摘要
目的对大庆糖尿病预防研究的参加者进行20年后的随访,比较饮食干预及运动干预对糖尿病预防的长期影响,确定对糖尿病预防最有效的生活方式;分析推迟糖尿病发病时间对全因死亡、心脑血管事件死亡、心脑血管事件和脑中风发生的影响,为对IGT人群进行早期干预推迟糖尿病发病以减少大血管病变提供依据。
方法对参加大庆糖尿病预防研究的576名IGT患者进行随访,调查其生存状态、死亡原因。对生存者进行体格检查(测身高、体重、血压),心电图、OGTT及各项生化检查,并做问卷调查,判定糖尿病、全因死亡、心脑血管事件死亡、心脑血管事件和脑中风等终点事件。比较饮食、运动干预对糖尿病发病的影响,并应用多因素分析探讨推迟糖尿病发病对心脑血管事件及死亡的影响。
结果调整BMI及小组随机因素后,强化干预期间,饮食组、运动组与对照组比较,糖尿病发病风险下降了46%(HR 0.54;95%CI 0.34-0.88)和51%(HR 0.49;95%CI 0.27-0.87);20年随访期间,该风险分别下降了41%(0.59;0.39-0.89,P=0.0152)和47%(0.53:0.33-0.85,P=0.0117);但饮食与运动组间比较无显著差异。将总人群以BMI25 kg/m~2分为两组,在BMI＜25 kg/m~2组,运动组的HR在干预期间和随访期间分别为0.34(95%CI 0.16-0.73,P=0.0076)和0.38(95%CI0.20-0.71,P=0.0041),而饮食与对照组比较及饮食与运动组间比较均无统计学差异。在BMI≥25 kg/m~2组,饮食、运动干预对糖尿病预防在干预期及随访期均有效果,且二者比较无明显差异。调整心血管疾病风险因素后,推迟糖尿病发病5年可使全因死亡下降38%,心脑血管疾病死亡下降26%,心脑血管疾病下降18%,脑中风下降18%。
结论6年的饮食干预和运动干预可预防或推迟糖尿病的发生,其作用可持续至干预后的14年,二种生活方式干预效果相同;在超重肥胖人群,预防糖尿病可采取饮食干预或运动干预;而在非超重人群,采取运动干预似乎效果更佳;推迟糖尿病分别每5年即可使全因死亡及心脑血管疾病死亡率,心脑血管疾病发生率,脑中风发生率有明显的下降。
OBJECTIVES(1) To compare the long-term effect of diet and exercise on prevention of diabetes in people with impaired glucose tolerance in DaQing diabetes study,in order to find which one will be the best option.(2)To Investigate the effect of delaying onset of diabetes on all cause and CVD mortality,incidence of CVD event and stroke in this prediabetes population.
METHODS 576 participants were followed-up for 20 years to assess the long-term effect of diet or exercise intervention.The causes of death,the status of survivors were investigated.Questionnaires were given to all the participants or their proxy.Height,weight,blood pressure were measured,ECG,oral glucose tolerance test and blood biochemical analysis were performed in the survivors.Long-term effect of lifestyle intervention were examed in relation to incidence of diabetes,stroke,first CVD event and mortality.
RESULTS Compared with control participants,those in the diet intervention group and exercise intervention group had 46%(hazard rate ratio[HRR]0.54;95%CI 0.34-0.88) and 51%lower incidence of diabetes(0.49;0.27-0.87)respectively during the active intervention period,their HRR were 0.59(95%CI 0.39-0.89,p=0.0152) and 0.53(0.33-0.85 p=0.0117) over the 20 year period,after controlling for age,BMI and clustering by clinic.There was no significant difference between the diet and exercise group in the incidence of diabetes.In the subgroup with BMI＜25kg/m~2,those in exercise intervention groups had a 66%lower incidence of diabetes(0.34;0.16-0.73) compared with control during the active intervention period and a 62%lower incidence(0.38;0.20-0.71) over the 20 year period.But the effect of the diet intervention was not obvious.In the subgroup with BMI≥25kg/m~2,both the diet intervention and exercise intervention were effective on prevention diabetes during the active intervention period and the 20 year follow-up period.There were no differences between diet and exercise intervention in the two subgroups.After adjustment of age,sex,BMI,blood pressure,smoking at baseline,the risk of all-cause mortality was 38%lower for 5-year increase of delaying diabetes onset,and the risk of stroke,CVD event and mortality were 18%,18%,26%lower respectively for the same increase in the time of delaying of diabetes onset.All these results were statistically significant.
