Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome

BACKGROUND: The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). METHODS: A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. RESULTS: The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). CONCLUSION: The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.     

Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome

BACKGROUND: Cross-sectional studies have shown a high frequency of impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus (NIDDM) in women with polycystic ovarian syndrome (PCOS). However, little is known about the change in glucose tolerance that occurs over a period of several years in women with PCOS. METHODS: Sixty-seven women with PCOS received a 75 g glucose tolerance test and measurement of lipids at baseline and at follow-up after an average time of 6.2 years. All women followed prospectively had normal glucose tolerance (n = 54) or IGT (n = 13) at the start of the study. RESULTS: Change in glycaemic control from baseline was frequent, with 5/54 (9%) of normoglycaemic women at baseline developing IGT and a further 4/54 (8%) moving directly from normoglycaemic to NIDDM. For women with IGT at baseline, 7/13 (54%) had NIDDM at follow-up. Body mass index (BMI) at baseline was an independent significant predictor of adverse change in glycaemic control. CONCLUSIONS: Women with PCOS, particularly those with a high BMI, should be reviewed regularly with respect to IGT or NIDDM, as the frequency of impaired glycaemic control is high, and that the rate of conversion from normal glucose tolerance to IGT or NIDDM, or from IGT to NIDDM is substantial.     

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.     

Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance

BACKGROUND: Few studies have evaluated insulin sensitizers in comparison/association with oral contraceptives (OC) in women with polycystic ovary syndrome (PCOS) with insulin resistance (IR). This study assessed the effects of a thiazolidinedione versus an anti-androgenic estrogen-progestin followed by their sequential combinations in overweight PCOS women. METHODS AND RESULTS: Twenty-eight candidates in whom elevated insulin was not normalized after 4 months of diet were randomly assigned to 6 months of rosiglitazone 4 mg/day or to ethinyl estradiol 35 mg/cyproterone acetate 2 mg (EE/CPA: 21/28 days cycle). Each group then received both medications for another 6 months. Rosiglitazone reduced insulin, IR indices [homeostasis model assessment (HOMA) and quantitative sensitivity check index (QUICKI)] and the insulin area under the curve in response to an oral glucose tolerance test (OGTT), but had limited effect on lipids, androgens and hirsutism. EE/CPA did not modify insulin and OGTT response but increased high-density lipoprotein cholesterol and triglycerides and decreased androgens and hirsutism. Similar changes occurred during combined treatments. End results were highly significant in combined groups without noticeable side-effects or changes in safety parameters. CONCLUSIONS: In obese PCOS women with high insulin not corrected by diet, the combination of rosiglitazone and EE/CPA may be used to achieve complementary beneficial effects on endocrine-metabolic anomalies and clinical symptoms.     

Adipocyte factors,high-sensitive C-reactive protein levels and lipoxidative stress products in overweight postmenopausal women with normal and impaired OGTT

Objective

In obese postmenopausal women we assessed leptin and adiponectin, high-sensitive C-reactive protein (hsCRP), serum lipids and lipoxidative stress products: oxidized LDL (oxLDL) and malondialdehyde (MDA), in relation to impaired glucose tolerance (IGT).

Methods

Thirty-eight overweight/obese postmenopausal women were included in the study. Eighteen with normal glucose metabolism (NGT) and twenty with IGT, as it is diagnosed by OGTT. Serum leptin, adiponectin, hsCRP and MDA were measured at time 0 and 120 min of OGTT while total-cholesterol, LDL, HDL, triglycerides, oxLDL and anti-oxLDL autoantibodies at time 0. Insulin resistance (HOMA)/sensitivity (QUICKI) indexes were estimated.

Results

In subjects with NGT, hsCRP was positively correlated with fasting leptin and HOMA, while in subjects with IGT negatively with QUICKI. In both groups, hsCRP was positively correlated with fasting insulin, body mass index and waist circumference. Fasting adiponectin was positively associated with HDL in both groups and negatively with triglycerides in subjects with NGT as well as with serum glucose levels at time 120 min of OGTT in subjects with IGT. No association was observed between oxLDL and adipokines. A significant positive association was found between oxLDL and HOMA in subjects with IGT. During OGTT there was a significant increase of leptin and MDA levels in both groups.

