Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist

Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.     

Impact of overnight dexamethasone suppression on the adrenal androgen response to an oral glucose tolerance test in women with and without polycystic ovary syndrome

In order to test the hypothesis that adrenocortical overactivity, possibly related to the stress of testing, may impact on the measurement of circulating androgen concentrations during glucose- induced hyperinsulinaemia, we prospectively screened 10 patients with the polycystic ovary syndrome (PCOS) and nine healthy control women with an oral glucose tolerance test (OGTT), before and after the administration of dexamethasone. Blood sampling was performed at 0, 30, 60, 90, and 120 min following the oral ingestion of 75 g of glucose, before and after the administration of 1.0 mg dexamethasone on the evening prior to testing. Total and free testosterone, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), cortisol, glucose and insulin were assessed during the 2 h OGTT. Women with PCOS had increased basal concentrations of free testosterone, total testosterone, androstenedione, and insulin compared to control women. In women with PCOS an acute decline in circulating concentrations of DHEAS occurred during the OGTT. In PCOS women there were no changes in other ovarian or adrenal androgens during OGTT before or following dexamethasone administration. In control women DHEA concentrations declined during the OGTT. Following overnight dexamethasone suppression in control women, circulating concentrations of DHEAS and testosterone also declined. It is concluded that: (i) in PCOS women only the concentration of circulating DHEAS decreased during glucose-induced hyperinsulinaemia and dexamethasone administration did not further alter androgen responses to an OGTT; (ii) it is possible that, in these hyperandrogenic patients, the insulin-related suppression of adrenocortical testosterone and DHEA is negated by their much greater ovarian secretion of these androgens; (iii) in control women DHEA concentrations acutely declined during the OGTT and the administration of dexamethasone resulted in the acute decline of DHEA, DHEAS, and testosterone; (iv) it appears that the stress related to testing impacts on the androgen response to OGTT, at least in healthy women.      

Endocrinology: Insulin hypersecretion together with high luteinizing hormone concentration augments androgen secretion in oral glucose tolerance test in women with polycystic ovarian disease

Female hyperandrogenism is often associated with hyper-insulinaemiaand insulin resistance. We evaluated the hormone responses inan oral glucose tolerance test to investigate the interactionsof gonadotrophins, insulin, C-peptide and androgens in womenwith polycystic ovarian disease (PCOD). In 28 patients withultrasonographically diagnosed PCOD, hyperinsulinaemia and insulinresistance were mainly associated with obesity. Both basal andcumulative sum of insulin to C-peptide ratios were high in obesesubjects, suggesting decreasing hepatic removal of insulin causedby obesity. Nevertheless, in some lean PCOD women, despite normalfasting insulin concentrations, insulin hyper-secretion existed.The mean concentration of testosterone decreased significantlyduring the oral glucose tolerance test both in PCOD and controlwomen, and of androstenedione in the PCOD patients only. However,an increase in androgen responses was found in a subgroup ofPCOD patients, who had both elevated luteinizing hormone (LH)concentrations and hyperinsulinaemic response to oral glucose.In the remaining PCOD patients an inverse correlation betweenLH and insulin was found. The patients with hyperinsulinaemiatogether with LH hypersecretion may represent a subgroup ofPCOD with deranged regulation of androgen secretion.     

Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.     

Follistatin and activin A serum concentrations in obese and non-obese patients with polycystic ovary syndrome.

BACKGROUND: Activin promotes ovarian follicular development, inhibits androgen production and increases FSH and insulin secretion. Follistatin, an activin-binding protein, neutralizes activin bioactivity. Therefore, a decrease in the ratio of activin/follistatin might encourage characteristic features of polycystic ovary syndrome (PCOS). We investigated whether women with PCOS showed disordered follistatin and/or activin serum concentrations. METHODS: The study group included 24 obese and 20 non-obese (body mass index vertical line and <27 kg/m2 respectively) clomiphene-failure PCOS patients. The control group included 16 obese and 46 non-obese patients with normal ovulatory cycles. Blood samples were obtained from the patients on day 3-5 of a progesterone-induced or spontaneous cycle and were assayed for LH, FSH, testosterone, 17-hydroxy-progesterone, androstenedione, follistatin, activin A, fasting glucose and insulin. RESULTS: Follistatin concentrations were comparable between obese and non-obese PCOS patients (mean +/- SE; 1171 +/- 103 and 1045 +/- 159 pg/ml respectively) and significantly higher than their respective controls (628 +/- 61 and 592 +/- 49 pg/ml, P < 0.0001 and P < 0.02 respectively). Activin A concentrations were comparable between the four groups (590 +/- 35, 513 +/- 74, 661 +/- 87 and 595 +/- 43 pg/ml in obese and non-obese PCOS and controls respectively). Stepwise regression analyses for relationships between follistatin or activin A levels and all other variables indicated that follistatin was significantly and independently positively affected by PCOS (P < 0.0001), age (P < 0.02), androstenedione (P < 0.03) and weight (P < 0.05). Activin A was significantly and independently negatively affected by PCOS (P < 0.003) and FSH (P < 0.03), and positively affected by weight (P < 0.009) and androstenedione (P < 0.02). CONCLUSIONS: Serum follistatin is increased in PCOS patients, regardless of obesity. PCOS is the most significant variable that relates to high follistatin and low activin A serum concentration. A high follistatin/activin ratio could well contribute to the pathophysiology of PCOS.     

