更年期妇女腰围、腰臀比、体质指数及血清雌二醇与胰岛素抵抗的关系
摘要
目的:探讨更年期妇女腰围、腰臀比、体质指数及血清雌二醇与胰岛素抵抗的相关性。方法:采用病例对照方法,应用放射免疫测定方法和己糖激酶法对我院妇女健康俱乐部成员中的年龄40～55周岁、腰围≥80cm者和腰围<80cm者各50例进行血清雌二醇、胰岛素、血糖测定;采用稳态模式胰岛素抵抗指数(HOMA-IR)作为胰岛素抵抗评价指标。结果:更年期妇女腰围≥80cm组HOMA-IR高于腰围<80cm组,两组比较有显著性差异;体质指数(BMI)、腰臀比(WHR)与HOMA-IR呈正相关性;腰围、BMI、WHR与血清雌二醇无相关性;雌二醇与HOMA-IR呈负相关性,其组间差异有显著性。结论:更年期妇女胰岛素抵抗的发生与腰围、WHR、BMI增加有关,与血清雌激素水平降低有关。妇女若在绝经前及绝经早期控制体重、减少BMI、腰围、WHR,在医生指导下恰当补充雌激素可减少胰岛素抵抗的发生,对降低更年期妇女糖尿病发病率、提高她们的生命质量有重要意义。
The classical definition of Insulin resistance (IR) is a situation characterized by a lack of physiological response for normal dose insulin .Insulin resistance and subsequent metabolic disorder are common soil of CHD、 diabetes 、 hypertensive.The incidence rate of normal people in abroad is about 25% but 44% in postmenopausal women. For this reason,it is an important route of discovering IR early and correcting it. The studies in home and abroad demonstrate the reasons of IR are versatile in recent years but the exact etiology is not sure. The researches have done demonstrated following points. 1.The studies in abroad demonstrate the increasing of waist circumstance (WC), waist-hip ratio(WHR)and BMI of postmenopausal women is relate to IR.2.The changing of androgen and SHBG is related to the development of IR.3. The changing of estrodiol is related to the development of IR.Some studies report estrogen is dose-relation to IR.High lever estrogen can cause IR but physiological dose estrogen can improve insulin sensitivity and reduce IR..So,the relation of estrogen and IR has to be debated further.
The studies in abroad mainly aim at postmenopausal women.Their ages are older. It is helpful to prevent finding related reasons of IR in perimenopause and earlier period of menopause. The reports are rare in the relation between IR and the increasing of WC and WHR as well BMI of menopause. The relation between IR and E2 is not seen.This study uses the case-control method and divided the women of our hospital's women health club whose ages between 40~55 years old into two groups.The two groups are divided based on WC: WC =80cm (n=50),WC<80cm (n=50). Monitored the estrodiol,insulin level by RIA(radioactive immunoassay) and blood glucose by HK .Using Foxpro to set up database. Applying SPSS 11.0 and case -control T-test method and correlated method to analyze datas.Results: the HOMA-IR of WC=80cm group is higher significantly compared with WC<80cm group.BMI,WHR was positively correlated with HOMA-IR.WC,WHR and BMI have no correlation with E2.E2 was negatively correlated with HOMA-IR. Based on all above results this study made following conclusions. 1. The development of IR is related to the increasing of WC,WHR and BMI. WC is a standard to measure abdominal adipose tissue , more exatly is visceral adiposity .WHR is closely correlate with visceral adiposity.The results of this study
demonstrate WC > BMI ^ WHR was positively correlated with HOMA-IR.It illustrate HOMA-IR increased follow by the increasing of WC, BMI and WHR.The mechanism include several points as follow.(l)Iyengar reports adipose tissue is now recognized not only an organ of saving fat and supplying energy and regulating temperature but also as an important source of metabolically active secretory products(adipocytokines).The finding of the endocrine function of adiposity is a great prosess of endocrinology in late years.Including tumor necrosis factor (TNF- a ), interleukin (IL-l,IL-6),leptin,resistin which are capable of affecting peripheral insulin action.The endocrine function disorder of adiposity is an important reason of diabetes caused by obesity.2)The increasing of free fatty acid(FFA) is correlated with IR.Visceral adipose tissue(AT) is drained by the portal venous system. Mobilization of free fatty acids (FFAs) is more rapid from visceral than from subcutaneous fat cells because of the higher lipolytic activity in visceral adipocytes, which probably contributes significantly to increase FFA concentrations in the systemic circulation. The elevated FFAflux into the liver associated with increased visceral AT accumulation would decrease the hepatic insulin extraction by inhibiting insulin binding and degradation, leading to systemic hyperinsulinemia as well as inhibiting the suppression of hepatic