Conclusions

A relationship exists between obesity, insulin and sub-clinical inflammation. Leptin and lipid peroxidation are linked to hyperglycaemic state while oxLDL might be considered as a predictor of insulin resistance. Adiponectin could exert its antiatherogenic effect through HDL independently of the presence of IGT.     

Vascular endothelial growth factor +405 G/C,−460 T/C and −2578 A/C polymorphisms are not associated with insulin resistance in polycystic ovary syndrome

Insulin resistance (IR) and pancreatic β-cell dysfunction are usual comorbidities in polycystic ovary syndrome (PCOS). Vascular endothelial growth factor (VEGF) is known to play an important role in the pathogenesis of PCOS. This study examined firstly the possible association of common +405 G/C,−460 T/C and −2578 A/C polymorphisms of VEGF gene with fasting glucose, fasting insulin and the indices of IR [glucose/insulin ratio (GIR), homoeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI)] in 137 patients with PCOS. None of the studied polymorphisms were found to affect IR indices significantly. However, there was a trend towards higher HOMA in +405 G and −460 T allele carriers in comparison with homozygotes +405 CC and −460 CC, respectively. With regard to −2578 A/C polymorphism, although not significant, in −2578 C carriers HOMA was lower, and GIR was higher in comparison with −2578 AA genotype. Alteration of QUICKI between genotypes was minimal and varied from 4% to 7%. Because of the relatively small sample size, more studies with greater number of cases are necessary to confirm our observations before any statement can be made about the relationship between VEGF gene polymorphism and IR parameters in PCOS.     

The effects of rosiglitazone and metformin on oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome

BACKGROUND: Oxidative stress and hyperhomocysteinaemia are risk factors for cardiovascular diseases. The aim of this study was to assess the effects of rosiglitazone and metformin on cardiovascular disease risk factors such as insulin resistance, oxidative stress and homocysteine levels in lean patients with polycystic ovary syndrome (PCOS). METHODS: Fifty lean patients (BMI <25 kg/m2) with PCOS and 35 healthy subjects were included this study. Serum homocysteine, sex steroids, fasting insulin, fasting glucose and lipid levels were measured. Total antioxidant status (TAS; combines concentrations of individual antioxidants) and malonyldialdehyde concentration (MDA) were determined. Insulin resistance was evaluated by using the homeostasis model insulin resistance index (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Area under the curve insulin (AUCI) and the insulin sensitivity index (ISI). Patients were divided into two groups. One group was treated with metformin (n = 25) and the other received rosiglitazone (n = 25) for 12 weeks. All measurements were repeated at the end of 12 weeks. RESULTS: Compared with healthy women, those with PCOS had significantly elevated serum MDA, homocysteine, HOMA-IR, AUCI and lipoprotein a levels, and significantly decreased serum TAS, QUICKI and ISI. Serum free testosterone levels showed a significant positive correlation with MDA, AUCI and HOMA-IR, and a negative correlation with TAS, ISI and QUICKI in PCOS patients. HOMA-IR and AUCI significantly decreased, while QUICKI and ISI significantly increased after treatment in both groups. Serum TAS level increased and serum MDA level decreased after the rosiglitazone treatment, but these parameters did not change after the metformin treatment. Serum homocysteine and lipid levels did not change in either group, while serum androgen levels and LH/FSH ratio significantly decreased after the treatment period in only the rosiglitazone-treated group. CONCLUSION: Elevated insulin resistance, oxidative stress and plasma homocysteine levels and changes in serum lipid profile (risk factors for cardiovascular disease) were observed in lean PCOS patients. Rosiglitazone seemed to decrease elevated oxidative stress when compared with metformin treatment in lean PCOS patients.     

Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian electrocautery in both obese and lean women with polycystic ovary syndrome

BACKGROUND: The aim of this study was to investigate serum and adipocyte mRNA expression of resistin in lean and obese women with polycystic ovary syndrome (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE). METHODS: Adipose tissue obtained from 12 women with PCOS (six obese and six lean, body mass index > 27 kg m(-1) as threshold point) before and after LOE was analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR. Ten lean, age-matched healthy women served as controls. RESULTS: Both lean and obese women with PCOS had significantly higher fasting and 2 h insulin and homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0) ratio was significantly increased 3 months after LOE. No difference was found in serum resistin levels between controls and either obese or lean women with PCOS before LOE, nor between PCOS patients before and after LOE. However, resistin mRNA expression levels in both lean and obese women with PCOS before LOE were significantly higher than that in controls and were decreased significantly after LOE back to control levels. CONCLUSION: Local resistin activity may be actively involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down-regulates resistin mRNA expression in lean and obese women with PCOS.     

多囊卵巢综合征患者的糖代谢特点分析

目的 研究多囊卵巢综合征（PCOS）患者的糖代谢特征。方法 选择2014年1月~2018年3月我院收治的符合鹿特丹标准、未经治疗的PCOS患者935例,测定身高、体重,并行口服葡萄糖耐量试验（OGTT）和胰岛素释放试验（IRT）,计算体重指数（BMI）、胰岛素抵抗稳态指数模型（HOMA-IR）、β细胞功能指数（HOMA-β）等参数。根据血糖水平将 PCOS 患者分为糖代谢正常（NGT）组、空腹血糖受损（IFG）组、糖耐量受损（IGT）组、混合型糖耐量受损（CGI）组及糖尿病（T2DM）组;根据体重指数     

Allelic variants of insulin receptor substrate-1 gene in Egyptian women with polycystic ovary syndrome

The insulin receptor substrate gene-1 (IRS-1) polymorphisms have been incriminated in insulin resistance; a frequent finding in polycystic ovary syndrome (PCOS). The commonest polymorphism associated with insulin resistance is gly972arg. Another polymorphism is the ala512 pro. This study aimed at elucidating the association of the gly972arg and the ala512pro polymorphisms of the IRS-1 gene with PCOS in Egyptian females. We employed a case–control study. The two polymorphisms were analyzed in 62 PCOS Egyptian female patients and 43 age-matched controls using a PCR-RFLP strategy. Fasting insulin, plasma glucose, and testosterone were analyzed by routine analytical methods and calculation of the homeostasis model assessment (HOMA) and the quantitative sensitivity check index (QUICK I) were done based on the results of the fasting insulin and glucose. It was found that 6.5% of the PCOS cases showed the Gly972Arg genotype. The Gly972Arg in IRS-1 polymorphism was not associated with PCOS (p?=?0.556). A positive association was found between the gly972arg and the HOMA quartiles (p?=?0.01). PCOS patients with the 972gly/arg genotype had higher glucose (p?=?0.040), insulin (0.000), HOMA (0.000), and lower QUICK I (0.023) than PCOS with wild 972arg/arg genotype. Patients of PCOS with the 972gly/arg genotype were more insulin resistant than other patients with the wild genotype. Neither the patients nor the controls showed the mutant ala512pro genotype. Screening for gly972arg genotype can be based on the HOMA quartile ranking. The ala512pro genotype was not found in studied Egyptian women.     

Prevalence of diabetes and pre‐diabetes in a cohort of Italian young adults with Williams syndrome

