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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.

Background and aims: Previous studies suggested that long-term perseverance of beta-cell function in patients with type 1 diabetes (T1DM) is associated with lower incidence of microvascular complications. The objective of this study was to evaluate preserved C-peptide secretion in patients with T1DM without overt chronic complications and to explore associations with resistin and uric acid as biomarkers of microvascular complication pathogenesis. ----- Materials and methods: We assessed residual beta-cell function in 164 T1DM patients (male/female = 91/73; age/diabetes duration range = 18-70/1-30 years) using an ultrasensitive C-peptide ELISA assay with detection limit of 2.5 pmol/L and total coefficient of variation (CV) 5,8% (Mercodia, Sweden). Serum level of uric acid was measured by enzymatic method (AU680, Beckman Coulter, USA) while resistin concentration was determined by the ELISA assay (Biovendor, Czech Republic). ----- Results: C-peptide secretors had shorter diabetes duration (5.1 vs. 16 years; p < 0,001), lower resistin (4.53 vs. 4.93 mg/mL p = 0.045), and higher uric acid (259 vs 238 μmol/L, p = 0.048) level than T1DM patients with no detectable C-peptide levels, while no differences in routine anthropometric and laboratory variables, including HbA1c, were observed. Although the proportion of C-peptide secretors significantly decreased across categories of diabetes duration (70%, 38%, 17% and 15% for

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

OBJECTIVES: Diabetes mellitus is a group of metabolic disorders associated with high risk for cardiovascular disease. Although troponins are primarily clinically used for the diagnosis of acute coronary syndrome, they are also used in risk assessment in patients with acute coronary syndrome as well as in a number of other conditions. The aim of this review was to investigate the relationship between hemoglobin A1c and serum troponin in patients with diabetes and cardiovascular events. METHODS: Hemoglobin A1(c) has been chosen as the best clinical indicator of glucose control and risk of micro and macrovascular complications. We investigated cardiac troponins as a group of markers of muscle injury which includes troponin T, troponin I and troponin C. Troponin T and I are specific for myocardial injury, compared to C which is specific for skeletal muscle. RESULTS: In this review, we showed that there was a causal relation between hemoglobin A1(c) levels and serum troponin concentrations. Hemoglobin A1(c) has shown to be a positive predictive factor of incidence, mortality and morbidity of conditions such as acute coronary syndrome, arrhythmias, stroke, pulmonary embolism and other conditions that causes troponin elevation by its release in circulation. CONCLUSIONS: Chronic hyperglycemia decreases glomerular filtration and consequently decreases troponin elimination and also by affecting the heart microcirculation it leads to microvascular damage and consequently to ischemia which contribute to troponin concentration elevation. Furthermore, correlation between hemoglobin A1(c) and troponin concentration manifests in their prognostic value for mortality.

Patients with diabetes have up to five times higher incidence of cataract, mainly at a younger age, and cataract in these patients progresses more rapidly than senile cataract, especially in eyes affected with sight-threatening diabetic retinopathy (DR). This study aimed to investigate the risk factors associated with cataract development in patients with type 2 diabetes (T2DM). This case-control cross-sectional study included 90 T2DM (56M/34F). Metabolic risk factors glycated hemoglobin (HbA1c), total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were determined using routine laboratory methods. Blood pressure was measured with a mercury sphygmomanometer after a 10-min resting period. Lens opacity was graded according to the Lens Opacity Classification System version III (LOCS III). According to the LOCS III, patients were divided into two groups: group 1—patients with clear crystalline lens, and group 2—patients with initial cataract. Compared to patients with a clear crystalline lens, those with initial cataract had longer diabetes duration (p = 0.002), higher HbA1c (p = 0.037), higher total cholesterol (p = 0.029), higher diastolic blood pressure (DBP) (p = 0.014), and lower creatinine clearance (p = 0.017). Cataract was positively associated with diabetes duration (p = 0.001), HbA1c (p = 0.035), LDL cholesterol (p = 0.042), and DBP (p = 0.009), while negatively with creatinine clearance (p = 0.005). Logistic regression analysis showed that the influence of DBP (AOR = 1.06, p = 0.014) and creatinine clearance (AOR = 2.93, p = 0.045) on cataract development remained significant even after adjustment for diabetes duration and HbA1c. Diabetes duration and various metabolic risk factors, particularly poor glycemic control, hypercholesterolemia, DBP, and diabetic nephropathy's coexistence, are associated with cataract development in T2DM.

