肥胖与胰岛素抵抗的关系HOMA-IR
The relationship between insulin-sensitive obesity and cardiovascular diseases in a Chinese population Results of the REACTION study
Jieli Lu a ,b ,1,2,Yufang Bi a ,b ,1,2,Tiange Wang a ,b ,1,2,Weiqing Wang a ,b ,2,Yiming Mu c ,2,Jiajun Zhao d ,2,Chao Liu e ,2,Lulu Chen f ,2,Lixin Shi g ,2,Qiang Li h ,2,Qin Wan i ,2,Shengli Wu j ,2,Guijun Qin k ,2,Tao Yang l ,2,Li Yan m ,2,Yan Liu n ,2,Guixia Wang n ,2,Zuojie Luo o ,2,Xulei Tang p ,2,Gang Chen q ,2,Yanan Huo r ,2,Zhengnan Gao s ,2,Qing Su t ,2,Zhen Ye u ,2,Youming Wang v ,2,Huacong Deng w ,2,Xuefeng Yu x ,2,Feixia Shen y ,2,Li Chen z ,2,
Liebing Zhao a ,b ,2,Meng Dai a ,b ,2,Min Xu a ,b ,2,Yu Xu a ,b ,2,Yuhong Chen a ,b ,2,Shenghan Lai aa ,2,Guang Ning a ,b ,?,2
a
Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health,Rui-Jin Hospital,Shanghai Jiao-Tong University School of Medicine,E-Institute of Shanghai Universities,China b
Shanghai Clinical Center for Endocrine and Metabolic Diseases,National Clinical Research Center,Department of Endocrine and Metabolic Diseases,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,China c
People's Liberation Army General Hospital,China d
Shandong Provincial Hospital,China e
Jiangsu Province Hospital on integration of Chinese and Western Medicine,China f
Wuhan Xiehe Hospital,Huazhong University of Science and Technology School of Medicine,China g
University of Guizhou School of Medicine,China h
University of Haerbin School of Medicine,China i
University of Luzhou School of Medicine,China j
Xinjiang Kelamayi Peoples Hospital,China k
University of Zhengzhou School of Medicine,China l
University of Nanjing School of Medicine,China m
University of Zhongshan School of Medicine,China n
University of Jilin School of Medicine,China o
University of Guangxi School of Medicine,China p
University of Lanzhou School of Medicine,China q
University of Fujian School of Medicine,China r
Jiangxi People's Hospital,China s
University of Dalian School of Medicine,China t
Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,China u
Zhejiang Center for Disease Control and Prevention,China v
University of Anhui School of Medicine,China w
University of Chongqing School of Medicine,China x
Wuhan Tongji Hospital,China y
Wenzhou University School of Medicine,China z
Qilu Hospital,University of Shandong School of Medicine,China aa
Johns Hopkins University School of Medicine,Baltimore,United States
International Journal of Cardiology 172(2014)388–394
?Corresponding author at:Shanghai Clinical Center for Endocrine and Metabolic Diseases,National Clinical Research Center,Department of Endocrine and Metabolic Diseases,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,197Rui-Jin 2nd Road,Shanghai 200025,China.Tel.:+862164370045x665340;fax:+862164373514.
E-mail address:gning@https://www.wendangku.net/doc/a47625075.html, (G.Ning).1
Contributed equally to this article.2
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed
interpretation.0167-5273/$–see front matter ?2014Elsevier Ireland Ltd.All rights reserved.
https://www.wendangku.net/doc/a47625075.html,/10.1016/j.ijcard.2014.01.073
Contents lists available at ScienceDirect
International Journal of Cardiology
j o u r n a l h o m e p a g e :w w w.e l s e vi e r.c o m/l o c a t e /i j c a r d
a b s t r a c t a r t i c l e i n f o
Article history:
Received23December2013 Accepted18January2014 Available online25January2014 Keywords:
Insulin resistance
Obesity
Cardiovascular diseases Epidemiology Objective:Obesity and insulin resistance are risk factors for cardiovascular diseases.Whether insulin-sensitive obese individuals are at higher risk for cardiovascular diseases is still debated.We aim to investigate whether insulin-sensitive obesity associates with prevalent cardiovascular diseases and10-year coronary heart disease (CHD)risk.
Research design and methods:At the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals:a lONgitudinal(REACTION)study,211,641participants aged40years or older were recruited from25communi-ties across the China mainland,in2011to2012.Participants were categorized by insulin-sensitive/resistant and general/abdominal obese status.Cardiovascular diseases included CHD,stroke,and myocardial infarction.Fra-mingham risk score(FRS)was calculated according to National Cholesterol Education Program-Adult Treatment Panel III and FRS greater than20%or cardiovascular diseases were identi?ed as high risk for10-year CHD. Results:Controlling for potential confounders,compared with insulin-sensitive normal weight individuals, insulin-sensitive general obese individuals had increased risks for prevalent cardiovascular diseases(men:OR, 2.55,95%CI,2.04–3.18;women:1.73,1.45–2.06)and10-year Framingham risk for CHD(men:2.26,1.86–2.76;women:1.73,1.46–2.06).Compared with insulin-sensitive normal waist subgroup,insulin-sensitive ab-dominal obesity was associated with higher risks for prevalent cardiovascular diseases(men:1.32,1.20–1.46; women:1.36,1.27–1.47)and10-year Framingham risk for CHD(men,1.34,1.23–1.45;women,1.37,1.27–1.47). Conclusion:Both general and abdominal obesity were associated with elevated prevalent cardiovascular diseases and10-year CHD risk,regardless of the presence or absence of insulin resistance.
?2014Elsevier Ireland Ltd.All rights reserved.
1.Introduction
Obesity is a well-recognized health hazard and has consistently been associated with substantial excess risks for morbidity and mortality, especially from cardiovascular diseases[1–3].A subset of obese individ-uals is known as metabolically healthy obese(MHO),which was charac-terized by an excessive body fat coupled with a benign metabolic pro?le, such as favorable insulin sensitivity,sound lipids,no sign of hypertension and in?ammation,and normal hormonal pro?les[4–6].These individuals seem to deviate from the development of obesity-related metabolic ab-normalities[7–9],however,several studies revealed inconsistent views that MHO individuals were still at risk of major cardiovascular diseases compared with healthy nonobese[10,11].
Insulin resistance is a core feature of metabolic disorders and usually coexists with obesity in some humans[12,13].But a subgroup of obese individuals displays better insulin sensitivity compared to that of normal weight individuals,and this phenotype was described as insulin-sensitive obesity[14].Until recently,the metabolic pro?le of this phenotype in the general population varies widely among different study populations. Previous studies that have examined the obesity-related complications in insulin-sensitive obese individuals have con?icting results[7,9,11,15]. Epidemiological data on the relationship between insulin-sensitive obesi-ty and cardiovascular diseases are rare in Chinese population.Given that Asians have a unique phenotype characterized by relatively high abdom-inal obesity and tend to have high prevalence of cardiovascular risk fac-tors even at low body mass index(BMI)[16–19],we hypothesize that both general and abdominal obesity are risk factors for cardiovascular diseases independent of insulin resistance,and insulin-sensitive obesity could also take responsibility for high cardiovascular risk.In this study, we investigate the association between insulin-sensitive obesity and car-diovascular diseases in Chinese population.
2.Research design and methods
2.1.Study population
The Risk Evaluation of cAncers in Chinese diabeTic Individuals:a lONgitudinal(REAC-TION)study has been set up as a multicenter prospective observational study aiming to evaluate the chronic diseases in Chinese population[20,21].The overall design of the REACTION study included two phases:the baseline and follow-up.The present study pre-sented the baseline data.At baseline,in2011to2012,a total of259,657individuals aged 40years or older were recruited from25research centers across China.These research centers were selected from both rural and urban areas of different geographic regions, with different degrees of urbanization and economic development status,and represented the general middle-aged and elderly population of China.Among the25communities, 233,736participants from24communities conducted insulin determination.Participants meeting the following criteria were excluded:1)those without complete data to de?ne in-sulin resistance and obesity(n=4967)and2)those who were receiving antidiabetic treatment(n=17,128).A total of211,641participants were included in the?nal analysis.
The REACTION study is sponsored by the Chinese Society of Endocrinology and led by Rui-Jin Hospital af?liated to Shanghai Jiao-Tong University School of Medicine.All proce-dures used in this study were in accordance with institutional guidelines.The Committee on Human Research at Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine, approved the study protocol,and all study participants provided written informed consents.
2.2.Data collection
At each study site,trained staff collected data according to a standard protocol in ex-amination centers at local health stations or community clinics in the participants'resi-dential https://www.wendangku.net/doc/a47625075.html,ing a standard questionnaire and face-to-face interviews,the staff collected information on sociodemographic characteristics,lifestyle factors,medical histo-ry and family https://www.wendangku.net/doc/a47625075.html,cation attainments were divided into high school education or above if9years of elementary or secondary education were completed,and less than high school if less than9years of elementary or secondary education.Participants were de?ned as never,former,or current smokers according to cigarette smoking habits.The type and frequency of alcohol consumptions were recorded,and never,former or current alcohol drinking status was de?ned according to alcohol consumption habits.The Global Physical Activity Questionnaire was used to estimate physical activities during work, transportation,and leisure time by collecting intensity,duration,and frequency of physical activity.The metabolic equivalent minutes per week(MET-min/week)was used to mea-sure physical activities[22].Clinical examinations of weight,height,waist circumference and blood pressures were measured according to a standard protocol and performed by experienced nurses.BMI was calculated as body weight in kilograms divided by body height squared in meters(kg/m2).An automated electronic device(OMRON Model HEM-725FUZZY,Omron Company,Dalian,China)was used to measure systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the non-dominant arm of seated par-ticipants three times consecutively at1-min intervals after a≥5-min rest.The last two readings were averaged for analysis.The Framingham risk score(FRS)was calculated ac-cording to the National Cholesterol Education Program-Adult Treatment Panel III algorithm, based on coronary risk factors including age,sex,total cholesterol,high-density lipoprotein cholesterol(HDL-C),SBP,and smoking habit[23].Among these risk factors,age,total choles-terol,HDL-C and SBP levels were categorized according to their values and smoking was clas-si?ed as either“current smoker”or“non-smoker”.The calculated total scores were used to estimate the10-year coronary heart disease(CHD)risk.
2.3.Biochemical evaluation
Blood samples were collected after an overnight fast for at least10h.Self-reported history of diabetes was con?rmed by clinical records,or by the use of insulin or hypogly-cemic agents.Participants without a known history of diabetes underwent the oral glucose tolerance test,and plasma glucose was obtained at0and2h during the test.Blood spec-imens were processed at the?eld centers with China National Laboratory Accreditation. Plasma glucose concentrations were evaluated at local hospitals by means of the glucose
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J.Lu et al./International Journal of Cardiology172(2014)388–394
oxidase or hexokinase method within2h after blood sample collection under a stringent quality control mechanism.
