.2-7.0 mg/(kg·min) vs. 3.8 (IQR 3.0-4.8) mg/(kg·min); P = 0.01]. Furthermore, in G2 group, the duration of remission was longer than in G1 group: (351 [IQR 206-561] days vs. 70 [IQR 0-289] days; P = 0.002). Also, the GDR value correlated positively with duration of remission (r = 0.42; P = 0.002). In the multivariate logistic regression model, including age, sex, body mass index at diagnosis, and presence of remission, the remission period was independently associated with a higher GDR value (odds ratio 10.88; 95% confidence interval: 1.70-69.50; P = 0.009]. Conclusions: Patients with type 1 diabetes who entered remission at the beginning of the disease, despite its ending, have higher insulin sensitivity at 7 years after diagnosis of diabetes than nonremitters.

An increased skin microvessel density is associated with neurovascular complications in type 1 diabetes mellitus.

The aim of this study was to assess the blood vessel density and maturity in the skin of adults with type 1 diabetes in relation to the presence of late neurovascular complications. We included 148 patients (87 men) with a median (interquartile range) age of 41 (31-49) and median diabetes duration of 21 (17-30) years. Microvessel (CD133, CD34, CD31 and von Willebrand factor) markers were evaluated by indirect immunohistochemistry assay in material from a skin biopsy. Diabetic retinopathy was diagnosed using direct ophthalmoscopy, and diabetic kidney disease was estimated in people with increased albuminuria and a 10-year duration of diabetes or evidence of diabetic retinopathy . Diabetic peripheral neuropathy diagnosis was based on Toronto definition, cardiac autonomic neuropathy on validated ProSciCard III program. Microvessel density, assessed by CD34 and CD133, was significantly higher in patients with cardiac autonomic neuropathy [160 (125-175) vs 121 (100-154)/1 mm2, p = 0.001 and 92 (83-104) vs 79 (63-92)/1 mm2, p = 0.007, respectively] and CD34 in patients with diabetic peripheral neuropathy [135 (106-168) vs 121 (95-145)/1 mm2, p = 0.018], as compared with subjects without complications. In multivariate logistic regression, density of CD34 and CD133 positive vessels was associated with presence of cardiac autonomic neuropathy [odds ratio 1.016 (95% confidence interval: 1.002-1.029), p = 0.019 and odds ratio 1.037 (95% confidence interval: 1.008-1.067), p = 0.011, respectively]. It was independent from age, sex, diabetes duration, smoking status, body mass index and HbA1c value. Density of CD34 positive vessels was also associated with diabetic peripheral neuropathy, independently from sex and diabetes duration [odds ratio 1.009 (95% confidence interval: 1.001-1.020), p = 0.037]. Skin microvessel density is increased in adults with clinical evidence of neurovascular complications of type 1 diabetes. This is associated with predominance of the vessels of low maturity.

Dermal microvessel density and maturity is closely associated with atherogenic dyslipidemia and accumulation of advanced glycation end products in adult patients with type 1 diabetes.

In patients with diabetes, functional changes in microcirculation and subclinical vascular pathology precede clinical manifestation of microangiopathic complications. The objective of this study was to evaluate the association between established vascular risk factors and density, maturity, and reactivity of dermal blood vessels in adults with type 1 diabetes (DM1). We included 148 DM1 patients (87 men) with a median (IQR) age of 40.5 (30.5-49) years and a median diabetes duration of 21 (17-29.5) years. The control group consisted of 13 healthy volunteers (6 men) with a median (IQR) age of 36 (31-43). Accumulation of advanced glycation end products (AGEs) was assessed using the AGE-Reader device. In the immunohistochemical (IHC) analyses, anti-CD133, anti-CD34, anti-CD31, and anti-vWF autoantibodies were used. Microvessel density (MVD) in the skin was calculated using the "hot spots technique". Microvascular function was examined by single-point laser-Doppler flowmetry (LDF). Median MVD, calculated for both papillary and reticular dermis, for CD31 antigen expression was 38 (19-56) per 1 mm2. The median CD34+ blood vessel density was 121 (100-155) per 1 mm2, CD133+ was 79 (63-92) per 1 mm2, and vWF+ was 50 (40-69) per 1 mm2. The average CD34/CD31 index was 2.78, the vWF/CD31 ratio was 1.32 and the CD133/CD31 ratio was 1.75. The CD34/CD31 index was positively associated with serum triglyceride concentration (Beta: 0.26, p = 0.012) and negatively associated with serum HDL cholesterol concentration (Beta: -0.22, p = 0.027), both independently from age, sex, diabetes duration, BMI, HbA1c value, presence of hypertension, and eGFR. We found a negative correlation between MVD assessed by CD31 and skin AF (r = -0.21, p = 0.016). In LDF, the area under the blood flow/time curve (AUC) correlated positively with CD31+ MVD (r = 0.21, p = 0.011) and negatively with CD34+ MVD (r = -0.20, p = 0.017). The MVD did not differ between participants with diabetes and healthy controls, and it did not differ according to the presence of retinopathy among the participants with diabetes. Atherogenic dyslipidemia is associated with increased formation of new blood vessels, characterized by high expression of CD34 and low reactivity in LDF. Conversely, chronic hyperglycemia and excessive formation of AGEs may result in decreased vascularity.

