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This was a cross-sectional study including 107 type 2 diabetic patients (67 male/40 female, mean age 66.74 ± 8.01 years, mean diabetes duration 15.05 ± 5.69 years). Metabolic risk factors: glycated hemoglobin (HbA1c), total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were determined using routine laboratory methods. Renal function was etermined using albumin/creatinine (A/C) ratio and estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI formula. Lens opacity was graded according to the Lens Opacity Classification System version III (LOCSIII). RESULTS AND CONCLUSION Patients were divided into three groups: group 1 - patients with clear crystalline lens (n=16), group 2 - patients with initial cataract (n=74), and group 3 - patients with immature cataract (n=17). Group 3 had significantly longer diabetes duration (17.12 ± 6.38 years vs. 10.81 ± 4.09 years ; p

PURPOSE. To assess the role of homocysteine in development of diabetic retinopathy in patients with type 2 diabetes and determine the parameters important in the prediction of homocysteine. METHODS. This cross-sectional study included 94 type 2 diabetic patients (39M/55F) with median age 60 years and median diabetes duration 10 years. Glycated hemoglobin (HbA1c), fasting blood glucose (fBG), fasting C-peptide, HDL and LDL cholesterol, triglycerides (TG)and uric acid (UA) were determined using routine laboratory methods. Glomerular filtration rate (GFR) was estimated using CKD-EPI formula. Homocysteine (HCY) in EDTA plasma, serum 25- hydroxy-vitamin D, vitamin B12 and folate were determined by CMIA method. Anthropometric parameters assessed waist circumference (WC) and waist-to-hip ratio (WHR). Ophthalmologic examination included fundus photography according to the EURODIAB methodology and optical coherence tomography of the macula. Patients with PDR and DME were not included in the study. RESULTS. Patients were divided into two groups: group 1 (no retinopathy ; n=69) and group 2 (NPDR ; n=25). The groups did not differ in age, gender, WC, WHR, fBG, C-peptide, HDL, LDL, TG, UA, folate and vitamin D. Group 2 had longer diabetes duration (p

PURPOSE. Aim of this study was to evaluate thickness of retinal nerve fibre layer (RNFL), ganglion cell and inner plexiform layer GCL/IPL) in patients without diabetic retinopathy and mild diabetic retinopathy, which are markers of retinal neurodegeneration, in type 2 diabetic patients using spectral domain optical coherence tomography. METHODS. This was a cross-sectional study including 50 eyes of 25 type 2 diabetic patients (15M/10F) with median age 64 year and median diabetes duration 13 years. Type 2 diabetes was defined according to the ADA classification, and hypertension according to the ESC/ESH classification. Ophthalmologic examination included binocular indirect slit lamp fundoscopy and color fundus photography of two fields (macular field, disc/nasal field) of both eyes according to the EURODIAB retinal photography methodology and optical coherence tomography (SDOCT) with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) macular thickness parameters, ganglion cell and inner plexiform layer (GCL/IPL). Patients with proliferative DR and diabetic macular edema were not included in the study. RESULTS. 50 eyes of 25 patients were divided into two groups: group 1 (no retinopathy ; n=16) and group 2 (nonproliferative DR ; n=34). There was no difference in age between groups. In group 2, there were more men compared to women than in group 1 (87.5% vs. 47.1%, p=0.016) Group 2 had longer diabetes duration (p=0.042), marginally more often hypertension (p=0.058) and significantly lower GCL (p=0.027) than group 1. No difference in RNFL was observed between groups. GCL was positively associated with RNFL (p

Purpose. Diabetic retinopathy (DR), a microvascular and visually devastating diabetic complication, is the leading cause of new blindness among working-age adults in developed countries. Its pathogenesis is insufficiently understood and presumed to possibly involve chronic, low-grade inflammation. The aim of this study was to investigate risk factors and role of systemic inflammation and obesity in development of retinopathy in type 1 and type 2 diabetes, and determine the differences in these two types of disease with possible impact on future research and treatment guidelines. Setting/Venue. Department of Ophthalmology, Department of Diabetes and Endocrinology, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia. Methods. This cross-sectional study included 84 patients with type 1 and 107 patients with type 2 diabetes. Basic and anthropometric parameters assessed were sex, age, diabetes duration, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR). C- reactive protein (CRP), fibrinogen (FIB), glycated hemoglobin (HbA1c), fasting and postprandial blood glucose (fBG, ppBG), total cholesterol, HDL and LDL cholesterol, triglycerides (TG) and serum creatinine were determined using routine laboratory methods. HbA1cmedian was obtained by statistical analysis of data from the National Diabetes Registry. Glomerular filtration rate was estimated using CKD-EPI formula. Albumin excretion rate (AER) was measured from a 24- hr urine sample. Blood pressure was measured with a mercury sphygmomanometer after a 10-min resting period. Ophthalmologic examination included indirect slit lamp fundoscopy and color fundus photography after mydriasis of two fields of both eyes according to the EURODIAB retinal photography methodology. Results. Patients were divided into three groups: group 1 (no retinopathy), group 2 (mild/moderate NPDR) and group 3 (severe NPDR/PDR). In both types of diabetes group 3 had longer diabetes duration than group 1 (type 1 p=0.002 ; type 2 p

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM.Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, GGT, uric acid, total leukocyte/neutrophil count, and urinary 8-oxo-deoxyguanosine (u-8-oxodG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications.BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-oxodG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Age-dependent increase in u-8-oxodG suggests that aging process, rather than metabolic disturbances or diabetes per se plays a pivotal role in development of oxidative DNA-damage in T2DM. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