Sera were aliquoted into0.5-ml Eppendorf tubes within2h after blood collection and shipped by air in dry ice at?80°C to the central laboratory located at Shanghai Institute of Endocrine and Metabolic Diseases,which is certi?ed by the College of American Pathologists.Total cholesterol,low-density lipoprotein cholesterol (LDL-C),HDL-C and triglycerides were measured with an autoanalyser(Abbott Laboratories,Illinois,USA).Serum insulin was measured by chemiluminescent immunoassay(ARCHITECT ci16200analyzer,Abbott Laboratories,Illinois,USA).The index of homeostasis model assessment of insulin resistance(HOMA-IR)was calcu-lated according to the formula:HOMA-IR=fasting insulin concentrations(mIU/L)×fasting plasma glucose concentrations(mmol/L)/22.5.Since venous blood collected in vacuum tubes with EDTA anticoagulant could only be kept for less than7days before hemoglobin A1c(HbA1c)detection,the HbA1c Capillary Collection System(Bio-Rad Laboratories,CA,USA)was used to collect capillary blood sample in strict accordance with the manufacturer's instructions.Previous studies have documented an excellent agreement between the capillary and venous HbA1c values[24,25].Sample prepared using HbA1c Capillary Collection System was stable for4weeks at2–8°C.Thus,the sampled HbA1c Capillary Collection System was shipped and stored at2–8°C and HbA1c was measured within a month after sample collection,by high-performance liquid chromatography using the VARIANT II Hemoglobin Testing System in the National Glycohemoglobin Standardization Program certi?ed central laboratory of the study.
2.4.Diagnosis of obesity,insulin resistance and cardiovascular diseases
General overweight was de?ned as BMI of25.0to b30.0kg/m2and obesity was de-?ned as BMI of30.0kg/m2or higher,according to World Health Organization de?nitions. Abdominal obesity was de?ned using the modi?ed National Cholesterol Education Program-Adult Treatment Panel III as waist circumference≥90cm for men and≥80cm for women.Insulin resistance was de?ned as HOMA-IR N2.41(the75%percentile).Diabe-tes was diagnosed as fasting plasma glucose≥7.0mmol/L,or postprandial plasma glucose ≥11.1mmol/L,or self-reported previous diagnosis of diabetes by physicians and taking antidiabetic medications.Hypertension was assessed by SBP≥140mmHg,or DBP ≥90mmHg,or self-reported previous diagnosis of hypertension by physicians and taking antihypertensive medications.Dyslipidemia was de?ned according to the modi?ed National Cholesterol Education Program-Adult Treatment Panel III as:hypercholesterol-emia,total cholesterol≥6.22mmol/L(240mg/dL),hypertriglyceridemia,triglycerides ≥2.26mmol/L(200mg/dL),high LDL-C,LDL-C≥4.14mmol/L(160mg/dL),and low HDL-C,HDL-C b1.04mmol/L(40mg/dL).Using a face-to-face interview questionnaire, we collected information on cardiovascular diseases.The question was open-ended:“Has a doctor or other health professional ever told you that you have CHD,stroke,or myocardial infarction”.We grouped cardiovascular diseases(reported CHD,stroke,or myocardial infarction)in the analysis.We performed validation of the self-reported cardiovascular disease in Shanghai Youyi Community,one of the25communities.The medical records from the relevant hospitalizations were reviewed by2physicians,who were blinded to the self-reported data,classi?ed the cases as de?nite,questionable,or misdiagnosed,and the validation rate of cardiovascular disease was91.07%.Individuals with FRS greater than20%or having cardiovascular diseases were identi?ed as at high risks for10-year CHD[23].
2.5.Statistical analysis
All statistical analyses were performed with SAS version9.3(SAS Institute Inc,Cary, NC,USA).Participants were categorized into normal weight,overweight,and obese groups with and without insulin resistance,or normal waist circumference and abdominal obese groups with and without insulin resistance.Cardiovascular risk factors are present-ed as medians(interquartiles)for continuous variables,or numbers(percentages)for categorical parameters.Logistic regression analysis was used to determine the relation-ships of insulin-resistant/sensitive obesity with cardiovascular diseases and10-year Framingham risk of CHD.Two sets of models were used:model1,unadjusted,and model2,adjusted for traditional risk factors of cardiovascular diseases including age, education attainment(high school education or above or not),current cigarette smoking (yes or no),current alcohol consumption(yes or no),MET-min/week,diabetes status, hypertension status,hypercholesterolemia status,hypertriglyceridemia status,high LDL-C status,and low HDL-C status.Results of logistic regression analysis are reported as odds ratios(ORs)and95%con?dence intervals(CIs).
Quantile regression analysis was performed for modeling the associations between10-year Framingham risk for CHD and independent variables including BMI,waist circumference and HOMA-IR,adjusted by lifestyle factors and demographic variables,that is,age,education attainment,cigarette smoking status,alcohol con-sumption status and MET-min/week.A major advantage of quantile regression is its ?exibility for modeling data with heterogeneous conditional distributions.The results of quantile regression are expressed as the regression coef?cients(β),depend on the quantile[26].Quantile regression provides a complete picture of the effect of obesity and HOMA-IR on10-year Framingham risk for CHD when a set of percentiles is modeled,and it makes no distributional assumption about the error term in the model.The P values reported are two-sided,and a P value less than0.05is indicated statistical signi?cance.3.Results
3.1.Characteristics of the participants
The study population comprised211,641study participants,includ-ing72,081men(34.1%)and139,560women(65.9%).In men,36.3%of general obesity and57.8%of abdominal obesity were insulin-sensitive. In women,insulin-sensitive obesity accounted for36.0%of general obesity,and62.6%of abdominal obesity.Descriptive data on cardiovas-cular risk factors in insulin-resistant/sensitive general obese phenotypes are presented in Table1.In each insulin-sensitive/resistant category, compared with normal weight individuals,overweight and obese indi-viduals had lower MET-min/week and HDL-C,and higher SBP,DBP, BMI,waist circumference,total cholesterol,LDL-C,triglycerides,HbA1c, fasting serum insulin and HOMA-IR.In each BMI category,compared with insulin-resistant individuals,insulin-sensitive individuals had lower proportions of high school education or above attainment,were more likely to be current alcohol consumers,had higher levels of MET-min/week,and had favorable metabolic pro?les.
Cardiovascular risk factors in insulin-resistant/sensitive abdominal obese phenotypes are given in Table2.In men and women,in each insulin-sensitive/resistant category,compared with normal waist indi-viduals,abdominal obese individuals had higher proportions of high school or above education attainment and were more likely to be current alcohol drinkers,and had lower levels of MET-min/week and HDL-C,and had higher levels of SBP,DBP,BMI,waist circumference, FRS,total cholesterol,LDL-C,triglycerides,fasting plasma glucose, HbA1c,fasting serum insulin and https://www.wendangku.net/doc/a47625075.html,pared with normal waist and insulin-sensitive individuals,abdominal obese or insulin-resistant individuals had worse metabolic pro?les.
3.2.Risk for cardiovascular diseases by obesity subgroups
There were11,577(5.5%)participants had cardiovascular diseases. Among different general obese categories,in men,insulin-sensitive obese individuals had the highest prevalence of cardiovascular diseases (10.1%),and in women,insulin-resistant obese individuals had the highest prevalence of cardiovascular diseases(10.5%).Among different categories of abdominal obesity,the prevalence of cardiovascular dis-eases increased gradually across the insulin-sensitive/resistant catego-ries and insulin-resistant obese individuals had the highest prevalence of cardiovascular diseases in men(8.4%)and in women(8.1%).
Insulin resistance was directly associated with higher prevalence of cardiovascular diseases and10-year Framingham risk for CHD,irrespec-tive of obesity.For instance,insulin-resistant normal weight participants had an OR of1.31(95%CI:1.12–1.53)for prevalent cardiovascular dis-eases in men,and the relative OR was1.19(95%CI:1.07–1.32)in women.Among insulin-sensitive general obese categories,the ORs for cardiovascular diseases increased across obese status in multivariable-adjusted models,and compared with insulin-sensitive normal weight individuals,insulin-sensitive obese subjects had markedly high risk for prevalent cardiovascular diseases in men(OR:2.55,95%CI:2.04–3.18) and in women(OR:1.73,95%CI:1.45–2.06).For10-year Framingham risk for CHD,compared with insulin-sensitive normal weight,insulin-sensitive obesity was associated with an elevated risk in men(OR:2.26, 95%CI:1.86–2.76)and in women(OR:1.73,95%CI:1.46–2.06),while insulin-resistant overweight/obesity seemed to be associated with higher risks(Table3).Among insulin-sensitive/resistant abdominal obese categories,insulin resistance and abdominal obesity were both indepen-dently associated with higher prevalence of cardiovascular diseases and 10-year Framingham risk for https://www.wendangku.net/doc/a47625075.html,pared with insulin-sensitive normal waist individuals,insulin-sensitive abdominal obese individuals had increased risks for prevalent cardiovascular diseases in men(OR: 1.32,95%CI:1.20–1.46)and in women(OR:1.36,95%CI:1.27–1.47). For10-year Framingham risk for CHD,insulin-sensitive obesity was asso-ciated with signi?cantly higher risk(men,OR:1.34,95%CI:1.23–1.45;
390J.Lu et al./International Journal of Cardiology172(2014)388–394
women,OR:1.37,95%CI:1.27–1.47),compared with insulin-sensitive normal waist (Table 4).
The relationships of obesity and HOMA-IR with 10-year Framingham risk for CHD by quantile regression analysis are shown in Supplementary Table 1and Supplementary Fig.1.Controlling for age,education attain-ment,current cigarette smoking,current alcohol consumption and MET-min/week,the relationships of BMI,waist circumference and HOMA-IR with 10-year Framingham risk for CHD were signi ?cant in all quantiles in both genders,except that in men,waist circumference was not signi ?cantly associated with 10-year Framingham risk for CHD until the 30%quantile (equivalent to waist circumference of 78.2to 81.6cm,β=7.5,P b 0.0001).The quantile regression coef ?cients for 10-year Fra-mingham risk for CHD were gradually increased over the quantiles of BMI,waist circumference,and HOMA-IR in men.In women,the quantile regression coef ?cient for 10-year Framingham risk for CHD was gradually increased with the quantile of HOMA-IR,while for BMI and waist circum-ference,the coef ?cients were increased until the 60%quantile of BMI (equivalent to 24.1to 24.9kg/m 2,β=7.0,P b 0.0001)and waist circum-ference (equivalent to 82to 85cm,β=11.4,P b 0.0001).4.Discussion
We found that insulin resistance with or without obesity was directly associated with increased risks for present cardiovascular diseases and 10-year Framingham risk for CHD.Both general and abdominal obese in-dividuals,regardless of the presence or absence of insulin resistance,had markedly higher risks for prevalent cardiovascular diseases and 10-year Framingham risk for CHD compared with insulin-sensitive nonobese individuals.The present data seems to take a stand against the ‘healthy obese ’concept that obesity in the absent of insulin resistance are in good shape.
