Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 +/- 1.7 yr; controls 2.9 +/- 2.1 yr). Based on World Health Organization glucose tolerance categories, there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group. In the PCOS group, 25 (37%) had impaired glucose tolerance (IGT) and seven (10%) had type 2 diabetes mellitus at baseline, compared with 30 (45%) and 10 (15%), respectively, at follow-up. There were also no differences within groups (PCOS or control) or between groups (PCOS vs. control) in the oral glucose tolerance test-derived measure of insulin sensitivity, but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus, there was a significant decrease (P < 0.0001). At the follow-up visit, the mean glycohemoglobin level was 6.1 +/- 0.9% in women with PCOS vs. 5.3 +/- 0.7% in the control women (P < 0.001). Women with PCOS and baseline IGT had a low conversion risk of 6% to type 2 diabetes over approximately 3 yr, or 2% per year. The effect of PCOS, given normal glucose tolerance (NGT) at baseline, is more pronounced with 16% conversion to IGT per year. Our study supports that women with PCOS (especially with NGT) should be periodically rescreened for diabetes due to worsening glucose intolerance over time, but this interval may be over several years and not annually.     

不同糖耐量水平人群血清真胰岛素和胰岛素原水平的临床意义

目的 探讨不同糖耐量者血清真胰岛素（ＴＩ）及胰岛素原（ＰＩ）水平的变化及临床意义。方法 用特异的单克隆抗体夹心放大酶联免疫分析法（ＢＡ－ＥＬＩＳＡ）检测１３５例正常糖耐量（ＮＧＴ）、８６例糖耐量低减（ＩＧＴ）及１０１例Ⅱ型糖尿病（ＤＭ）者口服葡萄糖耐量试验（ＯＧＴＴ）各点血清ＴＩ及ＰＩ水平。结果 ３组血清空腹ＴＩ差异无显著性（Ｐ〉０．０５）,免疫反应胰岛素（ＩＲＩ）Ⅱ型ＤＭ组明显升高（Ｐ〈０．０１     

Vascular dysfunction and metabolic parameters in polycystic ovary syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and the metabolic syndrome; however, the cardiovascular (CV) manifestations of PCOS remain unclear. OBJECTIVE: The objective of this study was to examine the relationships between IR, metabolic parameters, androgens, and markers of early CV disease in PCOS. DESIGN: We conducted an observational study examining noninvasive markers of early CV disease in women with PCOS including structural [carotid intimal media thickness (IMT)] and functional measures (arterial function with pulse wave velocity and endothelial function with brachial arterial flow-mediated vasodilation). Metabolic parameters included insulin and glucose during an oral glucose tolerance test and lipid and androgen levels. SETTING: Participants were recruited from the general community. PATIENTS: Eighty overweight women with PCOS who were nonsmokers and not on oral contraceptives or other medications known to affect IR participated in the study. RESULTS: Stepwise regression analysis showed that after adjustment for age and body mass index, IMT was significantly correlated with blood pressure (BP) load (P = 0.03) and inversely with dehydroepiandrosterone sulfate (DHEAS) (P = 0.01). After correction for androgen status, IMT was correlated with fasting glucose and area under curve (AUC) insulin. Flow-mediated vasodilation was inversely related to lipids (P = 0.02), whereas pulse wave velocity was related to BP (P < 0.001), AUC insulin (P = 0.04), and AUC glucose (P = 0.035). CONCLUSION: In overweight women with PCOS, insulin resistance and BP interacted negatively with arterial structural and functional measures. DHEAS correlated inversely with arterial structure, suggesting possible cardioprotective effects of endogenous DHEAS in women with PCOS. Additional research is needed to clarify these findings.     

Glucagon as a determinant of fibrinolytic activity in men with different stages of glucose tolerance: impact of glucagon on fibrinolysis.