Purpose: To investigate the influence of diabetes duration, metabolic risk factors, presence of diabetic retinopathy (DR) and nephropathy on cataract development in type 2 diabetes. Methods: 107 type 2 diabetic patients consecutively attending Vuk Vrhovac University Clinic in Zagreb were included in this cross-sectional study. Complete diabetologic, nephrologic and ophthalmologic examination was done. According to the LOCSIII standard patients were divided into three groups: group 1 - patients with clear crystalline lens (n=16), group 2 - patients with initial cataract (NO1-NO2, NC1-NC2, C1-C2, P1-P2 ; n=74), and group 3 - patients with immature cataract (NO3-NO4, NC3-NC4, C3-C4, P3-P4 ; n=17). Results: The three groups did not differ in age, gender, diabetes treatment and lipids. Group 3 had significantly longer diabetes duration, marginally higher hemoglobin A1c, significantly more severe DR and significantly lower creatinine clearance than group 1. Positive correlation was observed between cataract and diastolic blood pressure, DR and albumin/creatinine ratio. Regression analysis showed that diabetes duration, systolic and diastolic blood pressure, and DR were the main predictors of cataract development in type 2 diabetic patients. Conclusions: This study showed that diabetes duration, poor glycemic control, blood pressure, retinopathy and nephropathy play an important role in cataract development in type 2 diabetes. These findings point to the need for even more reducing risk factors as a means of preventing not only retinopathy but also cataract in order to improve the quality of life of diabetics and reduce the economic burden due to disability and surgery related to cataract.

Background and aims. Diabetic retinopathy (DR) is an important cause of visual impairment in developed countries, especially in working age adults. The aim of this study was to evaluate the 15-year incidence of development and progression of retinopathy in a sample of type 1 diabetic patients and determine the associated risk factors in these patients. Materials and methods. 123 type 1 diabetic patients (62 male / 61 female) were enrolled in this study and followed for 15 years. Basic and anthropometric parameters assessed were age, gender, diabetes duration and body mass index (BMI). Glycated hemoglobin (HbA1c), total cholesterol, HDL and LDL cholesterol, triglycerides (TG), C-reactive protein (CRP), homocysteine (HCY), fibrinogen (FIB), plasma viscosity and serum creatinine were determined using routine laboratory methods. Urinary albumin excretion rate (UAE) was measured from a 24-hr urine sample. Blood pressure was measured with a mercury sphygmomanometer after a 10-min resting period. Ophthalmologic examination included binocular indirect slit lamp fundoscopy, color fundus photography after mydriasis according to the EURODIAB retinal photography methodology and optical coherence tomography of the macula. Possible risk factors for the development and progression of DR were examined in backward stepwise Cox's multiple regression analysis. Results: At the beginning of the study patients were 24.60 ± 4.45 years old with mean diabetes duration of 9.64 ± 4.42 years. Mean/median values of BMI (23 ± 2.43 kg/m2), total cholesterol (4.92 ± 1.11 mmol/L), HDL cholesterol (1.57 ± 0.36 mmol/L), LDL cholesterol (2.73 ± 0.77 mmol/L), TG (0.82 ± 0.43 mmol/L), CRP (0.8 (0.1 - 5.1) mg/L), HCY (10.5 (7.5 -14.2) µmol/L), FIB (2.9 (1.9 - 4.1) mg/L), plasma viscosity (1.55 ± 0.10 mPa.s), serum creatinine (81.59 ± 15.05 µmol/L), systolic (113 (95 - 130) mmHg) and diastolic blood pressure (75 (60 - 85) mmHg) were within normal range for diabetic patients, whereas HbA1c (7.72 ± 1.48 %) and UAE (10.05 (3.18 - 8036.07) mg/24h) were elevated. At baseline, 87 (71%) patients had no retinopathy and 36 (29%) had nonproliferative diabetic retinopathy (NPDR). After 15 years, 54 patients (43.9% ; 29.3/1000 person-years) developed NPDR or progressed to proliferative diabetic retinopathy (PDR). None of the patients had diabetic macular edema (DME) at baseline, nor has it developed after 15 years. From the 87 patients with no retinopathy at baseline 24 (27.6% ; 18.4/1000 person-years) developed NPDR, while from the 36 patients with NPDR at baseline 30 (83.3% ; 55.5/1000 person-years) progressed to PDR. Higher HbA1c (HR=2.276, P=0.006), lower HDL cholesterol (HR=0.161, P=0.025) and higher UAE (HR=0.388, p=0.045) were significant risk factors for development and progression of retinopathy, whereas the presence of DR at baseline (HR=2.319, p=0.023) was significant factor for its progression to PDR. Diabetes duration, BMI, inflammatory and hemostatic disturbance markers showed no significant values in the statistical analysis. Conclusions: The results of this study suggest that 15-year incidence of development and especially progression of retinopathy in type 1 diabetic patients is still very high. This points to the need for close monitoring of type 1 diabetic patients aimed at early detection, prevention or limitation the progression of retinopathy, especially those with higher HbA1c, lower HDL cholesterol, higher UAE and the initial presence of DR.

We investigated parameters related to cerebrovascular insult (CVI) in relation to previous patient or family history. Lipids, including apolipoprotein (Apo) A1, Apo B and lipoprotein (a) [Lp(a)], parameters of glycaemia, inflammation, and blood pressure (BP) were assessed in 260 patients assigned into groups according to history of CVI, and the presence of glucose intolerance (GI), type 1 (DM1) and type 2 (DM2) diabetes. A control group (CG) was assigned. In all statistical tests (T-test, Mann Whitney test, ANOVA, correlation, logistic regression) α=0.05 was considered statistically significant. Significantly higher values of fasting (FCP) and postprandial C-peptide (PPCP) were observed in siblings whose parents had a history of CVI. Patients with CVI had significantly higher values of homocysteine (HCY) and low-density lipoprotein (LDL), lower albumin/creatinine (A/K) ratio and glomerular filtration rate (GFR). ANOVA revealed significant differences in UA, HCY, and GFR among the groups according to the presence of GI or DM. HCY and UA were significantly higher in patients with DM2 and GI compared to DM1. GFR was lower in DM2 compared to DM1. Patients with DM2 and CVI had significantly higher values of HCY, and decreased A/K ratio and GFR. Women had significantly higher values of PPCP, fibrinogen, high-density lipoprotein and ApoA1 compared to men, whereas fasting blood glucose (FBG), PPBG and uric acid (UA) were higher in men. After logistic regression, stepwise procedure for CVI as a dependent variable, the best model included GFR (OR=0.949 ; 95% CI: 0.925-0.972). In patients with history of CVI GFR correlated significantly with FBG (r=0.87) and Lp(a) (r=0.93) ; UA correlated with LDL (r=0.83). Patients, particularly with DM2, with increased HCY, and decreased renal function could be at increased risk for CVI. CP values were increased in siblings whose parents had a history of CVI. Due to the correlation with GFR, Lp(a) could be connected with CVI.