Effect of opiate receptor blockade on the insulin response to oral glucose load in polycystic ovarian disease.

In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCOD.     

Relationship between body mass index and insulin measured during oral glucose tolerance testing in severely obese children and adolescents

PRIMARY OBJECTIVE: The study evaluated the accuracy of body mass index (BMI) in detecting hyperinsulinaemia during oral glucose tolerance testing (OGTT) in severely obese children. RESEARCH DESIGN: A cross-sectional study was carried out. MATERIALS AND METHODS: A total of 118 obese children and adolescents (49 females and 69 males) aged 6-19 years were consecutively studied at an outpatient paediatric clinic. Hyperinsulinaemia was defined as a value of log-transformed fasting insulin >/= 80th percentile and OGTT hyperinsulinaemia as a value of the log-transformed area under the curve (AUC) of insulin >/= 80th percentile. The study hypothesis was tested using a logistic regression model with hyperinsulinaemia as the outcome variable and the z-score of BMI corrected for age (z-BMI(age)) as the predictor variable. Receiver-operator characteristic (ROC) curves were used to evaluate accuracy. RESULTS: The mean (SD) BMI for age of the children was 28.6 (4.0) kg m(-2), corresponding to 2.2 (0.5) standard deviation scores. The odds ratio (OR) of OGTT hyperinsulinaemia was 2.0 (95% CI 1.2-3.3; p = 0.007) for each unit increase of z-BMI(age) and the corresponding ROC-AUC was 0.74 (95% CI 0.61-0.86; p = 0.0001). In comparison, the OR of fasting hyperinsulinaemia was 1.1 (95% CI 0.7-1.7; p = 0.716) for each unit increase of z-BMI(age) and the corresponding ROC-AUC was 0.49 (95% CI 0.35-0.62; p = 0.863). CONCLUSION: BMI is reasonably accurate in detecting OGTT hyperinsulinaemia in severely obese children.     

Endocrine and metabolic effects of octreotide, a somatostatin analogue, in lean PCOS patients with either hyperinsulinaemia or lean normoinsulinaemia

The effects on insulin secretion and on the glycaemic and androgen status before and after short-term treatment with octreotide were evaluated in 16 normal weight patients with polycystic ovarian syndrome (PCOS). Hyperinsulinaemia was determined by measuring the insulin response after oral glucose tolerance test (OGTT). Seven patients (group A) were classified as normoinsulinaemic, while nine patients (group B) were considered hyperinsulinaemic according to insulin response after OGTT. Octreotide treatment did not modify either glycaemic or insulinaemic response after OGTT, or androgen profile, in normoinsulinaemic patients. On the contrary, a significant decrease in the basal concentrations of luteinizing hormone (LH), testosterone and androstenedione, and a significant increase in serum concentrations of sex hormone-binding globulin (SHBG) were observed in the hyperinsulinaemic group of patients, in which we observed also a significant decrease of insulinaemic response and a decompensation of the glycaemic profile after OGTT. Our study is the first report showing that: (i) octreotide does not appear to significantly influence pituitary release of gonadotrophins in this group of PCOS patients; (ii) octreotide is able to reduce insulin release, LH and androgen concentrations in lean PCOS patients with hyperinsulinaemia. Due to the presence of a decompensation of glucose homeostasis during treatment, octreotide does not seem advisable for long-term therapy of hyperandrogenism in lean PCOS patients with hyperinsulinaemia.     

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.     

Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization

BACKGROUND: The aim of this study was to evaluate the peripheral serum androgen concentrations in normal and polycystic ovarian syndrome (PCOS) women during pregnancy, in order to establish if PCOS may induce gestational hyperandrogenism and therefore constitute a potential source of androgen excess for the fetus. METHODS: Twenty pregnant PCOS (PPCOS) women and 26 normal pregnant (NP) women of similar age with singleton pregnancies were selected for the study. During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test (OGTT) was performed. For the OGTT, glucose and insulin were measured in each sample and testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), estradiol, progesterone and sex hormone-binding globulin were determined in the fasting sample. RESULTS: In the first study period (gestational weeks 10-16), the levels of androstenedione, testosterone and DHEAS and the free androgen index tended to be higher in the PCOS group. These differences became significant in the second study period (gestational weeks 22-28). In this second period, 2 h insulin concentrations were also significantly higher in PPCOS than in NP women. CONCLUSIONS: The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization.     

A pilot study of the long-term effects of acipimox in polycystic ovarian syndrome

BACKGROUND: To evaluate the effects of long-term acipimox administration on glucose-induced insulin secretion and peripheral insulin sensitivity in polycystic ovarian syndrome (PCOS), 20 PCOS subjects (eight lean and 12 obese) and 14 body mass index-matched controls (seven lean and seven obese) were investigated. METHODS: Fasting blood samples were collected for basal hormone and lipoprotein assays, after which patients underwent an oral glucose tolerance test (OGTT). The following day a euglycaemic-hyperinsulinaemic clamp was performed. After 4-6 weeks of treatment with acipimox at a dose of 250 mg given orally three times a day, the patients repeated the study protocol. RESULTS: No significant differences were found in the glucose, insulin or C-peptide responses to OGTT before and after anti-lipolytic drug administration in any group, nor was there any effect on insulin sensitivity. Concerning the lipid profile, acipimox administration led to a significant decrease of cholesterol and low-density lipoprotein levels in obese PCOS patients as well as in obese and lean controls. Lower triglycerides were found after the drug administration in both obese groups. Post-treatment free fatty acid levels were not significantly different when compared with basal values. CONCLUSIONS: Acipimox does not appear to be an effective insulin-lowering drug in PCOS, even if it can be used in obese women with PCOS as an additional therapeutic agent to ameliorate the atherogenic lipid profile of the syndrome.     

多囊卵巢综合征患者性激素水平与胰岛素抵抗相关性分析

目的探讨多囊卵巢综合征(PCOS)的病因、发病机理及寻找最佳的治疗方案提供依据。方法通过放射免疫(RIA)法测患者胰岛素释放试验,酶法测糖耐量试验,电化学发光免疫分析(ECLIA)法测血清LH、FSH、E2、P、T水平。结果表明28.2%患者有胰岛素抵抗(IR),13.1%有IR和糖耐量受损,5.5%糖耐量受损。单纯IR患者中,肥胖者占35.7%;单纯糖耐量受损者中,肥胖者占36.3%;IR伴糖耐量受损者中,肥胖者占34.6%;肥胖组LH、LH/FSH、E2、T水平与非肥胖组之间无显著性差异(P0.05);而肥胖组与非肥胖的空腹血糖及空腹胰岛素水平有显著性差异(P0.05);肥胖者与非肥胖者月经周期及卵泡数目两指标有显著性差异(P0.05)。结论有较多PCOS患者存在IR或糖耐量受损;在IR和糖耐量受损的患者中,肥胖者占有较高的比重,肥胖可促进IR形成;肥胖可加重IR和生殖功能障碍。     

Adipose cell size in obese Africans: evidence against the existence of insulin resistance in some patients.

Aspects of adipose tissue cellularity were examined in 15 non-diabetic premenopausal African women with simple obesity living in Johannesburg. A smaller group of six non-obese Black women served as controls. Adipose tissue was obtained by biopsy from the deltoid, gluteal, and abdominal regions, and the mean fat cell size for each site was determined. Fasting plasma glucose, insulin, and lipid levels, and the glucose and insulin responses to a 100 g oral glucose load, in these subjects provided metabolic data for correlative analyses. As expected, the overall mean and regional adipocyte sizes were significantly larger in the overweight subjects. Significant regional variations in fat cell size were also seen, the gluteal region adipocytes being larger than those of other sites in both obese and non-obese women. A significant positive correlation was found between fat cell size and the percentage of ideal body weight. There was no significant relationship between adipocyte size, however, and any of the metabolic variables measured--notably basal or stimulated plasma insulin. Nearly half of the overweight women showed large adipocytes with normal plasma insulin concentrations. A proportion of African women with hypertrophic obesity do not appear to demonstrate any classical metabolic features of insulin resistance; this may be related partly to their high carbohydrate intake and unusual degree of physical activity. Our results do not, however, indicate that hyperinsulinaemia is completely absent in obese Black women.     