Purpose: To determine the feasibility of non-invasive tear break-up time (NIBUT) assessment using the Handheld tear lipid layer thickness assessment instrument and compare it with the standard tear break-up time (TBUT) test and other dry eye tests.Subjects and methods: 108 subjects were enrolled, 56 with and 52 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms. Ocular signs were assessed by NIBUT, TBUT, lipid layer thickness (LLT), lid-parallel conjunctival folds (LIPCOF), conjunctival hyperemia, and corneal staining.Results: Median NIBUT and TBUT, and other clinical test values significantly differed among the dry eye symptoms group and control group. NIBUT yielded the most significant difference between the groups (NIBUT: 7 sec vs. 17.5 sec, p < .001, Z = 5.94; TBUT: 5 sec vs. 10 sec, p < .001, Z = 4.38; LLT: p = .007; LIPCOF: p < .001, conjunctival hyperemia: p < .047, corneal staining: p < .010). Spearman's test showed a significant correlation between NIBUT and TBUT (p < .001), NIBUT and LLT (p = .001), NIBUT and LIPCOF (p = .019), NIBUT and conjunctival hyperemia (p = .002), and NIBUT and corneal staining (p = .012) in the dry eye symptoms group. NIBUT did not significantly differ among the three measurements in both groups of patients (p = .061, p = .096), while TBUT values did in the control group (p < .001). Short NIBUT values were the main predictors and indicators of dry eye complaints (AOR = 0.87, p < .001), superior to TBUT (AOR = 0.88, p = .008) and other tests even after adjustment for age and gender.Conclusion: NIBUT measured by Handheld instrument is a simple, accessible, practical, and, most of all, reproducible and objective method that might allow NIBUT assessment on a regular basis.

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

This study aimed to assess the role of plasma homocysteine (Hcy) in the development of nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes (T2DM) without chronic kidney disease.This was a cross-sectional study that included 94 T2DM. Hcy, serum 25-hydroxy (25-OH) vitamin D, vitamin B12, and folate were determined by the CMIA method. NPDR was determined according to the EURODIAB retinal photography methodology and optical coherence tomography (OCT) of the macula.Compared to patients without NPDR, patients with NPDR had longer diabetes duration (p 0.001), higher Hcy (p 0.001), lower vitamin B12 (p = 0.028) and lower estimated glomerular filtration rate (eGFR) (p = 0.004). NPDR was positively associated with diabetes duration (p 0.001), HbAHigher Hcy is associated with NPDR and may play a role as a risk factor for its development in T2DM. Vitamins B12 and D seem to modify this association.

Results from studies investigating relationship between serum lipids and risk of development and progression of diabetic retinopathy (DR) in patients with type 1 diabetes (T1DM) are not consistent. The objective of this study was to explore the relationship between serum lipids and risk of development and progression of nonproliferative diabetic retinopathy (NPDR) in T1DM with normal renal function. A total of 103 T1DM with normal renal function, and before any interventions with lipid-lowering therapy, ACE inhibitors or angiotensin II receptor blockers were included in this study and followed for 41 months. Photodocumented retinopathy status was made according to the EURODIAB protocol. Patients who developed NPDR or progressed to proliferative retinopathy were older (44 vs 33 years, 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.

