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.

TG/HDL-C ratio and visceral adiposity index may be useful in assessment of insulin resistance in adults with type 1 diabetes in clinical practice.

BACKGROUND: Insulin resistance (IR) is an important clinical issue in patients with type 1 diabetes due to worse metabolic control and risk of development of chronic complications. OBJECTIVE: The aim of the study was to evaluate simple and easily available parameters as indirect markers of IR in adults with type 1 diabetes and correlate it with the results of hyperinsulinemic-euglycemic clamp. METHODS: The study included 88 patients (62 men), aged 34.1 ± 6.5 years, with type 1 diabetes with a median disease duration of 8 (7-13) years and mean HbA1c of 7.6 ± 1.5%. Tissue sensitivity to insulin was assessed on the basis of glucose distribution rate (GDR) obtained in the course of hyperinsulinemic-euglycemic clamp. In addition, indirect markers of IR, such as estimated GDR, presence of features of metabolic syndrome, visceral adiposity index (VAI), and the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio, were evaluated. RESULTS: In the study group, IR defined as GDR <4 mg/kg/min was observed in 33 (37.5%) patients. Group with IR had significantly higher postprandial glycemia (9.1 ± 2.0 vs 8.4 ± 1.1 mmol/L, P = .04), serum TG level (1.11 [0.75-1.92] vs 0.85 [0.60-1.08] mmol/L, P = .001), lower HDL-C level (1.59 ± 0.38 vs 1.8 ± 0.5 mmol/L, P = .02), higher TG/HDL-C ratio (1.60 [1.00-3.13] vs 1.05 [0.62-1.53], P = .001), and higher VAI (2.61 [1.31-4.25] vs 1.56 [0.96-2.25], P = .002). Significant relationship between GDR and TG/HDL-C ratio and VAI, adjusted for age, sex, HbA1c, and duration of diabetes was revealed (respectively, odds ratio 1.90 [95% confidence interval 1.15-3.15], P = .01 and odds ratio 1.47 [95% confidence interval 1.06-2.04], P = .01). CONCLUSIONS: TG/HDL-C ratio and VAI appear to be clinically useful tools to assess IR in adults 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.

Association between small fiber neuropathy and higher skin accumulation of advanced glycation end products in patients with type 1 diabetes.

INTRODUCTION Advanced glycation end products (AGEs) play a crucial role in the pathogenesis of diabetic peripheral neuropathy (DPN). OBJECTIVES The aim of the study was to assess the skin accumulation of AGEs in patients with long­lasting type 1 diabetes in relation to the presence of DPN. PATIENTS AND METHODS We evaluated 178 patients with type 1 diabetes (99 men; age, 43 years [interquartile range [IQR], 34-54 years]; disease duration, 25 years [IQR, 18-31 years]). DPN was diagnosed if 2 or more of the following 5 abnormalities were present: symptoms of neuropathy, lack of ankle reflexes, and impaired sensation of touch, temperature, and/or vibration. PGP 9.5­immunoreactive nerve fibers were counted to assess intraepidermal nerve fiber density (IENFD) in skin biopsy. The accumulation of AGEs in the skin was assessed on the basis of skin autofluorescence (AF).  RESULTS Patients with DPN (45%), compared with those without neuropathy, had higher skin AF (2.6 AU [IQR, 2.3-3.1 AU] vs 2.1 AU [IQR, 1.8-2.5 AU]; P <0.001) and lower IENFD (10 fibers/mm [IQR, 7-14 fibers/mm] vs 12 fibers/mm [IQR, 8-16 fibers/mm]; P = 0.005). We found a positive correlation between skin AF and patients' age (Rs = 0.44; P <0.001), diabetes duration (Rs = 0.32; P <0.001), and a negative correlation between skin AF and the estimated glomerular filtration rate (Rs = -0.26, P <0.001) and IENFD (Rs = -0.22; P = 0.004). In a multiple linear regression analysis, skin AF was independently associated with age (ß = 0.45; P <0.001), glycated hemoglobin level (ß = 0.19; P = 0.007), and IENFD (ß = - 0.14; P = 0.04) (R2 = 0.27; P <0.001). In multivariate logistic regression, the presence of DPN was independently associated with skin AF (odds ratio, 4.16; 95% confidence interval, 1.88-9.20; P <0.001). CONCLUSIONS The presence of DPN, and particularly small fiber neuropathy, is associated with a higher accumulation of AGEs in the skin of patients with type 1 diabetes.

