Increased mean glucose levels in patients with polycystic ovary syndrome and hyperandrogenemia as determined by continuous glucose monitoring.

OBJECTIVE: Women with polycystic ovary syndrome are at risk of developing type 2 diabetes mellitus. This study aimed to evaluate the influence of hyperandrogenemia on glucose metabolism in polycystic ovarian syndrome patients. DESIGN: Cohort study. SETTING: Reproductive Endocrinology Clinic of the Shanghai Sixth People's Hospital. SAMPLE: Fifty-three patients were recruited from June 2008 to December 2009, including 28 women with hyperandrogenism and 25 without hyperandrogenemia. METHODS: Anthropometric parameters, including weight, height, body mass index and waist-to-hip ratio, as well as sex hormones, were measured. An oral glucose tolerance test, including fasting and two hour glucose and insulin levels, was recorded. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance, and patients underwent continuous glucose monitoring. MAIN OUTCOME MEASURES: Mean blood glucose level, mean amplitude of glycemic excursion, frequency of glycemic excursion and the percentage of time of hypoglycemia and hyperglycemia during a 48 h period. RESULTS: No differences in age, body mass index, waist-to-hip ratio, fasting and two hour glucose and insulin concentrations were observed between the groups. The hyperandrogenism group had higher levels of luteinizing hormone and dehydroepiandrosterone sulfate (p < 0.05). However, continuous glucose monitoring showed that the minimal blood glucose and mean blood glucose were significantly higher in hyperandrogenemia group (p = 0.004). The percentage of time for hypoglycemia (≤70 mg/dL) was higher in the hyperandrogenemia group (p = 0.002). CONCLUSIONS: Polycystic ovarian syndrome patients with hyperandrogenemia had an increased mean glucose value, which may place them at increased risk for developing type 2 diabetes.

[Insulin release and daily glucose change in polycystic ovary syndrome women with normal glucose tolerance].

OBJECTIVE: To evaluate the characteristics of daily glucose change, insulin sensitivity, and insulin release in polycystic ovary syndrome (PCOS) women with normal glucose tolerance. METHODS: Oral glucose tolerance test (OGTT) with 75 g glucose was conducted on 20 PCOS women with normal glucose tolerance and 20 age-matched healthy women with normal menstruation. Before the glucose uptake and 30, 60, and 120 min after samples of venous blood were collected to detect the blood glucose and insulin. Continuous glucose monitoring system (CGMS) was used to monitor the glucose concentration of subcutaneous interstitial fluid so as to reflect the blood glucose level. Mean blood glucose level (MBG) and its standard deviation (SDBG), mean amplitude of glycemic excursion (MAGE), peak level of postprandial plasma glucose as well as its peaking time during a 48-hour period CGMS were calculated. Stumvoll first-phase and second-phase (1st PH and 2nd PH) insulin release during OGTT were evaluated by Stumvoll formula, whereas baseline insulin release by HOMA-B. Insulin sensitivity index (ISI) was evaluated by Cederholm formula. RESULTS: (1) The 1-hour and 3-hour plasma glucose levels during OGTT of the PCOS group were higher than those of the control group (P < 0.01 and P < 0.05 respectively). The fasting insulin level and insulin levels 30, 60, 120, and 180 min after the glucose uptake during OGTT of the PCOS group were all significantly higher than those of the control group (all P < 0.01). (2) The daily MBG, SDBG, and MAGE of the PCOS group were (5.43 +/- 0.44), (0.66 +/- 0.24), and (1.46 +/- 0.47) mmol/L respectively, all similar to those of the control group [(5.3 +/- 0.5), (0.67 +/- 0.27), and (1.7 +/- 0.7) mmol/L respectively, all P > 0.05]. The peaking time of post-breakfast plasma glucose level of the PCOS group was (40 +/- 18) min, significantly longer than that of the control group [(30 +/- 10) min, P < 0.05]. (3) The ISI of the PCOS group was 64 (59 - 81), significantly lower than that of the control group [95 (78 - 102), P < 0.01]. The Stumvoll 1st PH and 2nd PH insulin release levels of the PCOS group were 1779 (1411 - 2194) mU/L and 440 (361 - 545) mU/L respectively, both significantly higher than those of the control group [1217 (1056 - 1477) and 320 (283 - 375) mU/L respectively, P < 0.01 and P < 0.05]. CONCLUSION: With normal glucose tolerance, the PCOS women show (1) a backwardly-shifted peak of glucose -stimulated insulin secretion, (2) an abnormal mode of daily glucose change characterized by a delayed peak of post-breakfast plasma glucose level, and (3) significant decrease of peripheral insulin sensitivity with compensated increase of insulin secretion.

