Quality of life in postmenopausal women with osteoporosis and osteopenia: associations with bone microarchitecture and nutritional status.

PURPOSE: Primary aim of the study was to investigate the status of different health-related quality of life (HRQoL) domains in postmenopausal women with osteoporosis and osteopenia, and to explore possible associations with bone microarchitecture and nutritional status. METHODS: This was a single-center cross-sectional study that included 232 postmenopausal women, from which they were divided into three groups-osteoporosis (OP, N = 63), osteopenia (OPIA, N = 123), and control group (N = 46). Detailed medical history data and anthropometric measurements were taken from all women. Bone structure parameters were taken with DXA device, with additional analysis of bone microarchitecture status with Trabecular Bone Score (TBS). Nutritional status was assessed with Mini Nutritional Assessment (MNA) questionnaire, and HRQoL with Medical Outcomes Study Short Form-36 (SF-36) questionnaire. RESULTS: Nutrition evaluation analysis have shown that patients in OP group had significantly lower values of MNA score compared to the OPIA group and control group (P = 0.005). Furthermore, a significant positive correlation was found between all of the SF-36 domains and MNA scores, while significant positive correlation was found between TBS values and Physical functioning (P < 0.001), Bodily pain (P = 0.027), Social functioning (P = 0.029), and Vitality domains (P = 0.041) in total investigated population. Further analyses were performed only in OP and OPIA groups, and TBS score showed significant positive correlation with Physical functioning (r = 0.248, P < 0.001) and Bodily pain domains as well (r = 0.180, P = 0.014), while MNA score positively correlated with each of the SF-36 domains. Multiple regression models have shown that MNA score retained significant association with each SF-36 domains, and TBS value with Physical functioning (P = 0.003), Social functioning (P = 0.012), and Vitality domains (P = 0.014). CONCLUSION: This study highlights the associations that TBS has with some domains of HRQoL in postmenopausal women with osteoporosis and osteopenia. Moreover, nutritional status could play a role in the complex interplay between TBS and HRQoL.

Medical treatment of acromegaly-experience from the Croatian acromegaly registry.

PURPOSE: The aim of this study was to review therapeutic outcomes of the medical treatment of patients with acromegaly based on real-world data from the Croatian Acromegaly Registry. METHODS: In this retrospective study we investigated 163 patients (101 female, 62 male, age at diagnosis 47.2 ± 13.4 years) treated between 1990 and 2020, of which 53 were treated medically (32.5%). The duration of follow-up was 115.8 ± 304.4 months. The remission rate after the pituitary surgery was achieved in 66.5% (n = 105/158; 5 patients refused surgery). Patients who did not achieve disease remission or had a relapse during follow-up (n = 2), underwent reoperation (n = 18/60, 30%) and/or radiotherapy (n = 33/60, 55%) and/or medical treatment (n = 53/60, 88.3%). One patient refused further treatment after the failure of the first pituitary surgery. RESULTS: Out of 53 patients treated with medical therapy, monotherapy was used in 34 (64.2%) and combination therapy in 19 (35.8%) patients. Remission (IGF-I < 1.2 upper limit of normal, ULN) was achieved in 51 patients (96.2%). Out of 53 patients, 21 (39.6%) were treated with first-generation somatostatin receptor ligand (SRL-1) monotherapy, 10 (18.9%) with dopamine agonist (DA) monotherapy, one (1.9%) with pegvisomant monotherapy, 13 (24.4%) with a combination of SRL-1 and DA, three (5.7%) with a combination of SRL-1, DA and pegvisomant, two (3.8%) with a combination of second-generation somatostatin receptor ligand (SRL-2), DA and pegvisomant and in one (1.9%) temozolomide was added on top of SRL-1 and DA. Two patients currently have active disease, both on SRL-1 monotherapy, of whom one is non-adherent to the treatment. Radiotherapy was applied to 27 (50.9%) patients on medical therapy. CONCLUSION: Our results indicate that almost all patients with active acromegaly after pituitary surgery can achieve biochemical control with medical treatment.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

ADROPIN - POTENTIAL LINK IN CARDIOVASCULAR PROTECTION FOR OBESE MALE TYPE 2 DIABETES MELLITUS PATIENTS TREATED WITH LIRAGLUTIDE.

