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Objective Previously we have shown that plasma protein N-glycosylation is changed in children at the onset of type 1 diabetes. In this study, we aim to identify N-glycan changes in adults with T1DM, compare them to those in children, and investigate their associations with disease duration, complications, glycaemic status, and smoking. Methods Serum protein N-glycans from 200 adults with type 1 diabetes and 298 healthy controls were analysed using ultra-high performance liquid chromatography and divided into 39 directly measured glycan groups from which 16 derived traits were calculated. Results Compared to healthy controls, subjects with type 1 diabetes showed differences in 19 glycan groups and a decrease in monogalactosylated, an increase in digalactosylated, monosialylated, and antennary fucosylated derived traits, from which changes in monogalactosylation and seven directly measured traits overlapped with previously reported in children. Changes in four directly measured and two derived traits previously seen in children were not detected in adults. HbA1c was positively associated with sialylated and highly branched structures, whereas N-glycome was not influenced by disease duration or diabetic complications. Conclusions Our results suggest potential N-glycome involvement in different stages of type 1 diabetes, including processes underlying its development, the disease itself, as well as those occurring after disease establishment.

Aims: To evaluate the 15-year incidence of development and progression of diabetic retinopathy (DR) in type 1 diabetic patients (T1DM) and determine the associated risk factors. Methods: 123 T1DM were included in this prospective cohort study and followed for 15 years. Demographic, clinical, laboratory parameters, and retinal photographs were collected and analyzed. Risk factors for DR development and progression were identified using Cox regression analysis. Results: At baseline, 87 (71%) patients had no DR, and 36 (29%) had nonproliferative DR (NPDR). After 15 years, 54 patients (43.9% ; 29.3/1000 person- years) developed NPDR or progressed to proliferative DR (PDR) ; 24 (27.6%) developed new NPDR, and 30 (83.3%) progressed to PDR. HbA1c (HR = 1.48, p = 0.008) and urinary albumin excretion rate (AER) (HR = 1.58, p = 0.045) were associated with the risk of DR development and progression, and a protective association was found for HDL cholesterol (HR = 0.17, p = 0.021). The presence of DR at baseline (HR = 2.95, p = 0.023) was associated with the risk of its progression to PDR. Conclusions: The 15-year incidence of DR development and progression in T1DM is still very high, which points to the need for close monitoring of T1DM, especially those with higher HbA1c, higher AER, the initial presence of DR, and lower HDL cholesterol.

Diabetes mellitus is the leading cause of chronic kidney disease, and about 30–40% of patients with diabetes will develop kidney disease. Incretin hormones have received attention during the past three decades not only as a pharmacotherapy for the treatment of type 2 diabetes, but also for their cardiorenometabolic effects. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Additional to the pancreas, receptors for GLP-1 are widely distributed in various organs, causing positive effects on endothelial function and vascular atherogenesis. Along with glycemic control and weight reduction, GLP-1 receptor agonists also strongly improve cardiovascular and renal outcomes in patients with type 2 diabetes. Recently, a dual GIP and GLP-1 receptor agonist has been approved for the treatment of type 2 diabetes. Compared to GLP-1 receptor agonist semaglutide, dual GIP and GLP-1 receptor agonist tirzepatide showed a superior reduction in hemoglobin A1c and body weight. Preliminary results also suggest that tirzepatide improves kidney outcomes in adults with type 2 diabetes with increased cardiovascular risk. In this review, we present the nephroprotective properties of dual GIP and GLP-1 receptor agonists as a new drug to treat type 2 diabetes.

Aim To determine the diagnostic accuracy of non- invasive tear film break-up time (NIBUT) measured by the handheld lipid layer examination instrument. Methods 108 patients were enrolled in this cross- sectional study and divided into two groups: patients with dry eye (n = 57) categorized by the presence of dry eye symptoms obtained by Schein Questionnaire and minimally-one objective dry eye sign (tear film break-up time