Williams syndrome (WS) is a rare, multisystemic genomic disorder showing a high prevalence of impaired glucose metabolism in adulthood. The reason for this association is unknown, though hemizygosity for genes mapping to the WS chromosome region has been implicated. Twenty‐two Italian young adults with WS (13 females, 9 males) were studied. A 75 g oral glucose tolerance test (OGTT) was performed and β‐cell function was estimated with Homeostasis Model Assessment (HOMA)‐B%, Insulinogenic Index, and corrected insulin response whereas insulin sensitivity was assessed with HOMA‐Insulin Resistance Index, Quantitative Insulin Check Index, and composite Insulin Sensitivity Index. One patient had known diabetes mellitus (DM), whereas impaired glucose tolerance (IGT) was diagnosed in 12 patients and DM in one (63.6% prevalence of impaired glucose metabolism). IGT patients were more insulin resistant than those with normal glucose tolerance (NGT), whereas β‐cell function was unchanged or increased. Islet autoimmunity was absent. Logistic regression showed that impaired glucose metabolism was not associated with age, body mass index (BMI), or family history of DM. β‐cell function, insulin sensitivity, and post‐load insulin levels did not differ between WS patients with NGT and healthy controls comparable for gender, age, and BMI, though WS–NGT patients had higher post‐load glucose values. These data confirm the high prevalence of impaired glucose metabolism in WS young adults, thus suggesting the need for screening these patients with OGTT. IGT is associated with reduced insulin sensitivity, but not with impaired β‐cell function, islet autoimmunity, and traditional risk factors for type 2 DM. © 2013 Wiley Periodicals, Inc.     

Amelioration of insulin resistance in women with PCOS via reduced insulin receptor substrate-1 Ser312 phosphorylation following laparoscopic ovarian electrocautery

BACKGROUND: Increased Ser(312) phosphorylation of insulin receptor substrate (IRS)-1 is one possible molecular mechanism of insulin resistance in polycystic ovary syndrome (PCOS). We investigated whether laparoscopic ovarian electrocautery (LOE) improved insulin sensitivity in women with PCOS and examined the underlying molecular mechanism of LOE. METHODS: Adipose tissue and blood samples from 12 women with PCOS before, and 3 months after, LOE were analysed. RESULTS: Before LOE, women with PCOS were found to have significantly higher 2 h glucose, fasting and 2 h insulin levels, homeostasis model insulin resistance index and lower fasting glucose-to-insulin ratio (G(0)/I(0)) than healthy, lean, age-matched controls. Serum levels of glucose and insulin were significantly decreased, and G(0)/I(0) ratio was significantly increased 3 months after LOE. Levels of activated extracellular signal-regulated kinase 1/2 in PCOS women were higher than in controls, but were significantly decreased after LOE. Levels of insulin receptor, glucose transporter-4 and phosphatidylinositol 3-kinase were lower in PCOS patients before LOE than in controls and increased after LOE. Levels of Ser(312)-phosphorylated IRS-1 in PCOS women before LOE were higher than in controls and decreased significantly after LOE, whereas IRS-1 tyrosine phosphorylation in PCOS women before LOE was lower than in controls and increased significantly after LOE. CONCLUSION: Over the short observation period of this study, our results demonstrated that LOE effectively ameliorated insulin resistance in women with PCOS via decreased IRS-1 Ser(312) phosphorylation.     

Should we consider performing oral glucose tolerance tests more frequently in postmenopausal women for optimal screening of impaired glucose tolerance?

OBJECTIVE: To investigate an optimal screening protocol for impaired glucose tolerance (IGT) and type II or non-insulin-dependent diabetes mellitus (DM) by using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in postmenopausal women. DESIGN: One hundred consecutive postmenopausal women were screened with FPG determination, and then all underwent an OGTT. Basal serum lipid and insulin levels of these women were also determined. Insulin sensitivity was determined by using the homeostasis model assessment. Receiver operating characteristic analysis was performed to determine the efficacy of these variables in detecting women with IGT and DM, and optimal cutoff values were determined. RESULTS: FPG with a cutoff value of 98 mg/dL had the best combination of sensitivity (71%) and specificity (76%) for the detection of IGT and DM. Combined FPG and body mass index screening (with the optimal cutoff value of 26.5 kg/m2) improved the sensitivity to 96% but decreased the specificity to 47%. This combined screening protocol detected 94% of the women with IGT and all diabetic women. CONCLUSIONS: Given that IGT and DM are common among postmenopausal women and DM can be prevented by nonpharmacologic interventions in women with IGT, OGTT may be used more frequently among these women. Our data indicate that for optimal screening of non-insulin-dependent DM and IGT, OGTT should be considered in postmenopausal women, especially when risk factors in addition to age are present. This model may detect most of the women with IGT and almost all diabetic women.     

Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine

BACKGROUND: Elevated levels of plasma homocysteine have recently been implicated as a significant risk factor for cardiovascular disease, pre-eclampsia, and recurrent pregnancy loss, and have been found to be associated with insulin resistance in a number of clinical situations. We examined the relationship between plasma homocysteine and insulin resistance in patients with polycystic ovary syndrome (PCOS). METHODS: A total of 155 infertile patients with PCOS as defined by clinical, biochemical and ultrasound criteria were screened for insulin resistance utilizing single-sample fasting insulin and glucose measurement, calculated by glucose:insulin ratio or homeostasis model assessment (HOMA) index. Total plasma homocysteine was measured by fluorescence polarization immunoassay. One hundred normo-ovulatory women with normal ovaries being treated for other infertility diagnoses served as a control group. RESULTS: Insulin resistance was found in the majority of PCOS patients: -53.5% (83/155), 60.6% (94/155) and 65.8% (102/155), when defined by fasting insulin, glucose:insulin ratio, or logHOMA respectively. Mean plasma homocysteine in the PCOS group was significantly higher than in the normal ovary group (11.5 +/- 7.4 versus 7.4 +/- 2.1 micromol/l, P < 0.001). Insulin-resistant PCOS patients had significantly higher plasma homocysteine (12.4 +/- 8.4 micromol/l) than non-insulin-resistant PCOS patients (9.6 +/- 4.4 micromol/l) regardless of body mass index (P = 0.003 by groups, P = 0.005 by correlation of single samples). Thirty-four per cent (53/155) of the PCO patients had homocysteine values >95th percentile of the controls (11.0 micromol/l, P < 0.0001). Statistically significant correlations were found between all insulin resistance indices and homocysteine levels. Multiple logistic regression defined insulin resistance as the major factor examined that influenced homocysteine levels. CONCLUSIONS: Insulin resistance and hyperinsulinaemia in patients with PCOS is associated with elevated plasma homocysteine, regardless of body weight. This finding may have important implications in the short term regarding reproductive performance, and in the long term regarding cardiovascular complications associated with insulin-resistant PCOS.     

Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants

AIM: To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. METHODS: We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. RESULTS: When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. CONCLUSION: At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.     

Cutoff values of surrogate measures of insulin resistance for metabolic syndrome in Korean non-diabetic adults

We investigated the cutoff values of surrogate of insulin resistance for diagnosing metabolic syndrome in Korean adults. The data from 976 non-diabetic individuals (484 men and 492 women) aged 30-79 yr were analyzed. We determined the odds ratios for the prevalence of metabolic syndrome according to the quartiles of fasting insulin, homeostasis model for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as independent variables, while adjusting for age, sex, and body mass index. The cutoff values of fasting insulin, HOMA-IR, and QUICKI were estimated by the areas under the receiver-operating characteristic (ROC) curves. The cutoff points for defining insulin resistance are a fasting insulin level of 12.94 microU/mL, HOMA-IR=3.04 as the 75th percentile value, and QUICKI=0.32 as the 25th percentile value. Compared with the lowest quartile, the adjusted odds ratios for the prevalence of metabolic syndrome in the highest quartiles of fasting insulin, HOMA-IR, and QUICKI were 1.95 (1.26-3.01), 2.27 (1.45-3.56), and 2.27 (1.45-3.56), respectively. The respective cutoff values for fasting serum insulin, HOMA-IR, and QUIC-KI by ROC analysis were 10.57 microU/mL (sensitivity 58.5%, specificity 66.8%), 2.34 (sensitivity 62.8%, specificity 65.7%), and 0.33 (sensitivity 61.2%, specificity 66.8%). Fasting insulin, HOMA-IR, and QUICKI can be used as surrogate measures of insulin resistance in Korean non-diabetic adults.     

