Salivary testosterone measurement in women with and without polycystic ovary syndrome

Clinical and/or biochemical hyperandrogenism is one of the diagnostic criteria for PCOS. An evaluation of the role of salivary testosterone (salT) and androstenedione (salA) for the diagnosis of PCOS was undertaken in a cross sectional study involving 65 women without PCOS and 110 women with PCOS fulfilling all 3 diagnostic Rotterdam criteria. Serum and salivary androgen measurements were determined by LC-MS/MS. salT and salA were significantly elevated in PCOS compared to controls (P<001). No androgen marker was more predictive than another using ROC curves, but multiple logistic regression suggested salT was more predictive than free androgen index (FAI)(p<0.01). The combination of salT or FAI identified 100% of PCOS women. PCOS women with both biochemical and clinical hyperandrogenism as opposed to clinical hyperandrogenism alone showed a metabolic phenotype (p<0.05) and insulin resistance(p<0.001). PCOS patients with an isolated elevated FAI showed increased insulin resistance compared to those with an isolated salT(P<0.05). salT appeared to be at least as predictive as FAI for the diagnosis of the classical PCOS phenotype, and the combination of salT or FAI identified 100% of PCOS patients. This suggests that salT measurement by LC-MS/MS holds the promise of complementing existing laboratory tests as a means of assessing hyperandrogenemia

Effects of human recombinant growth hormone on exercise capacity, cardiac structure, and cardiac function in patients with adult-onset growth hormone deficiency

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group

Impact of severe hypoglycemia on the heat shock and related protein response

Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case–control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D. Trial registration: ClinicalTrials.gov NCT03102801

Physical Activity and Sedentary Behaviors Levels of Kuwaiti Adolescents: The Study of Health and Activity Among Adolescents in Kuwait.

BACKGROUND: There is only scarce number of studies available describing the lifestyle of adolescents living in Arab countries. Hence, we described physical activity (PA) and sedentary behaviors patterns among Kuwaiti adolescents and the associations with parental education. METHODS: Cross-sectional data from 435 adolescents (201 boys and 234 girls) were collected from the Study of Health and Activity among Adolescents in Kuwait conducted between 2012 and 2013. Outcome variables included PA (ActiGraph GT1M accelerometers) and sedentary behaviors. Exposure variable was parental education. Descriptive and multiple logistic regression analyses were used to examine the association between parental education and outcome variables. RESULTS: Total sedentary time (minutes per day) was higher in girls [568.2 (111.6)] than in boys [500.0 (102.0)], whereas boys accumulated more minutes in light, moderate, and vigorous PA (all Ps ≤ .001). In total, 3.4% of adolescents spent ≥60 minutes per day of moderate to vigorous PA (by accelerometry), while only 21% met the screen time guidelines. Low/medium maternal education was associated with a higher odds of exceeding screen time guidelines (odds ratio = 2.09; 95% confidence interval, 1.09-4.02). CONCLUSIONS: Most Kuwaiti adolescents in this sample were physically inactive and exceeded screen time guidelines. Objective PA was not socially patterned, yet an inverse association between maternal education and screen time behaviors was found

Hypoglycaemia in type 2 diabetes exacerbates amyloid-related proteins associated with dementia

ObjectiveHypoglycemia in diabetes (T2D) may increase the risk for Alzheimer's disease (AD). We hypothesized that hypoglycemia‐induced amyloid‐related protein changes would be exacerbated in T2D.MethodsA prospective, parallel study in T2D (n=23) and controls (n=23). Subjects underwent insulin‐induced hypoglycemia with blood sampling at baseline, hypoglycemia and post‐hypoglycemia; proteomic analysis of amyloid‐related proteins was undertaken.ResultsAt baseline: Amyloid‐precursor protein (APP) (

Glucose excursions in type 2 diabetes modulate amyloid-related proteins associated with dementia

We have reported that hypoglycemia was associated with changes in Alzheimer’s disease (AD)-related proteins in accord with the direct link of cognitive dysfunction to hypoglycemia. Dementia is a recognized complication of type 2 diabetes (T2D) with an increasing prevalence, and AD is the most common cause. However, whilst the stress induced by hypoglycemia was likely the trigger, the contribution of the fall in glucose alone was unclear, given that glucose variability is associated with lower level cognitive function.</p

Salivary and serum androgens with anti-Müllerian hormone measurement for the diagnosis of polycystic ovary syndrome

To determine the predictive value of a raised androgen level with an elevated anti-Müllerian hormone (AMH) for the diagnosis or exclusion of polycystic ovary syndrome (PCOS), a prospective cross-sectional study of 170 women (105 with PCOS type A and 65 normal) was undertaken. AMH was combined with one of, total serum testosterone (T); calculated free androgen index; salivary testosterone (salT); serum androstenedione (A); salivary androstenedione (salA). The diagnostic sensitivity and specificity of AMH (>35 pmol/l) alone for PCOS were 55% and 79% respectively. The diagnostic sensitivity and specificity of AMH (>35 pmol/l) with either an elevated T or raised FAI level for PCOS showed 100% specificity and a 100% positive predictive value. Conversely, diagnostic exclusion of PCOS was shown by an AM

The CD105:CD106 microparticle ratio is CD106 dominant in polycystic ovary syndrome compared to type 2 diabetes and healthy subjects

© 2019, The Author(s). Background: A retrospective analysis was carried out from patients and controls during the past 5 years from a series of studies investigating endothelial microparticles (MP). Methods: In total, 319 samples from 207 individuals were included in this analysis, from patients with type 2 diabetes (T2D, n = 105), women with polycystic ovary syndrome (PCOS, n = 145) and healthy volunteers (n = 69). All data were generated via the same flow cytometry protocol with the same antibody clones. Endothelial markers CD105 (Endoglin) and CD106 (Vascular cell adhesion molecule-1) were used to enumerate MP in venous blood. Results: The ratio of CD105MP:CD106MP was significantly different between groups (F = 63.43, p < 0.0001). Women with PCOS were found to have a median CD105MP:CD106MP ratio of 0.40 (IQR 0.24–0.57), suggesting approximately two CD106MP were found per CD105MP. The T2D group showed a median ratio of 2.32 (1.51–3.69) whereas in healthy volunteers the ratio was 2.21 (1.63–3.55). Serum intercellular adhesion molecule-1 was also shown to be significantly increased in PCOS when compared with control or T2D groups (F = 14.5, p < 0.001). Conclusion: These data suggest that women with PCOS have an altered endothelial MP release in favour of CD106. Thus a potential activated endothelial state exists in women with PCOS with a shift towards a predominantly CD106MP profile

Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes

Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS. Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose <2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1). Results: At baseline (BL), PPBP (p < 0.05), THBS1 (p < 0.05), and CDH1 (p < 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p < 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels. Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk. Clinical trial reg. no: NCT03102801