[Role of testosterone in tumor necrosis factor-alpha and monocyte chemotactic protein-1 expression in mouse macrophage RAW264.7 and its molecular mechanism].

OBJECTIVE: To investigate the role of androgen in TNF-alpha and MCP-1 expression in RAW264.7 macrophage and its molecular mechanism. METHODS: (1) RAW264.7 macrophage was treated with 10(-9) mol/L or 10(-7) mol/L testosterone (T) and then subjected to the measurement of: 1) the cellular expression of TNF-alpha and MCP-1 mRNA by RT-PCR; 2) the expression of TNF-alpha and MCP-1 in cell culture supernatant by ELISA; (2) The expression of phospho-NF-kappaB after treatment with T was measured by Western blot. (3) Cells were pre-incubated with 10(-4) mol/L PDTC (an inhibitor of NF-kappaB) for 1 hour, followed by T treatment. Expression of mRNA and supernatant levels of TNF-alpha and MCP-1 were measured by RT-PCR and ELISA. RESULTS: (1) 1) After a 6 h treatment with 10(-9) mol/L or 10(-7) mol/L T, the expression of TNF-alpha mRNA increased by 1.78 and 1.87 folds, MCP-1 by 1.58 and 1.66 folds respectively (all P < 0.05). 2) Incubated with both concentration of T for 6 h showed no significant changes of supernatant levels of TNF-alpha and MCP-1. After a 24 h treatment, the levels of TNF-alpha and MCP-1 increased significantly (all P < 0.05) while more significant increase was found in 10(-7) mol/L T group (P < 0.05). (2) The expression of phospho-NF-kappaB (ser276) increased significantly after cells were treated with 10(-7) mol/L T for 30 min (P < 0.05) and peaked at 60 min. (3) With 1 h PDTC pre-incubation, T (10(-9) mol/L or 10(-7) mol/L) treatment for 6 h led to a lower mRNA expression and 24 h led to lower supernatant levels of TNF-alpha and MCP-1 than those without (P < 0.05). However, both cellular and supernatant expression of TNF-alpha and MCP-1 with PDTC pre-incubation were still higher than those of blank controls (all P < 0.05, except for TNF-alpha in 10(-9) mol/L T treatment). CONCLUSION: Testosterone can increase TNF-alpha and MCP-1 expression in RAW264.7 macrophage in vitro. Activation of cellular NF-kappaB by testosterone may be one of underlying molecular mechanisms.

Highly efficient and stereoselective N-vinylation of oxiranecarboxamides and unprecedented 8-endo-epoxy-arene cyclization: expedient and biomimetic synthesis of some Clausena alkaloids.

[structure: see text]. Catalyzed by CuI/N,N-dimethylglycine, oxiranecarboxamides underwent a highly efficient and stereoselective N-vinylation reaction with (Z)-1-aryl-2-bromoethenes to afford the corresponding enamides. The method has been applied to a straightforward synthesis of (-)-(2R,3S)-SB204900, the enantiomer of the natural product. Following a hypothetic biomimetic pathway, both (+)-(5R,6S)-xi-Clausenamide and (-)-(5R,6S)-balasubramide have been efficiently synthesized for the first time through the unprecedented intramolecular 8-endo-epoxy-arene cyclization of (Z)-N-(phenylvinyl)oxiranecarboxamides.