Search

Background: Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. Methods: Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. Results: Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m²) and obese PCOS (BMI >25 kg/m²) but all were significantly higher than for controls (p < 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ±6 (p <0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ±5 and 29 ±4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p < 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p < 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non- obese PCOS. Conclusions: The ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5a reductase activity increasing ADTG formation in these women. [ABSTRACT FROM AUTHOR]

We evaluated a disease management and education programme delivered via telephone support (TS) to patients with poorly controlled diabetes (HbA1c >7%). All eligible patients were invited to participate in the programme, which involved education on lifestyle modification and disease management delivered via three scheduled monthly calls by trained nurses. Patients who declined or could not be contacted acted as the controls (usual care, UC). A per protocol analysis was conducted using a mixed effect model for two subgroups with different baseline HbA1c levels (i.e. baseline HbA1c <8.0% and HbA1c ≥8.0%). A total of 2646 patients with diabetes were eligible for enrolment. Of these, 1391 participants had HbA1c measurements available. The study comprised 633 patients (46%) who completed the programme (TS), 598 (43%) who were not contactable or refused to participate at the first telephone call (UC) and 160 patients who dropped out. In the patients with HbA1c ≥8%, TS reduced the adjusted mean HbA1c by 0.38% (P = 0.022) but the reduction in diabetes-related admissions (4.2% lower adjusted mean admission rate) was not significant. In patients with HbA1c <8%, TS had no additional effect on glycaemic control or diabetes-related admission. Telephone support appeared effective in improving glycaemic control in patients with poor diabetes control. [ABSTRACT FROM AUTHOR]

Background: There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. Methods: Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. Results: Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage β cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. Conclusions: The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. The clinical trial registration number for this study is ISRCTN65353256. [ABSTRACT FROM AUTHOR]

Objective Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with polycystic ovary syndrome (PCOS) compared to metformin. Studies have shown that significant weight regain occurs following the cessation of rimonabant therapy. This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS. Design An extension study for 3 months with the addition of metformin to the randomised open labelled parallel study of metformin and rimonabant in 20 patients with PCOS with a body mass index ≥ 30 kg/m2. Patients who were on 3 months of rimonabant were changed over to metformin for 3 months, whereas those on 3 months of metformin were continued on metformin for another 3 months. Measurements The primary end-point was a change in weight; secondary end-points were a change in FAI and insulin resistance. Results The mean weight loss of 6·2 kg associated with 3 months of rimonabant treatment was maintained by 3 months of metformin treatment (mean change +0·2 kg, P = 0·96). Therefore, the percentage reduction in weight remained significantly higher in the rimonabant/metformin group compared to metformin only subjects at 6 months compared to baseline (–6·0 ± 0·1% vs. –2·8 ± 0·1%, P = 0·04). The percentage change in testosterone and FAI from baseline to 6 months was also greater in the rimonabant/metformin group. [Testosterone (–45·0 ± 5·0% vs. –16 ± 2·0%, P = 0·02); FAI (–53·0 ± 5·0% vs. –17·0 ± 12·2%, P = 0·02)]. HOMA-IR continued to fall significantly in the rimonabant/metformin group between 0, 3 and 6 months (4·4 ± 0·5 vs. 3·4 ± 0·4 vs. 2·7 ± 0·3, respectively, P < 0·01) but not at all in the metformin only group (3·4 ± 0·7 vs. 3·4 ± 0·8 vs. 3·7 ± 0·8, respectively, P = 0·80). Total cholesterol and LDL reduced significantly in both groups, but improvements in triglycerides and HDL were limited to the rimonabant/metformin group. Conclusions In these obese patients with PCOS, metformin maintained the weight loss and enhanced the metabolic and biochemical parameters achieved by treatment with rimonabant, compared to 6 months of metformin treatment alone. [ABSTRACT FROM AUTHOR]

A single assessment of insulin resistance OR) by using HOMA-IR is insufficient due to the known variability of this measure (and presumably that of IR) within the same individual. We compared the mean and biological variation in insulin resistance levels in patients with polycystic ovarian syndrome to that of type 2 diabetes (T2DM) by repeated measurements of HOMA-IR thereby arriving at a value which represents the mean of the variation. The biological variation of IR was assessed by measuring IR at four day intervals on 10 consecutive occasions in 12 overweight patients with PCOS (BMI means ± SD; 33.2 ± 6.3), 12 postmenopausal Caucasian subjects with diet controlled T2DM (31.1 ± 3.3), 11 healthy women with normal menstrual periods (29.9 ± 3.25) and 11 healthy postmenopausal women (32.4 ± 5.3). The diagnosis of PCOS was based on the Rotterdam criteria. Plasma glucose was analyzed in singleton and serum samples were split before assay. Group differences were compared by analysis of variance. Where significant differences were indicated Scheffe's post-hoe test was applied. No significant difference in BMI was observed between all the groups, p=0.37. The HOMA-IR was 5.9±5.3 (mean±SD) in women with PCOS, 4.3±2.3 in postmenopausal T2DM, 1.7±0.6 in pre-menopausal women and 2.1±0.8 in postmenopausal women. All pairwise comparisons for HOMA-IR were significantly different (p = 0.005) except PCOS vs postmenopausal T2DM, postmenopausal T2DM vs healthy postmenopausal and healthy premenopausal vs healthy postmenopausal. Mean intraindividual variation of PCOS, postmenopausal T2DM, healthy pre-menopausal and healthy post-menopausal were 1.19, 1.05, 0.3, 0.15 respectively. This is the first analysis to show that when repeated measurements of HOMA-IR are made, the mean and biological variation of insulin resistance in PCOS women is as high as those seen in postmenopausal women with diet controlled T2DM, which in turn, is relatively greater than their age matched peers. Since insulin resistance itself is an independent predictor of vascular risk, it would support the hypothesis that there is increased cardiovascular risk in women with PCOS. [ABSTRACT FROM AUTHOR]