Background: Adiponectin, a protein synthesized in adipocytes, has been identified as an important regulator of metabolic homeostasis. Hypoadiponectinemia is associated with an increased risk for the development of metabolic syndrome, atherosclerosis, cardiovascular disease and type 2 diabetes, as well as diabetic complications. An ongoing search for interventions able to modulate adiponectin levels is expected to eventually improve patient outcomes. Recently proposed use of adiponectin as a routine clinical biomarker in identifying high-risk patients as potential candidates for such interventions, emphasized the need for an automated methodology suitable for use in clinical laboratory. The aim of this study was to validate Adiponectin Immunoturbidimetric assay (A- ITA ; Randox Laboratories Ltd, UK) in patients with type 1 (T1DM) and type 2 diabetes (T2DM) without complications in comparison to obese subjects with normoglycaemia (ONG). Methods: A-ITA was applied to an automated analyzer (AU680 Chemistry System, Beckman Coulter USA) and performance verified according to CLSI- EP15-A2 Aproved Guideline. High sensitivity human adiponectin sandwich ELISA (A-ELISA ; Biovendor, Czech Republic) was used as a laboratory comparator method. We tested fasting samples from ONG subjects and diabetic patients without clinical and laboratory signs of diabetic complications, attending their annual outpatient check-up. Results: Within-and total- run CVs for A-ITA ranged from 1, 4-1, 8% and 1, 6-2, 2%, respectively. Serum adiponectin levels were significantly lower with A-ITA than A- ELISA procedure (8, 36±5, 24 vs. 10, 66±5, 57 mg/L, respectively ; P

Purpose. The aim of this study was to investigate the relationship between inflammation markers, other markers of endothelial dysfunction and anthropometric parameters and their association with DR in patients with type 2 diabetes. Methods. This was a cross-sectional study including 107 patients with type 2 diabetes. Markers of inflammation: C-reactive protein (CRP) and fibrinogen plus other markers of endothelial dysfunction: glycated hemoglobin (HbA1c ; HbA1cmedian), total cholesterol, HDL, LDL and triglycerides were determined using routine laboratory methods. HbA1c was evaluated at the beginning of the study and HbA1cmedian was obtained by statistical analysis of data from the National Registry for Diabetes. Anthropometric parameters assessed were body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and conicity index (C index). Ophthalmologic examination included BCVA, Goldmann tonometry, binocular indirect slit lamp fundoscopy and color fundus photography after mydriasis of two fields (macular field, disc/nasal field) of both eyes according to the EURODIAB retinal photography methodology. Results. According to the EURODIAB standards patients were divided into three groups: group 1 (no retinopathy ; n=65), group 2 (mild/moderate NPDR ; n=19) and group 3 (severe NPDR/PDR ; n=23). The groups did not differ in the levels of inflammation markers, other markers of endothelial dysfunction and anthropometric parameters. C-reactive protein was positively correlated with fibrinogen (p=0.022), HbA1c (p=0.050), LDL (p=0.043), BMI (p=0.038), WC (p=0.000), WHR (p=0.038) and C index (p=0.008). HbA1c was positively correlated with total cholesterol (p=0.022), LDL (p=0.010), BMI (p=0.009) and WC (p=0.047). Logistic regression analyses showed that diabetes duration (OR=1.17, 95%CI 1.08-1.27) and prolonged poor glycemic control (HbA1cmedian) (OR=1.76, 95%CI 1.08-2.86) were the main predictors of DR in patients with type 2 diabetes. Conclusions. This study showed that the association between visceral obesity, inflammation and other risk factors plays an important role in endothelial impairment involved in the pathogenesis of diabetic retinopathy.

This study showed that diabetes duration, poor glycemic control, blood pressure, retinopathy and nephropathy play an important role in the cataract development in type 2 diabetes. These findings point to the need for even more reducing risk factors as a means of preventing not only retinopathy but also cataract in order to improve the quality of life of diabetics and reduce the economic burden due to disability and surgery related to cataract.

BACKGROUND: Recent evidence suggest that CKD- EPI-equation might be the most accurate tool for estimating glomerular filtration rate (eGFR) in routine evaluation and staging of chronic kidney disease (CKD) in diabetic patients. Analytical performance and specificity of serum creatinine assay are critical determinants of eGFR accuracy. The aim of this study was to evaluate possible influence of creatinine methodology on the performance of CKD-EPI-calculated eGFR for CKD evaluation and staging in diabetic patients.. METHODS: Serum creatinine was measured by both IDMS-traceable compensated Jaffe and enzymatic procedure with intra-assay imprecision (CV) of 1, 43% and 1, 39%, respectively. Assay-specific GFR was estimated by the 4-variable CKD-EPI equation using respective creatinine values, and their agreement regarding clinical CKD staging evaluated by kappa-analysis. RESULTS: A total of 391 diabetic patients [M/F: 181/210 ; age range 18-88 (median 64 years), plasma glucose range 2, 3-26, 3 (median 9, 2 mmol/L), all Caucasians] were included in this study. Passing-Bablok regression analysis revealed a small, but significant constant difference between the assays (y=2, 6667+0, 9744x) across a wide range of creatinine values (35-522 μmol/L). CKD-EPI-eGFR values, ranging from 9- 136 ml/min/1, 73m2, showed an insignificant difference depending on creatinine assay used for eGFR calculation (y=1, 000+1, 000x). Linear regression analysis identified plasma glucose as significant determinant of bias between eGFR values calculated using compensated Jaffe and enzymatic creatinine values in all patients (P8, 0% (63, 9 mmol/mol), N=115, P

Non-diabetic patients with repeated hypoglycaemia

In this paper the relationship between diabetic cataract, epidemiology, pathogenesis and treatment as well as its impact on diabetic retinopathy and macular edema are described.

Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE) acts as decoy for AGEs. The AGE-to-esRAGE ratio was hypothesized to be implicated in diabetic vasculopathy. We investigated an association of esRAGE and methylglyoxal-adducts serum level, as well as AGE- to-esRAGE ratio in subpopulation of diabetic patients with or without concomitant hyperlipemia and macrovascular disease in history. In diabetes with concomitant hyperlipemia esRAGE was significantly decreased compared to hyperlipemia with normal glucose metabolism (0.306±0.2 vs. 0.367±0.1 ; p=0.019) or diabetes alone (0.306±0.2 vs. 0.404±0.1 ; p=0.004). High AGE/esRAGE ratio, found in diabetic patients with hyperlipemia, pointed to increased production of AGEs and low expression of esRAGE. In multivariable analysis adjusted for several confounding factors, increased AGE/esRAGE ratio was recognized as a high risk for vascular disease outcomes.

After 48 months of following, UAE, male sex, systolic blood pressure and resting heart rate were risk factors for development or progression of diabetic retinopathy in our normoalbuminuric T1DM. Resting heart rate is an independent predictor of all-cause death and major cardiovascular complications in subjects with and without diabetes. Higher heart rate might promote higher UAE, indicating endothelial dysfunction, which are important factors in the development of retinopathy and nephropathy. Results from EURODIAB study found that diastolic blood pressure is significant risk factor for retinopathy in T1DM even after adjusting for albuminuria while the prospective UKPDS study also found higher relative risk for incidence of retinopathy with higher systolic blood pressure. The data relating gender and risk of microvascular complications in type 1 diabetes are inconsistent. Previous studies suggest that the relative imbalance between testosterone and estradiol plays an important role in the onset of microvascular diseases, rather than the absolute levels of hormones. In multiple regression analyses UAE was strongest variable that predict progression to incipient or progression to proliferative retinopathy confirming previous observations that retinal microvascular abnormalities are associated with renal dysfunction independently of age, diabetes, hypertension and other risk factors. Our results suggest that retinopathy is present and may progress in T1DM even when coexisting renal disease is excluded. This points to the need for close monitoring of normoalbuminuric T1DM aimed at early detecting, preventing or limiting the progression of retinopathy, especially in men with higher UAE, systolic blood pressure and higher resting heart rate.

Increased fibrinogen, white blood cell count, triglycerides, ALT, postprandial blood glucose and HbA1c, and decreased adiponectin, HDL cholesterol and eGDR pointed to increased inflammatory and procoagulant state in the presence of albuminuria and NAFLD. Decreased eGDR reflected increased insulin resistance even in normoalbuminuric patients with NAFLD. Reported correlations among the tested variables unravelled the association between inflammation, procoagulant state and glycaemia as a culprit of vascular complications in the studied patients.

Cardiovascular risk (CVR)

U radu je analiziran utjecaj upalnih čimbenika i endotelne disfunkcije u rwzvoju dijabetičke retinopatije.

Methods: Adiponectin (ApN), C-reactive protein (CRP), fibrinogen (FIB), homocysteine, interleukin-6, cystatin C (Cys C), sialic acid (SA), creatinine clearance, albumin excretion rate (AER), C-peptide, waist circumference (WC), waist/hip ratio (WHR), fasting plasma glucose (fPG), glycated haemoglobin (HbA1c), liver tests, lipids, ferritin, uric acid (UA) and leucocytes (WBC) were determined in 288 DM2 patients divided according to AER (300) and fatty liver index (FLI) (≤60 ; >60). FLI was calculated using BMI, WC, triglycerides (Tg) and gamma-glutamyl transpeptidase (GGT) to estimate the presence of FL. Insulin resistance was calculated using estimated glucose disposal rate (eGDR). Statistically significant differences between the variables according to FLI were determined using Student's t test and Mann Whitney test. Levels of statistical significance were at p60. If FLI was increased, ApN decreased significantly regardless of the AER category. ApN correlated significantly with HDL (r=0.47), FLI (r=-0.35), ALT (r=-0.47), ferritin (r=-0.36), C-peptide (r=-0.35) and eGDR (r=0.34). FLI correlated significantly with ApN (r=-0.35), CRP (r=0.35), ALT (r=0.43), ferritin (r=0.39), and eGDR (r=-0.45). AER correlated significantly with Cys C (r=0.33). Conclusion: This study pointed to the connection between ApN, eGDR, HDL and FLI, but Cys C emerged as a factor important in the prediction of nephropathy. FLI could be considered to be more important than AER in the determination of ApN level.

The pathogenesis of diabetic retinopathy (DR) is insufficiently understood and presumed to possibly involve inflammation and endothelial dysfunction. The aim of the study was to investigate the relationship between inflammation markers, other markers of endothelial dysfunction and anthropometric parameters and their association with DR in patients with type 2 diabetes, divided into three groups: no retinopathy (n=65), mild/moderate nonproliferative (NPDR ; n=19) and severe NPDR/proliferative retinopathy (PDR ; n=23). The groups did not differ in the levels of inflammation markers, other markers of endothelial dysfunction and anthropometric parameters. C-reactive protein was correlated with fibrinogen, HbA1c, LDL-cholesterol, BMI, WC, WHR and C index. HbA1c was correlated with cholesterol, LDL-cholesterol, BMI and WC. Logistic regression analysis showed that diabetes duration and HbA1cmedian were the main predictors of retinopathy. The study demonstrated that the association between obesity, inflammation and other risk factors plays an important role in endothelial impairment involved in the pathogenesis of DR.