glucose production by insulin.FFA has already increased when the people of obesity ortholiposis.When hepar oxidize FFA increased, inhibiting hepatic glucose utilization and periphery glucose utilization, down regulate insulin receptor,decreased insulin combination,develop IR.3) Fat tissue produces a variety of secreted proteins (adipocytokines)with important roles in metabolism. Japanese scientists isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.4)The function fo gene is very important in the development of IR.By using a large sample of twins, this study demonstrates that in postmenopausal women, genetic factors explain the majority of the population tendency to deposit fat centrally. Importantly, multivariate analysis shows that after adjusting for the genetic influences on total
fat mass, the strength of the genetic effect on central fat was unchanged. This indicates that in postmenopausal women, specific genetic factors determine central deposition of fat with its metabolic correlates.katrine thinks people and rodent animal's diabetes are affected by 'back gene'.The mice who taking 'thrifty gene' are incline to increase body weight and plasma insulin .WC is an index of abdominal fat.lt can reflect the condition of body healthy condition though BMI is normal.WC is fit to screening especially in basic hospital because measuring WC is convenient than BMI.2.The development of IR of postmenopausal women is related to the decrease of estrogen.Dong thinked estrogen can increase the B cell of pancreatic secret insulin and improve insulin sencitivity and increase glucose tolerance.This study demonstrate that HOMA-IR is negative to estrogen.lt illustrate the decreasing of estrogen is related to the development of IR and also demonstrate the risk of IR rise when women entry into menopause. The results of Rosario's prospective study suggest that in healthy, nonobese postmenopausal women, the use of transdermal 17-6-estradiol reduces the risk of developing type 2 diabetes.The mechanisms are follow. First, it is possible that the estrogens determine a lower incidence of diabetes via the improvement of the endothelial function. Second,estrogen therapy is
able to improve insulin sensitivity and to exert a beneficial effect on hepatic gluconeogenesis, reducing the hepatic production of glucose and affecting the metobolism of glucose and insulin .There are evidences indicate estrogen therapy can improve the insulin sensitivity in postmenopausal women.In various spontaneous rodent models of type 2 diabetes, female rodents are protected against hyperglycemia unless they are ovariectomized.The study of transgenic mice and mice with genetic alteration of E2 secretion or E2 action has shed light on the antidiabetic properties of E2 at a tissue-specific level.Some studies also indicate estrogen is dose-relatation to IR.The majority of studies think high level estrogen can induce IR.Collison find that high level estrogen can induce IR derectly through the studies on 3T3-Lladipocyte.3.WC\ WHR? BMI have no relation to estrogen. Data from the PEPI trial think HRT may have a protective effect in reducing central adiposity.This study is similar to PEPI.In summary, this study demonstrates it has great significance that in early and pre- postmenopausal women control their body weight and reduce their WC, BMI and WHR and take estrogen appropriate under the guide of doctor will reduce the risk of IR and reduce the concequence of diabetes,improve their life quality.
