Differential effects of raloxifene and estrogen on insulin sensitivity in postmenopausal women

OBJECTIVES: To test the hypothesis that both raloxifene and estrogen would improve insulin sensitivity in postmenopausal women and that the magnitude of the effect would be similar for both drugs. DESIGN: Placebo-controlled, double-blind, randomized study. SETTING: The General Clinical Research Center of the University of Michigan Medical Center, a university hospital. PARTICIPANTS: Forty-four healthy postmenopausal women 73 +/- 7 years old (mean age +/- standard deviation) who were not receiving hormone replacement therapy. INTERVENTION: Eight weeks of drug therapy with randomization to raloxifene (n = 16), estrogen (n = 14), or placebo (n = 14). MEASUREMENTS: These subjects underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity (SI) and total and regional (central) body composition measurements by dual-energy x-ray absorptiometry at baseline and after 8 weeks of drug therapy. RESULTS: There were no statistically significant differences in age, body mass index, total or central fat mass, or SI between the three groups at baseline. The major outcome variable was SI. After 8 weeks of drug therapy, there was no significant change in SI in the placebo group or in the estrogen group and a significant decrease in SI in the raloxifene group, P =.003. CONCLUSION: In contrast to estrogen's ability to maintain insulin sensitivity, raloxifene decreases insulin sensitivity in healthy nondiabetic postmenopausal women. The clinical significance of this effect of raloxifene to impair insulin sensitivity in postmenopausal women warrants further evaluation in future studies.     

短期能量限制对正常大鼠胰岛素敏感性的影响

目的探讨短期能量限制（CR）对正常大鼠胰岛素敏感性的影响及其机制。方法将24只F344/NSIc系雄性大鼠随机分为对照组（AL组）和能量限制组（CR组）各12只。AL组自由摄入食物及水,CR组限制食物摄入（不禁水）8周（饲料总摄入量为对照组的64%）。采用高胰岛素—正常血糖钳夹试验测定两组葡萄糖输注率（GIR）判断其胰岛素敏感性（GIR越高,胰岛素敏感性越高）;比较两组体质量增加及内脏脂肪重量;Western blot法检测骨骼肌葡萄糖转运体4（Glu T4）、蛋白激酶B底物蛋白160（AS160）及磷酸化AS160（p-AS160）蛋白表达。结果CR组GIR明显高于对照组,体质量及内脏脂肪重量明显低于对照组;两组Glu T4、AS160及p-AS160蛋白表达无显著差异。结论短期CR可提高大鼠正常状态下的胰岛素敏感性,其机制可能与AS160上游的胰岛素信号转导蛋白有关。     

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans

Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors. The "gold standard" glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo, but neither is easily implemented in large studies. Thus, it is of interest to develop a simple, accurate method for assessing insulin sensitivity that is useful for clinical investigations. We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sampled iv glucose tolerance tests on 28 nonobese, 13 obese, and 15 type 2 diabetic subjects. We obtained correlations between indexes of insulin sensitivity from glucose clamp studies (SI(Clamp)) and minimal model analysis (SI(MM)) that were comparable to previous reports (r = 0.57). We performed a sensitivity analysis on our data and discovered that physiological steady state values [i.e. fasting insulin (I(0)) and glucose (G(0))] contain critical information about insulin sensitivity. We defined a quantitative insulin sensitivity check index (QUICKI = 1/[log(I(0)) + log(G(0))]) that has substantially better correlation with SI(Clamp) (r = 0.78) than the correlation we observed between SI(MM) and SI(Clamp). Moreover, we observed a comparable overall correlation between QUICKI and SI(Clamp) in a totally independent group of 21 obese and 14 nonobese subjects from another institution. We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research.     

