Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes

Abstract Background Two types of fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA) have been approved for use in type 2 diabetes. One is insulin degludec/liraglutide (iDergLira), and the other is insulin glargine/lixisenatide (iGlarLixi). Direct comparisons between these two combination is not available. Methods The retrospective study included 186 patients with type 2 diabetes mellitus (DM) with inadequate glycemic control on metformin and basal insulin (degludec, glargine 100, glargine 300) who were switched to fixed-ratio combination GLP-1 RA and basal insulin. Patients were divided into two groups based on the basal insulin before study: group I (n = 86) treated with degludec were switched to iDegLira and patients group II (n = 99), treated with glargine were switched to iGlarLixi. The aim of this study was to directly compare the effects between two fixed – ratio combination on glycemic parameters and non glycemic parameters. Follow up was 6 months. Results Mean HbA1c decreased similarly (− 1.2% vs.-1.1%). Higher percentage patients in iDegLira group had reached the HbA1c  0.05). Change in body weight was significant in iDegLira group (1.8 kg vs. 0.7 kg, p < 0.001). At the end of the study patients showed decrease in total cholesterol (TC) and low-density lipoprotein (LDL) for 0.2 mmol/L in iDegLira, 0.1 mmol/l in iGlarLixi, triglycerides decreased 0.3 mmol/l in both groups, high-density lipoprotein(HDL) increased 0.1 mm/l in iGlarLixi. Conclusion Our results showed that more patients with iDegLira had HbA1c less than 7% and these combination had better effect on weight loss. There was no difference observed in FPG and PPG, lipid profile and rate of hypoglycemia

Adipocytokine responses to acute exercise in athletes with different body fat content and sedentary controls

Introduction: Recent research in the biology of adipose tissue indicates that it is far more than a simply an energy storage organ, and it is in fact an active endocrine organ secreting numerous bioactive mediators, called adipokines, including leptin, adiponectin and visfatin (Galic, 2010). To date, less attention has been focused on the kinetics of adipokines levels during and after high intensity exercise. Several reports pointed at the metabolic role of adipokines during exercise in elite athletes, but the data are currently equivocal (Bouassida et al., 2010; Jürimäe et al., 2011). Objectives: The aim of this study was to investigate adipocytokine responses to a single bout acute exercise in elite athletes with low percentage of body fat, elite athletes with a high percentage of body fat and sedentary controls. Methods: Sixteen athletes with low percentage of body fat (volleyball players, low fat athletes group, LFAG), fifteen athletes with high percentage of body fat (water polo players, high fat athletes group, HFAG) and fifteen sedentary subjects participated in this study (age [years] 20±2; 20±2; 20±1, respectively). All subjects were exposed to: anthropometric measurements; exercise test on treadmill in order to examine acute changes of adipocytokines; blood samples were obtained at baseline levels, immediately after the exercise test and 30 minutes after recovery. Separated serum or plasma were used for hormone (leptin, adiponectin and visfatin) ELISA analysis. Results: In athletes in LFAG, baseline leptin concentration was significantly lower, but adiponectin and visfatin concentrations were significantly higher, compared to sedentary controls and athletes in HFAG (p<0.05, all). There were no significant post exercise or recovery changes in adiponectin concentration (p>0.05). Conclusions: Our findings show leptin and visfatin levels, but not adiponectin respond to acute exercise. Acute exercise elicited an inverse visfatin response in athletes in HFAG and controls. Also, these results suggest that leptin is altered after acute exercise only in sedentary individuals

Pro12Ala gene polymorphism in the peroxisome proliferator-activated receptor gamma as a risk factor for the onset of type 2 diabetes mellitus in the Serbian population

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a gene candidate for the onset of type 2 diabetes mellitus (T2DM). We investigated the association of the PPAR gamma Pro12Ala gene with the onset of T2DM for the first time in the Serbian population. The study population consisted of 197 controls and 163 T2DM patients. The 12Ala allele tended to be more frequent in the group of T2DM patients (0.11) compared to the control subjects (0.09). The results from this study indicate that the PPAR gamma(2) 12Ala allele presents a non-significant risk factor for T2DM development in the Serbian population

AMP-activated protein kinase-dependent and -independent mechanisms underlying in vitro antiglioma action of compound C

We investigated the effect of compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), on proliferation and viability of human U251 and rat C6 glioma cell lines. Compound C caused G(2)/M cell cycle block, accompanied by apoptotic glioma cell death characterized by caspase activation, phosphatidylserine exposure and DNA fragmentation. The mechanisms underlying the pro-apoptotic action of compound C involved induction of oxidative stress and downregulation of antiapoptotic molecule Bcl-2, while no alteration of pro-apoptotic Bax was observed. Compound C diminished AMPK phosphorylation and enzymatic activity, resulting in reduced phosphorylation of its target acetyl CoA carboxylase. AMPK activators metformin and AICAR partly prevented the cell cycle block, oxidative stress and apoptosis induced by compound C. The small interfering RNA (siRNA) targeting of human AMPK mimicked compound C-induced G(2)/M cell cycle arrest, but failed to induce oxidative stress and apoptosis in U251 glioma cells. In conclusion, our data indicate that AMPK inhibition is required, but not sufficient for compound C-mediated apoptotic death of glioma cells. (c) 2009 Elsevier Inc. All rights reserved

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved

Pitfalls in diagnosing a small cystic insulinoma: a case report

<p>Abstract</p> <p>Insulinoma is a rare pancreatic endocrine tumour and is typically sporadic and solitary. Over 90% of all insulinomas are benign. Cystic insulinomas are also rare. It is not difficult to determine the site of such neoplasm, as cystic insulinomas are usually 4–10 cm in diameter. We present the case of a patient with a histologically confirmed cystic insulinoma diagnosed after approximately 10 years of hypoglycaemia symptoms. This case is unique because of the small size (2.2 cm) of the tumour. Endoscopic ultrasound (EUS) was useful for localizing this tumour.</p