Aberrant plasma protein N-glycosylation has been reported in children newly diagnosed with type 1 diabetes (T1D) and N-glycosylation has also been associated with poor glycaemic control and nephropathy in T1D. N-glycosylation features distinct for adult patients with T1D, however, remain to be assessed. In this study we compared the serum protein N-glycosylation between adult patients and corresponding healthy controls as well as examined the association of N- glycans with common diabetic complications, duration of the disease, glycaemic control, and smoking. Serum N-glycans were analysed by UPLC in 201 patients with T1D (18-70) and 298 healthy controls (18-79). N-glycome was divided into 39 glycan groups and 16 derived traits calculated based on structural similarities. Serum N-glycome in T1D subjects exhibited significant decrease in monogalactosylated and an increase in digalactosylated, monosialylated and antennary fucosylated structures, as well as changes in 19 directly measured N- glycan traits. None of the N-glycosylation features, however, correlated with the duration of the disease nor with the development or progression of microvascular complications, similarly to glycaemic parameters, excluding HbA1c. HbA1c was positively associated with sialylated and highly branched glycans, while the effect of smoking was observed through increased complexity of plasma N-glycome.This study shows that T1D associates with a multitude of changes in the N-glycome, reflecting the complexity of the disease. Some of the changes were previously described in newly diagnosed children, but a number of new are found to be present only in the adult patients: e.g., an increase in antennary-fucosylated structures commonly originating from alpha-1-acid glycoprotein, or a decrease in oligomannose structures associated with immunoglobulin M. Interestingly, glycans did not associate with the duration of the disease or with microvascular complications, while conversely poor glycaemic control and smoking were strongly reflected in the N-glycome. In general, this study provides a more comprehensive portrayal of N-glycan changes in adult patients with T1D and highlights changes in certain plasma proteins, but nevertheless warrants further research on N-glycosylation in T1D.

Aim To determine the diagnostic accuracy of non- invasive tear film break-up time (NIBUT) measured by the handheld lipid layer examination instrument. Methods 108 patients were enrolled in this cross- sectional study and divided into two groups: patients with dry eye (n = 57) categorized by the presence of dry eye symptoms obtained by Schein Questionnaire and minimally-one objective dry eye sign (tear film break-up time

The aim of this study was to investigate risk factors and role of systemic inflammation, dyslipidemia and obesity in development of diabetic retinopathy (DR) in type 1 and type 2 diabetes and determine the differences in risk factors between these two types of diabetes. 84 type 1 and 107 type 2 diabetic patients were included in this cross-sectional study. Diabetes duration, body mass index (BMI) and waist-to-hip ratio (WHR) were assessed. C- reactive protein (CRP), fibrinogen (FIB), glycated hemoglobin (HbA1c), fasting and postprandial blood glucose (fBG, ppBG), HDL and LDL cholesterol and triglycerides (TG) were determined using routine methods. HbA1cmedian was obtained by statistical analysis of the CroDiabNet data and used as a marker of long- term glycemic control. Albumin excretion rate (AER) was measured in a 24-hour urine collection. Ophthalmologic retinal examination included indirect slit-lamp fundoscopy, color fundus photography according to EURODIAB (EUROpe and DIABetes) protocol and optical coherence tomography. DR was positively related to diabetes duration (p < .001), HbA1cmedian (p < .001) and AER (p=.008) in type 1, and diabetes duration (p < .001), HbA1cmedian (p=.018), AER (p < .001), CRP (p=.048) and TG (p=.041) in type 2 diabetes. Regression analysis showed that diabetes duration (OR 1.20, p=.005) and HbA1cmedian (OR 6.92, p=.007) were the main predictors of DR in type 1, and diabetes duration (OR 1.17, p