Homeostasis model assessment of insulin resistance,quantitative insulin sensitivity check index,and oral glucose insulin sensitivity index in nonobese,nondiabetic subjects with high-normal blood pressure

To investigate the relationships between high-normal blood pressure (BP) and insulin resistance, we examined insulin sensitivity in 306 nonobese and nondiabetic Japanese subjects with various BP categories (optimal BP, normal BP, high-normal BP, and hypertension). Insulin sensitivity was measured from fasting plasma glucose and insulin values and those during a 75-g oral glucose tolerance test by five formulas: the homeostasis model assessment of insulin resistance (HOMA-R), the quantitative insulin sensitivity check index (QUICKI), the oral glucose insulin sensitivity (OGIS) index, and two insulin sensitivity indexes (ISI-composite and ISI-stumvoll). The HOMA-R was significantly higher, and the QUICKI was significantly lower in subjects with hypertension than in subjects with optimal BP. Both HOMA-R and QUICKI values showed that high-normal BP patients had a higher (but not significant) degree of insulin resistance than optimal BP patients. The OGIS index was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP. The ISI-composite was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP, and it was also significantly lower in subjects with hypertension than in subjects with normal BP. The ISI-stumvoll was significantly lower in subjects with high-normal BP or hypertension than in subjects with optimal BP. The OGIS index, ISI-composite, and ISI-stumvoll significantly decreased with increasing severity of BP status among the normotensive groups (optimal BP, normal BP, and high-normal BP). These findings indicate that insulin resistance is present even in the high-normal BP categories of nonobese and nondiabetic Japanese individuals.     

Effects of low- and high-glycemic index/glycemic load diets on coronary heart disease risk factors in overweight/obese men

Chronic insulin resistance contributes to subclinical inflammation, thrombosis/impaired fibrinolysis, and dyslipidemia. The effect of dietary carbohydrate, specifically of glycemic index (GI) and glycemic load (GL), on established and emerging coronary heart disease risk factors has not been elucidated fully. We conducted a randomized crossover feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity, inflammation, thrombosis/fibrinolysis, lipoproteins/lipids, and body composition. All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen. Each participant consumed both diets in random order for 4 weeks each, with a 4-week washout period in between. Each participant underwent a frequently sampled intravenous glucose tolerance test for assessment of insulin sensitivity; blood sampling for the measurement of inflammatory markers, coagulation factors, and lipoproteins/lipids; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period. There were no statistically significant differences in glucose metabolism factors, inflammatory markers, or coagulation factors after 4 weeks on the high- and low-GI/GL diets. The high-GI/GL diet resulted in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared with the low-GI/GL diet. The high-GI/GL diet resulted in significant, but unexpected, reductions in total and low-density lipoprotein cholesterol, whereas high-density lipoprotein cholesterol concentration was significantly reduced on the high-GI/GL diet compared with the low-GI/GL diet. Overall, high- and low-GI/GL diets of 4 weeks' duration had no consistent effects on coronary heart disease risk factors in this group of overweight/obese men.     

Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women

BACKGROUND: A possible relationship between thyroid hormones and adipose tissue metabolism in humans has been suggested. Aim of the study We sought to evaluate thyroid function and its possible relationship with body mass index (BMI), leptin, adiponectin and insulin sensitivity in euthyroid obese women. MATERIALS AND METHODS: Eighty-seven uncomplicated obese women (mean age 34.7 +/- 9 years, mean BMI 40.1 +/- 7 kg/m(2)) were studied. Levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3), plasma adiponectin and leptin were evaluated. Insulin sensitivity was assessed by euglycaemic hyperinsulinaemic clamp (M index), fasting insulin and HOMA-IR. RESULTS: Uncomplicated obese women with BMI > 40 kg/m(2) showed higher serum TSH than obese subjects with BMI < 40 kg/m(2) (P < 0.01). TSH was correlated with BMI (r = 0.44, P = 0.01) leptin (r = 0.41, P = 0.01), leptin/BMI ratio (r = 0.33, P = 0.03), body surface area (r = 0.26, P = 0.05), HOMA-IR (r = 0.245, P = 0.05) and inversely with adiponectin (r = -0.25, P = 0.05) and M index (r = -0.223 P = 0.05). CONCLUSIONS: Our data show that, although thyroid function was normal in the studied obese population, TSH and BMI were positively related. TSH has been found to be correlated also with leptin adjusted for BMI. TSH could represent a marker of altered energy balance in severe, but uncomplicated obese women.     

Comparison of the effects on insulin sensitivity of high carbohydrate and high fat diets in normal subjects.

