The role of gastrointestinal peptides in the pathogenesis and treatment of obesity

Pretilost predstavlja jedan od najvećih zdravstveno-ekonomskih i socijalnih problema današnjice te se sve veća učestalost pretilosti povezuje s porastom incidencije i pobola niza drugih bolesti, prije svega šećerne bolesti, kardiovaskularnih i cerebrovaskularnih oboljenja te malignih bolesti. U održavanju ravnoteže unosa i potrošnje energije najvažniju regulatornu ulogu ima središnji živčani sustav, odnosno osovina mozak-crijevo, koja se temelji na funkciji niza gastrointestinalnih peptidnih hormona. Djelovanje navedenih peptida izrazito je raznoliko i ovisi o nizu čimbenika, posebno vrsti i količini hrane, energetskom stanju organizma te pratećim bolestima i metaboličkim poremećajima. Djelovanje ovih hormona usko je povezano s endokrinom funkcijom gušterače, lučenjem inzulina i regulacijom glikemije, što ujedno ukazuje i na jasnu povezanost pretilosti i šećerne bolesti. Velik napredak na području razvoja i primjene novih antidijabetika u klasi peptidnih hormona, odnosno inkretina, te utvrđivanje njihovih dodatnih svojstava u smislu redukcije tjelesne težine, otvorili su tijekom posljednjih godina čitavo novo područje istraživanja farmakoterapije pretilosti. Obećavajuće rezultate prije svega pružaju nove mogućnosti kombinacije više lijekova, čime se ponovno stvara mogućnost razvoja adekvatne farmakoterapije kao alternative kirurškom pristupu liječenju pretilosti.Obesity is one of the biggest health-economic and social problems of today and its increasing incidence is aassociated with an increasing incidence and morbiditiy of a number of other diseases, primarily diabetes, cardiovascular and cerebrovascular diseases, and malignant diseases as well. The central nervous system, that is the brain-gut axis has the central role in maintaining the balance of input and energy consumption, which is regulated by a variety of gastrointestinal peptide hormones. The role and action of these peptides is highly variable and depends on a number of factors, especially the type and the amount of food, energy status of the organism, and the accompanying diseases and metabolic disorders. They are closely connected with the pancreatic endocrine function, insuline secretion and regulation of glycaemia, which also shows a clear link between obesity and diabetes. A great progress in the development and appication of new antidiabetics in the class of peptide hormones or incretins, and their additional weight-loss properties have opened a whole new field of the pharmacotherapy researches in the treatment of obesity. The promising results are provided by the new drug combinations, which leads to new possibilities of pharmacotherapy as an alternative to the surgical treatment of obesity

The Prevalence of Depression and Anxiety in Seafarers Type 2 Diabetic Patients

Depression and anxiety are co-morbid condition in diabetes as disease-related psychological reactions on this chronic metabolic illness. This study was aimed to determine the occurrence of depression and anxiety in seafarer’s type 2 diabetic patients. A random sample of 52 diabetic seafarers treated with diet and oral glucose lowering agents, and 56 healthy seafarers were screened for depression with The Beck Depression Inventory (BDI) and for anxiety with State- -Trait Anxiety Inventory (STAI 1, STAI 2). Depression (BDI>18.5) and anxiety (STAI<28.5) was significantly higher in the group of diabetic seafarers than in control group (more than 30%). Significant correlation was noted between depression and duration of diabetes mellitus, degree of obesity and poor glycaemic control (HbA1C>8%) and longer duration of shipping routes (over 6 months). The proportion of depression and anxiety was found higher in seafarer’s type 2 diabetic patients than in the healthy seafarers

Preliminary Report of Hypoglycemic Response in Obese Metabolic Syndrome Males Treated with Metformin after Weight Loss Intervention

We conducted this study to determine the degree of obesity influence on the hypoglycemic response of growth hormone and cortisol after weight loss of 5%. A total of 45 non-diabetic, male subjects followed in the outpatient endocrinological departments were divided into three groups comprising 15 subjects in each group, based upon body mass index (BMI) to healthy, overweight and obese group. Metformin was administered in the dose of 50 mg daily to the overweight and obese participants. Cortisol was measured at 0, 60 and 120 minutes. Growth hormone (GH) was measured at –15, 0, 30, 60, 90 and 120 minutes.Values of cortisol and GH were compared upon changes in hypothalamo-pituitary-adrenal (HPA) response to insulin induced hypoglycemia initially and after weight loss of 5% for overweight and obese participants.The BMI of the healthy group ranged 20.0–24.5 kg/m2 (median: 22.8); overweight group ranged 25.9–29.7 kg/m2 (median: 28.3); and obese group ranged 30.9–34.6 kg/m2 (median: 32.6). There were no significant differencesof cortisol values among groups at 0 (c²=2.0; p=0.365); 60 (c²=0.754; P=0.686) and at 120 minutes (c²=0.466; p=0.792). The comparisons among groups were significant for differences of GH values at –15 (c²=25.0; p<0.01); 0 (c²=16.2; p<0.01); 30 (c²=16.2; p<0.01); 60 (c²=32.8; p<0.01); 90 (c²=30.2; p<0.01) and at 120 minutes (c²=27.3; p<0.01).Healthy and obese subjects significantly differed in growth hormone response at –15 (Z=4.67; p<0.01); 0 (Z=3.83; p<0.01); 60 (Z=2.78; p=0.05); 90 (Z=4.67; p<0.01) and at 120 minutes (Z=4.23; p<0.01).Changes on the various levels of HPA axis, when it is activated by a stress as it is the case in insulin-induced hypoglycemia correspond to the degree of obesity. Weight loss of 5% was not enough for restoration of a normal stimulated growth hormone release and did not influence on the level of cortisol