Background and aim: Recently proposed use of HbA1c for the diagnosis of type 2 diabetes had been challenged for poor diagnostic accuracy in comparison to the conventional plasma glucose- based diagnostic tests. While it is obvious that different diagnostic criteria may identify different patient populations, the opportunity to detect undiagnosed diabetes and pre-diabetes with a specific measure of glycaemia, unaffected by high biological variability and preanalytical interferences, remains the major assumed benefit for the use of HbA1c as a diagnostic tool. The aim of this study was to evaluate diagnostic accuracy of HbA1c in subjects at high hisk of developing type 2 diabetes. Methods: Blood samples were taken from the subjects with a previous history of hyperglycaemia, reffered to our clinic for diagnosis of type 2 diabetes. After blood sampling for fasting plasma glucose (FPG) and HbA1c, a 75 g oGTT was performed, followed by a second blood sampling for plasma glucose at 2h (2hPG). Glucose was measured by enzymatic (hexokinase, Olympus AU400, Beckman Coulter, USA), and HbA1c by immunoturbidimetric procedure (TinaQuant HbA1c, Cobas Integra Plus, Roche Diagnostics, USA), respectively. WHO criteria were used to classify patients into diagnostic categories of glycaemia with FPG and 2hPG values. WHO- and ADA-recommended HbA1c values ≥6, 5% (48 mmol/mol), and 5.7-6.4% (39- 47 mmol/mol) were used as diagnostic for diabetes and pre-diabetes, respectively. Results: A total of 317 subjects (M/F: 139/178 ; age range 21-85 years) were included in this study. Multiple regression analysis identified FPG, 2hPG, and age as significant determinants of HbA1c values (P

Objective. Increased albumine/creatinine (A/C) ratio is a marker of endothelial dysfunction in patients with diabetes mellitus. The aim of the study was to determine the correlation of A/C ratio with parameters of metabolic syndrome (MS). Design. Observational, cross-sectional study. Patients. Three hundred and nineteen patients with type 2 diabetes mellitus (DM2), glucose intolerance (GI) and control group (CG) underwent the study. Methods. Clinical and laboratory parameters important for the definition of diabetes and metabolic syndrome: C-reactive protein (CRP), adiponectin (ApN), fibrinogen, homocystein, A/C ration, liver function tests, lipid values, uric acid (UA), glycated haemoglobin (HbA1c), fasting (fPG) and postprandial plasma glucose (ppPG), blood pressure, body mass index (BMI) and waist circumference (WC) have been determined. GI was diagnosed based on oral glucose tolerance test (OGTT). Insulin resistance (IR) was assessed using homeostatic model assessment (HOMA2) from fasting insulin (FI) and fPG. Fatty liver index (FLI) was calculated using BMI, WC, triglycerides (Tg) and gamma-glutamyl transpeptidase (GGT) to estimate the presence of fatty liver. Patients were divided according to the A/C ratio (≤2.5 and >2.5) and the FLI (60 and >60). Results. ANOVA revealed significant difference in A/C ratio between the three groups of patients ( DM2, GI and CG) (p=0.002). Significant difference was found in A/C between DM2 and GI (4.47  15.57 vs. 2.84  12.44) (p=0.002) and DM2 and CG (4.47  15.57 vs. 2.55  7.1) (p=0.032), but not between GI and CG. In patients with DM2 significant difference was found in IR (p=0.001), FLI (p=0.012), HbA1c (p=0.012) and GGT (p=0.034) between groups of patients according to A/C, and in ApN (p2.5mg/mmol. Conclusions. Patients with DM2 and A/C ratio >2.5 mg/mmol have significantly higher values of IR, FLI, HbA1c and GGT. FLI alongside glycaemia regulation and MS parameters has an influence on A/C ratio level in patients with DM2.

Background and aims. Diabetic retinopathy (DR), a microvascular and visually devastating diabetic complication, is the leading cause of new blindness among working-age adults in developed countries. Its pathogenesis is insufficiently understood and presumed to possibly involve chronic, low-grade inflammation. The aim of this study was to investigate the relationship between inflammation markers, other markers of endothelial dysfunction and anthropometric parameters and their association with DR in patients with type 2 diabetes. Materials and methods. This was a cross-sectional study including 107 patients with type 2 diabetes (67 male / 40 female, mean age 66.74 ± 8.01 years, mean diabetes duration 15.05 ± 5.69 years). Markers of inflammation: C-reactive protein (CRP) and fibrinogen as well as other markers of endothelial dysfunction: glycated hemoglobin value (HbA1c ; HbA1c median), total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were determined using routine laboratory methods. HbA1c was evaluated at the beginning of the study from a single venous blood sample, and HbA1c median was obtained by statistical analysis of data from the National Registry for Diabetes (CroDiabNet). Anthropometric parameters assessed were body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and conicity index (C index). Ophthalmologic examination included best corrected visual acuity (BCVA), Goldmann applanation tonometry, slit lamp biomicroscopy of the anterior eye segment, binocular indirect slit lamp fundoscopy and color fundus photography after mydriasis of two fields (macular field, disc/nasal field) of both eyes according to the EURODIAB retinal photography methodology. Results. According to the EURODIAB standards patients were divided into three groups: group 1 (no retinopathy ; n=65), group 2 (mild / moderate nonproliferative diabetic retinopathy ; n=19) and group 3 (severe NPDR / proliferative diabetic retinopathy ; n=23). The groups did not differ in the levels of inflammation markers, other markers of endothelial dysfunction and anthropometric parameters. C-reactive protein was positively correlated with fibrinogen (p=0.022), HbA1c (p=0.050), LDL cholesterol (p=0.043), BMI (p=0.038), WC (p=0.000), WHR (p=0.038) and C index (p=0.008). HbA1c was positively correlated with cholesterol (p=0.022), LDL cholesterol (p=0.010), BMI (p=0.009) and WC (p=0.047). Logistic regression analyses showed that diabetes duration (OR=1.17, 95%CI 1.08-1.27) and prolonged poor glycemic control (HbA1c median) (OR=1.76, 95%CI 1.08-2.86) were the main predictors of DR in patients with type 2 diabetes. Conclusions. This study showed that the association between visceral obesity, inflammation and other risk factors plays an important role in endothelial impairment involved in the pathogenesis of diabetic retinopathy. These findings point to the need for testing the effects of treatment aimed at reducing visceral obesity, decreasing inflammatory activity and improving endothelial function as a means of preventing or limiting the progression of retinopathy.