The classical definition of Insulin resistance (IR) is a situation characterized by a lack of physiological response for normal dose insulin .Insulin resistance and subsequent metabolic disorder are common soil of CHD、 diabetes 、 hypertensive.The incidence rate of normal people in abroad is about 25% but 44% in postmenopausal women. For this reason,it is an important route of discovering IR early and correcting it. The studies in home and abroad demonstrate the reasons of IR are versatile in recent years but the exact etiology is not sure. The researches have done demonstrated following points. 1.The studies in abroad demonstrate the increasing of waist circumstance (WC), waist-hip ratio(WHR)and BMI of postmenopausal women is relate to IR.2.The changing of androgen and SHBG is related to the development of IR.3. The changing of estrodiol is related to the development of IR.Some studies report estrogen is dose-relation to IR.High lever estrogen can cause IR but physiological dose estrogen can improve insulin sensitivity and reduce IR..So,the relation of estrogen and IR has to be debated further.
The studies in abroad mainly aim at postmenopausal women.Their ages are older. It is helpful to prevent finding related reasons of IR in perimenopause and earlier period of menopause. The reports are rare in the relation between IR and the increasing of WC and WHR as well BMI of menopause. The relation between IR and E2 is not seen.This study uses the case-control method and divided the women of our hospital's women health club whose ages between 40~55 years old into two groups.The two groups are divided based on WC: WC =80cm (n=50),WC<80cm (n=50). Monitored the estrodiol,insulin level by RIA(radioactive immunoassay) and blood glucose by HK .Using Foxpro to set up database. Applying SPSS 11.0 and case -control T-test method and correlated method to analyze datas.Results: the HOMA-IR of WC=80cm group is higher significantly compared with WC<80cm group.BMI,WHR was positively correlated with HOMA-IR.WC,WHR and BMI have no correlation with E2.E2 was negatively correlated with HOMA-IR. Based on all above results this study made following conclusions. 1. The development of IR is related to the increasing of WC,WHR and BMI. WC is a standard to measure abdominal adipose tissue , more exatly is visceral adiposity .WHR is closely correlate with visceral adiposity.The results of this study
demonstrate WC > BMI ^ WHR was positively correlated with HOMA-IR.It illustrate HOMA-IR increased follow by the increasing of WC, BMI and WHR.The mechanism include several points as follow.(l)Iyengar reports adipose tissue is now recognized not only an organ of saving fat and supplying energy and regulating temperature but also as an important source of metabolically active secretory products(adipocytokines).The finding of the endocrine function of adiposity is a great prosess of endocrinology in late years.Including tumor necrosis factor (TNF- a ), interleukin (IL-l,IL-6),leptin,resistin which are capable of affecting peripheral insulin action.The endocrine function disorder of adiposity is an important reason of diabetes caused by obesity.2)The increasing of free fatty acid(FFA) is correlated with IR.Visceral adipose tissue(AT) is drained by the portal venous system. Mobilization of free fatty acids (FFAs) is more rapid from visceral than from subcutaneous fat cells because of the higher lipolytic activity in visceral adipocytes, which probably contributes significantly to increase FFA concentrations in the systemic circulation. The elevated FFAflux into the liver associated with increased visceral AT accumulation would decrease the hepatic insulin extraction by inhibiting insulin binding and degradation, leading to systemic hyperinsulinemia as well as inhibiting the suppression of hepatic