Commentary: Short Body Height and Pre-pregnancy Overweight for Increased Risk of Gestational Diabetes Mellitus: A Population-Based Cohort Study

Li J et al. conduct a sufficiently large cohort study and show that the risk of gestational diabetes mellitus (GDM) is inversely correlated with the height of the pregnant women (1). This association is particularly seen among Asians and may not warrant biological plausibility for using short stature as screening criteria due to several reasons (2). First, short stature can be associated principally through the mechanism of greater risk of obesity/fat mass (3). Co-presence of short stature and overweight in the pre-pregnant women might be more useful screening criteria (4). Second, the same adaptive alterations that protected these women from undernourishment during their early development could have led them to short stature, as well as lead to glucose intolerance (thrifty phenotype hypothesis) (5, 6). It is also possible that a genetically determined insulin effect could lead to both failure to grow and to diabetes (thrifty genotype) ; which might have contributed to a predisposition for GDM (7, 8). GDM, as a form of diabetes is multifactorial disease in origin. Several factors such as greater prepregnancy BMI, age, weight gain and a parental history of diabetes mellitus are independently associated with the GDM (9). The epidemiologic studies using the selective criteria such as height as a risk factor may not mean much in a heterogeneous population with different types of genetic lineage and environmental influences. Height is merely a function of nutrition and genetic lineage ; therefore, measuring the height of the women in childbearing age will not reflect undernourishment or frequent infections in their infancy and through their life-course. Future studies have to reflect height as an intermediate variable between early exposures in fetal and childhood with subsequent risk of non-communicable diseases including the GDM

The Prevalence of Depression and Anxiety in Seafarers Type 2 Diabetic Patients

Depression and anxiety are co-morbid condition in diabetes as disease-related psychological reactions on this chronic metabolic illness. This study was aimed to determine the occurrence of depression and anxiety in seafarer’s type 2 diabetic patients. A random sample of 52 diabetic seafarers treated with diet and oral glucose lowering agents, and 56 healthy seafarers were screened for depression with The Beck Depression Inventory (BDI) and for anxiety with State- -Trait Anxiety Inventory (STAI 1, STAI 2). Depression (BDI>18.5) and anxiety (STAI<28.5) was significantly higher in the group of diabetic seafarers than in control group (more than 30%). Significant correlation was noted between depression and duration of diabetes mellitus, degree of obesity and poor glycaemic control (HbA1C>8%) and longer duration of shipping routes (over 6 months). The proportion of depression and anxiety was found higher in seafarer’s type 2 diabetic patients than in the healthy seafarers

Corticosteroids-induced diabetes mellitus: modern concepts and perspectives in the treatment

Kortikosteroidi izazivaju pojavu steroidnog oblika šećerne bolesti mnogobrojnim mehanizmima. Kortikosteroidi povećavaju otpornost na inzulin u stanicama jetre i stanicama drugih tkiva kao što su masno i mišićno tkivo. Imaju štetno djelovanje na beta-stanice gušterače, smanjenja unosa glukoze u stanice i indukcije apoptoze. Čimbenici rizika za razvoj steroidne šećerne bolesti su doza i dugotrajnost primjene kortikosteroida, dob, obiteljska anamneza šećerne bolesti, debljina, rasa i prethodno postojanje šećerne bolesti. Pristup pacijentima sa steroidnom šećernom bolešću je dijeta, tjelovježba i samokontrola glukoze u plazmi. Ako glikemija natašte ili nakon obroka naraste preko 11,1 mmol/l preporučena je primjena inzulina.The mechanism of corticosteroids-induced diabetes mellitus is multifactorial. Corticosteroids induce hepatic and extrahepatic insulin resistance. Corticosteroids have direct harmful effects on insulin-secreting beta cells of the pancreas, decreasing in glucose transport into the beta cells and inducing apoptosis. The risk of corticosteroids-induced diabetes increases with the corticosteroids dosage, duration of therapy, age, family history of diabetes mellitus, obesity, ethnicity and high blood glucose concentrations before corticosteroids therapy. Treatment of patients with corticosteroids-induced hyperglycaemia is diet, exercise and self-monitoring of blood glucose level. Patients with persistent fasting and daytime blood glucose concentrations over 11.1 mmol/L, the treatment with insulin is recommended