Bolesnici sa šećernom bolešću tipa 2 (ŠB2) su pod povećanim rizikom virusnih infekcija i pridruženih respiratornih komplikacija kao što je pneumonija. COVID-19 (Coronavirus Disease-2019) je virusna infekcija uzrokovana koronavirusom SARS-CoV-2 koja je dovela do pandemije zahvaćajući preko 100 zemalja u svijetu. Dosadašnji rezultati pokazuju da bolesnici sa ŠB2 imaju značajno veću smrtnost od COVID-19 infekcije. Upravo zbog toga važno je naglasiti moguće patofiziološke učinke farmakološkog liječenja ŠB2 na COVID-19 radi odabira optimalnog lijeka. Angiotenzinkonvertirajući enzim 2 (ACE2) te enzim dipeptidil-peptidaza 4 (DPP-4) su receptori za koronavirus, a ujedno su uključeni i u regulaciju upalnih procesa, bubrežnu i kardiovaskularnu fiziologiju te hemostazu glukoze. Metformin, zlatni standard u liječenju ŠB2, treba izbjegavati kod teže kliničke slike zbog rizika od dehidracije i laktične acidoze. Slično vrijedi i za inhibitore kotransportera natrij glukoza 2 receptora (SGLT-2 inhibitori) zbog rizika od dehidracije i euglikemijske ketoacidoze, a oni također povećavaju aktivnost bubrežnog ACE2. Preparati sulfonilureje su relativno sigurni kod oboljelih od COVID-19 infekcije uz veći rizik od hipoglikemije. DPP-4 inhibitori zbog svog imunomodulatornog učinka teoretski mogu prevenirati i reducirati rizik i progresiju akutnih respiratornih komplikacija (citokinska oluja) kod oboljelih od ŠB2. Agonisti glukagonu sličnog peptida-1 (GLP-1 agonisti) trebaju se upotrebljavati uz oprez i adekvatni unos tekućine i hrane zbog rizika od dehidracije, a također povećavaju aktivnost ACE2 u animalnim modelima. Inzulin, iako u animalnim modelima povećava bubrežnu ekspresiju ACE2, lijek je izbora kod hospitaliziranih bolesnika uz oprez zbog većeg rizika od hipoglikemije. Stručna društva preporučuju nastavak terapije inhibitorima sustava renin-angiotenzin-aldosteron (RAAS inhibitori)., Patients with type 2 diabetes (DM2) are at increased risk of viral infections and related respiratory complications. COVID-19 (Coronavirus Disease-2019) is a viral infection caused by coronavirus 2 (SARS-CoV-2), that has led to a pandemic affecting more than 100 countries across the globe. Studies to date have reported that patients with DM2 are at a significantly higher mortality risk from COVID-19. Accordingly, it is important to understand shared pathophysiology pathways between effects of pharmacological drugs and COVID-19 infection in order to choose the optimal treatment of DM2. Angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP-4) are coronavirus receptors that are also involved in glucose control, renal and cardiovascular physiology, and metabolic pathways including inflammation processes. Metformin, the gold standard treatment for DM2, should be avoided in patients with severe COVID-19 because of risk of dehydration and lactic acidosis. Sodiumglucose co-transporter-2 (SGLT2) inhibitors should also be avoided in patients with severe COVID-19 because of risk of dehydration and euglycemic diabetic ketoacidosis, and because they also promote renal ACE2 activity. Sulfonylureas are safe in patients with COVID-19, although there is a higher risk of hypoglycemia. Due to their immunomodulatory effect, DPP-4 inhibitors may prevent and reduce the risk and progression of acute respiratory complications (cytokine storm) in patients with DM2. Glucagon-like peptide-1 receptor (GLP-1) agonists should be used with caution, along with adequate intake of food and liquids because of higher risk of dehydration, and also because GLP-1 agonists upregulate ACE2 in animal models. Although insulin increases intrarenal ACE2 expression in animal models, insulin therapy should be prescribed in all hospitalized patients with severe or critical disease. However, regular monitoring of blood-glucose is needed. DM2 should continue with their antihypertensive regimens including renin–angiotensin–aldosterone system (RAAS) inhibitors.

Aims: To investigate the association between depressive symptomatology and health markers in type 1 diabetes. Methods: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated. Results: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA(1c) (79 vs. 72 mmol/mol, p

Study included 272 normoalbuminuric T1DM with normal thyroid function and before any interventions with statins and antihypertensive medications including those that might affect renal function (ACE inhibitors or angiotensin II receptor blockers). Euthyroidism was defined as TSH, fT3 and fT4 within the normal reference range. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. Study included patients with glomerular filtration rate (GFR) > 60 mlmin-11.73m-2, estimated with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULT AND CONCLUSION The average age was approximately 34 years and 55% of subjects were male. Mean/median values of BMI (24 kg/m2), systolic and diastolic blood pressure (120/80 mmHg), HDL cholesterol (1.6 mmol/L), and triglycerides (0.9 mmol/L) were within the normal range for T1DM, with slightly elevated HbA1c (7.3%) and LDL cholesterol (2.7 mmol/L) levels. fT4 significantly correlated with serum creatinine, eGFR and UAE (r=-0.12, 0.34 and -0.13, respectively, for all p