Obesity is a complicated condition in which genetic predisposi-tion interacts with environmental exposures to produce a heteroge-neous phenotype [27].MHO individuals have large quantities of fat mass but remarkably normal to high levels of insulin sensitivity and rather favorable metabolic pro ?les.In the present study,among Chinese adults aged 40years or older,nearly 40%of general obese adults,and over 60%of abdominal obese adults were insulin-sensitive.Previous studies suggested that MHO individuals could ac-count for up to 30%of the obese population [28],and the data of Na-tional Health and Nutrition Examination Surveys (NHANES)1999–2004showed that among American adults aged 20years or older,31.7%(approximately 19.5million adults)of obese adults were metabolically healthy,which was considered as having normal levels of blood pressure,triglycerides,HDL-C and glucose,favorable insulin sensitivity,and without systemic in ?ammation [29].
Concerning that insulin sensitivity varies in obesity,and both insulin resistance and obesity are strongly associated with cardio-vascular abnormalities [30–34],an interesting question raised about whether insulin-sensitive obesity protects against metabolic disorders,especially cardiovascular diseases.The Framingham Off-spring Study has reported that insulin-resistant individuals were at higher risk for cardiovascular diseases regardless of BMI status,whereas insulin-sensitive overweight/obese individuals were not at higher risk compared with insulin-sensitive normal weight indi-viduals [7].The Cremona Study have found that insulin-sensitive
Table 1
Cardiovascular risk factors in insulin-sensitive/resistant general obese phenotypes.
Normal weight Overweight Obese
Insulin-sensitive
Insulin-resistant Insulin-sensitive Insulin-resistant Insulin-sensitive Insulin-resistant
Men
Number,percentage (%)36,742(51.0)4229(5.9)
17,761(24.6)9332(13.0)
1460(2.0)
2557(3.6)
Age,years
58.5(51.0–65.7)59.2(51.6–66.7)57.2(49.3–63.9)57.4(49.2–64.4)57.0(49.0–63.8)55.9(48.0–62.8)High school education or above,n (%)13,363(36.4)1934(45.7)6891(38.8)4509(48.3)490(33.6)1111(43.5)Current cigarette smoker,n (%)15,846(43.1)1355(32.0)6551(36.9)2986(32.0)537(36.8)819(32.0)Current alcohol consumer,n (%)9899(27.4)
861(20.7)
4811(27.6)
2095(23.1)
422(29.74)
656(26.6)
MET-min/week 3360(1680–7200)2400(1680–4320)2520(1680–5040)1680(1680–3360)2520(1680–5040)1680(1680–3360)BMI,kg/m 2
22.5(20.9–23.7)23.7(22.6–24.4)26.5(25.7–27.6)27.3(26.2–28.4)31.1(30.5–32.3)31.4(30.6–32.8)Waist circumference,cm 81.0(75.7–86.0)86.0(81.2–90.0)91.0(87.0–95.0)94.0(90.0–98.0)100.0(95.0–104.0)103.0(99.0–107.5)HOMA-IR
1.1(0.8–1.5) 3.0(
2.7–
3.9) 1.6(1.2–2.0) 3.2(2.7–
4.0) 1.8(1.4–2.1) 3.8(3.0–
5.0)Hypertension,n (%)10,725(29.2)1656(39.2)7114(40.1)4292(4
6.0)668(45.8)1355(53.0)Diabetes,n (%)
4458(12.1)1826(43.2)2518(14.2)3754(40.2)235(16.1)1037(40.6)Hypercholesterolemia,n (%)2431(6.6)469(11.2)1419(8.0)1019(10.9)132(9.0)297(11.6)Hypertriglyceridemia,n (%)3591(9.8)1163(27.7)3709(21.0)3401(36.6)336(23.1)945(37.2)High LDL-C,n (%)1510(4.1)309(7.4)996(5.6)697(7.5)83(5.7)191(7.5)Low HDL-C,n (%)
7630(20.8)1358(32.1)5798(32.6)3763(40.3)506(34.7)1047(41.0)Women
Number,percentage (%)72,118(51.7)12,740(9.1)27,581(19.8)18,401(13.2)3138(2.3)
5582(4.0)
Age,years
55.0(48.2–61.6)57.0(50.4–63.5)56.3(49.5–62.6)57.8(51.6–64.0)56.8(50.0–63.5)58.3(51.7–64.5)High school education or above,n (%)24,947(34.6)4660(36.6)7233(26.2)5449(29.6)637(20.3)1257(22.5)Current cigarette smoker,n (%)977(1.4)160(1.3)355(1.3)205(1.1)33(1.1)88(1.6)Current alcohol consumer,n (%)1379(2.0)
163(1.3)
509(1.9)
254(1.4)
43(1.4)
65(1.2)
MET-min/week 2400(1680–5040)1680(1680–3360)2400(1680–4320)1680(1680–3360)1680(1680–4080)1680(1680–3360)BMI,kg/m 2
22.3(20.8–23.6)23.4(22.2–24.2)26.5(25.7–27.6)27.1(26.0–28.3)31.4(30.5–32.9)31.7(30.8–33.3)Waist circumference,cm 77.0(72.0–82.0)81.4(77.0–86.0)87.0(83.0–92.0)89.6(85.0–94.0)96.0(90.5–101.0)99.0(94.0–104.0)HOMA-IR
1.3(1.0–1.7) 3.0(
2.7–
3.7) 1.7(1.3–2.0) 3.2(2.7–
4.1) 1.8(1.5–2.1) 3.6(2.9–4.9)Hypertension,n (%)15,616(21.7)3888(30.5)8994(32.6)7412(40.3)1265(40.3)2689(48.2)Diabetes,n (%)
6219(8.6)4226(33.2)3234(11.7)6429(34.9)503(16.0)2311(41.4)Hypercholesterolemia,n (%)7834(10.9)2092(16.5)3398(12.3)3078(16.7)376(12.0)815(14.6)Hypertriglyceridemia,n (%)5871(8.2)3429(27.0)3823(13.9)5643(30.7)454(14.5)1594(28.6)High LDL-C,n (%)4505(6.3)1213(9.6)2157(7.8)1917(10.4)246(7.8)579(10.4)Low HDL-C,n (%)
9009(12.5)
2521(19.8)
4591(16.65)
4111(22.3)
510(16.3)
1295(23.2)
Data are medians (interquartiles)for continuous variables,or numbers (percentages)for categorical parameters.
Abbreviations:MET-min/week,metabolic equivalent minutes per week;BMI,body mass index;CHD,coronary heart disease;LDL-C,low-density lipoprotein cholesterol;HDL-C,high-density lipoprotein cholesterol;HOMA-IR,homeostasis model assessment-estimated insulin resistance.
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obesity do not show increased all-cause,cancer and cardiovascular mortality risks[9].Conversely,in the community-based Uppsala Longi-tudinal Study of Adult Men,insulin-sensitive obesity had remarkably higher risks for cardiovascular diseases and death[11].Taken together, it is still dif?cult to draw a?rm conclusion from the present literatures. Our results extended the view of the Sweden study[11]that both general
Table2
Cardiovascular risk factors in insulin-sensitive/resistant abdominal obese phenotypes?.
Normal waist Large waist
Insulin-sensitive Insulin-resistant Insulin-sensitive Insulin-resistant Men
Number,percentage(%)41,149(58.2)5798(8.2)13,699(19.4)10,009(14.2) Age,years57.9(50.2–65.0)58.0(49.9–64.7)58.3(50.8–65.0)57.4(49.2–64.5) High school education or above,n(%)14,855(36.1)2660(45.9)5473(40.0)4779(47.8) Current cigarette smoker,n(%)17,438(42.4)1797(31.0)5243(38.3)3295(32.9) Current alcohol consumer,n(%)11,120(27.5)1129(20.0)3863(28.7)2434(24.9)
MET-min/week3360(1680–8400)2400(1680–5040)2400(1680–5040)1680(1680–3360) BMI,kg/m223.0(21.2–24.6)24.8(23.4–26.3)26.8(25.2–28.3)28.1(26.5–30.0) Waist circumference,cm82.0(76.1–86.0)86.0(82.3–89.0)95.0(92.0–98.0)97.0(94.0–101.1) HOMA-IR 1.1(0.8–1.6) 3.0(2.7–3.8) 1.6(1.3–2.0) 3.4(2.8–4.3) Hypertension,n(%)12,722(30.9)2379(41.0)5695(41.6)4893(48.9) Diabetes,n(%)4854(11.8)2381(41.1)2127(15.5)4099(41.0) Hypercholesterolemia,n(%)2769(6.7)654(11.3)1129(8.3)1101(11.0) Hypertriglyceridemia,n(%)4542(11.1)1748(30.3)2946(21.6)3686(36.9)
High LDL-C,n(%)1740(4.2)427(7.4)798(5.8)758(7.6)
Low HDL-C,n(%)9084(22.1)1934(33.4)4670(34.1)4144(41.4) Women
Number,percentage(%)52,207(38.0)7011(5.1)48,974(35.6)29,204(21.3) Age,years53.8(47.3–60.0)54.7(48.0–61.2)57.1(50.8–63.6)58.2(52.2–64.5) High school education or above,n(%)18,849(36.1)2751(39.2)13,524(27.6)8496(29.1) Current cigarette smoker,n(%)656(1.3)67(1.0)689(1.4)382(1.3)
Current alcohol consumer,n(%)937(1.9)72(1.1)980(2.1)403(1.4)
MET-min/week2520(1680–5040)2172(1680–3600)1920(1680–3528)1680(1680–3360) BMI,kg/m221.9(20.4–23.4)23.3(21.9–24.7)25.2(23.5–27.1)27.0(25.1–29.2) Waist circumference,cm75.0(70.4–78.0)77.0(74.0–79.0)87.0(83.2–91.0)90.0(85.7–96.0) HOMA-IR 1.3(0.9–1.6) 3.0(2.6–3.6) 1.6(1.2–2.0) 3.3(2.8–4.2) Hypertension,n(%)10,366(19.9)2044(29.2)15,391(31.4)11,894(40.7) Diabetes,n(%)3812(7.3)2021(28.8)5879(12.0)10,723(36.7) Hypercholesterolemia,n(%)5327(10.2)1127(16.1)6096(12.5)4794(16.4) Hypertriglyceridemia,n(%)3489(6.7)1686(24.1)6503(13.3)8845(30.3)
High LDL-C,n(%)3028(5.8)662(9.5)3787(7.7)3009(10.3)
Low HDL-C,n(%)6065(11.6)1245(17.8)7861(16.1)6604(22.6)
Data are medians(interquartiles)for continuous variables,or numbers(percentages)for categorical parameters.