Depression and anxiety are co-morbid condition in diabetes as disease-related psychological reactions on this chronic metabolic illness. This study was aimed to determine the occurrence of depression and anxiety in seafarer’s type 2 diabetic patients. A random sample of 52 diabetic seafarers treated with diet and oral glucose lowering agents, and 56 healthy seafarers were screened for depression with The Beck Depression Inventory (BDI) and for anxiety with State-Trait Anxiety Inventory (STAI 1, STAI 2). Depression (BDI > 18, 5) and anxiety (STAI < 28, 5) was significantly higher in the group of diabetic seafarers than in control group (more than 30%). Significant correlation was noted between depression and duration of diabetes mellitus, degree of obesity and poor glycaemic control (HbA1C>8%) and longer duration of shipping routes (over 6 months). The proportion of depression and anxiety was found higher in seafarer’s type 2 diabetic patients than in the healthy seafarers.

Objective Endogenous secretory receptor for advanced glycation endproducts (esRAGE) an isoform of soluble RAGE, acts as decoy for AGEs. We hypothesized ratio of AGE-to-esRAGE could be link to atherosclerosis in diabetes. To examine this issue, we compared serum levels of esRAGE and methylglyoxal-adduct as well as the AGE-to-esRAGE ratio between type 2 diabetic patients with and without established macrovascular disease. Patients and Methods Methylglyoxal-adducts, AGEs and esRAGE were measured in type 2 diabetes (n=130) and healthy controls (n=30). A history of macrovascular events (cardiovascular disease, cerebral vasculopathy or peripheral vascular disease) was recorded in 50 subjects. Results esRAGE levels were lower in type 2 diabetic patients compared with control subjects (0.330±0.197 vs. 0.458±0.074 ng/ml, p=0.003). In diabetic population es RAGE correlated positively with MG-adducts, HbA1c, BMI, and triglyceride, and inversely with CRP, LDL and homocystein. Multiple stepwise regression analysis was performed to determine which parameters best predicted the esRAGE level. Finally, urinary MG-adduct excretion (p

The pathogenesis of diabetic retinopathy (DR) is insufficiently understood and presumed to possibly involve inflammation and endothelial dysfunction. The aim of the study was to investigate the relationship between inflammation markers, other markers of endothelial dysfunction and anthropometric parameters and their association with DR in patients with type 2 diabetes, divided into three groups: no retinopathy (N = 65), mild/moderate nonproliferative diabetic retinopathy (NPDR; N = 19) and severe NPDR/proliferative diabetic retinopathy (PDR; N = 23). The groups did not differ in the levels of inflammation markers, other markers of endothelial dysfunction and anthropometric parameters. C-reactive protein was correlated with fibrinogen, HbA1c, LDL-cholesterol, BMI, WC, WHR and C index. HbA1c was correlated with cholesterol, LDL-cholesterol, BMI and WC. Logistic regression analysis showed that diabetes duration and HbAlc median were the main predictors of retinopathy. The study demonstrated that the association between obesity, inflammation and other risk factors plays an important role in endothelial impairment involved in the pathogenesis of DR.

Background Endogenous secretory receptor (esRAGE) for advanced glycation end-product (AGE), a soluble receptor isoform, acts as decoy for AGEs. We hypothesized that AGE-to-esRAGE ratio could be a link to atherosclerosis in diabetes. To examine this issue, we compared serum levels of esRAGE and methylglyoxal-adduct as well as the AGE-to-esRAGE ratio between type 2 diabetic patients with and without concomitant hyperlipaemia. Methods Methylglyoxal-adducts, total AGEs and esRAGE were measured in diabetes without hyperlipaemia (n=32), diabetes with hyperlipaemia (n=98) and hyperlipaemia with normal glucose metabolism (n=38). A history of macrovascular events was recorded in 72 subjects. Results esRAGE level was lower in type 2 diabetic patients compared with the control subjects (0.330±0.197 vs. 0.458±0.074 ng/ml, p=0.003). In diabetes with concomitant hyperlipaemia esRAGE was significantly decreased in comparison with hyperlipaemia (0.306±0.2 vs. 0.367±0.1 ; p=0.019) or diabetes alone (0.306±0.2 vs. 0.404±0.1 ; p=0.004). The calculated AGE-to- esRAGE ratio pointed to increased production of AGEs and low expression of esRAGE. Significantly higher AGE/esRAGE values were found in the subpopulation of diabetic patients with hyperlipaemia (p

Adiponectin (ApN) is considered to be responsible for reduction of inflammation and is known to be included in lipid metabolism. This study was designed to assess the role of adiponectin in patients with type 1 and type 2 diabetes and to determine parameters important in the prediction of adiponectin. Adiponectin, high sensitive C-reactive protein, fibrinogen, homocysteine, C-peptide, and lipid panel in addition to clinical and laboratory parameters important for the definition of diabetes, obesity and the metabolic syndrome were measured in 118 patients included in the study. The best model (R2=0.989) for predicting adiponectin in type 1 diabetes included fibrinogen, white blood cell count, uric acid and triglycerides. In type 2 diabetes the best model (R2=0.751) included C-peptide, white blood cell count, systolic blood pressure, fasting blood glucose, glycated hemoglobin and high-density lipoprotein cholesterol. ANOVA showed statistically significant among-group differences in adiponectin (p=0.028), body mass index (p