To examine whether achievable dietary changes influence insulin sensitivity, we performed euglycemic hyperinsulinemic glucose clamps in eight normal subjects who were prescribed high carbohydrate and high fat diets. The high carbohydrate diet was more than 50% (of energy intake) carbohydrate and less than 30% fat; the high fat diet was more than 45% fat (predominantly saturated) and less than 40% carbohydrate. The diets were consumed over consecutive 3-week periods in random sequence. The mean whole body glucose uptake during the glucose clamps was similar after the high carbohydrate (48.3 mumol/kg.min) and high fat diets (47.0 mumol/kg.min; P = 0.5; 95% confidence interval for the difference, -3.4 to 5.9 mumol/kg.min). Fasting blood glucose and serum insulin concentrations were also unchanged. In contrast, there were substantial effects on lipoprotein metabolism. During the high carbohydrate diet, fasting serum cholesterol decreased by 17% (P = 0.06), low density lipoprotein cholesterol decreased by 20% (P = 0.05), high density lipoprotein cholesterol decreased by 24% (P less than 0.005), and triglyceride increased by 33% (P = 0.06) compared with levels during the high fat diet. These results suggest that practically achievable high carbohydrate diets do not enhance insulin sensitivity in nondiabetic subjects and have net effects on lipoprotein metabolism that may be unfavorable.     

Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy

Introduction

The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic).

Methods

Ten subjects with long-standing T1DM (n = 7) or T3cDM (n = 3) on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design.

Results

Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 (p < .05) and from 46 ± 7.7 to 37 ± 6.6 U on day 3 (p < .05) of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 (p < .01) and 34% ± 14% on day 3 (p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; the reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency (p < .002).

Conclusions

A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.     

雌激素对绝经后妇女原发性高血压患者胰岛素敏感性的影响

目的：探讨雌激素对绝经后妇女轻中度原发性高血压（EH）患胰岛素敏感性的影响。方法：35例绝经妇女轻中度EH患,每日口服倍美力（结合型雌激素）0．625mg,于服药前及服药后3个月末分别检测血压,空腹血糖（FBG）,空腹血浆胰岛素（FINS）,并作口服葡萄糖耐量试验,同时测定血浆胰岛素。结果：治疗后血压无明显变化（P＞0．05）,而FBG,FINS水平明显降低（P＜0．01）。FINS敏感指数提高（P＜0．01）,结论：雌激素可降低绝经后妇女轻中度EH患的血糖及FINS水平,显提高FINS敏感性。     

Glucose tolerance, insulin secretion, insulin sensitivity and glucose effectiveness in normal and overweight hyperthyroid women

OBJECTIVE Inter-relationships between insulin sensi-tivity and body weight in patients with hyperthyroidism remain incompletely understood. We have examined whether a mild excess of body weight exacerbates the metabolic abnormalities of spontaneous hyperthyroidism. DESIGN AND PATIENTS Insulin-modified intravenous glucose tolerance tests were performed on 14 hyperthy-roid women with body mass indices (BMI) ranging from 21 to 31 kg/m². A control group of 19 healthy women matched for age and BMI was also studied. MEASUREMENTS Intravenous glucose tolerance (KG), first and second-phase integrated insulin responses to glucose, the integrated glucose area under the curve (AUC), and minimal model parameters of insulin sensitivity (SI) and glucose effectiveness (SG) were determined. RESULTS Hyperthyroid women had mean KG, glucose-induced insulin secretion and SG values similar to those in control women. The mean glucose AUC was higher in hyperthyroid patients (P<0.05). Lower insulin sensitivity was observed in hyperthyroid patients than in control women (SI=0.38±0.07 vs 0.59±0.07 l/min pmol 10⁴ (mean±SEM), P<0.05). A steeper decline in insulin sensitivity with increase in body mass index was found in hyperthyroid women when compared with the control group, after adjusting for age. When groups were compared according to their BMI, hyperthyroid women with normal weight (BMI≤25 kg/m², n=8) had mean KG, insulin response to glucose, glucose AUC, SG and SI values similar to those in normal weight control women (n=11). Overweight hyperthyroid patients (BMI>25 kg/m², n=6) had a higher (P<0.05) second-phase insulin response to glucose than normal weight patients, a higher glucose AUC (P<0.05) than normal weight patients and overweight controls (n=8), and a lower SI (P<0.05) than normal weight patients and overweight controls. SG was not influenced by BMI in hyperthyroid patients. CONCLUSIONS These results suggest that overall glucose tolerance was not significantly affected in normal weight hyperthyroid women. However, when a moderate excess of weight is also present, a state of clear insulin resistance occurs.     