The aim of this study was to determine plasma adropin concentration and parameters of insulin resistance in obese male type 2 diabetes mellitus (T2DM) patients before and after 3-month liraglutide treatment. In this interventional study, we enrolled 15 obese male T2DM patients with body mass index (BMI) >35 kg/m2, uncontrolled disease and HbA1c >7.5%, having previously taken taking two oral antidiabetic drugs. We modified their therapy to metformin and liraglutide for the next three months. After three months of liraglutide treatment, we observed significant decrease in body weight (from 111.5±18.7 kg to 109.2±17.5 kg, p=0.016) and BMI (from 40.9±7.3 to 40.1±7.0 kg/m2, p=0.021). Plasma adropin concentration increased significantly (p=0.003) compared with baseline. Fasting plasma insulin level decreased from 17.79±6.53 to 13.38±3.51 mU/L (p=0.002), fasting plasma glucose level decreased from 8.66±3.07 to 7.41±2.21 mmol/L (p=0.004) and HbA1c decreased from 7.98±0.70% to 7.26±0.36% (p=0.003). Insulin resistance presented as HOMA-IR decreased significantly from 7.30±5.19 to 4.52±2.61 (p=0.002). Systolic blood pressure, lipid status, liver and kidney function improved, but not reaching statistical significance. Treating obese male T2DM patients with liraglutide resulted in a significantly higher plasma adropin concentration, significant weight loss and improved parameters of insulin resistance, i.e. decreased fasting plasma insulin, plasma glucose levels and HOMA-IR.

Hypoglycemia and Glucagon Utilization in Insulin-Treated Diabetic Patients.

BACKGROUND: First choice of therapy for severe hypoglycemia outside hospital environment is glucagon injection, an undertaught and underused remedy. Aim of this study was to investigate knowledge about glucagon therapy, possession rate and usage rate in insulin-treated diabetic patients, with special emphasis on history of hypoglycemia and severe hypoglycemia episodes. METHODS: In this cross-sectional study, 300 insulin-treated diabetic patients (146 males and 154 females, mean age 61.1±16.4 years) were recruited from comprehensive Diabetes Center in Croatia. Specialized self-administered, 13-item questionnaire regarding glucagon therapy and history of hypoglycemia was obtained from each patient, as well as data collected from medical history documentation. RESULTS: Experience of hypoglycemic episode was reported by 233 (77.7%), and severe hypoglycemia by 73 (24.3%) patients. Participants with experience of hypoglycemia have significantly longer diabetes duration (17.2±11.2 vs. 11.9±8.5 years, P<0.001) and lower BMI values (26.38±3.97 vs. 31.11±7.17 kg/m2, P<0.001). Knowledge about glucagon therapy had 55.3% patients, 44.7% obtained it from the pharmacy, while glucagon was used in 35.6% cases of severe hypoglycemia. Glucagon knowledge was better in patients that attended at least one diabetes lecture (P=0.038), while educational level showed no statistical significance (P=0.286). Main significant positive predictor of glucagon knowledge was history of severe hypoglycemia (OR 4.71, 95% CI 1.38 - 16.02, P=0.013). CONCLUSIONS: Glucagon therapy was underused in treating severe hypoglycemia. It is highly important to emphasize value of quality education as one of the fundamentals of good diabetes management.

Bone metabolism parameters and inactive matrix Gla protein in patients with obstructive sleep apnea†.

STUDY OBJECTIVES: The aim of this study was to investigate differences in dual-energy X-ray absorptiometry (DXA) parameters, trabecular bone score (TBS), bone turnover markers and inactive matrix Gla protein (dp-ucMGP) between patients with obstructive sleep apnea (OSA) and healthy controls. METHODS: This study enrolled 53 male patients diagnosed with OSA, and 50 age- and body mass index (BMI)-matched control subjects. All participants underwent DXA imaging, TBS assessment and blood sampling for biochemical analysis of bone metabolism markers. RESULTS: Mean apnea-hypopnea index (AHI) score of OSA patients was 43.8 ± 18.8 events/h. OSA patients had significantly higher plasma dp-ucMGP levels in comparison to controls (512.7 ± 71.9 vs. 465.8 ± 50.9 pmol/L, p < 0.001). OSA and control group did not significantly differ regarding standard DXA results, while TBS values were significantly lower in the OSA group (1.24 ± 0.17 vs. 1.36 ± 0.15, p < 0.001). AHI score was a significant independent correlate of plasma dp-ucMGP levels (ß ± SE, 1.461 ± 0.45, p = 0.002). In addition, TBS retained a significant relationship with dp-ucMGP values (ß ± SE, -93.77 ± 38.1, p = 0.001). CONCLUSIONS: dp-ucMGP levels are significantly higher in patients with OSA and correlate with disease severity. In addition, TBS values in OSA patients are lower in comparison with the control group and decrease with disease severity.

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: Implications of glycosphingolipid metabolism in pathophysiology of diabetes.