Cilj studije bio je utvrditi ulogu adiponektina u šećernoj bolesti i njegovu povezanost s biljezima metaboličkog sindroma (pretilošću, dislipidemijom i upalom). Relevantni klinički i laboratorijski čimbenici određeni su u osamdeset bolesnika sa tipom 1 šećerne bolesti (D1), tipom 2 šećerne bolesti (D2) i kontrolnoj skupini (D0). Statistički značajna razlika u vrijednostima adiponektina ApN utvrđena je između D1(ApN=12, 22&plusmn ; 6, 68), D2 (ApN=6, 86&plusmn ; 5, 42) i D0 (ApN=7, 85&plusmn ; 6, 47) (ANOVA) (p=0, 018). Statistički značajna razlika (ANOVA) utvrđena je i za vrijednosti glikemije na tašte (GUP b)(p30(C)] (p=0, 003 i 0.001). Statistički značajna povezanost (p

Šećerna bolest je obilježena nedostatnim stvaranjem inzulina i/ili nedostatnom utilizacijom glukoze u tkivima. Posljedica je hiperglikemija koja u konačnici vodi ka kroničnim komplikacijama šećerne bolesti. Značajnom za razvoj komplikacija smatra se postprandijalna hiperglikemija koja dovodi do oksidativnog stresa i upalnog stanja, što uzrokuje endotelnu disfunkciju. Za supstancije u ispitivanju: superoksid dismutazu, katalazu, L-propionil karnitin, lipoičnu kiselinu, LY 333351, PJ34, FP15 smatra se da će biti djelotvorni u oksidativnom stresu te tako u ranoj fazi prevencije endotelnog oštećenja. Za razliku od ovih lijekova koji se još istražuju i na čiju kliničku primjenu još treba pričekati, za tiazolidindione, statine i inhibitore renin-angiotenzinskog sustava je dokazano da posjeduju intracelularni antioksidativni potencijal uz njihove već etablirane indikacije. Time su otvorene široke mogućnosti da pravovremenim djelovanjem, usmjerenim na hiperglikemijska stanja te na posljedično nastali oksidativni stres, upalu i poremećeni sustav koagulacije, djelujemo na prevenciju endotelnog oštećenja prevenirajući tako i kasne komplikacije šećerne bolesti.

Aims: The study investigated the role of statin and ACE-inhibitor therapy in the development of atherosclerosis via their effect on C-reactive protein (CRP) and homocysteine (HCY). Methods: A total of 243 type 2 diabetics were studied during a 1-yr. follow-up period. Patients were randomized to receive either atorvastatin (n=59), simvastatin (n=64), pravastatin (n=38), or trandolapril (n=43). The control group included 39 patients. The patients were assigned to groups based on AER /mg/24h/ (300), pulse pressure (PP) (65) and body mass index (BMI) (30). Results: ANOVA revealed significant differences in initial CRP and atherogenic index of plasma (AIP) (p=0.01 and p=0.041, respectively) according to AER and BMI (both p

The aim was to investigate the role of adiponectin (ADN) in diabetes and its connection with obesity, dislipidemia and inflammation. Relevant clinical and laboratory parameters of diabetes, obesity and inflammation have been measured in eighty patients with type 1 diabetes (D1), type 2 diabetes (D2) and a control group (D0). A significant difference (p=0.045) in ADN was found between male (6.35± 3.43) and female patients (9.99± 7.89) (Mann-Whitney U test), as well as between D1 (ADN=12.22± 6.68), D2 (ADN=6.86± 5.42) and D0 (ADN=7.85± 6.47) (ANOVA: F=4.22, df=2, p=0.018). The Turkey post hoc test pointed to a significant difference in ADN between D1 and D2 (p=0.013). ANOVA revealed a significant difference in fasting blood glucose (FBG) [H(2, N=80)=32.2, p30(C)] (F=6.36, df=2, p=0.003). The Turkey post hoc test indicated a significant difference in ADN between A (ADN=12.44± 11.21) and B (ADN=5.55± 2.20) (p=0.004), and between A and C (ADN=5.84± 1.64) (p=0.007). ANOVA revealed a significant difference in CRP between groups in relation to BMI [H(2, N=46)=13.8, p=0.001] (A-1.72± 1.17, B-2.83± 3.83, C-4.31± 1.96). ADN correlated statistically significantly (p

Aims: Elevated homocysteine (HCY) level might increase the risk of diabetic nephropathy, particularly in hypertensive patients with albuminuria. The aim of the study was to investigate the association between homocysteine level, hypertension and albuminuria, as well as therapeutic possibilities associated with the above parameters in the prevention of nephropathy. Methods: A total of 266 type 2 diabetic patients (54.4 &plusmn ; 10.8 years old ; diabetes duration 12.1 &plusmn ; 7.4 years) were studied during a one-year follow-up. Patients were randomized to receive either atorvastatin (n = 59), pravastatin (n = 41), simvastatin (n = 48), folic acid (n = 44) or lisinopril (n = 35). The control group included 39 patients. HCY, atherogenic index of plasma (AIP), pulse pressure (PP) and albumin excretion rate (AER) were determined. The patients were assigned to groups based on AER (300 mg/24 h) and PP (< 45, 45– 50, 50– 65, > 65). Among-group differences were tested by one-way ANOVA and differences between the beginning and the end of the study using Wilcoxon signed ranks test. Results: ANOVA revealed significant differences in initial HCY and AIP (P = 0.001 and P = 0.041, respectively) according to AER, and in HCY and AIP (both P < 0.001) according to PP. PP and AER were significantly reduced in the lisinopril-treated group (P < 0.001) (Wilcoxon test). Both AIP and PP were significantly reduced in simvastatin- (P < 0.001 and P = 0.002, respectively) and atorvastatin– (P < 0.001 and P = 0.009, respectively) treated groups. HCY was significantly reduced in simvastatin– , pravastatin– and folic acid-treated groups (P = 0.012, P = 0.005 and P = 0.001, respectively), primarily in the group of patients with normoalbuminuria (P < 0.05). The reduction in HCY was most pronounced in the folic acid-treated group (P < 0.01). Conclusion: In addition to an effect of lisinopril on AER and PP, folic acid, reducing HCY, and statins, reducing HCY, AIP and PP, might be a support in the prevention of diabetic nephropathy.