Abbreviations:MET-min/week,metabolic equivalent minutes per week;BMI,body mass index;CHD,coronary heart disease;LDL-C,low-density lipoprotein cholesterol;HDL-C,high-density lipoprotein cholesterol;HOMA-IR,homeostasis model assessment-estimated insulin resistance.
*208,051participants with complete information were included in this analysis.
Table3
Association between insulin-sensitive general obesity and cardiovascular diseases.
Normal weight Overweight Obese
Insulin-sensitive Insulin-resistant Insulin-sensitive Insulin-resistant Insulin-sensitive Insulin-resistant Cardiovascular diseases
Men
Case percentage(%) 4.8 6.9 5.97.610.18.6
Unadjusted odds ratio(95%CI) 1.00 1.47(1.30–1.68) 1.24(1.15–1.34) 1.64(1.50–1.80) 2.23(1.86–2.66) 1.86(1.61–2.16) Multivariable-adjusted odds ratio(95%CI)? 1.00 1.31(1.12–1.53) 1.34(1.22–1.48) 1.54(1.37–1.73) 2.55(2.04–3.18) 2.11(1.75–2.53) Women
Case percentage(%) 3.9 5.8 6.07.77.310.5
Unadjusted odds ratio(95%CI) 1.00 1.52(1.40–1.66) 1.59(1.49–1.69) 2.07(1.94–2.21) 1.96(1.70–2.25) 2.93(2.67–3.22) Multivariable-adjusted odds ratio(95%CI)? 1.00 1.19(1.07–1.32) 1.48(1.37–1.60) 1.59(1.46–1.73) 1.73(1.45–2.06) 2.32(2.06–2.61) 10-year Framingham risk for CHD
Men
Case percentage(%)7.111.39.913.114.414.2
Unadjusted odds ratio(95%CI) 1.00 1.65(1.49–1.83) 1.43(1.35–1.53) 1.96(1.82–2.11) 2.18(1.88–2.54) 2.16(1.92–2.43) Multivariable-adjusted odds ratio(95%CI)? 1.00 1.36(1.20–1.55) 1.41(1.30–1.53) 1.55(1.41–1.71) 2.26(1.86–2.76) 1.99(1.70–2.32) Women
Case percentage(%) 3.9 5.9 6.17.87.410.7
Unadjusted odds ratio(95%CI) 1.00 1.53(1.41–1.66) 1.59(1.50–1.70) 2.09(1.95–2.23) 1.97(1.71–2.26) 2.93(2.67–3.21) Multivariable-adjusted odds ratio(95%CI)? 1.00 1.18(1.06–1.30) 1.48(1.37–1.60) 1.58(1.45–1.72) 1.73(1.46–2.06) 2.27(2.01–2.56) Abbreviations:CHD,coronary heart disease.
*Multivariable model adjusted for age,education attainment,current cigarette smoking,current alcohol consumption,MET-min/week,diabetes status,hypertension status,hypercho-lesterolemia status,hypertriglyceridemia status,high LDL-C status,and low HDL-C status.
392J.Lu et al./International Journal of Cardiology172(2014)388–394
and abdominal obese individuals had increased risks for cardiovascular diseases independent of insulin resistance,not only in men but also in women.One small-scale (413participants)study demonstrated that both general and abdominal obesity appear to have a predominant role compared with insulin resistance in relation with hypertension in Chi-nese population [35].Our study con ?rmed the speculation by exploring the interaction of obesity and insulin resistance on cardiovascular dis-eases in a large population.
A better understanding of obesity subgroups may have important implications for prevention and therapeutic medical decision making.Given that the previous studies revealed that MHO individuals seem to have favorable health outcome,the bene ?t of weight loss in this sub-set has been questioned [36,37].In fact,some investigators have sug-gested that an attempt to achieve weight loss in MHO individuals by lifestyle intervention might not be necessary or even could be potential-ly harmful given the favorable metabolic pro ?le [38,39].
In the present study,we found that the metabolic pro ?les among obe-sity with and without insulin resistance varied widely.Among general or abdominal obesity,compared to those with insulin resistance,insulin-sensitive individuals tended to have lower levels of blood pressures,BMI,and waist circumference,and have favorable lipids and glucose pro-?les.Interestingly,insulin-sensitive obesity seemed to be associated with better lipids and glucose pro ?les than insulin-resistant overweight.For cardiovascular diseases and 10-year Framingham risk for CHD,insulin-resistant obesity seemed to have the highest ORs,except that in men,insulin-sensitive general obesity had the highest risk for prevalent cardio-vascular diseases.In addition,using quantile regression analysis,we found that each of BMI,waist circumference and HOMA-IR was closely as-sociated with 10-year Framingham risk for CHD in nearly all quantiles.Our results suggested that although to some degree insulin-sensitive obe-sity has a better metabolic pro ?le than insulin-resistant obesity or even insulin-resistant overweight,the higher cardiovascular risks in insulin-sensitive obesity cannot be ignored,and if necessary,proper interven-tions on insulin-sensitive obesity are needed.Given the limited available evidence,future studies are warranted to investigate the intervention ef-forts on this unique obese phenotype.
The major strength of the present study is the large well-characterized population,which guaranteed a large number of cardiovascular diseases cases and limited the sampling bias.In addition,we investigated the in-teraction of insulin sensitivity with both general and abdominal obesity and extended the previous data.However,limitations are still needed to
be considered.One major limitation is that due to the cross-sectional na-ture,no causal inference can be drawn.Prospective studies are needed to clarify their precise interrelationship.Secondly,the study was performed in middle-aged and elderly Chinese,which limits its generalizability to other ages and ethnics.Thirdly,the cardiovascular diseases in this study were self-reported,which lead to inevitable recall bias.5.Conclusions