Glucagon plays an important role in postprandial hyperglycemia in type 2 diabetes (T2DM), and coexists with insulin resistance and impaired fibrinolysis. We analyzed the response of plasminogen activator inhibitor-1 (PAI-1) to a lipid-glucose-protein test and the relationship between glucagon and PAI-1, tissue plasminogen activator (t-PA) and PAI-1/t-PA in 26 men with normal glucose tolerance (NGT), nine with impaired glucose tolerance (IGT) and 12 with T2DM. Fasting and postprandial PAI-1 were higher in T2DM versus NGT (P < 0.05). In univariate analysis in NGT, fasting and area under the curve (AUC) PAI-1 showed a strong relationship with fasting (P = 0.003, P = 0.006) and postprandial (P = 0.041, P = 0.045) glucagon, t-PA with fasting glucagon (P = 0.014), and PAI-1/t-PA with fasting (P = 0.047) and AUC glucagon (P = 0.017). In IGT fasting, AUC PAI-1 and PAI-1/t-PA were associated with AUC glucagon (P = 0.035, P = 0.032, P = 0.023). In NGT with the fasting metabolic parameters and insulin resistance as independent variables, fasting glucagon remained an independent covariate for PAI-1 and PAI-1/t-PA. In another model, postprandial glucagon was independently associated with PAI-1/t-PA in NGT (P < 0.05). Besides the already established determinants, we found an independent association between glucagon and fibrinolysis in NGT. Further studies are needed to identify the link between glucagon, insulin resistance and hemostasis.     

Serum retinol-binding protein 4 is associated with insulin secretion in Chinese people with normal glucose tolerance

Background:  Serum levels of retinol‐binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β‐cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM. Methods:  A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC‐I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4–L5; subjects with VFA ≥80 cm² were considered to have visceral obesity (VO). Results:  Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC‐I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r = 0.162; P < 0.05) and AUC‐I (r = 0.195; P < 0.01) remained in NGT non‐VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC‐I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC‐I (β = 0.204) in NGT non‐VO subjects. Conclusions:  Serum RBP4 is correlated with glucose‐stimulated insulin secretion in NGT non‐VO subjects, but not in NGT VO subjects and T2DM patients.     

Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance.

Proinsulin release is increased relative to insulin secretion in subjects with type 2 diabetes, indicative of islet dysfunction. However, it has not been conclusively shown whether there is an increased relative proinsulin release in subjects with impaired glucose tolerance (IGT), i.e. whether it precedes the development of diabetes. We therefore determined the proinsulin to insulin ratios in the fasting state and after acute stimulation of insulin secretion in 23 postmenopausal women, aged 61-62 yr (mean +/- SD, 61.7 +/- 0.5 yr). Ten women had normal glucose tolerance (NGT), and 13 had IGT. The groups were matched for insulin sensitivity and did not differ in body mass index. Proinsulin and insulin secretion were measured after arginine stimulation (5 g, i.v.) at three glucose levels (fasting, 14 mmol/L, and >25 mmol/L), and the acute insulin (AIR(arg)) and proinsulin responses (APIR(arg)) were calculated as the mean 2-5 min postload increase. At fasting glucose, levels of insulin, proinsulin, or the proinsulin/insulin ratio (13.6 +/- 5.0% vs. 11.1 +/- 2.7%; P = NS) did not differ between NGT and IGT. Although the AIR(arg) values were decreased in the IGT group at all glucose levels (P < 0.05), the absolute proinsulin levels and the APIRs(arg) were similar between IGT and NGT women. Therefore, the IGT women had higher proinsulin/insulin ratios at 14 mmol/L (10.7 +/- 4.4% vs. 6.4 +/- 1.8%; P = 0.006) and more than 25 mmol/L glucose (11.4 +/- 5.2% vs. 6.7 +/- 2.1%; P = 0.007). The IGT group had increased APIR(arg)/AIR(arg) at fasting (2.2 +/- 1.4% vs. 1.3 +/- 0.6%; P = 0.047) and more than 25 mmol/L glucose (3.5 +/- 1.6% vs. 2.3 +/- 0.7%; P = 0.037). We conclude that women with IGT exhibit increased relative proinsulin secretion, suggesting a defect in the intracellular proinsulin processing before diabetes develops.     