Background. Albuminuria, heart rate (HR) and blood pressure are established predictors of chronic kidney disease and cardiovascular disease. The objective of this study was to explore the relationship between HR, systolic blood pressure (SBP) and diastolic blood pressure (DBP) with renal function parameters in patients with type 1 diabetes (T1DM) without therapeutical interventions. Material and methods. Study included 313 normoalbuminuric T1DM. HR was determined using a standard 12-lead ECG and blood pressure with a mercury sphygmomanometer, both after a resting period of 10 minutes. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. Data on serum creatinine levels, age, sex and race were used to calculate the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Results. eGFR was significantly associated with duration of diabetes, HbA1c, LDL-cholesterol, and HDL-cholesterol (for the duration of diabetes r = –0.29, p < 0.001). UAE significantly correlated with duration of diabetes, HDL-cholesterol, triglycerides, HR and DBP (for HR and DBP r = 0.21–0.23, p < 0.001). Subjects in the 4th quartile of UAE had significantly higher HR rate compared to subjects in 1st, 2nd, and 3rd quartiles (70 ± 11 vs. 74 ± 12 vs. 74 ± 12 vs. 79 ± 13 beats/min, p = 0.001). Conclusions. Results of our study suggest that interplay between HR with renal function parameters is present even in T1DM with normal renal function.

Waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) are superior to body mass index (BMI) in predicting type 2 diabetes mellitus (T2DM) development. The aim of this study was to investigate the predictive power of BMI, WC, WHR and WHtR for microvascular (chronic kidney disease (CKD), retinopathy and peripheral neuropathy) prevalence in obese (BMI ≥35 kg/m2) T2DM patients. This cross-sectional study included 125 T2DM patients of both genders. The validity of each test was assessed by Receiver Operating Characteristic (ROC) curves; the area under the curve (AUC) was calculated for each anthropometric parameter and microvascular complication. AUCs for WHtR were significantly higher than AUCs for WC with respect to CKD. Optimal cut-off for WHtR was >0.593 and WC >112 cm regarding CKD. The AUC for peripheral neuropathy was significant only for WHR and optimal cut-off for WHR was >1.409 with low sensitivity and high specificity. Our study demonstrated that WHtR, WC and WHR might be used as simple and noninvasive methods for detection of CKD and peripheral neuropathy in obese T2DM population., Opseg struka (OS), omjer opsega struka i bokova (OSB) i omjer opsega struka i visine (OSV) su bolji predskazatelji razvoja šećerne bolesti tipa 2 (ŠB2) nego široko upotrebljavani indeks tjelesne mase (ITM). Svrha ovoga istraživanja je bila istražiti učinkovitost ITM, OS, OSB i OSV u procjeni učestalosti mikrovaskularnih komplikacija (kronična bubrežna bolest (KBB), retinopatija i periferna neuropatija) u pretilih (ITM ≥35 kg/m2) bolesnika sa ŠB2. Ova presječna studija je uključila 125 bolesnika oba spola sa ŠB2. Dijagnostička vrijednost testova je procijenjena krivuljama ROC (engl. Receiver Operator Characteristic); područje ispod krivulje (AUC) je izračunato za svaki antropometrijski parametar i rizični čimbenik (mikrovaskularnu komplikaciju). AUC za OSV je bio značajno viši nego AUC za OS za KBB. Optimalna granična vrijednost za OSV je bila >0,593, a za OS >112 cm za KBB. AUC za perifernu neuropatiju je bio značajan samo za OSB i optimalna granična vrijednost za OSB je bila >1,409, uz nisku osjetljivost i visoku specifičnost. Rezultati našega istraživanja ukazuju na to da OSV, OS i OSB mogu biti jednostavna i neinvazivna metoda procjene učestalosti KBB i periferne neuropatije u pretilih bolesnika sa ŠB2.

Renal sympathetic denervation (RDN) with radiofrequency (RF) is being used to treat resistant hypertension in seven non-responder patients (62±6 years for age, 5F/2M) despite treatment with >4 different antihypertensive drugs in optimal doses. Prior to diagnosing a patient as having resistant hypertension, we document adherence and exclude white-coat hypertension, inaccurate measurement of blood pressure and secondary causes. Office blood pressure (BP) measurements at 1, 3, 6, 12 and 18 months follow-up visits were compared to baseline. We used STATISTICA 10, 2011 software (Stat Soft Inc., Tulsa, OK, USA). Values are mean SD and considered statistically significant if P, Denervacija bubrežnih arterija (DBA) radiofrekvencijom jedna je od obećavajućih novih metoda liječenja rezistentne hipertenzije refraktorne (RH) na optimalno liječenje kombiniranom antihipertenzivnom terapijom koja uključuje 3 i više lijekova iz različitih antihipertenzivnih skupina od kojih jedan mora biti diuretik. Nakon isključenja sekundarnih uzroka, neadekvatnog mjerenja tlaka te nesuradljivosti prikazujemo učinak DBA u 7 bolesnika (62±6 years for age, 5F/2M) tijekom razdoblja od 18 mjeseci praćenja. Za statističku analizu korišten je program STATISTICA 10, 2011 softwer (Stat Soft Inc., Tulsa, OK, USA), uz razinu značajnosti P