不同脂肪酸饮食对Wistar大鼠胰岛素敏感性的影响

目的 探讨饱和脂肪酸(SFA)、单不饱和脂肪酸(MUFA)、多不饱和脂肪酸(PUFA)饮食对大鼠胰岛素敏感性的影响.方法 48只雄性Wistar大鼠随机分为正常对照组、SFA组、MUFA组、PUFA组.正常对照组给基础饲料(脂肪占10.3%);SFA组饲料在基础饲料中添加15%猪油;MUFA组饲料在基础饲料中添加15%茶油;PUFA组饲料在基础饲料中添加15%豆油(脂肪占35.4%).8 w后4组各随机选8只大鼠行高胰岛素-正葡萄糖钳夹实验,同时留取空腹血清测定血脂、胰岛素等指标.结果 实验第8周末,与其他3组相比,正常对照组大鼠进食量有所增加,差异有统计学意义(P>0.05).除外进食量的影响,与SFA组相比,正常对照组、MUFA组、PUFA组血清TC、TG降低,差异有统计学意义(P<0.05),而正常对照组、MUFA、PUFA三组间无统计学意义(P>0.05).与正常对照组、MUFA组相比,SFA、PUFA组FINS、FPG升高,差异有统计学意义(P<0.05),GIR明显下降,差异有统计学意义(P<0.05),但该两组间无统计学差异(P>0.05).与正常对照组相比,MUFA组血清FINS、FPG有升高趋势,差异无统计学意义(P>0.05),GIR下降,差异有统计学意义(P<0.05). 结论 MUFA饮食较PUFA、SFA饮食可以改善胰岛素敏感性.     

Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women

The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking any hormone replacement therapy. Diabetic, obese, and smoking patients were excluded. After a 4-week placebo period, they were randomized to receive 2 mg of oral trandolapril (n = 45) or 50 mg of oral losartan (n = 44) for 12 weeks according to a double-blind, parallel group design. At the end of the placebo and active treatment periods, blood pressure (BP) was measured, plasma samples were drawn to evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2 mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the two treatments. The PAI-1 antigen levels were significantly decreased by trandolapril (from 36.9 ± 21 ng/dL to 27.2 ± 17 ng/dL, P < .05), but not by losartan (from 35.3 ± 22 ng/dL to 37.1 ± 23 ng/dL, P = not significant). Glucose infusion rate was significantly increased by trandolapril (from 6.67 ± 0.56 mg/min/kg to 7.9 ± 0.65 mg/min/kg, P < .05), but was not significantly modified by losartan (from 6.7 ± 0.47 mg/min/kg to 6.9 ± 0.50 mg/min/kg, P = not significant). In the trandolapril group the PAI-1 decrease correlated with glucose infusion rate increase (r = 0. 36, P = .045) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT₁ antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms. It remains to be seen whether these findings apply to other patient populations than postmenopausal women.     

Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism

Prediabetes is a heterogeneous term that encompasses different origins of insulin resistance and insulin secretion that contribute to distinct patterns of hyperglycemia. In fact, prediabetes is an umbrella term that characterizes individuals at high risk for developing type 2 diabetes (T2D) and/or cardiovascular disease (CVD). Based on current definitions there are at least 3 distinct phenotypes of prediabetes: impaired fasting glucose (IFG), impaired glucose tolerant (IGT), or the combination of both (IFG + IGT). Each phenotype is clinically relevant as they are uniquely recognized as having different levels of risk for progressing to T2D and CVD. Herein, we discuss the underlying pathophysiology that characterizes IFG, IGT and the combination, as well as examine how some of these phenotypes appear resistant to traditional exercise interventions. We propose that substrate metabolism differences between the prediabetes phenotypes may be a unifying mechanism that explains the inter-subject variation in response to exercise seen across obese, metabolic syndrome, pre-diabetic and T2D patients in the current literature. Ultimately, a better understanding of the pathophysiologic mechanisms that govern disturbances responsible for fasting vs. postprandial hyperglycemia and the combination of both is important for designing optimal and personalized exercise treatment strategies that treat and prevent hyperglycemia and CVD risk.     