多囊卵巢综合征患者性激素结合球蛋白和总睾酮与胰岛素抵抗的相关性

目的 了解性激素结合球蛋白(SHBG)和总睾酮在预测多囊卵巢综合征(PCOS)患者胰岛素抵抗和生殖内分泌以及糖脂代谢紊乱中的作用.方法 选择2004年6月至2006年5月在复旦大学附属妇产科医院就诊的344例PCOS患者为病例组,年龄12～35岁,平均年龄(23±5)岁.选择同期月经规律、基础体温双相的100名妇女作为对照组,比较PCOS患者SHBG和总睾酮与对照组的差异,并用Spearman相关分析法分别分析SHBG和总睾酮与其他指标的相关性,Logistic回归分析胰岛素抵抗的风险因子并做SHBG对胰岛素抵抗的受试者操作特征(ROC)曲线,获得预测胰岛素抵抗的风险值,比较不同水平SHBG患者的糖脂代谢紊乱的程度.结果 PCOS患者SHBG为(114±88)mmol/L,与对照组[(201±106)mmol/L]比较差异有统计学意义(t=-5.60,P<0.01),总睾酮为(2.8±1.0)nmol/L,与对照组[(1.7±0.6)nmol/L]比较差异有统计学意义(t=7.73,P<0.01);SHBG与空腹胰岛素、胰岛素释放试验曲线下面积、口服葡萄糖耐量试验(OGTT)的葡萄糖曲线下面积、胰岛素抵抗指数、甘油三酯和腰围/臀围比呈负相关(r值分别为:-0.30、-0.26、-0.29、-0.19、-0.20、-0.29、-0.22,均P<0.01);总睾酮与空腹胰岛素(r=0.14,P<0.01)、胰岛素释放试验(1、2、3 h的r值分别为0.15、0.12、0.11,均P<0.05)以及相应的曲线下面积(r=0.15,P<0.05)、胰岛素抵抗指数(r=0.11,P<0.05)呈正相关.Logistic回归分析发现SHBG是PCOS患者胰岛素抵抗的独立危险因素(OR=3.741).由ROC曲线得到SHBG预测胰岛素抵抗的大致风险值为88 mmol/L(95%CI为0.668～0.774).在低SHBG(<88 mmol/L)患者中,空腹胰岛素、胰岛素释放试验相应的曲线下面积、胰岛素抵抗指数、空腹血糖、OGTT的葡萄糖曲线下面积与高SHBG(≥88 mmoL/L)患者比较差异有统计学意义(t值分别为-6.45、-5.08、-6.19、-3.16、-3.66,均P<0.01),甘油三酯也高于高SHBG患者(t=-2.06,P<0.05).结论 PCOS患者总睾酮水平高于对照组,SHBG低?     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

Effects of low intensity exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance and type 2 diabetes mellitus

This study was designed to evaluate effects of exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The subjects consisted of overweight subjects with normal glucose tolerance (NGT, n=10), IGT (n=10) and DM (n=10) (age: 51.1+/-8.2, 56.3+/-8.8 and 58.5+/-6.2 years, respectively). All of these patients performed exercise therapy at lactate threshold intensity for 12 weeks. Before intervention, area under the glucose curve (AUC(PG)) was higher in DM, IGT and NGT groups, and area under the insulin curve (AUC(IRI)) and the early phase insulin secretion as calculated by insulinogenic index was higher in the NGT group than in either the IGT or DM groups (p<0.05). After exercise therapy, the insulin sensitivity, AUC(PG) and AUC(IRI) improved in three groups (p<0.05, respectively). The insulinogenic index increased in IGT and DM groups (p<0.05, respectively), but the changes in the insulinogenic index showed no significant differences between IGT and DM groups. These results suggest that the ss-cell function in subjects with IGT and DM could therefore improve after exercise therapy. Moreover, AUC(PG), AUC(IRI) and insulin sensitivity were also improved no relation to NGT, IGT and DM.     

Effects of thorough mastication on postprandial plasma glucose concentrations in nonobese Japanese subjects

Thorough mastication has the potential to affect postprandial plasma glucose concentrations by improving digestibility and absorption of nutrients. To evaluate the effects of mastication on postprandial plasma glucose concentration, we compared usual and thorough mastication in subjects with normal glucose tolerance (NGT group, n = 16) and subjects predisposed to type 2 diabetes (first-degree relatives of type 2 diabetic patients, subjects with impaired glucose tolerance, and type 2 diabetic patients) (predisposed group, n = 10) in a crossover trial of 52 test meals. Plasma glucose and serum insulin concentrations were measured for 3 hours postprandially, and the insulinogenic index (the ratio of incremental serum insulin to plasma glucose concentration during the first 30 minutes after meal) was calculated. In the NGT group, thorough mastication reduced the postprandial plasma glucose concentration at 90 minutes (5.8 +/- 0.3 vs 6.5 +/- 0.4 mmol/L, P < .05) and 120 minutes (5.4 +/- 0.2 vs 6.3 +/- 0.4 mmol/L, P < .05) and the area under the curve (AUC) from -15 to 180 minutes (19.1 +/- 0.6 vs 20.6 +/- 0.8 [mmol . L]/h, P < .05) without an increase in the AUC for insulin. In the predisposed group, thorough mastication significantly augmented plasma glucose and serum insulin concentrations and the AUCs compared with usual mastication. Thorough mastication elicited a significantly higher insulinogenic index than usual mastication in the NGT group (205.0 +/- 27.6 vs 145.6 +/- 17.7 pmol/mmol, P < .05), whereas the predisposed group showed significantly less early-phase insulin secretion than the NGT group. In the NGT group the postprandial plasma glucose concentration upon thorough mastication of meal was significantly lower, most probably because of the potentiation of early-phase insulin secretion. In the subjects predisposed to type 2 diabetes, thorough mastication did not potentiate early-phase insulin secretion and elicited a higher postprandial plasma glucose concentration.     