Reg IV Protein is Expressed in Normal Rat Tissue

The Reg IV gene has been documented in the colon, small intestine, stomach and pancreas of the human. Expression of the Reg IV in different cell types has been associated with regeneration, cell growth and cell survival, cell adhesion and resistance to apoptosis. It is unknown whether the Reg IV protein is present in the normal rat tissue. The aim of this study was to reveal the expression of the Reg IV protein in the rat spleen and colon. Western blot analysis using antibody specific for Reg IV protein were performed on rat spleen and colon extracts. Low level of Reg IV expression was found in all examined colon samples. The expression of Reg IV protein in spleen tissue was significantly higher than in the colon. Reg IV protein was immunohistochemically stained in a few epithelial cells in the basal portion of colon crypts and in a large spleen cells which were scattered in the red pulp. Our results demonstrate for the first time the presence of the Reg IV protein expression in the healthy spleen and colon tissue of the rat. Other members of the Reg family, Reg I and Reg III proteins have been shown to act as a growth factors in gastrointestinal tract, but without further experiments we can only assume the potential role of the Reg IV protein in spleen and colon cell growth

Preliminary Report of Hypoglycemic Response in Obese Metabolic Syndrome Males Treated with Metformin after Weight Loss Intervention

We conducted this study to determine the degree of obesity influence on the hypoglycemic response of growth hormone and cortisol after weight loss of 5%. A total of 45 non-diabetic, male subjects followed in the outpatient endocrinological departments were divided into three groups comprising 15 subjects in each group, based upon body mass index (BMI) to healthy, overweight and obese group. Metformin was administered in the dose of 50 mg daily to the overweight and obese participants. Cortisol was measured at 0, 60 and 120 minutes. Growth hormone (GH) was measured at –15, 0, 30, 60, 90 and 120 minutes.Values of cortisol and GH were compared upon changes in hypothalamo-pituitary-adrenal (HPA) response to insulin induced hypoglycemia initially and after weight loss of 5% for overweight and obese participants.The BMI of the healthy group ranged 20.0–24.5 kg/m2 (median: 22.8); overweight group ranged 25.9–29.7 kg/m2 (median: 28.3); and obese group ranged 30.9–34.6 kg/m2 (median: 32.6). There were no significant differencesof cortisol values among groups at 0 (c²=2.0; p=0.365); 60 (c²=0.754; P=0.686) and at 120 minutes (c²=0.466; p=0.792). The comparisons among groups were significant for differences of GH values at –15 (c²=25.0; p<0.01); 0 (c²=16.2; p<0.01); 30 (c²=16.2; p<0.01); 60 (c²=32.8; p<0.01); 90 (c²=30.2; p<0.01) and at 120 minutes (c²=27.3; p<0.01).Healthy and obese subjects significantly differed in growth hormone response at –15 (Z=4.67; p<0.01); 0 (Z=3.83; p<0.01); 60 (Z=2.78; p=0.05); 90 (Z=4.67; p<0.01) and at 120 minutes (Z=4.23; p<0.01).Changes on the various levels of HPA axis, when it is activated by a stress as it is the case in insulin-induced hypoglycemia correspond to the degree of obesity. Weight loss of 5% was not enough for restoration of a normal stimulated growth hormone release and did not influence on the level of cortisol

Nutritional Risk Screening in Hospitalized and Haemodialysis Patients

Malnutrition is an independent risk factor impacting on higher complications and increased length of hospital stay and costs. The aim of this study was to determine the prevalence of nutritional risk among patients on regular haemodialysis (HD) (Group I, N=105) and among the patients at Gastroenterology, Endocrinology, Hematology and Clinical Immunology (Group II, N=652). Cross-sectional nutritional evaluation was done using Nottingham Hospital Screening Tool (NS). The prevalence of nutritional risk was 9% in Group I and 21% in Group II (p=0.0002). We found statistically significant larger quantity of malnourished patients among acute internistic patients than among chronic from the same Group II. Malnutrition among patients on HD didn’t differ statistically to chronic internistic patients. We didn’t found a significantly higher percentage of nutritional risk among elderly patients (65 years and more). Correlation between body mass index (BMI) and NS was significant, but weak (r=–0.32). We can conclude that the prevalence of nutritional risk among HD patients was lower than we had expected. It seems that the screening tool we used is not sensitive enough for HD patients and needs further investigations

The Effects of Long-Term Experimental Diabetes Mellitus Type I on Skeletal Muscle Regeneration Capacity

Muscle fibers are dynamic structures capable of altering their phenotype under various pathological conditions. The aim of the present study was to investigate the influence of long-lasting diabetes mellitus on the process of muscle regeneration in the skeletal muscle. Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (STZ). The regeneration process in the skeletal muscle was induced in slow (m. soleus, SOL) and fast (m. extensor digitorum longus, EDL) muscles by injection of local anesthetic (bupivacaine). Skeletal muscles were analyzed 10 days, 4 and 8 weeks after bupivacaine treatment. Diabetes mellitus has changed morphological properties of both slow and fast skeletal muscles during the process of regeneration. These changes are evident in redistribution of muscle fibers and significant level of atrophy. All fiber types of diabetic fast muscles showed stronger atrophy than muscle fibers in slow muscles which have more oxidative metabolism. The changes of redistribution of muscle fibers depend on duration of diabetes and affect all types of muscle fibers