Purpose Diabetic retinopathy (DR) is the most frequent complication among patients with type 1 diabetes mellitus (T1DM). Dipeptidyl peptidase–4 (DPP4) is a protease with elevated activity in patients with T1DM. Several studies indicate that DPP4 inhibitors might have beneficial effect on nonproliferative retinopathy (NPR) development as well as on its progression to proliferative retinopathy (PR). We aimed to explore the relationship between serum DPP4 activity and DR in patients with T1DM. Methods This cross-sectional study recruited 44 patients with T1DM. The DPP4 activity was measured by colorimetric assay in a microplate reader. Photodocumented retinopathy status was made according to the EURODIAB protocol. Results A total of 28 (63.6%) patients were men, mean age 45.36 years, diabetes duration 23.71 years, glycated hemoglobin A1c (HbA1c) 7.4%. Patients were stratified into 2 groups according to retinopathy prevalence. Group 1 comprised 14 (31.85%) patients with DR absence while the second group consisted of 30 (68.15%) patients with both PR and NPR. Group 1 had lower fasting serum DPP4 activity (25.85 vs 33.84 U/L, pConclusions Serum DPP4 activity may be independently associated with both DR types in patients with T1DM. Further study is warranted to elucidate whether there is an association between DPP4 activity and DR severity and/or progression.

Previous studies have reported that retinopathy might be present already in normoalbuminuric state in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the risk factors for development and progression of nonproliferative retinopathy (NPR) in normoalbuminuric T1DM. A total of 223 T1DM with normal renal function and normoalbuminuria were included in this study and followed for 48 months. Photodocumented retinopathy status was made according to the EURODIAB protocol. Urinary albumin excretion rate (UAE) was measured from at least two 24-h urine samples. The possible risk factors for development or progression of NPR were examined in backward stepwise Cox's multiple regression analysis. The majority of patients (70%) had no retinopathy while 67 (30%) had NPR at baseline. Patients with NPR were older, had longer duration of diabetes, higher systolic blood pressure, BMI, resting heart rate, UAE and lower estimated glomerular filtration rate (p≤0.04 for all). After 48 months twenty-four patients (10.7%) developed NPR or progressed to proliferative retinopathy. Systolic blood pressure (HR 1.03, CI 1.01-1.05, p=0.02), UAE (HR 1.14, CI 1.07-1.21, p

Hyperfiltration has been documented in type 1 diabetes and may contribute to the high risk for development of albuminuria and progression of nephropathy. However, recent studies suggest that the risk of progression to albuminuria in type 1 diabetes was not increased by hyperfiltration. We investigated associations of estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (UAE) in normoalbuminuric type 1 diabetic patients. Study included 313 normoalbuminuric patients with type 1 diabetes, none showed signs of adrenal, renal, or cardiovascular diseases. GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Glomerular hyperfiltration was defined as eGFRor = 125 mL min(-1) 1.73 m(-2). Renal hyperfiltration was present in 12% of the study group. Subjects with eGFRor = 125 mL min(-1) 1.73 m(-2) were younger, had shorter duration of diabetes, lower levels of total and LDL cholesterol, and higher HbA1c than subjects with an eGFR below 125 mL min(-1) 1.73 m(-2). Type 1 diabetic patients with hyperfiltration also had significantly lower UAE. In a multiple logistic regression analysis, higher eGFR was associated with lower UAE. Our results indicate that normoalbuminuric type 1 diabetic patients with hyperfiltration have lower UAE than those with renal function in the normal range. Together with other recent studies this may suggest that creatinine-based estimates of GFR indicating hyperfiltration is not associated with higher UAE and subsequent development of microalbuminuria.

