Papers by Kristina Blaslov
Diabetologia Croatica, 2014
Nonalcoholic fatty liver disease (NAFLD), previously also named diabetes hepatitis, is characteri... more Nonalcoholic fatty liver disease (NAFLD), previously also named diabetes hepatitis, is characterized by accumulation of fat in the liver and refers to a spectrum of disorders ranging from simple hepatic steatosis to more severe manifestations including nonalcoholic steatohepatitis. Although the etiology is still unclear, NAFLD is strongly associated with hepatic and adipose tissue insulin resistance. Glucagon-like peptide 1 (GLP-1) receptor agonists represent a novel class of therapies for the treatment of type 2 diabetes with a potent blood glucose-lowering action mediated via its ability to induce insulin secretion and reduce glucagon secretion in a glucosedependent manner. In addition, GLP-1-based therapy has direct effects on decreasing hepatic steatosis invitro by modulating elements of the insulin signaling pathway via functional GLP-1 receptor, resulting in the regulation of gene expression associated with insulin resistance and lipid metabolism, and the suppression of oxidative stress in liver cells.
Diabetologia Croatica, 2014
Nonalcoholic fatty liver disease (NAFLD), previously also named diabetes hepatitis, is characteri... more Nonalcoholic fatty liver disease (NAFLD), previously also named diabetes hepatitis, is characterized by accumulation of fat in the liver and refers to a spectrum of disorders ranging from simple hepatic steatosis to more severe manifestations including nonalcoholic steatohepatitis. Although the etiology is still unclear, NAFLD is strongly associated with hepatic and adipose tissue insulin resistance. Glucagon-like peptide 1 (GLP-1) receptor agonists represent a novel class of therapies for the treatment of type 2 diabetes with a potent blood glucose-lowering action mediated via its ability to induce insulin secretion and reduce glucagon secretion in a glucosedependent manner. In addition, GLP-1-based therapy has direct effects on decreasing hepatic steatosis invitro by modulating elements of the insulin signaling pathway via functional GLP-1 receptor, resulting in the regulation of gene expression associated with insulin resistance and lipid metabolism, and the suppression of oxidative stress in liver cells.
Endocrine oncology and metabolism, 2018
Although bone health is primarily associated with age, recent studies have shown that individuals... more Although bone health is primarily associated with age, recent studies have shown that individuals with diabetes mellitus (DM) have up to 6 times higher incidence of osteoporotic fractures compared to the general population. So far, there is no single entity for this condition, primarily due to the different mechanisms of development in type 1 DM (T1DM) and type 2 DM (T2DM), as well as different mechanisms of osteoporosis development. Diabetes affects bone metabolism by various mechanisms including changes in insulin concentration, insulin-like growth factor-1 (IGF-1), and amylin. Hyperinsulinemia (the predominant characteristic of the T2DM) can stimulate bone formation, whereas in contrast to hypothyroidism (the predominant characteristic of T1DM), both lead to bone density reduction. Chronic hyperglycemia leads to the creation and accumulation of advanced glycation end products (AGEs) in collagen. The aforementioned changes in the bone architecture, decreasing its strength and increasing its fragility. In addition, hyperglycemia leads to glycosuria resulting in hypercalciuria, leads to hypocalcemia, accelerated bone resorption, and thus contributes to osteoporosis. Finally, the microvascular complications of DM result in decreased blood flow to the bone and thus additionally contribute to the onset of osteoporosis. Here, we review the current knowledge in epidemiology, pathophysiology, diagnosis, and treatment of osteoporosis in diabetes.