Association between adjunctive metformin therapy in young type 1 diabetes patients with excess body fat and reduction of carotid intima-media thickness.

INTRODUCTION    Lipoprotein-associated phospholipase A2 (Lp-PLA2) and cholesteryl ester lipase (CEL) may oxidize low-density lipoproteins (oxLDL). OBJECTIVES    The aim of the study was to determine the influence of metformin on the metabolism of atherogenic lipid fractions in relation to Lp-PLA2 and CEL levels, as well as assess consequent improvement in the intima-media thickness (IMT) of the common carotid artery in young type 1 diabetes patients with excess body fat. PATIENTS AND METHODS    It was an open-label randomized clinical trial that lasted 6 months. It included a total of 84 people with metabolic decompensation (glycated hemoglobin >7.5%, >58.5 mmol/mol) of diabetes. Adjunctive metformin therapy (in addition to insulin) was administered in 42 patients, and the remaining 42 patients received insulin alone. Glycated low-density lipoproteins (LDLs), oxLDL, Lp-PLA2, and CEL were assessed by commercially available enzyme-linked immunosorbent assay kits. Cartoid IMT was measured using the Carotid Analyser for Research tool. Biochemical analyses were performed using routine laboratory techniques. RESULTS    The reduction of mean carotid IMT was observed in young type 1 diabetic adults treated additionally with metformin (0.6 ±0.1 cm vs 0.53 ±0.1 cm; P = 0.002). This effect was probably due to weight reduction (90 ±16 kg vs 87 ±15 kg, P = 0.054) and the decrease in atherogenic glycated LDL levels (1.5 ±0.5 mg/dl vs 1.6 ±1.046 mg/dl, P = 0.006). No such correlations were observed in patients treated with insulin alone. Additionally, in patients receiving metformin, glycated LDL levels were inversely correlated with Lp-PLA2 levels (r = -0.31, P <0.05). CONCLUSIONS    Additional use of metformin in young type 1 diabetic patients with excess body fat leads to a significant reduction of mean IMT in the common carotid artery. Concentrations of CEL and Lp-PLA2 were significantly increased in both study arms despite improved glucose metabolism.

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.

In diabetic Charcot neuroarthropathy impaired microvascular function is related to long lasting metabolic control and low grade inflammatory process.

AIMS: The aim of this study was to assess microvascular function associated with the occurrence of Charcot neuroarthropathy (CN) in patients with diabetes. METHODS: We evaluated 70 diabetic patients (54 men) with Charcot neuroarthropathy (CN-DM), median age 59 (IQR: 51-62), mean disease duration 16±8years. The control group were 70 subjects with diabetes and without Charcot neuroarthropathy (DM), 54 men, median age 60 (54-62), mean diabetes duration 15±7years. We assessed metabolic control of diabetes, serum C-reactive protein concentration (CRP) and cardiovascular autonomic neuropathy (CAN). We used AGE-Reader to measure skin autofluorescence (AF) associated with accumulation of advanced glycation end products that reflects long lasting metabolic control. Microvascular function was examined by laser Doppler flowmetry (PERIFLUX 5000) with thermal hyperemia (TH) and postocclusive reactive hyperemia (PORH). RESULTS: CN-DM patients as compared to DM subjects had lower HbA1c level [7.6 (6.6-8.4) vs 8.4 (7.3-9.7)%, p<0.001], lower eGFR [75.9±24.1 vs 86.6±17.8ml/min/1.73m(2), p=0.003], higher CRP serum concentration [3.8 (2.3-10.1) vs 1.9 (0.8-4.4)mg/l, p<0.001] and higher skin autofluorescence [2.8 (2.5-3.1) vs 2.6 (2.3-2.9)AU, p=0.03]. The cardiovascular autonomic neuropathy (CAN) was more frequently diagnosed in CN-DM subjects [59 vs 27%, p<0.001]. The peak flow during thermal hyperemia (THmax) was lower in CN-DM subjects as compared to DM group [156 (93-240) vs 235 (155-300)PU, p=0.001]. We found negative correlation between THmax and CRP concentration (Rs=-0.34, p=0.003), TG concentration (Rs=-0.37, p=0.002) and skin AF (Rs=-0.32, p=0.04) and positive correlation between THmax and HDL cholesterol level (Rs=0.42, p<0.001) in CN-DM patients. There was also a positive correlation between PORHpeak and HDL cholesterol level (Rs=-0.23, p=0.04). CONCLUSION: Deterioration of microvascular function and autonomic system dysfunction are present in Charcot neuroarthropathy. Impaired microvascular reactivity is associated with worse long lasting metabolic control of diabetes and low grade inflammatory process.