In conclusion,in middle-aged and elderly Chinese,both general and abdominal obesity place individuals at increased risks for cardiovascular diseases,regardless of the presence or absence of insulin resistance.Thus,the present study data do not support the existence of a MHO phe-notype based on the de ?nition of absence of insulin resistance.Whether the necessary of diagnosing MHO in clinical practice is still be questioned,so further studies are needed to investigate the effects of interventions on obese subgroups.
Supplementary data to this article can be found online at https://www.wendangku.net/doc/a47625075.html,/10.1016/j.ijcard.2014.01.073.Acknowledgment
This work is supported by the Chinese Society of Endocrinology,the Key Laboratory for Endocrine and Metabolic Diseases of Minis-try of Health (1994DP131044),the National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology (2012ZX09303006-001),the National Clinical Re-search Center for Metabolic Diseases of Ministry of Health (2013BAI09B13),the EFSD-CDS-Lilly Program for Collaborative Re-search between China and Europe (2011),and the National Natural Science Foundation of China (81030011,81222008,81130016).References
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Table 4
Association between insulin-sensitive abdominal obesity and cardiovascular diseases ?.
Normal waist Large waist Insulin-sensitive
Insulin-resistant
Insulin-sensitive
Insulin-resistant
Cardiovascular diseases Men
Case percentage (%)
4.9 6.5
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208,051participants with complete information were included in this analysis.?
Multivariable model adjusted for age,education attainment,current cigarette smoking,current alcohol consumption,MET-min/week,diabetes status,hypertension status,hypercho-lesterolemia status,hypertriglyceridemia status,high LDL-C status,and low HDL-C status.
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胰岛素抵抗与肥胖的关系
胰岛素抵抗与肥胖的关系 一）胰岛素抵抗与肥胖 我们知道，脂肪-胰岛素内分泌轴是重要的维持机体代谢平衡的内分泌系统之一。胰岛素可刺激脂肪组织产生瘦素，而血浆瘦素浓度的增加可作用于下丘脑的ob-Rb受体，抑制神经肽Y基因的表达，导致摄食减少和能量消耗，并能抑制胰岛β细胞分泌胰岛素，同时也能减轻高胰岛素血症，继而减少瘦素的产生达到内分泌平衡，很明显，下丘脑的ob-Rb受体对瘦素不敏感，发生高胰岛素血症，导致食欲亢进、肥胖和2型糖尿病。那么，下丘脑的ob-Rb受体为何对瘦素抵抗（不敏感）呢？因为胰岛素抵抗使胰岛素靶组织（如脂肪细胞）、靶器官对胰岛素不敏感，血浆葡萄糖不能被胰岛素靶组织（如脂肪细胞）、靶器官摄取而血浆葡萄糖水平升高，机体需要保持血浆高胰岛素水平，才能指令靶组织靶器官摄取血浆中过多的葡萄糖合成脂肪储存于脂肪细胞，机体就这样以超重、肥胖的代价降低血糖，暂时维持着糖代谢平衡。因此肥胖是中枢神经系统-内分泌系统的调节网络失调（主要是胰岛素抵抗）的结果。 肥胖的发病枢纽：从上述可知，肥胖是由中枢神经-内分泌系统调节网络失调引起的，而中枢神经系统-内分泌系统调节网络失调的发病枢纽是胰岛素抵抗。 什么叫胰岛素抵抗？胰岛素抵抗（IR）是指机体对一定量的胰岛素的生物学反应低于预计正常水平的一种现象。也就是胰岛素靶组织对胰岛素不敏感。在胰岛功能正常的情况下，胰岛素抵抗必然产生高胰岛素血症，高胰岛素血症必然导致食欲亢进，产生多食症状，于是能量摄入过多血糖升高，由于脂肪细胞的胰岛素抵抗发生较晚，高胰岛素血症促使过多的能量被脂肪组织摄取、利用，合成脂肪，于是脂肪细胞膨胀，出现肥胖。脂肪是体内各种能量贮存的主要形式，脂肪主要贮存于皮下组织，内脏器官周围、胃肠系膜、肌间质等处，一般来说，脂肪的贮存量约占成年男子体重的10%-20%，成年女子则更多一些。脂肪细胞又是内分泌细胞，它能接受胰岛素信息，又能释放多种内分泌激素，如：瘦素、脂联素、抵抗素, 还能分泌TNF-α。抵抗素、TNF-α则是肥胖相关胰岛素抵抗的激素和因子。脂肪细胞释放抵抗胰岛素的一系列激素是机体脂肪、体重保持平衡的本能。过量的脂肪细胞又是调节机体脂肪、体重平衡的中枢神经-内分泌系统的调节网络失调的重要因素。过多的瘦素还是肥胖症致病的激素之一。 如果个体固有的脂肪、体重调定点较高，肥胖就较严重；如果个体固有的脂肪、体重调定点较低，血糖就升得快，所以有些人吃得多也不肥胖，而有些糖尿病患者肥胖不很明显。其原本是正常体重代谢性肥胖者。 1、压力与肥胖：为什么压力大会造成肥胖呢？首先来看看压力如何造成胰岛素抵抗的。压力是应激源，较长时间承受压力产生慢性应激状态，胰高血糖素升高，肾上腺糖皮质激素分泌量增加，出现胰岛素抵抗，血脂、血糖升高，必然产生高胰岛素血症，使脂肪-胰岛素内分泌轴失调，导致食欲亢进，使能量摄入和消耗不平衡，引起能量正平衡，形成肥胖；而肥胖又加重胰岛素抵抗/高胰岛素血症，更加肥胖，引发与肥胖相关的系列疾病。《黄帝内经》说：“恬淡虚无，精神从之”，不然，“气血逆乱，发为薄厥”（脑卒中）。但是我们的家长和学校对孩子从小就开始追逐名次的“竞争”教育，在教育上造成千军万马过独木桥的声势，孩子压力大，怎么不发生胰岛素抵抗，造成肥胖症？即使体重正常范围也属“正常体重代谢性肥胖”啊!（第六版《内科学》将“正常体重代谢性肥胖”定义为：“虽然体重在正常范围，但存在高胰岛素血症和胰岛素抵抗”。） 2、食欲与肥胖：中国饮食原来多素少荤，国医提倡熟食热饮的饮食方式，饮食西方化以后美味可口的高热量、高脂饮食吸引国人，特别是吸引儿童过量进食高热量、高脂肪。人类的食欲本是受神经-内分泌网络调控的，如上所述，能量摄入过多，脂肪-胰岛素内分泌轴启动，
腰身指数与胰岛功能的关系
2型糖尿病患者腰身指数与胰岛功能的相关性 吴晓明，张雅静，姜春艳，梁馨桐，李维，张宏天津医科大学代谢病医院肥胖代谢科，卫生部激素与发育重点实验室，天津300070 摘要：目的研究2型糖尿病（T2DM）患者腰身指数（WHtR）与胰岛功能各指数之间的相关性。方法T2DM患者179例，以WHtR 0.5为切点分为非肥胖组和肥胖组，比较两组间的稳态模型胰岛素抵抗指数（HOMA-IR）、胰岛素分泌指数 （HOMA-IS）、胰岛素曲线下面积（AUC INS ）和血糖曲线下面积（AUC BG ），并行Pearson 相关分析和多元逐步回归分析。结果肥胖组较非肥胖组ln(AUC INS )、ln(HOMA-IR)和ln(HOMA-IS)升高，差别具有统计学意义(P<0.05)；WHtR与ln(AUC INS)、ln(HOMA-IR)和Ln(HOMA-IS)呈正相关,r值分别为0.392、0.359、0.414，P< 0.01；多元逐步回归分析显示，ln(HOMA-IS)是WHtR的独立影响因素(P <0.01)。结论WHtR是胰岛素抵抗和高胰岛素血症良好的预测因子。 关键词：腰身指数；胰岛素抵抗指数；胰岛素分泌指数；胰岛素曲线下面积 The relationship between waist height ratio and insulin function in type 2 diabetes patients Wu Xiao-ming, Zhang Ya-jing, Jiang Chun-yan, Liang Xin-tong, Li Wei, Zhang Hong 【Abstract】Objective: To investigate the relationship between waist height ratio (WHtR) and insulin function index in type 2 diabetes mellitus(T2DM) patients. Method With the cut point of WHtR at 0.5, 179 T2DM patients were divided into non-obesity group and obesity group. The difference in insulin resistance index(HOMA-IR) , insulin secretion index(HOMA-IS) ，area under curve of insulin（AUC INS ） and area under curve of blood glucose（AUC BG ） were compared. The Pearson correlation analysis and multivariant stepwise regression analysis were then made. Results： The ln(AUC INS ), ln(HOMA-IR),ln( HOMA-IS) in obesity group is higher than non-obesity group (p<0.05), the difference have statistical significance. WHtR is positively correlated with ln(AUC INS )（r=392,p<0.01）、ln(HOMA-IR) 作者简介：吴晓明（1980-），河北省人，住院医师，在读博士研究生，从事糖尿病及慢性并发症临床及机制的研究。 通讯作者：张宏（1952-）,女，天津人，教授，博士生导师，从事糖尿病及慢性并发症临床及机制的研究，E-mail:zh80008@https://www.wendangku.net/doc/a47625075.html,
腹型肥胖与胰岛素抵抗