Diabetes, Jun 1, 2019
Insulin resistance (IR) represents one of the key regulatory mechanisms in the development of non... more Insulin resistance (IR) represents one of the key regulatory mechanisms in the development of non - alcoholic fatty liver disease. It is a common hepatocyte injury in hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). Higher plasma platelet-derived growth factor A (PDGF- A) concentration is associated with increased hepatic steatosis and fibrosis in T2DM. PDGFs are key regulators of the connective tissue formation and potent mitogens for hepatic stellate cells. We investigated whether there is an association between PDGF-A serum concentration, IR and HCV mediated hepatic steatosis and fibrosis. This cross-sectional study comprised 90 nondiabetic participants aged 47.11±1.54 years divided into 3 groups: HCV negative group with IR (HCV-/IR-, N=12), HCV positive group without IR (HCV+/IR-, N=34), HCV positive group with IR (HCV+/IR+, N=44). The fasting PDGF-A concentration was determined by enzyme-linked immunoadsorbent assay. Homeostatic Model Assessment of IR score over 1.64 was categorised as IR. Fibrosis and steatosis were evaluated by elastography. Steatosis severity accessed by Controlled Attenuation Parameter (p<0.001) had the mean value of 15.9 kPa in the HCV+/IR+ (p<0.001) revealing the highest value in HCV-/IR+ (296.5 dB/m) group. The PDGF-A concentration correlated positively with steatosis (r=0.341, p=0.007) and fibrosis (r=0.264, p=0.071). Both IR positive groups had higher PDGF-A compared to HCV+/IR- group (p=0.006). In accordance with more pronounced steatosis, the HCV-/IR+ group revealed the highest PDGF-A. Concentration of PDGF-A is associated with the severity of hepatic steatosis in HCV and non-HCV patients with IR; i.e., that PDGF-A could represent one of the key regulatory mechanisms in the pathway from hepatic steatosis towards fibrosis. These results provide better understanding of pathways that regulate fibrosis. Disclosure K. Blaslov: None. V. Kokic Males: None. S. Kokic: None. I. Kruljac: None.
Medical Hypotheses, May 1, 2018
European Journal of Ophthalmology, 2017
ABSTRACT There is evidence from animal studies that treatment with glucagon-like peptide-1 (GLP-1... more ABSTRACT There is evidence from animal studies that treatment with glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide suppressed the progression of diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect. A total of 42 overweight type 2 diabetic patients with normal or mildly decreased (estimated GFR ≥ 60 mlmin-11.73 m2) renal function were included in this study and followed for 7 months. The 7-months administration of liraglutide caused a significant decrease in albuminuria from 19.9 (3.2-6250.1) to 17.3 (7.5-420.1) mg/24h (p=0.04), while serum creatinine (from 71±15 to 76±19 umol/L (p=0.3)) and estimated GFR (from 90±13 to 88±18 mlmin-11.73m2 (p=0.3)) did not significantly changed. The results of our study suggest that therapy with GLP-1 receptor agonist liraglutide may significantly reduce UAE in overweight type 2 diabetic patients.
Eksenatid je GLP-1 (engl. glucagon-like peptide-1) mimetik i agonist GLP-1 receptora. Iniciran je... more Eksenatid je GLP-1 (engl. glucagon-like peptide-1) mimetik i agonist GLP-1 receptora. Iniciran je za lijecenje oboljelih od secerne bolesti tipa 2 (SB2) s indeksom tjelesne mase (ITM) ≥35 kg/m2 nezadovoljavajuce reguliranih na oralnim hipoglikemicima. Terapija eksenatideom dovodi do poboljsanja glukoregulacije i snižavanja hemoglobina A1c (HbA1c) ali također dovodi do snižavanja tjelesne težine. Lijek se primjenjuje supkutano 2x dnevno, a osim utjecaja na tjelesnu težinu i HbA1c primijecen je i utjecaj na serumske lipide, ponajvise na razinu triglicerida. Cilj naseg istraživanja bio je utvrditi utjecaj terapije eksenatideom na HbA1c, tjelesnu težinu te serumske lipide u pretilih bolesnika sa SB2. Terapija GLP-1 agonistom eksenatidom je dovela do znacajnog sniženja ukupnog i LDL-kolesterola u pretilih bolesnika sa SB2. Utjecaj na serumske lipide je dijelom posljedica povoljnog utjecaja terapije eksenatideom na regulaciju glikemije i tjelesnu težinu ali je dokazano i da eksenatid putem GLP-1 receptora na jetri smanjuje jetrenu sintezu lipida, poglavito VLDL-kolesterola.
Medical Hypotheses, Oct 1, 2019
Journal of Diabetes, Oct 3, 2014
Metabolic syndrome (MS) is found in approximately% 30-40% of patients with type 1 diabetes mellit... more Metabolic syndrome (MS) is found in approximately% 30-40% of patients with type 1 diabetes mellitus (T1DM). Meal-induced glucagon-like peptide-1 (GLP-1) secretion in T1DM patients with MS is yet to be clarified. The aim of the present study was to analyse the relationship between total fasting GLP-1 concentrations and the meal-induced GLP-1 response with MS prevalence in T1DM patients compared with lean, normal glucose tolerance (NGT), control subjects. The study included 77 T1DM patients (61% male), 26 (34%) with MS, who had a mean age of 45.08 years, mean body mass index (BMI) of 25.42 kg/m(2) , and median diabetes duration of 21 years. Ten age-, gender, and BMI-matched NGT control subjects were also included in the study. Circulating GLP-1 concentrations ere measured before and 30 min after a meal by ELISA. The difference between the 30-min postprandial and fasting GLP-1 concentration (ΔGLP-1) was calculated by subtracting fasting GLP-1 concentrations from postprandial GLP-1 concentrations. The NGT group had significantly higher total fasting, postprandial, and meal-induced GLP-1 concentrations than the T1DM groups. The T1DM patients without MS had a higher increase in circulating GLP-1 concentrations compared with the T1DM group with MS. After adjustment for age, gender, disease duration, and meal caloric value, GLP-1 response levels were inversely correlated with MS prevalence in binary logistic regression analysis. A higher meal-induced GLP-1 response is associated with lower MS prevalence, but whether GLP-1 has a protective role in MS development is yet to be determined. This may provide further insight into the implementation of GLP-1-based therapies in the T1DM population.