Background and Aims: Changes in the vascular compartment in diabetic nephropathy result in the elevation of Doppler sonographic renal resistance index (RI). The aim of this study was to investigate the influence of blood pressure (BP) compared to other factors on RI changes. Materials and Methods: Fifty-four type 2 diabetic patients with arterial hypertension (25 male and 29 female ; age-range: 49 5.84 years ; diabetes duration: 12 5.44 years) were studied. Twenty-nine patients were treated with ACE-inhibitor (group A) and 25 with ACE-inhibitor/Ca2+ antagonist combination (group B). Patients were followed during a 2-year period. RI was determined at the beginning and at the end of the study. At the beginning of the study, stepwise regression method was used to analyze the influence of predictor variables: patient’ s age, diabetes duration, systolic (SBP) and diastolic blood pressure, albumin excretion rate (AER), Tamm-Horsfall protein excretion rate (THPER), lipid values, glycated hemoglobin, serum creatinine and creatinine clearance on the elevation of the resistance index. Results: Stepwise regression method showed that SBP, disease duration and AER together explained nearly 54% of RI variance. SBP explained almost 22%, disease duration nearly 24% and AER nearly 7.5% of RI variance. At the end of the study a significant reduction in BP was found (p=0.0001), but it was not accompanied by RI reduction. Significant RI elevation was found in group A (p=0.006) and in the group of patients with diabetes duration ≥ 10 years (p=0.001). Group A consisted of significantly more (19 of 27) patients with diabetes duration ≥ 10 years compared to the group B (10 of 22). Significant differences in predictive variables between group A and group B were not found. Significant difference was found between the groups of patients with diabetes duration

The aim of the study was to compare the effect of two different therapeutic approaches on lipid metabolism and glycaemic regulation in type 2 diabetic patients at similar blood pressure reduction. Sixty-four type 2 diabetic patients with newly diagnosed arterial hypertension (36 male and 28 female ; age-range: 56± ; ; ; 8.45 yrs ; diabetes duration: 12± ; ; ; 4.85 yrs) were studied. Thirty patients were treated with lisinopril (group A) and 34 with a lisinopril/nifedipin combination (group B). Patients were followed during a 2-year period. Systolic (SBP) and diastolic (DBP) blood pressure, albumin excretion rate (AER), glycated hemoglobin (A1c), total cholesterol, HDL, LDL, triglycerides, and body mass index (BMI) were measured at baseline, 6, 12, and 24 months of active treatment. At the beginning of the study, no significant difference was found in predictive variables between the two treatment groups. At the end of the study, a significant difference was found in A1c (p=0.040), but not in blood pressure (SBP: p=0.069 vs. DBP: p=0.188) and BMI (p=0.426). At the end of the study significant reductions in SBP (p=0.0001), DBP (p=0.0005), A1c (p=0.004), total cholesterol (p=0.002), and LDL (p=0.004) were found, but no reductions in AER (p=0.339) and BMI (P=0.470). Significant reduction was found in group B for A1c (p=0.010), total cholesterol (p=0.027) and LDL (p=0.037), but not in group A. No significant reduction in BMI was found in group A (p=0.220), nor in group B (p=0.851). Reduction of BP at the end of the study was similar in the two treatment groups. After a 2-yr treatment period, patients in group B had lower A1c, total cholesterol and LDL values compared to group A. A lisinopril/nifedipin combination seems to have a favorable effect on metabolic control in type 2 diabetic patients.

Background and Aims: The abnormalities in small blood vessels have also been described in the lungs of patients with diabetes mellitus. The aim of this study was to assess the presence of pulmonary function abnormalities in patients with diabetes mellitus and verify possible association with renal microangiopathy. Materials and Methods: Forty type 1 diabetic patients (19 male and 21 female ; age: 44 9.09 years ; diabetes duration: 16 12.03 years) without overt lung disease and with no history of smoking were studied. Stepwise regression method was used to analyze the influence of predictor variables: patient’ s age, diabetes duration, systolic (SBP) and diastolic blood pressure, protein excretion rate (PER), serum creatinine, creatinine clearance, lipid values, glycated haemoglobin, body mass index and C-peptide level on diffusion capacity for carbon monoxide (DLCO), forced expiratory flow in the first second (FEV1), and forced expiratory flow when 50% of the forced vital capacity had been exhaled (FEF50). Results: DLCO correlated significantly with PER (p=0.0002), creatinine (p=0.011) and creatinine clearance (p=0.0009), but not with diabetes duration (p=0.146). After stepwise regression method PER was pointed out as the most important variable in the prediction of DLCO (R2=0.55), PER, RRS, and creatinine in the prediction of FEV1 (R2=0.38), and PER and diabetes duration in the prediction of FEF50 (R2=0.31). Significant difference (Mann-Whitney U test) was found between lung parameters: DLCO, FEF50, and FEV1 in the groups of patients with and without significant proteinuria (p=0.001 vs. p=0.001 vs. p=0.039). Conclusions: Pulmonary function abnormalities are common in patients with IDDM and signs of diabetic microangiopathy. This could be explained by impaired pulmonary microvasculature but also with pulmonary interstitial changes. PER was found to be the important variable in the prediction of DLCO, FEV1 and FEF50.