CONCLUSIONS(1) Both the diet and exercise interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention.But the exercise intervention seems better on diabetes prevention in the non-overweight people.(2) There were significant decrease in the risk of all-cause and CVD mortality, incidence of stroke and first CVD event when diabetes onset was delayed for 5 years.
引文
(1)Zimmet P,Alberti KG,Shaw J.Global and societal implications of the diabetes epidemic.Nature 2001;414(6865):782-787.
(2)Pan XR,Yang WY,Li GW,Liu J.Prevalence of diabetes and its risk factors in China,1994.National Diabetes Prevention and Control Cooperative Group.Diabetes Care 1997;20(11):1664-1669.
(3)King H,Aubert RE,Herman WH.Global burden of diabetes,1995-2025:prevalence,numerical estimates,and projections.Diabetes Care 1998;21 (9):1414-1431.
(4)Pan XR,Hu YH,Li GW,Liu PA,Bennett PH,Howard BV.Impaired glucose tolerance and its relationship to ECG-indicated coronary heart disease and risk factors among Chinese.Da Qing IGT and diabetes study.Diabetes Care 1993;16(1):150-156.
(5)Pan XR,Li GW,Hu YH,Wang JX,Yang WY,An ZX et al.Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance.The Da Qing IGT and Diabetes Study.Diabetes Care 1997;20(4):537-544.
(6)Knowler WC,Barrett-Connor E,Fowler SE,Hamman RF,Lachin JM,Walker EA et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med 2002;346(6):393-403.
(7)Tuomilehto J,Lindstrom J,Eriksson JG,Valle TT,Hamalainen H,Ilanne-Parikka P et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med 2001;344(18):1343-1350.
(8)Herman WH,Eastman RC:The effects of treatment on the direct costs of diabetes.Diabetes Care 1998;21 (Suppl.3):C19-C24.
(9)Amos AF,McCarty DJ,Zimmet P:The rising global burden of diabetes and its complications:estimates and projections to the year 2010.Diabet Med 1997;14:SI-85.
(10)International Diabetes Federation.Diabetes Atlas,Third Edition,2006.http://www.eatlas.idf.org/media/ (accessed Aug 4,2008)
(11)Edelstein SL,Knowler WC,Bain RP,AndresR,Barrett-Connor EL,Dowse GK,Haffner SM,Pettitt DJ,Sorkin JD,Muller DC,Collins VR, Hamman RF:Predictors of progression from impaired glucose tolerance to NIDDM:an analysis of six prospective studies.Diabetes 1997,46:701-710.
(12)Gabir MM,Hanson RL,Dabetea D,Imperatore G,Roumain J,Bennett PH,Knowler WC:The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes.Diabetes Care 2000,23:1108-1112.
(13)Stern MP,Williams K,Haffner SM:Identification of persons at high risk for type 2 diabetes mellitus:do we need the oral glucose tolerance test? Ann Intern Med 2002,136:575-581.
(14)Kahn SE:The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes.Diabetologia 2003,46:3-19.
(15)Chan JM,Rimm EB,Colditz GA,et al.Obesity,fat distribution,and weight gain as risk factors for clinical diabetes in men.Diabetes Care 1994,17:961-9.
(16)Colditz GA,Willett WC,Rodnitzky A,et al.Weight gain as a risk factor for clinical diabetes mellitus in women.Ann Intern Med 1995,122:481-6
(17)Hamman RF,Wing RR,Edelstein SL,Lachin JM,Bray GA,Delahanty L,Hoskin M,Kriska AM,Mayer-Davis EJ,Pi-Sunyer X,Regensteiner J,Venditti B,Wylie-Rosett J.Effect of weight loss with lifestyle intervention on risk of diabetes.Diabetes Care.2006,29:2102-7.
(18)Ramachandran A,Snehalatha C,Mary S,et al.The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-l).Diabetologia 2006;49 (2):289-97
(19)Liao D,Asberry PJ,Shofer JB,et al.Improvement of BMI,body composition,and body fat distribution with lifestyle modification in Japanese Americans with impaired glucose tolerance.Diabetes Care.2002;25 (9):1504-10.
(20)Bo S,Ciccone G,Guidi S,et al.Diet or exercise:what is more effective in preventing or reducing metabolic alterations? Eur J Endocrinol.2008 Dec;159(6):685-91.
(21)Petersen AMW & Pedersen BK.The anti-inflammatory effect of exercise.Journal of Applied Physiology 2005;98:1154-1162.
(22)Bruun JM,Helge JW,Richelsen B & Stallknecht B.Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects.American Journal of Physiology.Endocrinology and Metabolism 2006,290:E961-E967.