ABSTRACT There is evidence from animal studies that treatment with glucagon-like peptide-1 (GLP-1... more ABSTRACT There is evidence from animal studies that treatment with glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide suppressed the progression of diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect. A total of 42 overweight type 2 diabetic patients with normal or mildly decreased (estimated GFR ≥ 60 mlmin-11.73 m2) renal function were included in this study and followed for 7 months. The 7-months administration of liraglutide caused a significant decrease in albuminuria from 19.9 (3.2-6250.1) to 17.3 (7.5-420.1) mg/24h (p=0.04), while serum creatinine (from 71±15 to 76±19 umol/L (p=0.3)) and estimated GFR (from 90±13 to 88±18 mlmin-11.73m2 (p=0.3)) did not significantly changed. The results of our study suggest that therapy with GLP-1 receptor agonist liraglutide may significantly reduce UAE in overweight type 2 diabetic patients.
European Journal of Ophthalmology, 2017
Hashimoto’s thyroiditis and juvenile type 1 diabetes mellitus (T1DM) are the most common combinat... more Hashimoto’s thyroiditis and juvenile type 1 diabetes mellitus (T1DM) are the most common combination of autoimmune (AI) disorders. It was recently proposed that besides genetic susceptibility central obesity might contribute to unknown mechanisms underlying the thyroid-antibody production. Latent AI diabetes in adults (LADA) is characterized by clinical presentation resembling type 2 diabetes but with T1DM autoimmune markers, primarily glutamic acid autoantibody (GAD Ab). Little is known about the presence of Hashimoto’s thyroiditis in LADA and adult onset T1DM. We aimed to investigate the relationship between Hashimoto's disease presence, AI markers and metabolic features in patients with LADA and adult-onset T1DM. Four hundred and seven patients diagnosed with AI diabetes over the age of 30 years were divided according to Ab positivity into three groups: GAD single positive group (representing LADA) ; islet cell Ab (ICA)+GAD positive and ICA+GAD+protein thyrosine phosphatase Ab (IA2) positive group representing adult-onset T1DM. ICA Ab was measured by indirect immunofluorescence. GAD and IA2 Abs were detected by enzyme like immunoadsorbent assay (ELISA). Hashimoto’s thyroiditis was diagnosed by thyroid ultrasound guided needle biopsy and serologic tests for thyreoiglobulin and tissue peroxidase Abs by chemiluminescent immunoassay (CLIA). Body mass index (BMI), waist circumference, arterial hypertension (AH), THS, fT3, fT4, triglycerides, HDL cholesterol and statin use were also evaluated. LADA group showed significantly higher Hashimoto's thyroiditis presence compared to the groups of adult-onset T1DM. Althought all patients had TSH and peripheral thyroid hormone levels within the normal range, TSH was significantly higher in the LADA group compared to other two groups. Higher BMI, waist circumference, statin use and AH presence were more common in the LADA group. In the regression analysis including Ab status, BMI, waist circumference, the use of statins and the presence of AH adjusted for gender and age at diagnosis, single GAD positivity was significantly associated with Hashimoto's thyroiditis (OR 1.977 (1.174-3.328), p=0.001). The association was also significant for waist circumference and statin use (OR 1.038 (1.003- 1.072), p=0.031 ; OR 1.525 (1.171 -1.716), p=0.008). Hashimoto's thyroiditis is more prevalent in patients with LADA compared to other forms of AI diabetes in adults. The possible association of both GAD positivity and waist circumference with the presence of Hashimoto's thyroiditis in LADA patients was found. These results might indicate the potential contribution of central obesity in Hashimoto's pathogenesis which needs to be clarified in further studies.
Diabetologia Croatica, 2014
Interdisciplinary journal of microinflammation, 2014
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Papers by Kristina Blaslov