Endothelial function,insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women

BACKGROUND: Hyperprolactinemia has been reported to be associated with abnormalities of carbohydrate metabolism. The aim of this study was to evaluate the effects of hyperprolactinemia and bromocriptine (Brc) treatment on endothelial function, insulin sensitivity and inflammatory markers in pre-menopausal women. METHODS: Sixteen hyperprolactinemic pre-menopausal women with pituitary adenomas were recruited and 20 healthy subjects were included as controls. Patients were given Brc in doses of 2.5-20 mg/dl until normal levels of prolactin were reached. Prior to treatment and 2 months after prolactin levels were normalized, the following tests were performed. Insulin sensitivity was determined by an oral glucose tolerance test based on a formula named the insulin sensitivity index (ISI composite). Endothelial function was measured as flow-mediated dilatation (FMD) on a brachial artery using high resolution ultrasound. RESULTS: Serum glucose, insulin, estrogen, highly sensitive C-reactive protein (hsCRP), fibrinogen, homocysteine and uric acid levels were measured. Calculated ISI composite and FMD were significantly lower in the hyperprolactinemic group in comparison with the controls and improved after Brc treatment. Serum homocysteine, hsCRP and uric acid levels were significantly higher in hyperprolactinemic patients than in the controls and returned to normal levels with Brc treatment. Serum prolactin concentrations were inversely correlated with FMD measurements (r=-0.68; P<0.0001), ISI composite (r=-0.48; P<0.005) and serum estrogen (r=-0.54; P<0.005), and positively correlated with serum homocysteine concentrations (r=0.55; P<0.0001) in the hyperprolactinemic group. CONCLUSIONS: The hyperprolactinemic state is associated with impaired endothelial function and decreased insulin sensitivity, which are early markers of atherosclerosis. These alterations may predispose to the development of atherosclerosis in non-treated cases. Correction of the hyperprolactinemic state is associated with improved endothelial function and insulin sensitivity.     

Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin

CONTEXT: Brain insulin is critically involved in the regulation of body weight and memory processing. Long-term administration of intranasal insulin reduces body weight in men, but not in women, while improving hippocampus-dependent memory processing in both genders. OBJECTIVES: Our objectives were to assess the effects of a single dose of intranasal insulin on food intake and memory function in men and women, and to determine any gender differences. METHODS: A total of 32 healthy, normal-weight subjects (14 men, 18 women) were intranasally administered 160 IU regular human insulin or vehicle before performing a hippocampus-dependent two-dimensional-object location task, a working memory task (digit span), and a hippocampus-independent mirror tracing task. Subsequently, food intake from an ad libitum breakfast buffet was measured. RESULTS: Insulin treatment decreased food intake in men but not in women (difference to placebo condition, men: -192.57 +/- 78.48 kcal, P < 0.03; women: 18.54 +/- 42.89 kcal, P > 0.67). In contrast, hippocampus-dependent memory and working memory were improved in women (P < 0.03, P < 0.05, respectively), whereas men did not benefit from acute insulin treatment (P > 0.17, P > 0.20). Performance on the hippocampus-independent mirror tracing task was not affected by insulin in women or men. CONCLUSIONS: In accordance with animal data, results indicate that men are more sensitive than women to the acute anorexigenic effect of central nervous insulin signaling, whereas insulin's beneficial effect on hippocampus-dependent memory functions is more pronounced in women. Our findings provide support for the notion of a fundamental gender difference in central nervous insulin signaling that pertains to the regulation of energy homeostasis and memory functions.     

Differences in insulin sensitivity between normal men and women

An incremental intravenous low-dose insulin infusion has been used to examine differences in insulin sensitivity between normal young men and women. Fasting blood glucose concentration did not differ significantly at the start of the infusion but women had significantly higher plasma insulin and C-peptide concentrations. Similar changes in blood glucose occurred during insulin infusion but insulin concentrations were higher in women. Blood total ketone bodies and alanine were lower in women over the four hours of infusion. Significant differences were found between normal men and women for the effect of insulin upon blood glucose concentration.     