Exenatide is an incretin mimetic that acts through glucagon-like peptide 1 receptor accepted as a successful novel glucose-lowering agent in type 2 diabetes. The aim of this study was to explore the possible predictive factors for exenatide efficacy among baseline characteristics of type 2 diabetic patients. We observed basic anthropometric measurements, laboratory findings and diabetic complications in ninety-one type 2 diabetic patients starting exenatide therapy. There were forty-six (50.5%) male and forty-five (49.5%) female patients, median age 58 (31-76) years, body mass index 38.95}4.35 kg/m2, duration of diabetes 10 (1-30) years and HbA1c level 8.3}1.4%. Thirty (33%) patients stopped therapy because of glycemic dysregulation during 105 (21-390) days on therapy. These patients differed statistically significantly from those that continued therapy according to the following seven variables: higher fasting glucose blood concentration (11.5 mmol/L (5.6-20) vs. 10.2 mmol/L (5-19), higher serum creatinine concentration (93 μmol/L (44-149) vs. 72 μmol/L (44-124), more frequent diabetic complications including retinopathy (56.7% vs. 27.9%), chronic kidney disease (43.7% vs. 24.7%), coronary artery disease (53.3% vs. 31.1%) and peripheral artery disease (60% vs. 34.4%), and less often concomitant metformin and exenatide therapy (62% vs. 82%). Bivariate logistic regression identified peripheral artery disease, coronary artery disease, retinopathy, and chronic kidney disease as risk factors for glycemic dysregulation on exenatide therapy. We found reasonable to consider that a higher rate of microvascular and macrovascular complications may indicate failure of exenatide therapy in the majority of patients., Eksenatid je inkretinski mimetik koji djeluje putem receptora proteina nalik glukagonu 1, široko prihvaćen kao uspješan novi lijek u terapiji šećerne bolesti tipa 2. Svrha ovoga istraživanja bila je istražiti moguće čimbenike predviđanja učinkovitosti terapije analizom osnovnih nalaza među bolesnicima sa šećernom bolešću tipa 2. Provedena je analiza antropometrijskih obilježja, laboratorijskih nalaza i evaluacija dijabetičnih komplikacija kod 91 bolesnika koji su započeli terapiju eksenatidom. Bilo je 46 (50,5%) bolesnika muškog spola i 45 (49,5%) ženskog spola; medjian dobi bio je 58 (31-76) godina, indeks tjelesne mase 38,95}4,35 kg/m2, trajanje šećerne bolesti 10 (1-30) godina s prosječnom vrijednosti HbA1c 8,3}1,4%. Tridesetoro (33%) bolesnika prekinulo je terapiju zbog loše regulacije glikemije tijekom 105 (21-390) dana. Sedam varijabli statistički ih je razlikovalo od skupine koja je postigla zadovoljavajuću glukoregulaciju na eksenatidu: više vrijednosti glukoze natašte (11,5 mmol/L (5,6-20) prema 10.2 mmol/L (5-19), više vrijednosti kreatinina u serumu (93 μmol/L (44-149) prema 72 μmol/L (44-124), viša učestalost razvijenih dijabetičnih komplikacija: retinopatije (56,7% prema 27,9%), kronične bubrežne bolesti (43,7% prema 24,7%), koronarne arterijske bolesti (53,3% prema 31,1%) i periferne arterijske bolesti (60% prema 34,4%), te rjeđa upotreba metformina u kombinaciji s eksenatidom (62% prema 82%). Bivarijatna logistička regresija identificirala je perifernu arterijsku bolest, koronarnu arterijsku bolest, retinopatiju i kroničnu bubrežnu bolest kao statistički značajne čimbenike rizika za disregulaciju glikemije na terapiji eksenatidom. Navedeni rezultati navode na zaključak kako bi razvijene mikrovaskularne i makrovaskularne komplikacije mogle biti čimbenik koji predviđa neuspjeh glukoregulacije eksenatidom.