Insulin sensitivity in non-obese women with polycystic ovary syndrome during treatment with oral contraceptives containing low-androgenic progestin.

BACKGROUND: Combined oral contraceptives (COC) effectively suppress hyperandrogenism in women with polycystic ovary syndrome (PCOS), though deterioration of insulin sensitivity during treatment is assumed. The study aim was to investigate insulin action and androgen production during treatment with COC containing low-androgenic progestin. METHODS: A total of 13 PCOS women and nine controls was enrolled into the study. Only non-obese women with a body mass index (BMI) 相似文献   

Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls

BACKGROUND: We aimed to evaluate the influence of the Gly972Arg variant of the insulin receptor substrate-1 gene (IRS-1) and the Gly1057Asp variant in IRS-2 on insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: Genotypes, allelic frequencies, indexes of insulin resistance, glucose tolerance and hormone profiles were studied in a large sample of Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women matched for body mass index. RESULTS: No differences in genotype or allelic frequencies were found between PCOS patients and healthy controls. When considering control subjects and PCOS patients as a whole, IRS-1 Arg972 carriers also presented with increased fasting insulin (133 +/- 60 versus 95 +/- 67 pmol/l, P = 0.008) and insulin resistance measured by homeostasis model assessment (4.3 +/- 2.1 versus 3.1 +/- 2.4, P = 0.009) compared with subjects homozygous for Gly972 alleles. These differences were even higher when restricting the analysis to PCOS patients. Subjects homozygous for the Gly1057 allele of IRS-2 presented with increased 60 and 90 min oral glucose tolerance test (OGTT) glucose levels compared with carriers of one or two Asp1057 alleles (7.9 +/- 2.1 versus 7.1 +/- 2.1 mmol/l, P = 0.042 and 7.0 +/- 2.1 versus 6.0 +/- 1.8 mmol/l, P = 0.014), and a similar tendency was observed for 120 min OGTT glucose levels. CONCLUSIONS: The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS.     

Leptin, soluble leptin receptor, adiponectin and resistin in relation to OGTT in overweight/obese postmenopausal women

OBJECTIVE: In obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. METHODS: Thirty in total, overweight/obese postmenopausal women, were included in the study: 15 with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30 min intervals, leptin, sOB-R, adiponectin and resistin at 60 min intervals during the 120 min OGTT. RESULTS: In fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. CONCLUSION: In overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.     

Relationship between body mass index and insulin measured during oral glucose tolerance testing in severely obese children and adolescents

Primary objective: The study evaluated the accuracy of body mass index (BMI) in detecting hyperinsulinaemia during oral glucose tolerance testing (OGTT) in severely obese children.

Research design: A cross-sectional study was carried out.

Materials and methods: A total of 118 obese children and adolescents (49 females and 69?males) aged 6–19 years were consecutively studied at an outpatient paediatric clinic. Hyperinsulinaemia was defined as a value of log-transformed fasting insulin ≥?80th percentile and OGTT hyperinsulinaemia as a value of the log-transformed area under the curve (AUC) of insulin ≥?80th percentile. The study hypothesis was tested using a logistic regression model with hyperinsulinaemia as the outcome variable and the z-score of BMI corrected for age (z-BMI_age) as the predictor variable. Receiver-operator characteristic (ROC) curves were used to evaluate accuracy.

Results: The mean (SD) BMI for age of the children was 28.6 (4.0)?kg?m^?2, corresponding to 2.2 (0.5) standard deviation scores. The odds ratio (OR) of OGTT hyperinsulinaemia was 2.0 (95% CI 1.2–3.3; p = 0.007) for each unit increase of z-BMI_age and the corresponding ROC-AUC was 0.74 (95% CI 0.61–0.86; p = 0.0001). In comparison, the OR of fasting hyperinsulinaemia was 1.1 (95% CI 0.7–1.7; p = 0.716) for each unit increase of z-BMI_age and the corresponding ROC-AUC was 0.49 (95% CI 0.35–0.62; p = 0.863).

Conclusion: BMI is reasonably accurate in detecting OGTT hyperinsulinaemia in severely obese children.     