glucose production by insulin.FFA has already increased when the people of obesity ortholiposis.When hepar oxidize FFA increased, inhibiting hepatic glucose utilization and periphery glucose utilization, down regulate insulin receptor,decreased insulin combination,develop IR.3) Fat tissue produces a variety of secreted proteins (adipocytokines)with important roles in metabolism. Japanese scientists isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.4)The function fo gene is very important in the development of IR.By using a large sample of twins, this study demonstrates that in postmenopausal women, genetic factors explain the majority of the population tendency to deposit fat centrally. Importantly, multivariate analysis shows that after adjusting for the genetic influences on total
fat mass, the strength of the genetic effect on central fat was unchanged. This indicates that in postmenopausal women, specific genetic factors determine central deposition of fat with its metabolic correlates.katrine thinks people and rodent animal's diabetes are affected by 'back gene'.The mice who taking 'thrifty gene' are incline to increase body weight and plasma insulin .WC is an index of abdominal fat.lt can reflect the condition of body healthy condition though BMI is normal.WC is fit to screening especially in basic hospital because measuring WC is convenient than BMI.2.The development of IR of postmenopausal women is related to the decrease of estrogen.Dong thinked estrogen can increase the B cell of pancreatic secret insulin and improve insulin sencitivity and increase glucose tolerance.This study demonstrate that HOMA-IR is negative to estrogen.lt illustrate the decreasing of estrogen is related to the development of IR and also demonstrate the risk of IR rise when women entry into menopause. The results of Rosario's prospective study suggest that in healthy, nonobese postmenopausal women, the use of transdermal 17-6-estradiol reduces the risk of developing type 2 diabetes.The mechanisms are follow. First, it is possible that the estrogens determine a lower incidence of diabetes via the improvement of the endothelial function. Second,estrogen therapy is
able to improve insulin sensitivity and to exert a beneficial effect on hepatic gluconeogenesis, reducing the hepatic production of glucose and affecting the metobolism of glucose and insulin .There are evidences indicate estrogen therapy can improve the insulin sensitivity in postmenopausal women.In various spontaneous rodent models of type 2 diabetes, female rodents are protected against hyperglycemia unless they are ovariectomized.The study of transgenic mice and mice with genetic alteration of E2 secretion or E2 action has shed light on the antidiabetic properties of E2 at a tissue-specific level.Some studies also indicate estrogen is dose-relatation to IR.The majority of studies think high level estrogen can induce IR.Collison find that high level estrogen can induce IR derectly through the studies on 3T3-Lladipocyte.3.WC\ WHR? BMI have no relation to estrogen. Data from the PEPI trial think HRT may have a protective effect in reducing central adiposity.This study is similar to PEPI.In summary, this study demonstrates it has great significance that in early and pre- postmenopausal women control their body weight and reduce their WC, BMI and WHR and take estrogen appropriate under the guide of doctor will reduce the risk of IR and reduce the concequence of diabetes,improve their life quality.
引文
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13. Ivandic A, Pprpic-Krizevac I,Bozic D, et al. Insulin resistance and androgens in healthy women different body fat distributions.Wien Klin Wochenschr, 2002,15;114(8-9):321-6
14. Alice S. Ryan, Barbara J. Nicklas, Dora M. Berman, et al Hormone replacement therapy, insulin sensitivity, and abdominal obesity in postmenopausal women. Diabetes Care ,2002,25:127-133
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2. Borugian MJ, Sheps SB, kim-Sing C, et al .Waist-to-hip ratio and breast cancer mortality.Epidemiol,2003,15;158(10):963-8
3. Ascaso JF, Romero P, Real JT, et al.Abdominal obesity, insulin resistance, and metabolic syndrome in a southern southern European population.Eur J Intern Med,2003,Mar;14(2):101-106
4. Kuo cs, Huw CIII,Chiang SC,et al.Waist circumference predict insulin resistance in offspring of diabetic patients.Diabetes Nutr Metab,2002, 15(2): 101-8