Serum resistin level in essential hypertension patients with different glucose tolerance.

AIMS: To investigate resistin concentrations in patients with essential hypertension and different glucose tolerance and the relationship between serum resistin level and blood glucose. METHODS: Sixty-five patients with essential hypertension [13 with Type 2 diabetes mellitus (DM), 26 with impaired glucose tolerance (IGT), and 26 with normal glucose tolerance (NGT); 30 males, 35 females] were studied. Fasting serum resistin concentrations were measured by enzyme immunoassay (EIA). Oral glucose tolerance tests and insulin release tests were used to calculate glucose area under the curve (AUCG), the ratio of insulin to glucose (DeltaI30/DeltaG30), and insulin sensitivity index (ISI) according to Cederholm's formula. RESULTS: Fasting serum resistin concentrations (microg/l) in DM (34.9 +/- 10.2) patients were significantly higher than those in IGT (25.1 +/- 10.4) (P < 0.05) and in NGT (21.5 +/- 7.9) (P < 0.05) patients. Pearson correlation showed that fasting serum resistin concentration was correlated with AUCG (r = 0.445, P < 0.001), ISI (r = -0.322, P < 0.01) and DeltaI30/DeltaG30 (r = -0.366, P < 0.01), but not body mass index and waist-hip ratio. After adjustment for gender, age and body mass index (BMI), partial correlation analysis showed that the fasting serum resistin concentrations were still correlated with AUCG (r = 0.327, P < 0.01) and DeltaI30/DeltaG30 (r = -0.348, P < 0.01), but ISI. CONCLUSION: Resistin may be involved in the development of diabetes in humans.     

2型糖尿病患者血管紧张素Ⅱ与胰岛β细胞分泌功能的关系探讨

目的 探讨不同糖耐量状态下血管紧张素Ⅱ与胰岛β细胞分泌功能的关系.方法 新诊断2型糖尿病患者42例(DM组)、空腹血糖受损/糖耐量受损者38例(IFG/IGT组)、正常对照者40名(NGT组)行静脉葡萄糖耐量试验,ELISA法测定空腹血管紧张素Ⅱ(AngⅡ)及脂联素水平.计算急性胰岛素分泌反应(AIR3-10)、第一时相(0～10min)胰岛素分泌曲线下面积(AUCⅠ)及峰值浓度、第二时相(10～120min)胰岛素分泌曲线下面积(AUCⅡ)、稳态模型评估胰岛β细胞功能指数(HOMA-β)及胰岛素抵抗指数(HOMA-IR).探讨AngⅡ与AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素、HOMA-β及HOMA-IR的关系.结果 (1)DM组和IFG/IGT组AngⅡ显著高于NGT组(P＜0.05);DM组和IFG/IGT组AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素显著低于NGT组(P＜0.05),DM组降低更为显著;(2)AngⅡ与AIR3-10、AUCⅠ及峰值浓度、AUCⅡ、脂联素、HOMA-β呈显著负相关(P＜0.01),与空腹血糖、糖负荷后2 h血糖、空腹胰岛素、HOMA-IR呈正相关(P＜0.05);(3)多元逐步回归分析,AngⅡ与AUCⅠ、AUCⅡ独立相关.结论 AngⅡ为胰岛β细胞分泌功能的独立影响因素.排除血压、体位、药物等因素的影响,高AngⅡ水平可预测2型糖尿病患者胰岛β细胞功能受损及胰岛素抵抗.