腹型肥胖致IR 的机制 主要有两大方面:脂肪细胞存储信号反馈学说和脂肪转移学说。 1. 脂肪储存信号的过度反馈(图1) :发生肥胖尤其是腹型肥胖时,皮下脂肪组织储存容量不足,脂肪细胞对脂肪储存信号反馈过度,各种脂肪细胞因子水平发生变化,引起IR。 (1) 蛋白酪氨酸磷酸酶( PTP) 的激活:酪氨酸蛋白激酶(PTK) 和PTP 通过对酪氨酸的磷酸化和去磷酸化,调节着胰岛素受体( InsR) 及其底物的活性。肥胖时,脂肪过量储存,为了减少Ins的脂肪合成作用,机体明显使PTP活化,使InsR 及其底物去磷酸化, Ins 信号不能下传,进而导致IR。王淼等[4 ]选取正常对照者和初诊T2DM 患者共16 例,于手术时取内脏脂肪组织,用Western blot 测定PTP-1B 水平。结果发现BMI 正常的T2DM 组(CDM 组) 、超重或肥胖的T2DM 组(ODM 组) 均存在明显的IR ,CDM 组PTP-1B 表达几乎是对照组的3 倍,而ODM 组PTP-1B 表达几乎是CDM组的4 倍。可以认为PTP-1B 表达增多与T2DM 及代谢综合征(MS) 的发病密切相关。 (2) 瘦素抵抗:流行病学资料表明,肥胖者常合并高Ins血症和高瘦素血症,可伴随InsR 后缺陷所致的IR。瘦素抵抗是引起IR 的重要机制之一。目前认为,发生瘦素抵抗时,细胞因子信号转导抑制物-3 (SOCS-3) 增多、活性增强。SOCS-3 是瘦素诱导的瘦素信号转导抑制物, 是瘦素抵抗的标志,并与肥胖的发病有明显相关性[5 ] 。在肥胖瘦素抵抗模型中SOCS-3 水平升高,而SOCS-3 可通过降解In-sR 底物蛋白,抑制Ins 信号转导,导致IR 的发生。章建梁等[6 ] 发现:人体血清瘦素浓
说说“胰岛素抵抗”那些事
龙源期刊网 https://www.wendangku.net/doc/a47625075.html, 说说“胰岛素抵抗”那些事 作者：邢小燕 来源：《大众健康》2016年第09期 胰岛素抵抗作为一个“温床”或“土壤”，滋生了高血糖、高血压、血脂异常等心血管危险因素。 53岁的刘女士，去年出现糖尿病症状，去医院做了检查确诊，期间一直在吃治疗糖尿病 的药物。上个月，刘女士发现自己血糖升高，于是马上去医院做了检查。刘女生问医生，是不是因为吃的药物失效了？医生告诉她，她出现了胰岛素抵抗的症状。 那么，什么是胰岛素抵抗？为什么会出现胰岛素抵抗？胰岛素抵抗有什么危害？怎样才能预防胰岛素抵抗呢？ 什么是胰岛素抵抗 我们先来看看什么是胰岛素。胰岛素是由胰腺的胰岛β细胞分泌的一种肽类激素，是机体内唯一降低血糖的激素，也是唯一同时促进糖原、脂肪、蛋白质合成的激素。在正常情况下，胰岛β细胞会感应机体血糖浓度的变化，如进餐时血糖升高了它会多分泌胰岛素，反之，血糖低时它会少分泌胰岛素，以此来维持血糖的动态平衡。 胰岛素抵抗，是指机体对胰岛素的生理作用反应性降低（即不敏感），主要表现在胰岛素的作用靶点例如肝脏、骨骼肌和脂肪组织等对葡萄糖的摄取和利用障碍。 胰岛素抵抗：滋生疾病的“温床” 为了克服胰岛素抵抗，胰岛β细胞不得不代偿性分泌胰岛素增多，来维持正常的生理效应。长期胰岛素抵抗和高胰岛素血症将会引发一系列临床异常： 高血糖 胰岛素抵抗和胰岛素分泌缺陷是2型糖尿病发病过程中的两个主要病理生理环节，但胰岛素抵抗可以发生得更早。在病程早期，胰岛β细胞可通过多分泌胰岛素来维持正常血糖；随着病程发展，机体这种代偿机制逐渐衰退，胰岛素分泌开始减少，当不能与胰岛素抵抗相抗衡时，血糖不可避免地升高，出现糖耐量异常甚或糖尿病。在糖尿病治疗过程中，如不能很好解决胰岛素抵抗，还会影响血糖控制效果。 原发性高血压
肥胖和胰岛素抵抗有关系吗
肥胖和胰岛素抵抗有关系吗 文章目录*一、肥胖和胰岛素抵抗有关系吗*二、胰岛素抵抗如何减肥*三、糖尿病的症状 肥胖和胰岛素抵抗有关系吗1、肥胖和胰岛素抵抗有关系吗肥胖和胰岛素抵抗有关系。研究表明,肥胖(尤其是腰围大于臀围的“苹果型”肥胖)者易发生胰岛素抵抗。这与脂肪细胞体 积增大,受体相对减少,对胰岛素敏感性降低有关。这种肥胖者尤其易发生糖尿病、高血压、冠心病及脂肪肝等疾病的发生。 2、胰岛素抵抗的原因 2.1、衰老 随着年龄的增长,我们的人体复杂过程变得更慢或减少。胰 腺也不例外。有时,当我们变老时,胰腺自然会产生更少的胰岛素。 2.2、脂肪 很多糖友肚子特别大,其他地方胖,成为中心肥胖。因为内脏脂肪和腹部脂肪含量过多。腹部脂肪,胰岛素抵抗,由此产生的高血糖之间存在相关性。内脏脂肪直接影响胰岛素的抵抗。携带额外的腹部脂肪不仅会导致糖尿病,它也可以增加高血压和心血管 疾病的风险。 2.3、运动 当有人过着久坐不动的生活方式,用最少的体力来完成一天 的任务,他们的身体就不会有效使用胰岛素,从而导致胰岛素抵抗。美国心脏协会建议每周锻炼30次,每周五次,用于心脏健康。
将这一量的运动融入你的生活中也提高了胰岛素的敏感性,并有助于减肥。 2.4、药物 其他疾病的一些药物增加了胰岛素抵抗的风险。一些用于治疗双相情感障碍的药物属于这一类。其他的药物,如一些类固醇药物,也会导致胰岛素抵抗。 3、胰岛素抵抗的危害 胰岛素抵抗不仅可以触发高血糖的发生,而且会使血液中胰岛素水平过高(即高胰岛素血症),而引起高血压和血脂异常,这两方面都会导致造成全身大血管的严重受损,因此胰岛素抵抗是大血管病变发生和加重的根源。因此,防止并阻断大血管病变的关键是有效解除胰岛素抵抗。 胰岛素抵抗是糖尿病并发症的病理基础。目前已经有更多的研究表明,胰岛素抵抗与十余种代谢疾病相关。这些疾病包括:中心性肥胖、糖代谢异常、2型糖尿病、脂肪代谢紊乱、高血压、微量白蛋白尿、冠心病等。胰岛素抵抗是这些疾病共同的发病基础。 胰岛素抵抗如何减肥1、服用甲福明二甲双胍 胰岛素抵抗型的肥胖,首先就应该要关注如何解决胰岛素抵抗的现象,很多肥胖者必须要做的一件就是要改善胰岛素抵抗的现象,改善胰岛素抵抗的现象是能够改善人体的内分泌系统紊乱
胰岛素抵抗
胰岛素抵抗（胰岛素敏感性） 一：什么是胰岛素抵抗 胰岛素抵抗（英语：insulin resistance），是指脂肪细胞、肌肉细胞和肝细胞对正常浓度的胰岛素产生反应不足的现象，亦即这些细胞需要更高的胰岛素浓度才能对胰岛素产生反应。 在脂肪细胞内，胰岛素抗性导致储存的甘油三酸酯的水解，进而提高血浆内自由脂肪酸的含量。在肌肉细胞内，胰岛素抗性降低葡萄糖的吸收；而在肝细胞内，降低葡萄糖的储备，两者共同导致血糖含量的提高。胰岛素抗性引起的血浆中高胰岛素和高糖含量经常导致代谢综合征、痛风和2型糖尿病。 胰岛素抵抗理论结束了用胰岛素分泌不足来解释糖尿病的历史。更真实地再现了人体的复杂性，为行为医学技术进入提供了学术支持。更科学的为指导糖尿病患者运动指明了方向。 二：胰岛素抵抗的形成原因 导致胰岛素抵抗的病因很多，包括遗传性因素或称原发性胰岛素抵抗如胰岛素的结构异常、体内存在胰岛素抗体、胰岛素受体或胰岛素受体后的基因突变(如Glut4基因突变、葡萄糖激酶基因突变和胰岛素受体底物基因突变等)，原发性胰岛素抵抗大多数是由于多基因突变所致，并常常是多基因突变协同导致胰岛素抵抗。 除了上述遗传因素之外，许多环境因素也参与或导致胰岛素抵抗，称之为继发性胰岛素抵抗，如肥胖(是导致胰岛素抵抗最主要的原因，尤其是中心性肥胖；这主要与长期运动量不足和饮食能量摄人过多有关，2型糖尿病患者诊断时80%伴有肥胖)、长期高血糖、高游离脂肪酸血症、某些药物如糖皮质激素、某些微量元素缺乏如铬和钒缺乏、妊娠和体内胰岛素拮抗激素增多等。 另外还有原因是肿瘤坏死因子a(TNF-a)增多。TNF-a活性增强可以促进脂肪分解引起血浆FFA水平增高，抑制肌肉组织胰岛素受体的酪氨酸激酶的活性，抑制IRS-1的磷酸化和Glut4的表达，从而导致胰岛素抵抗和高胰岛素血症。近年来尚发现脂肪细胞能分泌抵抗素( resistin )，抵抗素可降低胰岛素刺激后的葡萄糖摄取，中和抵抗素后组织摄取葡萄糖回升。其他如瘦素抵抗和脂联素水平的降低或活性减弱也与胰岛素抵抗有关。骨骼肌细胞内甘油三酯(TG)含量增多也被认为是胰岛素抵抗的原因之一，B细胞内TG积聚过多可造成其功能减退。 三：胰岛素抵抗的监测方法 1.正常血糖胰岛素钳夹技术 正常血糖胰岛素钳夹技术（EICT），是目前公认的检测胰岛素抵抗的方法，并被认为是评价其他检测胰岛素抵抗方法的金标准。本方法是测定组织对外源性胰岛素敏感性的方法，快速连续胰岛素灌注使血浆胰岛素浓度迅速升高并维持在一定水平，改变葡萄糖灌注率而使血糖稳定在基线水平。在这种水平下可通过抑制肝糖输出和内源性胰岛素分泌，即阻断内源性葡萄糖一胰岛素反馈，这时葡萄糖灌注率等于外源性胰岛素介导的机体葡萄糖代谢率。具体方法为:空腹12h，抽血测基础血糖、胰岛
13--肠道菌群与肥胖、胰岛素抵抗的关系
专题导读 2012年第9卷第16期 药品评价 13 Guided Reading 肥胖以及2型糖尿病已成为当今世界重要的社会和健康问题。肥胖和2型糖尿病的发生与多种遗传和环境因素有关，其中人体肠道菌群与肥胖和2型糖尿病的发生有着密切的关系。 肠道菌群(gut microbiota)为定植在人体消化道内的微生物，数量众多，种类复杂。正常成人的肠道菌群总重量约1～2kg ，数量至少达1014个，是人体细胞的10倍，包含的基因数量是人类基因数量的150倍。主要位于大肠。根据细菌16S rRNA 序列分类，含有细菌500～1000种，主要包括9个门，即厚壁菌门(Firmicutes)、拟杆菌门(B a c t e r o i d e t e s )、放线菌门(A c t i n o b a c t e r i a )、梭杆菌门(F u s o b a c t e r i a )、变形菌门(P r o t e o b a c t e r i a )、疣微菌门(Ve r r u c o m i c r o b i a )、蓝藻菌 门(C y a n o b a c t e r i a )、螺旋体门(Spirochaeates)、VadinBE97菌门和另外一种古菌——史氏甲烷短杆菌(Methanobrevibacter smithii)。其中大部分属于拟杆菌门(G -菌)或厚壁菌门(G +菌)(共约占90%)。肠道菌群与能量代谢 与正常小鼠相比，完全清除肠道菌群后的小鼠摄食量增多，但体内脂含量却明显减少；植入正常小鼠肠道菌群后，摄食量减少，体脂含量却明显增加。由于无菌小鼠的耗氧率明显减少，提示体脂的减少并不是由于能量的消耗增加所致，而是因为能量摄入减少。肠道菌群可通过多种机制参与宿主的能量代谢：①大肠中的肠道菌群能将不被小肠消化的碳水化合物(如膳食纤维、抗性淀粉等)发酵，使其降解成短链脂肪酸，为宿主提供能量。 R elationship of gut microbiota, obesity and insulin resistance 肠道菌群与肥胖、胰岛素抵抗 的关系 中山大学附属二院内分泌科 李焱 梁绮君 中图分类号 587.1 文献标识码 A 文章编号 1672-2809(2012)16-0013-03关键词 肠道菌群；肥胖；胰岛素抵抗 万方数据
胰岛素过高的问题及治疗
胰岛素的过高会出现的问题 会导致低血糖的发生，尤其在运动时，另外高胰岛素血症是冠心病、高血压、高血脂、Ⅱ型糖尿病、肥胖、脑卒中等共同的发病基础。 治疗如下： 加强体育锻练：体力活动可增加组织对胰岛素的敏感性，降低体重，改善代谢，减轻胰岛素抵抗，使高胰岛素血症缓解，降低心血管并发症。 改善饮食结构：如果人们的饮食结构都以高热量、高脂肪为主。而热量摄入过多超过消耗量，则造成体内脂肪储积引发肥胖。所以，饮食要多样化，以保持营养平衡，避免营养过剩。 该病若要药物治疗，必须在医生指导下。边服药，边监测，以调节激素水平到健康指数范围内。 一、案例：我每次月经都会迟一二个月，今天查出来了，说我胰岛素过高，需要降低。这是什么 原因导致胰岛素过高的，是不是胰岛素过高，才会使月经推迟几个月才来的重要原因 呢？？？怎么降低胰岛素 主要原因：1、是胰脏功能失调引起的高胰岛素血症；（胰腺功能亢进，有可能是胰腺癌） 2、胰岛素高了打破了与其它激素的平衡，内分泌紊乱了，月经也就不正常了； 3、疏通胰脏微循环滋养胰岛，使胰脏恢复正常。 4、可能是胰岛素抵抗造成的。长时间胰岛素过高容易引起糖尿病以及高胰岛素血 症 5、偏胖的人一般都出现胰岛素抵抗情况，正规医院做糖尿病筛查（OGTT），减轻体重．晕 倒可能是由于胰岛素分泌高峰延后导致的，一般发生在中饭或晚饭前，早期糖尿病患者会经常出现． 主要建议：1、减肥。在选择减肥方法时应以物理减肥和减少饮食为主。不应该以口服药物为主。 常用减肥方法有：①预防性减肥；②运动减肥；③行为减肥；④机械减肥；⑤桑那浴减 肥；⑥石膏减肥；⑦石腊减肥；⑧手术减肥；⑨按摩减肥；⑩电子减肥。其中药物减肥 不可泛用。药物减肥是在以上理化减肥的基础上效果不佳最后才采取的一种减肥方法。 药物减肥有食欲抑制法和代谢促进法。药物减肥有许多副作用，应尽量避免使用。 二、如果是女孩儿的话会因为胰岛素过高影响怀孕吗？ 你好，胰岛素水平增高不一定能诊断糖尿病，血糖不特别高的话，不一定有什么症状的，但是，最有可能是糖尿病前期的高胰岛素血症，考虑存在胰岛素抵抗，这个时候需要查一下血糖，如果血糖正常说明还在代偿期，这个时候需要生活习惯控制了，比如饮食、运动，如果血糖高于正常，但不能诊断糖尿病，这是可诊断为糖耐量异常，需要用药干预的！对于你来说可能就是另一型，妊娠糖尿病（如果你现在妊娠ing的话），血糖高了就会影响怀孕，需要治疗！ 三、胰岛素过高人体正常的胰岛素是多少啊? 我的胰岛素检查是48.53 1.9--23uIU/mL 胰岛素测定。测定标准：①空腹时正常值为5～15mU/L，胰岛素依赖型则低于正常的下限 或测不出，非胰岛素依赖型在正常范围或高于正常人。②胰岛素释放试验：胰岛素依赖型无高峰出现，呈低平曲线；非胰岛素依赖型高峰较正常为低，或高峰延迟。 总结如下： 糖尿病的主要症状为： （1）多尿：糖尿病患者尿量增多，每昼夜尿量达3000～ 4000毫升，最高达10000毫升 以上。排尿次数也增多，有的患者日尿次数可达20余次。因血糖过高，体内不能被充分