5. Hwu CM, Fuh JL, Hsiao,et al.Waist cicumference predicts metabolic cardiovascular risk in postmenopausal Chinese women. Menopause, 2003,10(1) :73 -80
6. Lerario, Gimeno, Franco, et al.Weight excess and abdominal fat in the metabolic syndrome among Japanese-Brazilians. Rev Saude Publica,2002 Feb;36(1):4-11
7. Collison M, Cambell IW, Salt IP, et al.Sex hormones induce insulin resistance in 3T3-L1 adipocytes by reducing cellular content of IRS proteins. Diabetologia,2000,43(11): 1374-80
8. Jee-Young,Elizabeth Barrett-Connor,Nicole et al. Endogenous sex hormones and the development of type 2 diabetes in older men and women.The Rancho Bernardo Study Diabete Care ,2002,25:55-60
9. Pasquali R, Vicennati V, Bertazzo D, et al. Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Metabolism, 1997,46(1):5-9
10. Sowers M, Derby C, Jannausch ML, et al. Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN.Clin Endocrinol Metab,2003,88(10): 4904-10
11. Sherif K, Kushner H, Falkner B, et al Sex hormone-binding globulin and insulin resistanse in African-american women. Metabolism, 1998, 47: 70-74
12. Grover-Paez F, Martinez-Abundis E, Gonzalez-Ortiz et al. Effect of hormone replacement therapy including a progestin on insulin sensitivity and lipid profile in postmenopausal women. Rev Med Chil ,2001,129(9):989-94
13. Ivandic A, Pprpic-Krizevac I,Bozic D, et al. Insulin resistance and androgens in healthy women different body fat distributions.Wien Klin Wochenschr, 2002,15;114(8-9):321-6
14. Alice S. Ryan, Barbara J. Nicklas, Dora M. Berman, et al Hormone replacement therapy, insulin sensitivity, and abdominal obesity in postmenopausal women. Diabetes Care ,2002,25:127-133
15.熊辉,李惠明.围绝经期及绝经期妇女体重指数与血压血脂水平的相关性分析.江西医学院学报,2005,45(1):73-75
16. Banerji MA, Lebovitz J,Chaiken RL,et al.Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects.Am J physiol, 1997,273:425-432
17. Marieke B, Snijder, MSC, Jacqueline M ,et al. Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels. Diabetes Care,2004, 27:372-377
18. Carey DG,Jenkins AB,Campbell LV, et al.Abdominal fat and insulin resistance in normal and overweight women:derect measurement reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes,1996;45(5):633-8
19. Sonia C, Lauren H, Shirley M,et al.Early expression of central adiposity and its metablic correlations in overweight anolescent girls.Diabetes. 1995,43suppl: 55 A-174
20. Susan l,Scott B,Haruo M,et al.Relationship of body mass index to insulin, repeptide and heptic insulin clearance in females. Diabetes, 1995,43suppl:55A-174
21. Iyengar P, Scherer PE, Adiponectin/Acrp30, an adipocyte-specific secretory factor: physiological relevance during development. Pediatr Diabetes, 2003 ,M ar;4(1):32-7
22.刘彩艳,魏健.胰岛素抵抗与2型糖尿病的关系.实用医药杂志,2004,21(6):558-560
23.王树海,王文健.胰岛素抵抗的发病机制及中西医结合防治策略.中西医结合学报,2004,2(1):14-16
24. Susan A.Phillips, Theodore P, Ciaraldi,et al. Modulation of Circulating and Adipose Tissue Adiponectin Levels by Antidiabetic Therapy.Diabetes, 2003,52:667-674
25. Lyle RE, Richon VM, McGehee RE.TNF-α disrupts mitotic clonal expansion and regulation of retinoblastoma proteins P130 and P107 during 3T3-L1 adipocyte differentiation.Biochem Biophys Res Commun, 1998,247:374
26. Xing H,Jeffrey P, Northrop,et al.TNF α-mediated inhibition and reversal ofadipocyte differentiation is accompanied by suppressed expression of PPARγ without effects on pref-lexpression. Endocrinology, 1997,138:2776
27. Gagnon AM, Pardasani D, Sorisky A.,et al. Extrace-llular matrix induced by TGF impaires insulin signal transduction in 3T3-L lpreadipose cells.Cell Physiol, 1998,175:370
28. Hofmann C, Lorenz K, Braithwaite SS, et al. Altered gene expression for TNF α and its receptors during drug and diet modulation of insulin resistance. Endocrinology,1994,134:264
29. Marie,John Weisnagel, Louise Corneau,et al. Contribution of abdominal visceral obesity and insulin resistance to the cardiovascular risk profile of postmenopausal women.Diabetes, 2005,54:770-777
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