Habitual dietary intake versus glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women.

OBJECTIVE: The major aim was to study the relation between habitual dietary intake and glucose tolerance, insulin sensitivity and insulin secretion in postmenopausal women. Dietary intake was also compared between women with normal (NGT) or impaired glucose tolerance (IGT). DESIGN: Habitual dietary intake was studied using a modified diet history method, from which the energy, carbohydrate, fat and protein intake was calculated. Glucose tolerance was determined as the 2 h glucose value after a 75 g oral glucose tolerance test. Insulin sensitivity was studied with a euglycemic, hyperinsulinaemic clamp, whilst insulin secretion was measured as the acute (2-5 min) response to iv arginine (5 g) at fasting, 14 and >25 mmol L(-1) glucose. SETTING: Clinical research unit at the University Hospital in Malmo, Sweden. Subjects. A total of 74 women (mean+/-SD age 58.7+/-0.4 years). RESULTS: In the entire group, the 2 h glucose level correlated with polyunsaturated fat intake (PUFA, r = 0.41, P < 0.001), and negatively with carbohydrate intake (r = -0.23, P = 0.05). The relation between 2 h glucose and PUFA was independent of body fat content and insulin sensitivity in a multivariate model. Insulin sensitivity correlated with energy intake (r = 0.31, P = 0.007) and PUFA (r = -0.27. P = 0.022). However, these correlations were not significant after adjustment for body fat content in a multivariate model. There were no correlations between insulin secretory variables and habitual dietary intake. Of the 74 women, 60 had NGT and 14 had IGT. The NGT and IGT groups did not differ in intakes of total energy, carbohydrate or protein. The IGT women had higher intake of PUFA (P = 0.003), whilst the total, saturated and monounsaturated fat intake did not differ between the groups. CONCLUSION: Dietary parameters are not independently associated with insulin sensitivity or insulin secretion in postmenopausal women. Furthermore, dietary habits are largely similar in women with NGT and IGT, although subtle differences cannot be excluded due to the small study size. Therefore, habitual intake of total carbohydrate or total fat seems not to be the major determinant of glucose tolerance in nondiabetic Caucasian postmenopausal women.     

Clinical features in women with polycystic ovaries: relationships to insulin sensitivity, insulin gene VNTR and birth weight

OBJECTIVE: Polycystic ovaries are a common ultrasound finding, yet few of these women have many clinical features of polycystic ovary syndrome. Clinical presentation may relate to degree of insulin resistance, common polymorphism at the insulin gene VNTR, and birth weight. We therefore examined the relationship between insulin sensitivity, insulin gene VNTR genotype, birth weight and presence of polycystic ovaries/features of polycystic ovary syndrome in a normal population study. DESIGN AND PATIENTS: In 224 young women recruited as normal volunteers, ovarian morphology was determined by transabdominal ultrasound and features of polycystic ovary syndrome were identified on clinical and biochemical examination. Insulin sensitivity was estimated from fasting glucose and insulin levels using the homeostasis model. Insulin gene VNTR genotypes were determined in women and their parents. MEASUREMENTS AND RESULTS: Thirty-three per cent (74/224) had polycystic ovaries on ultrasound. These women had higher birth weights (P = 0.004), higher insulin sensitivity (P = 0.02) and higher leptin levels for body mass index (P = 0.04) than women with normal ovaries. However among women with polycystic ovaries, increasing severity of clinical phenotype (based on number of features of: menstrual irregularity, acne, hirsutism, serum testosterone > 3 mmol/l and LH > 10 IU/l) was associated with decreasing insulin sensitivity (P < 0.0001) and related to paternally transmitted insulin gene VNTR class III alleles (P = 0.03). CONCLUSION: Women with polycystic ovaries on ultrasound have increased insulin sensitivity and possible leptin resistance, which could predispose to future weight gain. However, in these women the appearance of clinical features of polycystic ovary syndrome is related to insulin resistance and insulin gene VNTR class III alleles.