State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

IL-21 and other serum proinflammatory cytokine levels in patients with multiple myeloma at diagnosis

Background: IL-6, IL1-β, TNF-α and IL-21 have been identified in the growth, progression and dissemination of multiple myeloma. To dte, there is no published data about serum levels of IL-21 in patients with multiple myeloma. In the present study we have investigated circulating levels of cytokines, such as IL-6, IL-1β, TNF-α, IL-21 and the association of these levels with the disease stage in newly diagnosed multiple myeloma patients. Materials and Methods: Twenty healthy controls and 44 newly diagnosed multiple myeloma patients were evaluated. Patients were classified according to Durie-Salmon criteria, international staging system (ISS) and bone disease. Quantification of cytokine levels in serum were performed by using ELISA. Results: The levels of cytokines in patients′ serum are found elevated than healthy controls. However, only the serum levels of IL-1β and TNF-α were found statistically significant. TNF-α levels of patients with ISS stage 3 were significantly higher than patients with ISS stage 1 and 2 (P 0.000). IL-1β was significantly elevated in advanced stage patients (stage II-III) (P 0.040). There was no correlation between IL-1β, TNF-α, IL-21 levels and bone lesions. IL-6 levels were significantly elevated who have at least three visible lytic bone lesions and/or bone fracture in comparison to patients who have one or two visible or no visible lytic bone lesions (P 0.048). Conclusion: It appears that there is no association of serum IL-21 level with multiple myeloma in contrast to the other cytokines such as IL-6, IL-1β, TNF-α

IL-21 and other serum proinflammatory cytokine levels in patients with multiple myeloma at diagnosis

Background: IL-6, IL1-β, TNF-α and IL-21 have been identified in the growth, progression and dissemination of multiple myeloma. To dte, there is no published data about serum levels of IL-21 in patients with multiple myeloma. In the present study we have investigated circulating levels of cytokines, such as IL-6, IL-1β, TNF-α, IL-21 and the association of these levels with the disease stage in newly diagnosed multiple myeloma patients. Materials and Methods: Twenty healthy controls and 44 newly diagnosed multiple myeloma patients were evaluated. Patients were classified according to Durie-Salmon criteria, international staging system (ISS) and bone disease. Quantification of cytokine levels in serum were performed by using ELISA. Results: The levels of cytokines in patients′ serum are found elevated than healthy controls. However, only the serum levels of IL-1β and TNF-α were found statistically significant. TNF-α levels of patients with ISS stage 3 were significantly higher than patients with ISS stage 1 and 2 (P 0.000). IL-1β was significantly elevated in advanced stage patients (stage II-III) (P 0.040). There was no correlation between IL-1β, TNF-α, IL-21 levels and bone lesions. IL-6 levels were significantly elevated who have at least three visible lytic bone lesions and/or bone fracture in comparison to patients who have one or two visible or no visible lytic bone lesions (P 0.048). Conclusion: It appears that there is no association of serum IL-21 level with multiple myeloma in contrast to the other cytokines such as IL-6, IL-1β, TNF-α

Diabetes Attitudes, Wishes and Needs second study (DAWN2: cross-national benchmarking of diabetes-related psychosocial outcomes for people with diabetes

AimsThe second Diabetes Attitudes, Wishes and Needs (DAWN2) study aimed to assess psychosocial outcomes in people with diabetes across countries for benchmarking.MethodsSurveys included new and adapted questions from validated questionnaires that assess health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improving diabetes care. Questionnaires were conducted online, by telephone or in person.ResultsParticipants were 8596 adults with diabetes across 17 countries. There were significant between-country differences for all benchmarking indicators; no one country's outcomes were consistently better or worse than others. The proportion with likely depression [WHO-5 Well-Being Index (WHO-5) score ? 28] was 13.8% (country range 6.5–24.1%). Diabetes-related distress [Problem Areas in Diabetes Scale 5 (PAID-5) score ? 40] was reported by 44.6% of participants (17.2–67.6%). Overall quality of life was rated ‘poor’ or ‘very poor’ by 12.2% of participants (7.6–26.1%). Diabetes had a negative impact on all aspects investigated, ranging from 20.5% on relationship with family/friends to 62.2% on physical health. Approximately 40% of participants (18.6–64.9%) reported that their medication interfered with their ability to live a normal life. The availability of person-centred chronic illness care and support for active involvement was rated as low. Following self-care advice for medication and diet was most common, and least common for glucose monitoring and foot examination, with marked country variation. Only 48.8% of respondents had participated in diabetes educational programmes/activities to help manage their diabetes.ConclusionsCross-national benchmarking using psychometrically validated indicators can help identify areas for improvement and best practices to drive changes that improve outcomes for people with diabetes

Diabetes attitudes, wishes and needs: second study (DAWN2). Cross-national comparisons on barriers and resources for optimal care-healthcare professional perspective

Aims The second Diabetes Attitudes, Wishes and Needs (DAWN2) study sought cross-national comparisons of perceptions on healthcare provision for benchmarking and sharing of clinical practices to improve diabetes care. Methods In total, 4785 healthcare professionals caring for people with diabetes across 17 countries participated in an online survey designed to assess diabetes healthcare provision, self-management and training. Results Between 61.4 and 92.9% of healthcare professionals felt that people with diabetes needed to improve various self-management activities; glucose monitoring (range, 29.3–92.1%) had the biggest country difference, with a between-country variance of 20%. The need for a major improvement in diabetes self-management education was reported by 60% (26.4–81.4%) of healthcare professionals, with a 12% between-country variance. Provision of diabetes services differed among countries, with many healthcare professionals indicating that major improvements were needed across a range of areas, including healthcare organization [30.6% (7.4–67.1%)], resources for diabetes prevention [78.8% (60.4–90.5%)], earlier diagnosis and treatment [67.9% (45.0–85.5%)], communication between team members and people with diabetes [56.1% (22.3–85.4%)], specialist nurse availability [63.8% (27.9–90.7%)] and psychological support [62.7% (40.6–79.6%)]. In some countries, up to one third of healthcare professionals reported not having received any formal diabetes training. Societal discrimination against people with diabetes was reported by 32.8% (11.4–79.6%) of participants. Conclusions This survey has highlighted concerns of healthcare professionals relating to diabetes healthcare provision, self-management and training. Identifying between-country differences in several areas will allow benchmarking and sharing of clinical practices