(23)Church TS,Barlow CE,Earnest CP,Kampert JB,Priest EL & Blair SN.Association between cardiorespiratory fitness and C-reactive protein in men.Arteriosclerosis,Thrombosis,and Vascular Biology 2002,22:1869-1876.
(24)Salmeron J,Manson JE,Stampfer MJ,Colditz GA,Wing AL & Willett WC.Dietary fiber,glycemic load,and risk of non-insulin dependent diabetes mellitus in women.Journal of the American Medical Association 1997,277:472-477.
(25)Kelley DE,Wing R,Buonocore C,Sturis J,Polonsky K,Fitzsimmons M:Relative effects of calorie restriction and weight loss in noninsulin-dependent diabetes mellitus.J Endocrinol Metab 1993,77:1287-1293.
(26)N.Ross R,Dagnone D,Jones P,Smith H,Paddags A,Hudson R & Janssen I.Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men.Annals of Internal Medicine 2000,133:92-103.
(27)Wing RR,Blair EH,Bononi P,Marcus MD,Watanabe R,Bergman RN:Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients.Diabetes Care 1994,17:30-36.
(28)Haskell WL,Lee IM,Pate RR,et al.Physical activity and public health:updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.Med Sci Sports Exerc 2007,39 (8):1423-34
(29)Sigal RJ,Kenny GP,Wasserman DH,et al.Physical activity/exercise and type 2 diabetes:a consensus statement from the American Diabetes Association.Diabetes Care 2006,29(6):1433-8
(30) Geiss LS,Herman WH,Smith PJ:Mortality in non-insulin-dependent diabetes.In Diabetes in America.2nd ed.Bennett PH,Boyko EJ,Cowie CC,Harris MI,Stern MP,Reiber GE,Eds.Bethesda,MD,National Institutes of Health,National Institute of Diabetes and Digestive and Kidney Diseases,1995,p.233-258(NIH publ.no.95-1468)
(31) McEwen LN,Kim C,Haan M,Ghosh D,Lantz PM,Mangione CM,Safford MM,Marrero D,Thompson TJ,Herman WH:Diabetes reporting as a cause of death:results from the Translating Research Into Action for Diabetes(TRIAD) study.Diabetes Care 2006,29:247-253
(32) Morrish NJ,Wang SL,Stevens LK,Fuller JH,Keen H:Mortality and causes of death in the WHO multinational study of vascular disease in diabetes.Diabetologia 2001,44(Suppl.2):S14-S21.
(33) Stamler J,Vaccaro O,Neaton JD,Wenteorth D.Diabetes,other risk factors,and 12-yr cardiovascular morality for men screened in the Multiple Risk Factor intervention Trial.Diabetes Care.1993;16:434-444
(34) Manson JE,Colditz GA,Stampfer MJ,et al.A prospective study study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women,Arch Intern Med.1991,151:1141-1147
(35) Laakso M.Hyperglycemia and cardiovascular disease in type 2diabetes.Diabetes,1999;48:937-942
(36) Chiasson JL,Josse RG,Gormis R,et al.Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomized trial.Lancet,2002,359:2072-2077.
(37) Li GW,Zhang P,Wang JP;et al.The long-term effect of lifestyle intervention to prevent diabetes in the China Da Qing Diabetes Prevention Study:a 20-year follow-up study.Lancet.2008;371:1783-1789.
(38) Haffner SM,Stern MP,Hazuda HP,Mitchell BD,Patterson JK.Cardiovascular risk factors in confirmed prediabetic individuals.JAMA.1990,263:2893-2998
(39)Unwin N,Shaw J,Zimmet P,Alberti KG.Impaired glucose tolerance and impaired fasting glycaemia:the current status on definition and intervention.Diabet Med.2002,19:708-723.
(40)Gerstein HC,Pogue J,Mann JF,Lonn E,Dagenais GR,McQueen M,Yusuf S.The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study:a prospective epidemiological analysis.Diabetologia.2005,48:1749-1755.
(41)Chiasson JL,Josse RG,Gomis R,Hanefeld M,Karasik A,Laakso M.Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance:the STOP-NIDDM trial.JAMA 2003,290:486-94.
(42)DECODE study group:Glucose tolerance and cardiovascular mortality:comparison of fasting and 2-hour diagnostic criteria.Arch Intern Med 2001,161:397-405
(43)Kim NH,Pavkov ME,Looker HC,Nelson RG,Bennett PH,Hanson RL,Curtis JM,Sievers ML,Knowler WC.Plasma glucose regulation and mortality in pima Indians.Diabetes Care.2008,31 (3):488-92.