Zinc transporter 8 autoantibodies (ZnT8-ab) are associated with higher prevalence of multiple diabetes-related autoantibodies in adults with type 1 diabetes.

AIM: The study aimed to assess the prevalence of zinc transporter 8 autoantibodies (ZnT8-ab), other diabetes-related autoantibodies and clinical manifestation of type 1 diabetes in adults, depending on age of the onset of disease. METHODS: 119 patients with type 1 diabetes, 66 at age <35 years (T1DM < 35) and 53 T1DM at age ≥35 years (T1DM ≥ 35). We assessed clinical features, GAD-ab, IA2-ab, ICA, ZnT8-ab and thyroid peroxidase antibodies (ATPO). RESULTS: In T1DM < 35 lower initial serum C-peptide concentration was observed and diabetes ketoacidosis (DKA) was more common. ATPO positivity was more prevalent in T1DM ≥ 35 (35.8 vs 21.2%, p = 0.04). The prevalence of GAD-ab, IA2-ab and ZnT8-ab was similar in both groups, the titres of IA2-ab and ICA were higher in T1DM < 35 but titre of ZnT8-ab was higher in T1DM ≥ 35. The majority of T1DM < 35 patients were positive for three autoantibodies (40.9%), while T1DM ≥ 35 subjects most often presented with only one (30.2%) antibody, most commonly GAD-ab (81.2%). 45% T1DM < 35 and 34% T1DM ≥ 35 subjects were positive for ZnT8-ab. ZnT8-ab positive patients had higher titre and more frequent occurrence of multiple diabetes-related autoantibodies than ZnT8-ab negative patients. CONCLUSIONS: Adults with T1DM < 35 and T1DM ≥ 35 differ in the severity of autoimmune response at diagnosis. ZnT8-ab positivity is related to higher titre and more frequent occurrence of multiple diabetes-related autoantibodies.

Metformin added to intensive insulin therapy improves metabolic control in patients with type 1 diabetes and excess body fat.

INTRODUCTION Bad nutritional habits and administration of insulin in supraphysiological doses lead to the development of insulin resistance and poor metabolic control in patients with type 1 diabetes. Accumulation of visceral fat is the main cause of the decrease in insulin sensitivity. OBJECTIVES We aimed to evaluate changes in anthropometric parameters, indirect measures of insulin resistance, and safety of treatment with metformin added to intensive insulin therapy in patients with type 1 diabetes and excess body fat. PATIENTS AND METHODS We analyzed 114 patients (60 women and 54 men; median age, 31 years [range, 18-60 years]), with a median diabetes duration of 14 years (range, 10-20 years). Metformin was administered for at least 6 months in 74 patients, while 40 patients did not receive metformin. The study group was randomized in a 2:1 ratio. Total body fat assessment and laboratory tests were performed before the study and at 6-month follow-up. RESULTS At 6 months, in the metformin group, compared with the non-metformin group, an improvement was noted for adiposity parameters (reduction in body mass index, -0.4 kg/m2 vs 0.6 kg/m2, P = 0.006; waist circumference, -5 cm vs 3.5 cm, P = 0.02; and total body fat, -1.7 kg vs 1.4 kg; P <0.001; glycated hemoglobin A1c: -0.6% vs 0.2%, P <0.001), as well as for lipid parameters and blood pressure. An increase in the estimated glomerular filtration rate was greater in the metformin compared with the non-metformin group: 0.9 mg/kg/min vs -0.2 mg/kg/min, P <0.001). CONCLUSIONS In patients with type 1 diabetes and excess body fat, treated with intensive functional insulin therapy, the addition of metformin improves metabolic control of diabetes at 6 months. Metformin added to insulin therapy in patients with type 1 diabetes and excess body fat appears to be safe.