Serum and follicular resistin levels in women with polycystic ovarian syndrome during IVF-stimulated cycles

BACKGROUND: Resistin is a hormone linking obesity and insulin resistance. The aim of this study was to compare resistin levels in serum or follicular fluid from women with polycystic ovarian syndrome (PCOS) and controls, both of whom were undergoing IVF. METHODS: We compared serum and follicular resistin levels in 21 PCOS women and in 18 healthy, normal ovulation, age- and body mass index (BMI)-matched non-PCOS women undergoing IVF. Correlations between serum or follicular fluid resistin levels and reproductive outcome were evaluated. RESULTS: There was no significant difference in either serum or follicular resistin levels between the control group and the PCOS group as a whole or those with insulin resistance [homeostasis model assessment of insulin resistance index applied to oral glucose tolerance test (HOMA(OGTT)) <4.7]. However, resistin levels in follicular fluid were unexpectedly significantly lower than serum levels (P<0.0001) in both the PCOS and control groups. No significant correlation was found between resistin levels and BMI, estradiol, LH, or fasting or 2 h glucose or insulin levels or between follicular resistin levels and fertilization rate, implantation rate, clinical pregnancy rate, or early miscarriage rate in PCOS. CONCLUSION: Resistin is unlikely to be a major determining factor in the growth and maturation of oocytes during IVF-stimulated cycles in PCOS.     

2型糖尿病一级亲属不同糖耐量者第一时相胰岛素分泌功能的变化

目的：探讨胰岛素分泌功能和胰岛素抵抗（IR）在2型糖尿病（T2DM）发生、发展中的作用。 方法： T2DM一级亲属正常糖耐量（NGT+）组32例，T2DM一级亲属糖耐量异常（IGT+）组36例，新诊断的T2DM组35例，计算各组的第一时相胰岛素分泌功能指数（AIR3-5）及胰岛素敏感性指数（SIM），与无糖尿病家族史的正常糖耐量（NGT-）组（38例）比较。 结果： T2DM一级亲属T2DM组、IGT+和NGT+组AIR3-5均低于NGT-组（P值分别为<0.01、<0.01、＜0.05）；T2DM组和IGT+组SIM均低于NGT-组（均P<0.01），而NGT+组SIM值与NGT-组比较无统计学差异（P>0.05）。结论： 胰岛素分泌功能缺陷可能是T2DM发病的始动因素。当发展为IGT及T2DM时，胰岛素分泌功能进一步降低，并伴有胰岛素敏感性的降低。     

DM2患者胰岛β细胞功能观察

目的：观察2型糖尿病（DM2）患者胰岛β细胞功能,探讨DM2人群胰岛β细胞功能的变化及不同浓度葡萄糖对胰岛分泌功能的影响。方法：对172例糖尿病患者停用药物24h后,口服75g葡萄糖行葡萄糖耐量实验（OGTT）及胰岛素释放试验（IRT）。根据我院172例DM2患者入院治疗情况,按其空腹胰岛素水平分为空腹低值组（A组）,空腹低值有峰组（B组）,空腹中值组（C组）,空腹高值组（D组）及30例正常对照组（N组）。计算早期胰岛素分泌功能指数（△I30/△G30）,基础胰岛素分泌指数（HOMAβ）,修正胰岛β细胞功能指数（MBCI）。分析各组胰岛功能指数的变化。结果：DM2各组胰岛素水平较正常人组差异有显著性意义（P〈0.05）。DM2△I30/△G30在A、B组比较差异有统计学意义。MBCI在C、D组比较差异有统计学意义。HOMAβ在A、B及C、D组比较差异有统计学意义。△I30/△G30及HOMAβ在各组呈正相关。△I30/△G30及MBCI在各组均无相关性。结论：△I30/△G30、MBCI及HOMAβ可用于临床粗略评估胰岛β细胞功能,DM2患者在治疗前做IRT、OGTT对其诊断、治疗有重要的临床意义。     

Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance

Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated.Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed.Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05).Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.