Anemia is a prevalent finding in patients with type 1 diabetes, particularly in those with albuminuria or reduced renal function. We investigated the relationship between red blood cell count (RBC) and renal function in type 1 diabetic patients with normal or mildly impaired renal function and urinary albumin excretion rate (UAE)30 mg/24 h. Study included 313 type 1 diabetic patients with estimated glomerular filtration rate (eGFR)60 mL min(-1) 1.73 m(-2), and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. UAE was measured from at least two 24-h urine samples. Hemoglobin (Hb), hematocrit (Hct), erythrocytes (E), serum iron and ferritin levels were significantly lower in subjects in the highest quartile of serum creatinine compared to those in lowest quartile (132 vs 148 g/L, 0.39 vs 0.42 L/L, 4.5 vs 4.8 x 10(12)/L, 13 vs 18 micromol/L, and 25 vs 103 microg/L, respectively, for all p0.001). Hb and Hct levels were significantly lower in subjects in the highest quartile of UAE compared to those in lowest quartile (135 vs 140 g/L, and 0.40 vs 0.41 L/L, respectively, for all p = 0.03). Finally, those with mildly impaired eGFR had significantly lower levels of Hb, Hct and E compared to those with normal eGFR or hyperfiltrating subjects (133 vs 140 g/L, 0.38 vs 0.41 L/L, and 4.4 vs 4.7 x 10(12)/L, respectively, for all p = 0.01). We have detected that interplay between RBC and renal function parameters occurs even in type 1 diabetic patients with normal or mildly impaired renal function.

In patients with resistant hypertension (RH) we investigated the importance of urinary neutrophil gelatinase-associ- ated lipocalin (uNGAL- a chemiluminescent microparticle immunoassay (CMIA) method became using (Abbott Diag- nostics) for the measurement of NGAL in urine samples) and incidence of chronic kidney disease using the Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in estimating glomerular filtration rate (eGFR) based on standardised serum creatinine method traceable to isotope di- lution mass spectrometry (IDMS) method. It would have been difficult to predict that levels of these biomarker would per- form better organ damage than traditional measurements of kidney function such as standardised serum creatinine, MDRD, or CKD-EPI equations in special population such as RH. Serum creatinine concentrations were measured in 50 patients (24M:26F, from RH Registar in Clinical Hospital Merkur) by the kinetic Jaffe method. There were no significant differences between the GFR values derived by MDRD and CKD-EPI equations in the group of patients with RH. 62% of patients have eGFR >60 mL/min/1.73 m 2 , while a 38% of patients have eGFR

Objective: Adiponectin is known to be decreased in insulin resistance (IR) and metabolic syndrome (MS). MS can be present in patients with type 1 diabetes mellitus (T1DM) representing an independent risk factor for micro- and macrovascular complications. The aim of this study was to evaluate the relationship between adiponectin level, MS, and insulin sensitivity in T1DM patients. Research design and methods: Study included 77 T1DM patients divided into two groups based on the median adiponectin value (14.1 µg/ml). Insulin sensitivity was calculated with the equation for eGDR: 24.31–12.2X(WHR)– 3.29X(AHT)–0.57X(HbA1c), where the units are mgkg– 1min–1, WHR indicates the waist to hip ratio, AHT indicates blood pressure, and is expressed as: 0- no, 1-yes. MS was defined both according to National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) and International Diabetes Federation (IDF) criteria. Results: Patients with higher adiponectin levels (n=39) in comparison with the group with lower adiponectin (n=38) had significantly lower waist circumference (80.9 vs 90.5 cm, p

Although insulin resistance is usually associated with the development of type 2 diabetes, it can also be a feature of patients with type 1 diabetes. Insulin resistance has been documented in type 1 diabetes and may contribute to the high risk of cardiovascular disease in this population. To investigate the relationship of insulin resistance with metabolic and inflammatory parameters we divided 304 patients according to median estimated glucose disposal rate (eGDR =9.72 mgkg-1min-1) into lower (n=153) and higher (n=151) insulin sensitivity groups. Patients with lower insulin sensitivity had higher levels of serum lipids (except for HDL cholesterol), duration of diabetes, daily insulin dose, white blood cell count, C-reactive protein, homocysteine and ferritin. Spearman correlation analysis showed significant associations between individual components of insulin resistance and various metabolic and inflammatory parameters. Multiple logistic regression models found significant association of age, sex, duration of diabetes, serum lipids, daily insulin dose, white blood cell count and ferritin with progression to insulin resistance. The presence of insulin resistance indicates a greater risk of micro- and macrovascular disease and health care professionals need to be alerted that this subset of individuals with type 1 diabetes will require stringent control of hypertension, glycemia and serum lipids., Inzulinska rezistencija u tipu 1 šećerne bolesti dokazano doprinosi povećanom riziku razvoja kardiovaskularne bolesti. U ovoj studiji istraživana je razina inzulinske osjetljivosti koristeći kliničke parametre (eGDR ) u bolesnika sa šećernom bolešću tipa 1 i istraživan je odnos razine inzulinske osjetljivosti s metaboličkim i upalnim parametrima. Od 304 bolesnika uključena u studiju njih 153 imalo je nižu inzulinsku osjetljivost (eGDR