The prevalence of diabetes and its complications is constantly increasing worldwide, and it is responsible for increased morbidity, disability, and mortality. The most devastating consequences of diabetes are associated with its long-term micro- (retinopathy, nephropathy and neuropathy) and macrovascular complications (cardiovascular and cerebrovascular disease). Up to 75% of patients with diabetes may experience symptoms of gastrointestinal complications. The pathogenesis of gastrointestinal complications is complex, primarily related to autonomic dysfunction of the gastrointestinal tract and also associated with hyperglycemia and duration of diabetes. The metabolic and anatomic changes cause abnormalities in vascular flow, peristalsis, reflective relaxation and interstitial segmentation manifesting clinically as dysphagia, gastroparesis, diarrhea, constipation, abdominal pain, interstitial pseudo-obstruction, and anal incontinence. The management of patients with gastrointestinal complications is challenging and requires a multidisciplinary approach. Genetic components in the genesis of gastrointestinal tract disorders such as esophageal achalasia, functional dyspepsia, irritable bowel syndrome, celiac and Crohn’s disease have been established. Genetic predisposition, environmental factors such as infections and gut dysbiosis play an important role in the development of autoimmune diseases such as type 1 diabetes and Crohn’s disease.

AIM: The pathophysiology of insulin resistance (IR) comprises a complex adipokine mediated cross-talk between white adipose tissue and other organs. Dipeptidyl peptidase-4 (DPP4) is protease recently proposed as a novel adipokine linked to IR. We aimed to assess the relationship between fasting serum DPP4 activityand IR in type 1 diabetic (T1DM) patients. ----- METHODS: A cross-sectional study comprised 44 T1DM patients aged >18 and

Dipeptidyl peptidase-4 (DPP4) was recently proposed as a novel adipokine linked to insulin resistance (IR). As IR represents a cluster of disorders in hepatic and muscle cells insulin signalisation, we aimed to assess the possible correlation between fasting serum DPP4 activity, IR and liver enzymes in order to elucidate the question of hepatic contribution to serum DPP4 activity. This cross-sectional study comprised 44 T1DM patients aged 18 to 65 years. IR was estimated using the equation derived from euglycemic-hyperinsulinemic clamp studies-estimated glucose disposal rate (eGDR). DPP4 serum activity was determined spectrophotometrically as a rate of cleavage of 7-Amino-4-Methyl Coumarin (AMC) from H-Gly-Pro-AMC The patients were divided into two groups according to the mean value of fasting serum DPP4 activity (31.42 U/L). The group with lower fasting serum DPP4 activity had lower mean rate of liver biomarkers alanine aminotransferase (ALT) (p=0.001) and aspartate aminotransferase (AST) (p=0.002) while higher eGDR (p=0.003) compared to group with higher DPP4 activity. DPP4 activity showed positive correlation with AST (r=0.358, p=0.017) and ALT (r=0.364, p=0.015) while negative correlation with eGDR (r=-0.612, p

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.

Previous studies suggested that total serum bilirubin levels are negatively associated with diabetic retinopathy (DR) and nephropathy in patients with diabetes mellitus. The objective of this study was to explore the relationship between serum total bilirubin levels and prevalence of DR in patients with type 1 diabetes (T1DM) and normal renal function. Study included 163 T1DM with normal renal function (urinary albumin excretion rate < 30 mg/24h, estimated glomerular filtration rate (eGFR) >60 mlmin-11.73m-2). Photodocumented retinopathy status was made according to the EURODIAB protocol. Patients with DR were older (49 vs 42 years, p=0.001), had higher systolic blood pressure (130 vs 120 mmHg, p=0.001), triglycerides (0.89 vs 0.77 mmol/L, p=0.01), and lower serum total bilirubin (12 vs 15 U/L, p=0.02) and eGFR (100 vs 106 mlmin-11.73m-2, p=0.03). In multivariate logistic regression analysis, only total serum bilirubin was significantly associated with risk of DR in our subjects (OR 0.88, CI 0.81- 0.96, p=0.006). These data suggest that serum total bilirubin levels are independently negatively associated with DR in T1DM with normal renal function. Prospective studies are needed to confirm whether lower serum total bilirubin has predictive value for the development of DR in T1DM with normal renal function.