Abstract：

Objective To investigate the relationship between angiotensin Ⅱ and pancreatic islet β cell secretion function under different glucose tolerance statuses. Method Forty-two patients with newly diagnosed type 2diabetes mellitus ( DM group), 38 subjects with impaired fasting glucose/impaired glucose tolerance ( IFG/IGTgroup) ,and 40 normal control subjects (NGT group) underwent intravenous glucose tolerance test. Fasting plasma angiotensin Ⅱ ( Ang Ⅱ ) and adiponectin were assayed by ELISA. Acute insulin response from 3 to 10 min( AIR3-10 ),the area under the curve( AUCⅠ ) and the peak concentration of the first-phase ( 0-10 min) insulin secretion, the area under the curve of the second-phase( 10-120 min) insulin secretion( AUCⅡ), homeostasis model assessment for β cell function index(HOMA-β) and homeostasis model assessment for insulin resistance index(HOMA-IR) were calculated to explore the relationship with Ang Ⅱ. Result ( 1 ) The levels of Ang Ⅱ in DM group and IFG/IGT group were significantly higher than that in NGT group( P＜0.05 ). The AIR3-10, AUCⅠ and peak concentration, AUCⅡ ,adiponectin in DM group and IFG/IGT group were significantly lower than those in the NGT group ( P＜0. 05), and these results were more significantly reduced in DM group compared with those in IFG/IGT group. (2) Ang Ⅱ was negatively correlated with AIR3-10, AUCⅠ and the peak concentration, AUCⅡ, adiponectin, HOMA-β ( P＜0. 01 ), and positively correlated with fasting blood glucose,2 h blood glucose after glucose loading, fasting insulin, HOMA-IR (P＜0. 05 ). (3)Multiple stepwise regression analysis showed that Ang Ⅱ was independently associated with AUCⅠ and AUCⅡ.Conclusion Ang Ⅱ was an independent factor that affected the insulin secretion function of pancreatic islet βcells. Ruling out the effect of blood pressure, body position, drugs, and other factors, high levels of Ang Ⅱ could predict the dysfunction of pancreatic islet β cell as well as insulin resistance in patients with type 2 diabetes.     

Neither homeostasis model assessment nor quantitative insulin sensitivity check index can predict insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus

To clarify whether homeostasis model assessment (HOMA IR) and quantitative insulin sensitivity check index (QUICKI) may be indicators of insulin resistance in elderly patients with type 2 diabetes mellitus, their relationship with the glucose infusion rate during the euglycemic hyperinsulinemic clamp study (clamp IR) was assessed. This study comprised 56 Japanese patients with type 2 diabetes mellitus; of these, 28 were 70 yr of age or older (group 1) and 28 were less than 70 yr of age (group 2). Their blood sugars were in poor control (fasting plasma glucose levels: group 1, 9.0 +/- 2.6 mmol/liter; group 2, 8.9 +/- 2.3 mmol/liter; hemoglobin A1c: group 1, 9.5 +/- 2.0%; group 2, 9.2 +/- 1.7%). Log-transformed HOMA IR was significantly correlated with the clamp IR in group 2 patients (r = -0.51, P < 0.01), but not in group 1 patients (r = -0.28, P = 0.15). There was a significant positive correlation between QUICKI and clamp IR in group 2 patients (r = 0.50, P < 0.01). However, no significant correlation was observed between QUICKI and clamp IR in group 1 patients (r = 0.31, P = 0.12). There was a significant correlation between log-transformed HOMA IR (r = -0.37, P < 0.01) or QUICKI (r = 0.37, P < 0.01) and clamp IR when both groups were combined. In conclusion, neither HOMA IR nor QUICKI should be used as an index of insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus. The results of this study suggest the need for developing a new noninvasive method for evaluating insulin resistance in those patients.     