肥胖与胰岛素抵抗的关系HOMA-IR
The relationship between insulin-sensitive obesity and cardiovascular diseases in a Chinese population Results of the REACTION study Jieli Lu a ,b ,1,2,Yufang Bi a ,b ,1,2,Tiange Wang a ,b ,1,2,Weiqing Wang a ,b ,2,Yiming Mu c ,2,Jiajun Zhao d ,2,Chao Liu e ,2,Lulu Chen f ,2,Lixin Shi g ,2,Qiang Li h ,2,Qin Wan i ,2,Shengli Wu j ,2,Guijun Qin k ,2,Tao Yang l ,2,Li Yan m ,2,Yan Liu n ,2,Guixia Wang n ,2,Zuojie Luo o ,2,Xulei Tang p ,2,Gang Chen q ,2,Yanan Huo r ,2,Zhengnan Gao s ,2,Qing Su t ,2,Zhen Ye u ,2,Youming Wang v ,2,Huacong Deng w ,2,Xuefeng Yu x ,2,Feixia Shen y ,2,Li Chen z ,2, Liebing Zhao a ,b ,2,Meng Dai a ,b ,2,Min Xu a ,b ,2,Yu Xu a ,b ,2,Yuhong Chen a ,b ,2,Shenghan Lai aa ,2,Guang Ning a ,b ,?,2 a Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health,Rui-Jin Hospital,Shanghai Jiao-Tong University School of Medicine,E-Institute of Shanghai Universities,China b Shanghai Clinical Center for Endocrine and Metabolic Diseases,National Clinical Research Center,Department of Endocrine and Metabolic Diseases,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,China c People's Liberation Army General Hospital,China d Shandong Provincial Hospital,China e Jiangsu Province Hospital on integration of Chinese and Western Medicine,China f Wuhan Xiehe Hospital,Huazhong University of Science and Technology School of Medicine,China g University of Guizhou School of Medicine,China h University of Haerbin School of Medicine,China i University of Luzhou School of Medicine,China j Xinjiang Kelamayi Peoples Hospital,China k University of Zhengzhou School of Medicine,China l University of Nanjing School of Medicine,China m University of Zhongshan School of Medicine,China n University of Jilin School of Medicine,China o University of Guangxi School of Medicine,China p University of Lanzhou School of Medicine,China q University of Fujian School of Medicine,China r Jiangxi People's Hospital,China s University of Dalian School of Medicine,China t Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,China u Zhejiang Center for Disease Control and Prevention,China v University of Anhui School of Medicine,China w University of Chongqing School of Medicine,China x Wuhan Tongji Hospital,China y Wenzhou University School of Medicine,China z Qilu Hospital,University of Shandong School of Medicine,China aa Johns Hopkins University School of Medicine,Baltimore,United States International Journal of Cardiology 172(2014)388–394 ?Corresponding author at:Shanghai Clinical Center for Endocrine and Metabolic Diseases,National Clinical Research Center,Department of Endocrine and Metabolic Diseases,Rui Jin Hospital,Shanghai Jiao Tong University School of Medicine,197Rui-Jin 2nd Road,Shanghai 200025,China.Tel.:+862164370045x665340;fax:+862164373514. E-mail address:gning@https://www.wendangku.net/doc/a47625075.html, (G.Ning).1 Contributed equally to this article.2 All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.0167-5273/$–see front matter ?2014Elsevier Ireland Ltd.All rights reserved. https://www.wendangku.net/doc/a47625075.html,/10.1016/j.ijcard.2014.01.073 Contents lists available at ScienceDirect International Journal of Cardiology j o u r n a l h o m e p a g e :w w w.e l s e vi e r.c o m/l o c a t e /i j c a r d
胰岛素抵抗及各种评估方法优缺点比较
胰岛素抵抗及其在临床研究中的应用 李光伟作者单位:100029北京中日友好医院 从理论上说胰岛素抵抗很普遍,但实践中判定胰岛素抵抗并不容易,因为胰岛素抵抗是指机体胰岛素介导的葡萄糖代谢能力下降,而机体对葡萄糖的代谢不仅受靶组织对胰岛素反应敏感程度(胰岛素抵抗)的影响,而且受机体产生胰岛素量(β细胞分泌功能)的影响。换言之,即胰岛素敏感性不变的情况下,只有那些能“排除”胰岛素缺乏影响的测定葡萄糖代谢能力的方法,才能准确地评估真实的胰岛素敏感性。令人遗憾的是目前文献中评估胰岛素敏感性的方法中能“纠正”或“排除”胰岛素缺乏“干扰”的能力相差悬殊,加上胰岛素测定方法精确性和可重复性的限制,实用价值也不尽相同。 本文对常用的几种胰岛素敏感性评估方法的优点及局限性作一介绍,仅供参考。 一、评估胰岛素敏感性的方法 1.几种复杂的胰岛素敏感性测定1)正常血糖胰岛素钳夹技术(下称正糖钳或ｃｌａｍｐ):这一技术由ｄｅｆｒｏｎｚｏ1979年创立,经同时静脉输入胰岛素和葡萄糖,使体内胰岛素达某种特殊浓度(纠正胰岛素缺乏)。同时调整葡萄糖输入速度使血葡萄糖水平稳定在4.48～5.04ｍｍｏｌ/ｌ,频繁取血测定血糖及胰岛素浓度2小时,计算稳态情况下单位体表面积(或每公斤代谢体重)每分钟代谢葡萄糖的量。这是目前世界上公认的测定机体胰岛素抵抗的“金标准”。血浆胰岛素浓度接近100μｕ/ｍｌ时维持正常血糖所需的外源葡萄糖不足150ｍｇ?ｍ-2?ｍｉｎ-1时为胰岛素抵抗。它以同时输入外源胰岛素及葡萄糖的方法避免了“内源性胰岛素缺乏”(如在糖尿病病人)及“低血糖”(如在胰岛素耐量试验中)对胰岛素敏感性测定的影响,成为在糖耐量正常、糖耐量低减及糖尿病人群均可信赖的技术。任何其他胰岛素敏感性评估方法都不能与之相比拟。但这种测定十分昂贵费时,在国外大型研究中心也只用于少量病例的研究。有些研究者为了节省时间和经费随意延长血糖测定间隔时间,其研究结果的可靠性会大受影响。(2)微小模型(ｍｉｎｉｍａｌｍｏｄｅｌ)计算公式:这是另一较为公认的胰岛素敏感性测定方法。该法需要取血32次,将血糖值输入计算机数学模型中进行计算。这种方法在科研中应用较胰岛素钳夹技术更为广泛。主要缺点是取血次数太多,且测定的胰岛素敏感性受胰岛素缺乏(即β细胞功能衰竭)的影响。与任何涉及静脉葡萄糖耐量的胰岛素敏感性测定法一样,ｍｉｎｉｍａｌｍｏｄｅｌ需有足够的内源性胰岛素才能正确评价胰岛素敏感性(ｓ1)。在胰岛素分泌功能受损者中,是胰岛素缺乏而非胰岛素抵抗使糖清除率下降,此模型会低估胰岛素敏感性。这一种缺点即使是在1986年增加甲磺丁脲(ｔｏｌｂｕｔａｍｉｄｅ)300～500ｍｇ注射后也不能克服。所以1990年又修正该法,给糖耐量正常者输胰岛素0.02ｕ/ｋｇ,给糖尿病患者输0.05ｕ/ｋｇ试图纠正在糖尿病患者中胰岛素分泌不足对准确测定ｓ1的影响。但是不同的2型糖尿病患者胰岛素缺乏程度不同,一律给予0.05ｕ/ｋｇ的剂量似欠合理。关于取血次数,1993年以来人们进行了多种尝试,减少为22点,14点,13点,12点的试验。结果显示取血次数低于14个点时所测定的ｓ1与胰岛素钳夹技术测定的ｍ值(胰岛素敏感性指标,每分钟代谢每公斤体重胰岛素介导的葡萄糖代谢率)相关性在2型糖尿病明显变弱。结果是这种减少次数的模型仅能适用于非糖尿病人群,常规用于糖尿病人群前需进一步研究。微小模型及ｃｌａｍｐ技术都因复杂、费时、价格贵,在群体研究中较难使用,必然要在某些领域让位于一些较为简便、经济的评估方法。这就是为什么近20年来有近20种指数陆续显露头角的原因。 2.几种简单的胰岛素敏感性指数1)空腹血胰岛素:在非糖尿病人群空腹血胰岛素是很好的胰岛素抵抗指数,它与ｃｌａｍｐ测定ｍ值密切相关,相关系数0.7～0.8,曾应用于国外许多著名的研究,为学者们广泛接受。而在糖尿病人群,因有胰岛素分泌缺乏,此时降低了的空腹血胰岛素水平已不再能代表机体的胰岛素抵抗情况。(2)空腹血糖(ｆｐｇ)/空腹胰岛素(ｆｉｎｓ)比值及ｏｇｔｔ血糖曲线下面积/胰岛素曲线下面积比值:美国著名糖尿病专家ｃａｒｏ著
内分泌激素紊乱可引起肥胖其中胰岛素变化被公认为肥胖.