Association investigation of BACH2 rs3757247 and SOD2 rs4880 polymorphisms with the type 1 diabetes and diabetes long-term complications risk in the Polish population.

Genetic factors are indicated in the development of type 1 diabetes (DM1). Recently, nucleotide variants of BACH2 and SOD2 have been associated with this chronic condition. Therefore, the purpose of the present study was to investigate the contribution of BACH2 rs3757247 and SOD2 rs4880 (Ala16Val) polymorphisms to the risk of DM1 and diabetes long-term complications. Selected polymorphic variants of BACH2 and SOD2 were investigated in a group of 141 patients with DM1 and in a group of age, gender-matched healthy subjects (n=369) using a high-resolution melting curve method. There was no evidence for either allelic or genotypic association with the risk of DM1 and diabetes chronic complications for analysed polymorphisms. In addition, no interaction between BACH2 and SOD2 variants in the development of this condition was observed. However, the frequency of BACH2 rs3757247 AG and AA genotypes was statistically different between DM1 patients with retinopathy and healthy individuals (odds ratio, 2.455; 95% confidence interval, 0.999-6.035; P=0.044), but this result did not survive multiple testing corrections. The present study did not confirm the involvement of BACH2 rs3757247 and SOD2 rs4880 polymorphisms in the development of DM1 and diabetes long-term complications. Further studies in a larger population sample are required.

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.

Expression of mitochondrial superoxide dismutase in polymorphonuclear leukocytes from patients with type 1 diabetes with and without microvascular complications.

INTRODUCTION: One of the causes of impaired antioxidant response in patients with type 1 diabetes might be decreased expression of mitochondrial manganese superoxide dismutase (MnSOD). OBJECTIVES: The aim of this study was to evaluate the expression of MnSOD on transcript and protein levels in polymorphonuclear leukocytes (PMNLs) from patients with type 1 diabetes and analyze its association with microvascular complications. PATIENTS AND METHODS: The MnSOD expression was assessed in PMNLs from 46 patients with type 1 diabetes and 12 age- and sex -matched healthy subjects. The study group was divided into 2 subgroups: with and without microvascular complications. The MnSOD expression on the transcript level was evaluated by real -time quantitative polymerase chain reaction, while that on the protein level by Western blot analysis. RESULTS: A significant increase in the MnSOD transcript level was observed in all patients with diabetes with and without microvascular complications (P = 0.01, P = 0.02, respectively). The MnSOD protein level was higher in patients without microvascular complications compared with those with complications and the control group (P = 0.05, P = 0.03, respectively). The MnSOD expression was positively correlated with fasting plasma glucose and total cholesterol levels both at the transcript level (r = 0.4, P <0.05 for both correlations) and at the protein level (r = 0.3 and r = 0.4, respectively, P <0.05). CONCLUSIONS: Although an increased MnSOD transcript level in patients with type 1 diabetes suggests enhanced antioxidant mobilization in all diabetic patients, decreased levels of the MnSOD protein in PMNLs from patients with microvascular complications compared with those without complications indicates that patients with microvascular complications may have impaired antioxidant response.

