Treatment of osteoporosis with teriparatide: The Slovenian experience.

The aim of this study was to investigate the characteristics of postmenopausal women prescribed with teriparatide in Slovenia, during the first decade after its approval, and the predictors of bone mineral density (BMD) improvement with treatment. We retrospectively studied postmenopausal osteoporotic patients prescribed with teriparatide at tertiary center from 2006 to 2015. BMD was measured at standard sites by DXA at baseline, after 12 and 24 months. 25-hydroxyvitamin D and procollagen type I N-terminal propeptide (PINP) were measured at the same time-points. The inclusion criteria were met by 188 women (aged 71 years on average), 151 (80.3%) with postmenopausal and 37 (19.7%) with glucocorticoid-induced osteoporosis. Everyone had at least one fracture, 159 (84.6%) had ≥2 fractures, with vertebral fractures in 172 patients (91.5%). All patients had been previously on antiresorptives for 8.6 years on average. The average BMD change at lumbar spine, total hip, and femoral neck was +5.0%, -1.1%, and +0.3% after 24 months of treatment, respectively. Higher baseline PINP was associated with higher BMD increase at all sites after the first 12 months. Teriparatide was prescribed mostly to elderly women with severe osteoporosis who had sustained two or more fractures despite long-term antiresorptive therapy. Baseline PINP might predict initial BMD increase with teriparatide.

SLC6A4 5HTTLPR Polymorphism Affects Insulin Secretion in Patients with Polycystic Ovary Syndrome.

PURPOSE: To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. RESULTS: Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p = 0.030) and with the area under the curve of insulin blood levels during OGTT (p = 0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. CONCLUSIONS: Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.

SORCS1 polymorphism and insulin secretion in obese women with polycystic ovary syndrome.

We investigated the influence of SORCS1 polymorphisms on insulin secretion in obese women with PCOS. Metabolic status was recorded in 50 clinically well characterized PCOS patients. Oral glucose tolerance test was performed and laboratory parameters of insulin resistance measured. All patients were genotyped for SORCS1 rs1358030, rs1416406 and rs11192966 polymorphisms. Statistical analysis was performed using the Mann-Whitney test. SORCS1 rs1416406 significantly influenced stimulated glucose plasma levels (p = 0.006) and increased glucose stimulated insulin secretion (p = 0.034). None of the polymorphisms influenced insulin resistance as measured by homeostatic model assessment. We report for the first time the relevance of SORCS1 polymorphisms for glycemic control and glucose stimulated insulin secretion in obese women with PCOS.

Comparison of different methods investigating functional and morphological markers of early atherogenesis in obese women with polycystic ovary syndrome.

BACKGROUND: The prognostic importance of preclinical markers of atherosclerosis and their interrelationship are inconclusive. In this study interrelationship between different methods investigating endothelial function and intima media thickness (IMT) was investigated in patients with polycystic ovary syndrome (PCOS). METHODS: Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD), nitrate-mediated dilation (NMD), low-flow-mediated constriction (L-FMC) and peripheral arterial tonometry (PAT). Arterial stiffness was determined by pulse wave velocity (PWV) and the Augmentation Index (AI). The IMT of carotid arteries was measured. RESULTS: Twenty-eight obese women were recruited with the diagnosis of PCOS, mean age 27±7.2 years and Body Mass Index 38.8±6.3 kg/m2. A relationship between FMD and NMD (r=0.44, P=0.02) was shown. FMD as well as NMD of the brachial artery were not correlated with L-FMC or PAT. The AI and PWV, indicators of arterial stiffness were not interrelated with FMD, and there was no significant interrelationship between IMT and FMD or NMD. The AI was related only to IMT (r=0.45, P=0.30). CONCLUSIONS: The relationship between available methods for evaluation of endothelial function/dysfunction is weak in PCOS. This indicates that different methods investigate different mechanisms and various sections of the circulatory system.

Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.

OBJECTIVE: The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory. In this study, we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost <5% body weight during pretreatment with metformin. METHODS: A total of 40 obese women with PCOS, who had been pretreated with metformin for at least 6 months, participated in a 12-week open-label, prospective study. They were randomized to one of three treatment arms: metformin (MET) arm 1000 mg BID, liraglutide (LIRA) arm 1.2 mg QD s.c., or combined MET 1000 mg BID and LIRA (COMBI) 1.2 mg QD s.c. Lifestyle intervention was not actively promoted. The primary outcome was change in body weight. RESULTS: Thirty six patients (aged 31.3 ± 7.1 years, BMI 37.1 ± 4.6 kg/m²) completed the study: 14 on MET, 11 on LIRA, and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI, and waist circumference. Subjects treated with COMBI lost on average 6.5 ± 2.8 kg compared with a 3.8 ± 3.7 kg loss in the LIRA group and a 1.2 ± 1.4 kg loss in the MET group (P<0.001). The extent of weight loss was stratified: a total of 38% of subjects were high responders who lost ≥5% body weight, 22% of them in the COMBI arm compared with 16 and 0% in the LIRA and MET arm respectively. BMI decreased by 2.4 ± 1.0 in the COMBI arm compared with 1.3 ± 1.3 in LIRA and 0.5 ± 0.5 in the MET arm (P<0.001). Waist circumference also decreased by 5.5 ± 3.8 cm in the COMBI arm compared with 3.2 ± 2.9 cm in LIRA and 1.6 ± 2.9 cm in the MET arm (P=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss. CONCLUSIONS: Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had previously been poor responders regarding weight reduction on metformin monotherapy.

Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome.

In addition to its effects on reproductive health, it is now well recognized that polycystic ovary syndrome (PCOS) is a metabolic disorder, characterized by decreased insulin sensitivity which leads to an excess lifetime risk of type 2 diabetes and cardiovascular disease. PCOS patients are often obese, hypertensive, dyslipidemic and insulin resistant; they have obstructive sleep apnea and have been reported to have higher aldosterone levels in comparison to normal healthy controls. These are all components of an adverse cardiovascular risk profile. Many studies exploring subclinical atherosclerosis using different methods (flow-mediated dilatation, intima media thickness, arterial stiffness, coronary artery calcification) as well as assessing circulating cardiovascular risk markers, point toward an increased cardiovascular risk and early atherogenesis in PCOS. The risk and early features of subclinical atherosclerosis can be reversed by non-medical (normalization of weight, healthy lifestyle) and medical (metformin, thiazolidinediones, spironolactone, and statins) interventions. However, the long-term risk for cardiovascular morbidity and mortality as well as the clinical significance of different interventions still need to be properly addressed in a large prospective study.