Lipoprotein lipase (LPL) mass in preheparin serum reflects insulin sensitivity

Lipoprotein lipase (LPL) is one of the enzymes regulated by insulin and its plasma activity reflects insulin sensitivity. Although intravenous heparin injection is required to measure LPL activity, we can detect LPL mass in preheparin serum (Pr-LPL mass) by immunoassay. In this study, we examined whether Pr-LPL mass reflects insulin sensitivity. We measured Pr-LPL mass, insulin sensitivity (Si), and acute insulin release in response to a glucose bolus (AIRg) in subjects with normal glucose tolerance (NGT; n = 23), impaired glucose tolerance (IGT; n = 10), and Type II diabetes mellitus (DM; n = 48). Si and AIRg were determined by minimal model analysis. We also compared Pr-LPL mass with the homeostasis model assessment of insulin resistance (HOMA-R) and the urinary excretion of C-peptide (urine CPR). We found that Pr-LPL mass correlated significantly with Si ( r = 0.354, P < 0.01) in all the subjects. This correlation was still significant in the NGT group (P < 0.472, P < 0.05), DM group (r = 0.311, P < 0.01), and DM group with a fasting plasma glucose >150 mg/dl ( n = 20, r = 0.459. P < 0.05). Moreover, Pr-LPL mass correlated negatively with HOMA-R (r = -0.272. P < 0.05) and fasting IRI (r = -0.256, P < 0.05). By contrast, Pr-LPL mass was not correlated with either urine CPR or logAIRg that reflect the ability to secrete insulin. In conclusion, Pr-LPL mass reflects insulin sensitivity. We speculate that Pr-LPL mass might be used to assess insulin sensitivity not only in the general population but also in advanced diabetic patients.     

Proinsulin in girls: relationship to obesity,hyperinsulinemia, and puberty

In adults with impaired glucose tolerance (IGT) and obesity (OB), an elevated proinsulin (PI) is predictive of type 2 diabetes mellitus (DM) and precedes the diagnosis by 5-20 yr. In type 2 DM, the PI is disproportionately elevated, i.e. increased PI/insulin ratio (PI/I). Few studies have evaluated PI in children at risk for type 2 DM. In the face of the current epidemic, we evaluated the relationship of PI and PI/I to IGT, insulin resistance (IR) defined by homeostasis model of assessment (HOMA), degree of OB, and stage of puberty in 70 girls (mean age 10.8 yr; body mass index z-score 3.5; ethnicity 64% Hispanic, 19% white, 16% African-American, and 1% other). Family history of DM was reported in 83%, and acanthosis nigricans was present in 80%. Subjects underwent a 2-h oral glucose tolerance test with glucose, insulin, and PI determinations every 30 min. All had normal hemoglobin A1c and fasting glucose. Five had IGT. With higher HOMA-IR, PI increased (P < 0.05), yet the ratio of fasting PI/I was lower (P < 0.05). Girls with body mass index z-score greater than 4 (n = 29) had higher PI than nonobese girls (n = 19, P < 0.05), but PI/I ratios were not different. PI-0 was increased in late puberty (n = 29), compared with prepuberty (n = 26, P < 0.05), but PI/I ratios showed no statistical difference. We found PI increased with increasing IR and OB in girls. Overall, PI/I was not different, suggesting the elevated PI reflects increased beta-cell output proportional to the elevated insulin in these groups and not a defect in PI processing or secretion. In fact, the lower fasting PI/I of the highest HOMA-IR quartile vs. the lowest HOMA quartile indicates more efficient conversion of PI to I in the presence of increasing IR in these girls.     

Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents

Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.     

Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P 相似文献   

Preserved insulin sensitivity and {beta}-cell activity, but decreased glucose effectiveness in normal-weight women with the polycystic ovary syndrome

Insulin resistance and hyperinsulinemia are often considered intrinsic features of the polycystic ovary syndrome (PCOS). Nevertheless, conflicting results of insulin sensitivity and secretion have been obtained in the subgroup of normal-weight women with PCOS. Differences in body composition, ethnicity, and diet composition and a family history of metabolic diseases may act as confounding variables in women with PCOS. In the present study, insulin sensitivity and secretion were estimated by an iv glucose tolerance test (IVGTT), analyzed by minimal models, in 20 normal-weight healthy women with PCOS and no family history of type 2 diabetes mellitus and in 20 normally ovulating women, matched for age and body mass index. Insulin sensitivity [mean (95% confidence intervals); PCOS 4.0 (2.8-5.1) vs. controls 4.5 (3.5-5.4) 10(-4) min(-1)/microU.ml], and insulin secretion, expressed as the acute insulin response to glucose [PCOS 3.7 (3.3-4.2) vs. controls 3.7 (3.4-4.0) microU/ml] were similar in the two groups. The women with PCOS showed an increased proportion of total body fat (PCOS 29% vs. controls 27.2%; P < 0.01). They also showed decreased glucose effectiveness, i.e. the proportion of glucose uptake independent from insulin activity [PCOS 2.6 (2.1-3.0) vs. controls 3.8 (3.0-4.6) mg x 100 min(-1); P = 0.01]. The levels of insulin sensitivity and of glucose effectiveness did not correlate in either group. Whether the isolated finding of decreased glucose effectiveness could reflect an early stage in the development of the metabolic aberrations often associated with the syndrome remains to be clarified.     