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

OBJECTIVE: The diagnosis of autoimmune diabetes in non-obese adults is based on the detection of glutamic acid decarboxylase autoantibodies (GADA), islet cell antibodies (ICA) and antibodies to tyrosine phosphatase (IA-2A). Zinc transporter 8 (ZnT8) has been identified as a new autoantigen in patients with type 1 diabetes mellitus. The coincidence of autoimmune thyroiditis (AITD) with diabetes is common; therefore, screening of TSH and thyroid peroxidase antibodies (ATPO) is recommended during the diagnosis of diabetes. In this study, we determined whether the occurrence of islet autoantibodies is associated with a positive titre of ATPO in newly diagnosed adult-onset autoimmune diabetic patients. DESIGN AND METHODS: THE STUDY INVOLVED 80 NON-OBESE ADULTS AGED 44 (INTERQUARTILE RANGE (IQR): 37-51) years with a BMI of 24.0 (IQR: 22.2-26.0) kg/m(2) and new-onset diabetes. The markers of autoimmune diabetes (GADA, ICA, IA-2A and ZnT8A), TSH and thyroid peroxidase antibodies (ATPO) were evaluated. RESULTS: IN THE STUDY POPULATION, 70% (N=56) OF THE SUBJECTS WERE POSITIVE FOR AT LEAST ONE OF THE FOUR ASSESSED MARKERS OF AUTOIMMUNE DIABETES (83.9% GADA, 62.5% ICA, 42.8% IA-2A AND 33% ZNT8A) AND 37.5% OF THE SUBJECTS WERE POSITIVE FOR ATPO. THE ZNT8A-POSITIVE SUBJECTS HAD HIGHER ATPO TITRES THAN THE ZNT8A-NEGATIVE SUBJECTS (172.7 (IQR: 0.36-410.4) vs 92.4 (IQR: 0-23.7) IU/ml, P=0.001). Based on the assessed islet autoantibodies, the occurrence of positive ZnT8A and GADA was found to be related to a positive titre of ATPO using logistic regression (OR=5.48, 95% CI: 1.65-18.14, P=0.006 and OR=3.42, 95% CI: 1.09-10.71, P=0.03 respectively). CONCLUSIONS: In non-obese adults with new-onset diabetes, the presence of GADA and especially ZnT8 autoantibodies increases the risk of AITD.

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.

Metformin added to intensive insulin therapy reduces plasma levels of glycated but not oxidized low­density lipoprotein in young patients with type 1 diabetes and obesity in comparison with insulin alone: a pilot study.

INTRODUCTION: There are scarce data about the effect of metformin on lipid profile in patients with type 1 diabetes. OBJECTIVES: The present study is the first prospective clinical trial evaluating the effect of combined therapy of metformin and insulin on the pool of oxidized and glycated low­density lipoproteins (LDL) in young patients with type 1 diabetes and concomitant obesity. PATIENTS AND METHODS: A total of 33 obese patients with type 1 diabetes treated with intensive insulin therapy were randomized into a group where metformin was added. The remaining 19 patients continued to receive intensive insulin therapy (control group). In all patients, lipid profile and glycemia were assessed using routine laboratory tests. Oxidized and glycated LDL were measured using commercially available kits. Laboratory tests were performed at baseline and at a control visit after 6 months of treatment. RESULTS: A significant decrease in the levels of glycated hemoglobin, fasting plasma glucose, postprandial glucose, average glucose, triglycerides, glycated LDL, and body mass index was observed in the group receiving combined therapy. A similar decrease was not observed in the control group. The remaining lipid parameters were not changed during follow­up in any of the groups. CONCLUSIONS: Addition of metformin to intensive insulin therapy in young obese patients with type 1 diabetes results in a significant reduction of glycated LDL levels. This can be possibly explained by better glucose control, which improved insulin sensitivity of the peripheral tissues and reduced body mass in this patient group.

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.

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 (ß=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.

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.