Studies have generally suggested a positive association between dyslipidemia and chronic kidney disease, but sparse data are available on the relation of lipids and glomerular filtration rate in patients with normal renal function. We in- vestigated the associations of serum lipids, including total, LDL, HDL, VLDL cholesterol, and triglyceride levels with es- timated glomerular filtration rate (eGFR) in type 1 diabetic patients. Study included 313 normoalbuminuric type 1 diabetic patients with normal or mild decrease (eGFR > 60 mL/min per 1.73 m 2 ) renal function and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. eGFR was significantly associated with total, LDL, and HDL cholesterol (r= –0.21, –0.18, and –0.17, respectively, for all p

It has been suggested that association between hypothyroidism with dyslipidemia might be present already at the stage of normal thyroid function through altered insulin sensitivity. We analyzed the role of insulin sensitivity as a mediator of thyroid-induced lipid changes in euthyroid type 1 diabetic patients. Study included 304 patients with type 1 diabetes and normal thyroid function. Insulin sensitivity was measured with estimated glucose disposal rate calculated using the equation: eGDR = 24.31 - (12.22 × WHR) - (3.29 × HT) - (0.57 × HbA1c); WHR = waist-to-hip ratio, HT = hypertension. TSH, FT4, FT3, and serum lipids were measured. Correlations and multiple linear regressions analysis were performed to identify relationships between thyroid status and serum lipid parameters after stratifying patients in quartiles of eGDR. After adjustment for age, sex, BMI, duration of diabetes and insulin dose TSH, FT3, and FT4 was not significantly associated with serum lipids in all patients, independently of level of insulin sensitivity. However, after stratifying patients for the degree of insulin sensitivity in subjects in the lowest quartile of insulin sensitivity TSH was independently associated with LDL cholesterol (β = 0.210, p = 0.02). The independent relation of eGDR with TSH and LDL cholesterol suggests that the influence of thyroid function on lipid metabolism might extend into euthyroid range through altered insulin sensitivity.

Although metabolic syndrome was not extensively studied in type 1 diabetes, higher insulin resistance, the core feature of the syndrome was found to be associated with increased risk of developing microvascular complications. As diabetic nephropathy may progress to advanced lesion before microalbuminuria appears, we investigated the association of the metabolic syndrome and estimated glucose disposal rate (eGDR) with urinary albumin excretion (UAE), retinopathy and neuropathy in normoalbuminuric type 1 diabetic patients. Two hundred and 98 patients (UAE30 mg / 24 h at three occasions) were divided according to the IDF metabolic syndrome; eGDR (mg kg(-1) min(-1)) was calculated: 24.31-(12.22 x WHR) - (3.29 x HT) - (0.57 x HbA1c), (WHR = waist-to-hip ratio, HT = hypertension). Patients with (n = 99) compared to those without metabolic syndrome (N = 199) showed higher UAE (15.96 +/- 9.10; 13.48 +/- 8.36 mg /24 h), C-reactive protein (2.39 +/- 4.09;1.12 +/- 2.03 mg/L), prevalence of retinopathy (70.7; 55.27%) and polyneuropathy (80.8; 68.3%), and lower eGDR (5.75 +/- 1.74; 8.96 +/- 1.9), (p0.05). In patients with high-normal UAE, retinopathy and polyneuropathy eGDR was significantly lower compared with patients with low-normal UAE, and without retinopathy and polyneuropathy. In multiple regression analysis UAE and retinopathy were associated with diabetes duration (beta = -0.20, beta = -0.62), eGDR (beta = - 0.106; beta = -0.041), metabolic syndrome (beta = 0.49, beta = 0.28), (p0.05). In type 1 diabetic patients insulin resistance and IDF defined metabolic syndrome are associated with high-normal UAE, retinopathy and polyneuropathy. The predictive value of the metabolic syndrome for development of microalbuminuria and retinopathy needs to be assessed in further follow-up studies.