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

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.

Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes.

AIMS: To assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset. METHODS: The study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine. RESULTS: The autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (Rs - 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0-5.94), p = 0.04]. CONCLUSIONS: Children are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.

The Higher the Insulin Resistance the Lower the Cardiac Output in Men with Type 1 Diabetes During the Maximal Exercise Test.

BACKGROUND: The aim of this study was to assess the hemodynamic parameters analyzed in bioimpedance cardiography during maximal exercise in patients with type 1 diabetes differing in insulin resistance. METHODS: The study group consisted of 40 men with type 1 diabetes. Tissue sensitivity to insulin was assessed on the basis of the glucose disposal rate (GDR) analyzed during hyperinsulinemic-euglycemic clamp. Patients were divided into groups with GDR <4.5 mg/kg/min (G1 group-lower insulin sensitivity) and GDR ≥4.5 mg/kg/min (G2 group-higher insulin sensitivity). During the exercise test, the heart rate, systolic volume, cardiac output, cardiac index were measured by the impedance meter (PhysioFlow). RESULTS: Compared with the G2 group, the G1 group had a lower cardiac output (CO): during exercise 8.6 (IQR 7.7-10.0) versus 12.8 (IQR 10.8-13.7) L/min; P < 0.0001, at the maximal effort 13.1 (IQR 12.2-16.7) versus 18.6 (IQR 16.9-20.2) L/min; P = 0.001, and during observation after exercise 8.4 (IQR 6.3-9.6) versus 11.9 (IQR 10.1-13.1) L/min; P < 0.0001. We noticed a positive correlation of GDR and cardiac output: during the exercise test (r = 0.63, P = 0.0002), at the maximal effort (Rs 0.56, P = 0.001), and during observation after the exercise test (r = 0.72, P < 0.0001). In multivariate logistic regression, cardiac output during exercise and during observation was associated with high GDR, regardless of the age and duration of diabetes [OR: 1.98 (95% CI 1.10-3.56), P = 0.02 and OR: 1.91 (95% CI 1.05-3.48), P = 0.03; respectively]. CONCLUSION: In nonobese subjects with type 1 diabetes, with good metabolic control, insulin resistance is associated with cardiac hemodynamic parameters assessed during and after exercise. The higher the insulin resistance the lower the cardiac output during maximal exercise in men with type 1 diabetes.

Evaluation of sudomotor function in adult patients with long­lasting type 1 diabetes.

INTRODUCTION The function of the sweat glands appears to be impaired in patients with diabetic complications. OBJECTIVES The aim of the study was to evaluate sudomotor function in adult patients with type 1 diabetes (DM1) and healthy controls and its relationship with metabolic control and diabetic complications. PATIENTS AND METHODS The study group included 404 patients with DM1 (194 women), aged 41 years (interquartile range [IQR], 32-51 years) and with disease duration of 23 years (IQR, 18-31 years). The control group included 84 healthy volunteers. Electrochemical skin conductance (ESC) in the feet and hands was measured in both groups. RESULTS Patients with DM1 had lower ESC than controls (feet: 80 µS [IQR, 65-85 µS] vs 83 µS [IQR, 78.5-87 µS], P <0.001; hands: 63 µS (IQR, 51-75 µS) vs 69 µS (IQR, 61.5-78.5 µS), P <0.001). In the study group, there was a negative correlation between ESC and patients' age, duration of diabetes, waist­to­hip ratio, skin autofluorescence, vibration perception threshold, as well as hemoglobin A1c and triglyceride levels, and a positive correlation with estimated glomerular filtration rate. Microvascular complications were diagnosed in 73.3% of the patients. Patients with retinopathy, diabetic kidney disease, peripheral neuropathy, and cardiac autonomic neuropathy had lower ESC in the feet and hands compared with those without complications. In multivariate logistic regression models, ESC was associated with the presence of any microvascular complications independently of potential confounders. CONCLUSIONS Diabetic microangiopathy, and in particular neuropathy, is related with reduced sudomotor function in DM1. A longer duration of diabetes, worse metabolic control, and reduced renal function are associated with greater sudomotor dysfunction.

Small intestinal bacterial overgrowth in adult patients with type 1 diabetes: its prevalence and relationship with metabolic control and the presence of chronic complications of the disease.