Insulin binding to erythrocytes in hyperinsulinemic patients with precirrhotic hemochromatosis and cirrhosis

Summary This study investigated insulin receptor binding (number and affinity) to erythrocytes in patients with precirrhotic hemochromatosis, patients with cirrhosis, and healthy subjects. To evaluate plasma glucose and insulin levels, an oral glucose tolerance test (OGTT) was performed in all subjects. In the fasting state, all patients exhibited normal glucose levels. Precirrhotic patients showed slight impairment of glucose tolerance while cirrhotic patients were strikingly glucose intolerant. In both patient groups, fasting plasma insulin levels were increased. Following the glucose load, plasma insulin levels were significantly enhanced in precirrhotic patients at 90 and 120 min and increased at all times in cirrhotic patients. In the postabsorptive state (in the presence of hyperinsulinemia) insulin binding and the number and affinity of insulin receptors of erythrocytes were not different in precirrhotic or cirrhotic patients when compared to controls. We conclude that studies of insulin binding on erythrocytes do not contribute to the evaluation of the pathogenesis of insulin resistance in liver disease.Abbreviations K_a affinity constant - OGTT oral glucose tolerance test - R₀ receptor number This work was presented in part at the annual meeting of the German Association for the Study of the Liver, Göttingen, FRG, January 1986, and at the annual meeting of the Deutsche Gesellschaft für Innere Medizin, Wiesbaden, FRG, April 1986     

C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women

Hyperleptinaemia is known to be positively associated with obesity in females. Therefore, circulating leptin concentrations are predicted by body mass index (BMI). Additional effects of endogenous C19-steroids, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), C-peptide and insulin on the predictive value of BMI on serum leptin were investigated in 56 hyperandrogenaemic and/or hyperinsulinaemic and/or obese premenopausal women. Serum concentrations (after an overnight 12 h fast) of leptin, total testosterone, free testosterone, SHBG, dehydroepiandrosterone sulphate (DHEAS), LH, FSH, and oestradiol as well as serum concentrations of C- peptide and insulin prior to, and 1 h after, an oral 100 mg glucose load (1 h values) were determined by immunoassays. Subjects with regular menstrual cycles were studied in the mid-follicular phase while the remainder were studied at random. Nineteen normotestosteronaemic, normoinsulinaemic, lean and ovulatory volunteers served as controls; in order to determine the effect of different stages of the menstrual cylce, serum concentrations of leptin (and of oestradiol in 12 out of the 19 individuals) were determined at the preovulatory, the mid-luteal and the following mid-follicular phase. Significant differences between the patients versus control were not found possibly because of the heterogeneity in the patient group. Multiple regression indicated a hyperbolic correlation between BMI and leptin concentrations. As expected, BMI was the major determinant responsible for >50% (R2=0.51) of the elevation of leptin concentrations. The combination of BMI with fasting C-peptide or fasting insulin enhanced the R2 up to 0.59. The multiple regression with two explaining parameters showed a significant regression coefficient for BMI at the 0.001 level, and for fasting C- peptide and fasting insulin at the 0.01 level, which was as statistically significant as the combination of BMI with the 1 h values of C-peptide and of insulin. In contrast, total testosterone, free testosterone, SHBG, free testosterone/SHBG ratio, DHEAS and LH/FSH ratio had no effect. Similarly, models with more than two variables did not measurably improve the explained variation. In the control group, leptin concentrations were significantly higher in preovulatory and mid- luteal phases than the two mid-follicular phases (P < or = 0.05) and must be considered when determining sampling time. In conclusion, hyperandrogenaemia does not have a predictive value on leptin concentrations in premenopausal subjects but hyperinsulinaemia exerts an effect independent of obesity that is the strongest predictor for elevation of leptin concentrations. Hyperinsulinaemia might contribute to the hyperbolic correlation of circulating leptin in obese patients.      

Hyperinsulinemia in polycystic ovary syndrome: relationship to clinical and hormonal factors

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19–30 years. None of the patients or control women had a body mass index above 27 kg/m². Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.Abbreviations BMI body mass index - 17OHP 17-hydroxyprogesterone - DHEAS dehydroepiandrosterone sulfate - FTI free testosterone index - I/G insulin/glucose ratio - OGTT oral glucose tolerance test - PCOS polycystic ovary syndrome - P_max maximun peak of insulin - SHBG sex hormone binding globulin - LH luteinizing hormone - FSH follicle-stimulating hormone