BACKGROUND: Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin-stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). METHODS: Diabetes was induced in male Sprague-Dawley rats by streptozotocin injection (55 mg/kg, i.p., for T1DM induction; 35 mg/kg, i.p., for T2DM induction), followed by feeding of rats with either a normal pellet diet (T1DM) or a high-fat diet (T2DM). Rats were killed 2 weeks after diabetes induction and samples of skeletal muscle were collected. Frozen quadriceps muscle sections were stained with a primary antibody against GM3 (Neu5Ac) and visualized using a secondary antibody coupled with Texas Red. The muscle content of ganglioside GM3 and its precursors was analyzed by high-performance thin-layer chromatography (HPTLC) followed by GM3 immunostaining. RESULTS: Muscle GM3 content was significantly higher in T2DM compared with control rats (P < 0.001). Furthermore, levels of the GM3 precursors ceramide, glucosylceramide, and lactosylceramide were significantly higher in T2DM compared with control rats (P < 0.05), whereas ceramide content was significantly lower in T1DM rats (P < 0.05). The intensity of the GM3 band on HPTLC was significantly higher in T2DM rats (P < 0.001) and significantly lower in T1DM rats (P < 0.05) compared with control. CONCLUSIONS: The expression patterns of GM3 ganglioside and its precursors in diabetic rats suggest that the role of glycosphingolipid metabolism may differ between T2DM and T1DM.

Renal distribution of ganglioside GM3 in rat models of types 1 and 2 diabetes.

Ganglioside GM3 is particularly abundant in the kidney tissue and is thought to play an important role in the maintenance of the charge-selective filtration barrier of glomeruli. Altered expression of ganglioside GM3 was pathologically related with glomerular hypertrophy occurring in diabetic human and rat kidneys. Considering the role of GM3 ganglioside in kidney function, the aim of this study was to determine the difference in expression of GM3 ganglioside in glomeruli and tubules using immunofluorescence microscopy both in rat models of types 1 and 2 diabetes mellitus. Diabetes was induced with streptozotocin (55 mg/kg for type 1 diabetes and 35 mg/kg for type 2 diabetes) injection to male Sprague-Dawley rats which were fed with normal pellet diet (type 1 diabetes) or high-fat diet (type 2 diabetes). Rats were sacrificed 2 weeks after diabetes induction, frozen renal sections were stained with primary antibody GM3(Neu5Ac) and visualized by secondary antibody coupled with Texas red. In addition, renal gangliosides GM3 were analyzed by high-performance thin-layer chromatography followed by GM3 immunostaining. Immunofluorescent microscopy detected 1.7-fold higher GM3 expression in tubules and 1.25-fold higher GM3 in glomeruli of type 1 diabetes mellitus compared with control group. Type 2 diabetes mellitus rats showed slight GM3 increase in whole kidney, unchanged GM3 in glomeruli, but significant higher GM3 expression in tubules, compared with control animals. Taking into consideration increased tubular GM3 content in both types of diabetes, we could hypothesize the role of GM3 in early pathogenesis of diabetic nephropathy.

Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes.

BACKGROUND: Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis. METHODS: A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence. RESULTS: Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated α isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of α, ß, γ, and δ isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged. CONCLUSIONS: Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.

[New insights in steroid diabetes]. / Nove spoznaje o steroidnom dijabetesu.

Glucocorticoids (GC) are the cornerstone in the treatment of numerous chronic autoimmune and inflammatory diseases. GC treatment is accompanied by significant metabolic adverse effects, including insulin resistance, glucose intolerance and diabetes, visceral adiposity, dyslipidemia and skeletal muscle atrophy. GCs are the most common cause of drug-induced diabetes mellitus. However, not everyone treated with glucocorticoids develops diabetes. Predictors of development of diabetes are age, weight, family history of diabetes mellitus, or personal history of gestational diabetes. There is evidence that patients with decreased insulin secretory reserve are much more likely to develop diabetes. Diabetes from topical steroid use is uncommon, but high-dose steroids have been associated with significant hyperglycemia, including development of hyperglycemic hyperosmolar syndrome and even diabetic ketoacidosis in patients with type 1 diabetes mellitus. Several mechanisms contribute to the development of hyperglycemia and steroid-induced diabetes, including decreased peripheral insulin sensitivity, increased hepatic glucose production, and inhibition of pancreatic insulin production and secretion. Physicians treating patients with GCs should be aware of the induction of metabolic disturbances and should not solely rely on fasting measurements. In addition, our review indicates that insulin therapy could be considered when treating patients on GC therapy.