INTRODUCTION Gastrointestinal symptoms may occur in 50% to 70% of patients with diabetes. OBJECTIVES The aim of this study was to evaluate the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with diabetes, as well as the relationship between SIBO and metabolic control of diabetes and the presence of chronic complications of the disease. PATIENTS AND METHODS The study group included 148 patients with type 1 diabetes, treated in the years 2013-2015. The control group consisted of 41 healthy volunteers. The presence of SIBO was assessed with a noninvasive breath test using 20 g of lactulose suspended in 200 ml of water, with the assessment of exhaled hydrogen concentrations. The measurements were performed at 15-minute intervals in the first hour and at 30-minute intervals in the second hour of the test. A positive result was considered as the output value of exhaled hydrogen of 20 parts per million (ppm) or higher or an increase in the output value of the exhaled hydrogen of 12 ppm during the first 60 minutes of the test.  RESULTS We observed a lower prevalence of SIBO in the study group in comparison with controls (56 patients [37.8%] vs 30 healthy volunteers [73%]; P = 0.006). In the logistic regression model, this association was independent of age, sex, body mass index, cigarette smoking, serum C-reactive protein concentrations, and estimated glomerular filtration rate (odds ratio, 0.26; 95% confidence interval, 0.10-0.68; P = 0.006). CONCLUSIONS The prevalence of SIBO in patients with type 1 diabetes is lower than that in healthy subjects. One of the possible causes might be the beneficial effect of nutritional therapy in patients with diabetes.

[Prevalence of chronic complications in patients with over 30-year history of type 1 diabetes depending on the age of onset of diabetes]. / Czestosc wystepowania przewleklych powiklan w zaleznosci od wieku rozpoznania cukrzycy typu 1 u chorych z ponad 30-letnim wywiadem choroby.

ABSTRACT: The aim of this study was to evaluate the prevalence of chronic complications in patients with type 1 diabetes with more than 30 years of history of the disease, depending on the age of onset of diabetes. The criterion for inclusion in the study was over 30-year history of type 1 diabetes. The study group was divided into two subgroups according to the age of diagnosis of type 1 diabetes (either before or after 18 years of age). Anthropometric parameters, degree of metabolic control and the presence of markers of chronic diabetic micro- and macrovascular complications were assessed. The study was performed in 215 type 1 diabetic patients with more than 30 years history of the disease, aged 54±10 years, 98 men, 117 women. In 110 patients (group I), type 1 diabetes was diagnosed before age of 18 years, in 105 patients (group II) after 18 years of age. Patients in group I were younger, with a longer duration of the disease, more often treated with intensive functional insulin. There were no differences in terms of metabolic control between the assessed groups. Patients in group I were significantly more often diagnosed with chronic diabetic kidney disease, in group II hypertension was more often observed. CONCLUSIONS: The diagnosis of type 1 diabetes before or after the age of 18 had no significant effect on the lack of chronic complications. Patients with diabetes diagnosed in childhood, after 30 years of disease, presented a higher incidence of diabetic kidney disease.

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 Cox's 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.

Skin autofluorescence is associated with carotid intima-media thickness, diabetic microangiopathy, and long-lasting metabolic control in type 1 diabetic patients. Results from Poznan Prospective Study.

AIMS: Our aim was to assess the association between skin autofluorescence (AF) related to advanced glycation end products (AGEs) accumulation and long-term metabolic control, microvascular complications and carotid intima-media thickness (IMT) in an observational cohort of type 1 diabetes (DM1). METHODS: The analysis included 77 patients with DM1 (28 women and 49 men) aged 38 (IQR: 34-41), diabetes duration 15 (14-17), participating in Poznan Prospective Study (PoProStu). Skin AF was measured with AGE Reader (DiagnOptics). RESULTS: We found 50% of any microvascular complication; 37% of retinopathy, 37% of diabetic kidney disease and 22% of distal symmetrical neuropathy. Median carotid IMT was 0.57 (0.52-0.67) mm and skin AF 2.2 (IQR: 1.9-2.6). We found positive correlation between skin AF and patients' age (r=0.31, p=0.006), mean HbA1c from the observation time (r=0.35, p=0.001) and IMT (r=0.39, p<0.001). In multivariate logistic regression presence of microvascular complications was independently associated with skin AF: for retinopathy (OR 3.49; 95% CI: 1.08-11.28, p=0.03), for diabetic kidney disease (OR 3.62; 95% CI: 1.16-11.28, p=0.02), for neuropathy (OR 5.01; 95% CI: 1.21-20.77, p=0.02) and for any microangiopathy (OR 3.13; 95% CI: 1.06-9.18, p=0.03). CONCLUSION: Skin AF is a reliable marker of past glycemic control of diabetes. Increased accumulation of AGEs is related to the presence of diabetic microangiopathy as well as subclinical macroangiopathy in patients with type 1.