Glukagonu sličan peptid-1 (GLP-1) je probavni hormon koji stimulira lučenje inzulina u ovisnosti o razini glukoze. GLP-1 analog liraglutid ima 97 %-tnu sličnost ljudskom GLP-1 i ima učinke neovisne o regulaciji glikemije jer su receptori za GLP-1 široko rasprostranjeni po našem organizmu i to u srcu (uključujući vaskularni endotel i miokard), gastrointestinalnom sustavu, jetri, bubrezima, perifernom i centralnom živčanom sustavu. GLP-1 agonisti predstavljaju značajan napredak u liječenju šećerne bolesti tipa 2, jer oni jedinstveno djeluju na širok spektar rizičnih čimbenika kardiovaskularne bolesti snižavanjem tjelesne težine, sistoličkog krvnog tlaka, albuminurije i serumskih lipida. Studije su pokazale kardioprotektivni učinak terapije liraglutidom na vaskularni endotel i miokard uključujući vazodilataciju i antiupalne učinke. Liječenje liraglutidom značajno snižava razinu ukupnog i LDL-kolesterola te triglicerida. Liječenje liraglutidom snižava sistolički krvni tlak djelujući na bubrežno izlučivanje natrija te perifernu vazodilataciju. Terapija liraglutidom smanjuje jetrenu lipogenezu, inzulinsku rezistenciju jetre i masnog tkiva i upalne procese masnog tkiva u bolesnika s nealkoholnom masnom bolešću jetre te nealkoholnim steatohepatitisom. Aktivacija GLP-1 receptora ima presudnu ulogu u zaštiti bubrega od oksidativnog stresa pod utjecajem hiperglikemije te terapija liraglutidom smanjuje albuminuriju, reducira mezangijalnu ekspanziju, povisuje razinu dušičnog oksida te poboljšava glomerularnu fi ltraciju. GLP-1 agonisti također imaju neuroprotektivnu ulogu u animalnim modelima s Alzheimerovom i Parkinsonovom bolešću., Glucagon-like peptide-1 (GLP-1) is a gut hormone that stimulates insulin secretion in a glucose-dependent manner. The GLP-1 analog liraglutide has 97% homology to native GLP-1, and across the six LEAD (Liraglutide Effect and Action in Diabetes) trials, liraglutide improved hemoglobin A1c and was associated with sustained body weight with a low risk of hypoglycemia in different type 2 diabetes populations. However, trial data suggest that GLP-1 receptor agonists have effects beyond their glycemic actions because GLP-1 receptors are widely expressed in extra-pancreatic tissues such as heart (including endothelium and cardiac and vascular myocytes), gastrointestinal tract, liver, kidney, and peripheral and central nervous systems. Type 2 diabetes is commonly associated with hypertension, dyslipidemia, obesity and nephropathy, and cardiovascular disease is a major cause of mortality. GLP-1 receptor agonists represent signifi cant advance in the treatment of type 2 diabetes because they uniquely affect a broad array of cardiovascular risk factors through signifi cant weight, systolic blood pressure, serum lipids and albuminuria reduction. Studies support a cardioprotective role of liraglutide on vascular endothelium and myocardium, including vasodilatation and anti-infl ammatory effects. Treatment with liraglutide was associated with reductions in total cholesterol, LDL-cholesterol and triglycerides. Treatment with liraglutide reduces systolic blood pressure via effects on renal sodium excretion and peripheral vasodilatation. Liraglutide signifi cantly reduces hepatic lipogenesis, hepatic and adipose insulin resistance, and adipose infl ammation in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Activation of GLP-1 receptor has a crucial role in the protection against increased renal oxidative stress under chronic hyperglycemia, and treatment with liraglutide reduces albuminuria, attenuates mesangial expansion, enhances nitric oxide levels and improves glomerular fi ltration. GLP-1 receptor agonists have also been shown to exert a neuroprotective role in animal models of Alzheimer’s disease and Parkinson’s disease. Long-term, prospective, randomized LEADER study (the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) with large patient populations demonstrated that persons with type 2 diabetes who were at a high risk of cardiovascular events had lower rates of cardiovascular events with liraglutide than with placebo.