Relationship between insulin resistance and left ventricular diastolic dysfunction in patients with impaired glucose tolerance and type 2 diabetes

AIM: The aim of this study was to explore the relationship between insulin resistance (IR) and the left ventricular diastolic function in patients with type 2 diabetes and subjects with impaired glucose tolerance (IGT). METHODS: The study included 119 subjects who underwent oral glucose tolerance test (OGTT). IR was assessed using Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI). Left ventricular diastolic function was assessed using trans-thoracic Doppler echocardiography. RESULTS: Based on the OGTT results, 29 subjects had normal glucose tolerance (NGT), 20 subjects had impaired glucose tolerance (IGT), and 70 patients had type 2 diabetes. There were significant differences among the patients in groups with NGT, IGT and diabetes regarding HOMA-IR (4.20 +/- 1.20 vs. 6.45 +/- 3.83 vs. 8.70 +/- 6.26; P < 0.001) and QUICKI (0.54 +/- 0.11 vs. 0.49 +/- 0.08 vs. 0.47 +/- 0.08; P < 0.001). In subjects with NGT, IGT and patients with diabetes, the pulsed Doppler transmitral variables were: E-wave (0.72 +/- 0.16 cm/s vs. 0.62 +/- 0.13 cm/s vs. 0.58 +/- 0.17 cm/s; P < 0.001), A-wave (0.61 +/- 0.13 cm/s vs. 0.62 +/- 0.11 cm/s vs. 0.71+/- 0.14 cm/s; P = 0.006) and E/A ratio (1.22 +/- 0.33 vs. 1.02 +/- 0.24 vs. 0.85 +/- 0.26; p < 0.001). The proportion of subjects with an E/A ratio <1 was 27.6% in the group with NGT, 55% in the group with IGT and 75.7% in the group with diabetes (P < 0.001). The E/A ratio correlated with HOMA-IR (r = -0.30, p = 0.001) and QUICKI (r = 0.37, p < 0.0001). Multiple linear regression model showed that IR (assessed by QUICKI) was an independent correlate of diastolic dysfunction (P = 0.034). CONCLUSIONS: In subjects with impaired glucose tolerance and patients with type 2 diabetes, insulin resistance is associated with impaired diastolic function of the left ventricle.     

非糖尿病高胰岛素血症人群的胰岛b细胞功能分析

目的 分析正常血糖及糖调节受损合并高胰岛素血症（HINS）人群的胰岛β细胞功能状态。方法对北京某高校年度查体人员中无糖尿病史者行口服75g葡萄糖耐量试验（75gOGTT）,资料完整的非糖尿病人群共634例,其中HINS者94例,分析正常血糖及糖调节受损HINS人群的胰岛功能的差异。结果正常血糖及糖调节受损人群中高胰岛素组胰岛素抵抗指数HOMA—IR、△I120／△G120、第一时相及第二时相胰岛素分泌指数显著高于对照组（P〈0．05）;胰岛素敏感指数（ISI～Stumvoll）、HOMA—IR校正后β细胞功能指数（HBCI／IR）显著低于对照组（P〈0．05）;β细胞功能指数（HBCI）高于对照组,但差异无统计学意义（P〉0．05）;△I120/△G120／IR两组间无统计学差异（P〉0．05）。糖调节受损HINS组年龄、服糖后2h血糖、总胆固醇、低密度脂蛋白胆固醇、收缩压、2h胰岛素水平显著高于正常血糖HINS组（P〈0．05）;HBCI、HBCI／IR、第一时相及第二时相胰岛素分泌指数显著低于正常血糖HINS组（P〈0．05）;HOMA—IR和ISI—Stumvoll两组间无统计学差异（P〉0．05）。结论正常血糖及糖调节受损HINS人群虽然胰岛素分泌绝对值增加,但实际的胰岛6细胞功能在逐渐减退。正常血糖-HINS和糖调节受损-HINS是2型糖尿病发生发展的中间过渡状态,应该尽早检出、早期干预。