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 (ß=-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.

Influence of lifestyle on the course of type 1 diabetes mellitus.

Type 1 diabetes (T1DM) is an autoimmune disease that requires insulin treatment from the time of diagnosis. Its clinical course depends on both genetic and environmental factors, and the lifestyle of a patient modulates their interaction. The evidence about the influence of lifestyle on the course of T1DM is increasing. In this paper, we present evidence on the relationship between lifestyle parameters and diabetes-related outcomes. We discuss the most commonly addressed factors associated with lifestyle, such as physical activity, nutrition and smoking, and those with sparse evidence in T1DM, such as socioeconomic status, sleep duration, psychological stress and illicit drugs intake.

C-Reactive protein and soluble intracellular adhesion molecule-1 are related to pulse wave reflection in type 1 diabetes 1C-1.

BACKGROUND: The association of inflammation with cardiovascular (CV) complications in diabetes remains a matter of considerable debate. Arterial stiffness and enhanced wave reflection play an important role in CV complications. Therefore, in the present study we investigated whether markers of inflammation are correlated with parameters of wave reflection in type 1 diabetes (T1D). METHODS: In all, 145 T1D patients were included in the study (median age 32 years, disease duration 10 years, HbA1c 8.2%). Serum concentrations of high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase (MMP)-9, soluble intracellular adhesion molecule-1 (sICAM-1), and myeloperoxidase (MPO) were estimated as markers of inflammation. Parameters of pulse wave reflection (central augmentation index [cAIx] and peripheral augmentation index [pAIx]) were assessed using pulse wave analysis. RESULTS: Multivariate linear regression analysis revealed that, after adjustment for age, mean blood pressure, HbA1c, low-density lipoprotein-cholesterol, and the presence of at least one microangiopathic complication of diabetes, cAIx and pAIx were associated with serum concentration of hs-CRP (ß = 1.838, 95% confidence interval [CI] 0.336-3.339 [P = 0.017]; and ß = 2.041, 95% CI 0.683-3.400 [P = 0.004], respectively) and sICAM-1 (ß = 0.073, 95% CI 0.015-0.131 [P = 0.014]; and ß = 0.066, 95% CI 0.013-0.119 [P = 0.016], respectively) in the study group. CONCLUSIONS: In T1D parameters of wave reflection are related to markers of inflammation.

Controversies in diabetes in 2013 - a brief update.

Incidence of diabetes is increasing worldwide at an alarming rate. Therefore, a proper understanding of the mechanisms and efficient treatment of the disease is becoming increasingly important. The article briefly describes controversies in type 1 diabetes (T1DM) pathogenesis and diagnosis (genetic background, accelerator hypothesis, new autoantibodies, new information on LADA - latent autoimmune diabetes in adults, and the role of TRAIL - tumor necrosis factor-related apoptosis-inducing ligand) and treatment (how to deal with fluctuations of blood glucose concentrations and the occurrence of hypoglycemia, the role of healthy lifestyle, especially physical exercise, and a proper diet, treatment of insulin resistance and the challenges in detecting diabetic neuropathy). Moreover, issues in the pathogenesis of macrovascular complications in type 2 diabetes (T2DM) are considered (novel risk factors - vascular hyperglycemic memory, hypoglycemia, altered profile of microRNAs expression, impaired function of vascular progenitor cells, altered fibrin clot properties and iron-induced blood coagulation). Modern treatment of T2DM, based on lifestyle intervention and antidiabetic drugs, is full of controversies and it seems that over time the number of uncertainties is constantly increasing. Recent trials have reported disappointing results in lifestyle intervention (LOOK-AHEAD) and antihyperglycemic treatment (ACCORD, SAVOR-TIMI 53, EXAMINE, concerns about sulfonylureas safety). Moreover, there are considerable deviations from treatment targets that are recommended by the guidelines (blood glucose, hypertension, blood lipids) in real-life clinical practice in patients at different stages of the disease development. It seems that beneficial modification of the natural history of diabetes is unlikely in the foreseeable future unless we are able to obtain a more in-depth understanding of the pathomechanisms of the disease.

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 (HbA(1c)) 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 (CAI(x)) (mean ± SD: 120.2 ±19.4% vs. 110.5 ±17.1%, p = 0.016) and higher peripheral augmentation index (PAI(x)) (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, HbA(1c) and triglycerides predicted the presence of diabetic microangiopathy independently of age and sex. The CIMT, CAI(x) and PAI(x) 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.