内分泌激素紊乱可引起肥胖。其中胰岛素变化被公认为肥胖发病机制中最关键的一环，其次为肾上腺皮质激素的变化。 （一）胰岛素胰岛素是胰岛β细胞分泌的激素。其功能是促进肝细胞糖元合成，抑制糖异生；促进脂肪细胞摄取葡萄糖合成脂肪，抑制脂肪分解。后两作用在肥胖症发病机制中特别重要。 肥胖症者胰岛素分泌特点为： ①空腹基础值高于正常或正常高水平； ②口服葡萄糖耐量试验过程中，随血糖升高，血浆胰岛素更进一步升高； ③血浆胰岛素高峰往往迟于血糖高峰，故在餐后3～4小时可出现低血糖反应。近年还发现肥胖病人胰岛素受体数量及亲和力均降低，存在胰岛素不敏感性和抵抗性。由于存在胰岛素不敏感和抵抗，为满足糖代谢需要，胰岛素必须维持在高水平，而高胰岛素血症对脂肪细胞和脂肪代谢来说，会使脂肪合成增加，分解减少，使肥胖进一步发展。 肥胖症者体重减轻至正常后，血浆胰岛素水平及胰岛素受体可恢复正常，表明这种改变是继发性的。（二）肾上腺糖皮质激素肾上腺糖皮质激素是肾上腺皮质束状带分泌的激素，在人体中主要为皮质醇。单纯性肥胖者可有一定程度的肾上腺皮质功能亢进，血浆皮质醇正常或升高；而在继发性肥胖中，柯兴综合征血浆皮质醇明显增高。 由于血浆皮质醇增高，血糖升高，引起胰岛素升高，后者导致脂肪合成过多，形成肥胖。由于躯干及四肢脂肪组织对胰岛素和皮质醇反应性不同，故呈向心性肥胖。 （三）生长激素生长激素是垂体前叶分泌的一种蛋白质激素，具有促进蛋白质合成，动员储存脂肪及抗胰岛素作用，但在作用的初期，还表现为胰岛素样的作用。生长激素与胰岛素在糖代谢的调节中存在着相互拮抗作用。如果生长激素降低，胰岛素作用相对占优势，可使脂肪合成增多，造成肥胖。现已证实肥胖病人生长激素基础水平降低以及精氨酸、低血糖、饥饿和体育活动等刺激条件下分泌反应也是低水平的，结果在饥饿和体育活动时大量能量就不能来自脂肪分解。如禁食2天，正常人血浆生长激素从10微克/升上升到15微克/升，而肥胖者从2微克/升升至5微克/升。这种变化会随着肥胖消失而恢复正常。 （四）甲状腺激素甲状腺激素与肥胖症的关系尚不明确。肥胖者一般不存在甲状腺功能异常，即使肥胖者基础代谢率可能比正常人稍低，也不代表甲状腺功能低下。偶见两者合并存在。 （五）性腺激素男性激素主要为睾丸酮，90％以上由睾丸合成和分泌。女性可由卵巢、肾上腺皮质合成和分泌少许。雌激素和孕激素，主要由卵巢合成和分泌。性激素本身并不直接作用于脂肪代谢。 女性机体脂肪量多于男性，女性机体脂肪所占百分率明显高于男性，皮下脂肪除个别部位外，一般比男性相应部位厚度增加一倍。在妇女妊娠期、绝经期、男性或雄性家畜去势后均可出现肥胖。但其机制尚不清楚。有认为绝经期肥胖与垂体促性腺激素分泌过多有关。动物去势后胰岛增生肥大，胰岛素分泌增多，促进脂肪合成。除少数性腺功能低下性肥胖外，一般肥胖者不存在性激素分泌紊乱。 （六）胰高血糖素胰高血糖素由胰岛α细胞分泌，其作用和胰岛素相反，抑制脂肪合成。肥胖病人胰高血糖素是否有紊乱，有待研究。 （七）儿茶酚胺儿茶酚胺是由脑、交感神经末梢、嗜铬组织主要是肾上腺髓质生成的，能促进脂肪分解，大脑皮层通过儿茶酚胺及5羟色胺调节下丘脑功能，交感神经通过儿茶酚胺调节胰岛素分泌。肥胖病人脂肪组织对儿茶酚胺类激素作用不敏感，但体重减轻后可恢复正常。 总之，肥胖的病因是多方面的，如遗传倾向、饮食习惯，体力活动减少及精神因素等，都是重要原因。
中医王婷肥胖的病因及发病机理
人类肥胖的病因迄今尚未阐明，有若干因素需要考虑，如遗传、神经系统、饮食生活习惯、代谢紊乱。特别是能量供需失调，以及内分泌调节功能失常等。具体发病机制是一致的，即饮食能量入量多于机体消耗量，形成过剩，过剩的能量以脂肪形式储存于机体，脂肪组织增多，形成肥胖。 一、遗传因素 肥胖常与遗传有关。据统计，双亲体重正常其子女肥胖发生率为10％；双亲中一人肥胖，子女肥胖发病率为50％； 双亲均肥胖，子女肥胖发病率高达70％。同卵孪生儿在同一环境成长，其体重近似；即使在不同环境成长，其体重差别也小于异卵孪生子之间的差别。肥胖患者不但肥胖具有遗传性，而且脂肪分布的部位及骨胳状态也有遗传性。肥胖的遗传倾向还表现在脂肪细胞数目和（或）细胞体积增大。 二、饮食、生活习惯及社会环境因素 肥胖者往往有饮食增多史，食量较大，喜食甜食或每餐中间加食引起能量过剩。在同等热量情况下，有睡前进食及晚餐多食的习惯。体力活动过少或因骨折、结核、肝炎或其他原因而卧床休息，热量消耗少而引起肥胖。尤其人到中年以后，体力劳动量逐渐下降，常常脂肪壅存在腹部与臀部。大部分人停止有规律的运动以后即发展成肥胖。此外肥胖者之能量消耗与正常人有明显差别，休息及轻微活动时动用能量较正常人少；同样饮食情况下合成代谢较正常人亢进；基础代谢率相对较低，造成能量消耗较少，引起肥胖。 社会环境改变和肥胖发生有一定关系。解放前，由于生活水平低，肥胖发生率很低。解放后，随着生活改善，肥胖发生率急剧增加。家庭教育与儿童肥胖有关。研究发现独生子女或一家中最小子女容易肥胖。主要原因是错误认为婴儿喂养越胖越好，小孩从哺乳期就营养过度；过分溺爱，养成不良习惯，如零食尤其是糖果甜食太多；不必要的营养药物刺激食欲，增大食量；缺乏必要的体育锻炼。现已公认儿童营养过度是造成儿童及成年后肥胖的主要原因。 三、下丘脑与高级神经活动 饱食中枢位于下丘脑腹内侧核，摄食中枢位于下丘脑腹外侧核，它们之间有神经纤维联系，在功能上相互调节、相互制约。动物实验证明，这两个中枢受机体内糖、脂肪及氨基酸的影响。所以当下丘脑病变或体内某些代谢改变时可影响食欲中枢发生多食，产生肥胖。这是下丘脑综合征的主要原因。单纯性肥胖时多认为下丘脑有功能性改变。
肥胖与2型糖尿病的共同起源：能量过剩引发肝脏胰岛素抵抗
近几十年来，西方化的饮食结构以及城市化生活方式 导致我国肥胖与2型糖尿病（T2DM）患病率大幅度上升。 一系列国外大型和长期随访研究表明，T2DM的风险随着体 质指数（BMI）的增加而明显增加，女性尤为明显[1-3]。反之，T2DM患者的肥胖发病率也明显增高。中国国家糖尿病和代谢性疾病研究组2013年的研究数据表明，与总体人群相 比，T2DM人群肥胖的比例呈近2倍的增加[4]。从这些研究 我们看到肥胖人群患T2DM的风险明显增高，T2DM或血糖 异常者也更容易产生肥胖，并且二者同样都是心血管事件 的高危因素，因此，便引出一个思考：肥胖和T2DM是一个 相似的过程，还是有显著差异，两者的发病过程之间有什么 联系？ 一、肥胖与T2DM的共同起源 1.降糖治疗悖论：降糖同时增加体重：肥胖与T2DM是否存在明确的因果关系？在实际临床工作中，许多肥胖患者并没有T2DM，T2DM患者中也有体重正常者。噻唑烷二酮类药物（TZDs）为过氧化物酶体增殖物激活受体γ（PPAR-γ）的强效激动剂，能够提高胰岛素的敏感性而有效地控制血糖。Kahn等[5]的研究显示：单药治疗情况下，相比于二甲双胍和格列本脲，罗格列酮在4年的时间里可以更好地控制患者的糖化血红蛋白（HbA1c）水平，胰岛素抵抗也明显改善，但同时也显著增加了患者的体重。Holman等[6]研究表明，不管是双相、餐时还是基础胰岛素都可以很好地控制患者的HbA1c、空腹血糖和餐后血糖等，但同时这三种胰岛素也都不同程度地增加了患者的体重。通过TZDs和胰岛素等治疗策略的悖论来看，它们在改善血糖控制的同时却加重了肥胖。另外，Roux-en-Y胃旁路术(RYGB)术后，早期即出现胰岛素抵抗快速显著下降，并且这一改善效应持续到术后1年，但与体重关系不大[7]。减重手术的代谢获益最初认为是术后体重大幅度下降所致。但后续研究表明，在RYGB术后1周，胰岛素敏感性在体重下降之前就已有明显改善，并且有趣的是，对照组肥胖患者在限制热量饮食（同RYGB术后低热量流质饮食）后胰岛素敏感性也明显改善，尽管体重无明显变化[8]。无论是采取低碳水化合物饮食还是低血糖指数饮食，HbA1c的改变均独立于体重的变化[9]。另一些研究也表明，体重降低可能并非是改善血糖和糖尿病并发症所必须的，尽管体重下降更有助于控制血糖[10]。这些研究均提示：肥胖和T2DM之间密切相关，但也存在明确的差异，体重改变和血糖控制并不存在严格意义上的一致，二者可能并不存在明确的因果关系。 2.高热量的摄入可能是肥胖与T2DM的共同起源：越来越多的证据表明减重手术可以显著改善甚至治愈T2DM[11]。减重手术主要通过限制脂肪和碳水化合物的消化和吸收，减少热量摄入，并调节肠道激素水平，从而达到降低体重和改善代谢的目的。而限制热量摄入可以显著改善T2DM患者β细胞功能，减少肝糖生成，提高肝脏和肌肉对胰岛素的敏感性[10,12]。快速的能量负平衡可以逆转胰岛β细胞和肝脏胰岛素抵抗。Lim等[12]给予T2DM患者8周低热量饮食，每周检测其血糖、胰岛素和BMI等指标。结果显示，限制热量摄入后第1周，患者的空腹血糖和胰岛素抵抗即恢复到正常水平，肝糖生成呈现出与空腹血糖同样的快速下降趋势，而肝脏甘油三酯的含量则呈现出与BMI类似的改善趋势。随访至第20周时（干预于第8周结束）受试者的体重较干预后增加明显，而其HbA1c维持稳定。试验中血糖对热量摄入的快速反应以及血糖与BMI改善速率的不一致提示，高热量摄入本身而不是继发的肥胖导致了血糖升高，高热量的摄入可能是肥胖和糖尿病的一个共同起源。 3.肝糖输出量增加是血糖升高的重要原因：肝脏在血糖的调节方面起重要作用，T2DM患者空腹血糖升高和肝糖输出增加密切相关。Mitrakou等[13]发现，口服葡萄糖后，在正常人对照组中，肝脏的内源性葡萄糖产生率快速降低，而在T2DM患者中，肝脏的内源性葡萄糖产生率并没有显著 ·综述· 肥胖与2型糖尿病的共同起源：能量过剩引发肝脏胰岛素抵抗 杨茜邹大进 DOI:10.3760/cma.j.issn.1674-5809.2016.02.012 基金项目：国家自然科学基金项目（81170738） 作者单位：200433上海，第二军医大学长海医院内分泌科本文要点 ?超重和肥胖是2型糖尿病的重要致病因素，目前，其共同的确切发病机制尚不十分清楚 ?肝脏对高能量物质负荷的反应以及肝脏的自我保护机制参与了肥胖与2型糖尿病的发生 ?高碳水化合物通过诱导胰岛素抵抗保护肝脏免于物质负荷过重，肝脏为了阻止无机磷丧失维持肝内磷酸盐稳态并阻止肝内ATP的消耗及免于糖负荷过重导致肝糖不耐受（肝胰岛素抵抗） ?高热量摄入可能是肥胖与2型糖尿病的共同起源