(44)Hanefeld M,Chiasson JL,Koehler C,et al.Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance.Stroke 2004,35:1073-1078.
(45)Diabetes Prevention Program Research Group:Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Eng J Med.2002;346:393-403.
(46)Diabetes Prevention Program Research Group:Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the diabetes prevention program.Diabetes Care 2005,28:888-894.
(47)Holman RR,Paul SK,Bethel MA,Matthews DR,Neil HA.10-year follow-up of intensive glucose control in type 2 diabetes.N Engl J Med.2008,359 (15):1577-89.
(48)Gaede P,Lund-Andersen H,Parving HH,Pedersen 0.Effect of a multifactorial intervention on mortality in type 2 diabetes.N Engl J Med 2008,358:580-91.
(49) The ADVANCE Collaborative Group.Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med 2008,358:2560-72.
(50) The ACCORD Study Group.Effects of intensive glucose lowering in type 2 diabetes.N Engl J Med 2008;358:2545-59.
(51) Keaney JF Jr,Larson MG,Vasan RS,Wilson PW,Lipinska I,Corey D,Massaro JM,Sutherland P,Vita JA,Benjamin EJ:Obesity and systemic oxidative stress:clinical correlates of oxidative stress in the Framingham study.Arterioscler Thromb Vasc Biol 2003,23:434-439.
(52) Detre KM,Lombardero MS,Brooks MM,Hardison RM,Holubkov R,Sopko G,Frye RL,Chaitman BR,Bypass Angioplasty Revascularization Investigation Investigators:The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction.N Engl J Med 2000,342:989-997.
(1)King H,Aubert RE,Herman WH:Global burden of diabetes,1995-2025:prevalence,numerical estimates,and projections.Diabetes Care 1998,21:1414-1431.
(2)Pan XR,Yang WY,Li GW,Liu J.Prevalence of diabetes and its risk factors in China,1994.National Diabetes Prevention and Control Cooperative Group.Diabetes Care 1997,20(11):1664-1669.
(3)Chiasson JL,Josse RG,Gormis R,et al.Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomized trial.Lancet,2002,359:2072-2077.
(4)Buchanan TA,Xiang AH,Peters RK,et al.Preservation of pancreatic 0-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic Women.Diabetes,2002,51:2796-2803.
(5)Edelstein SL,Knowler WC,Bain RP,AndresR,Barrett-Connor EL,Dowse GK,Haffner SM,Pettitt DJ,Sorkin JD,Muller DC,Collins VR,Hamman RF:Predictors of progression from impaired glucose tolerance to NIDDM:an analysis of six prospective studies.Diabetes,1997,46:701-710.
(6)Gabir MM,Hanson RL,Dabetea D,Imperatore G,Roumain J,Bennett PH,Knowler WC:The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes.Diabetes Care,2000,23:1108-1112.
(7)Stern MP,Williams K,Haffner SM:Identification of persons at high risk for type 2 diabetes mellitus:do we need the oral glucose tolerance test? Ann Intern Med,2002,136:575-581.
(8)Edelstein SL,Knowler WC,Bain RP,et al.Predictors of progression from impaired glucose tolerance to NIDDM:an analysis of six prospective studies.Diabetes 1997,46:701-10
(9)Kahn SE,Prigeon RL,McCulloch DK,Boyko EJ,Bergman RN,Schwartz MW,Neifing JL,Ward WK,Beard JC,Palmer JP:Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects:evidence for a hyperbolic function.Diabetes 1993,42:1663-1672.
(10)Cavaghan MK,Ehrmann DA,Byrne MM,Polonsky KS:Treatment with the oral antidiabetic agent troglitazpne improves beta cell responses to glucose in subjects with impaired glucose tolerance.J Clin Invest 1997,100:530-537.
(11)Ryan EA,Imes S,Liu D,McManus R,Finegood DT,Polonsky KS,Sturis J.Defects in insulin secretion and action in women with a history of gestational diabetes.Diabetes.1995,44:506-512.
(12)Buchanan TA,Xiang AH,Kjos SL,Trigo E,Lee WP,Peters RK:Antepartum predictors of the development of type 2 diabetes in Latino women 11-26 months after pregnancies complicated by gestational diabetes.Diabetes 1999,48:2430-2436.
(13)Larsson H,Ahren B:Islet dysfunction in obese women with impaired glucose tolerance.Metabolism 1996,45:502-509.
(14)Weyer C,Bogardus C,Mott DM,Pratley RE:The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus.J Clin Invest 1999,104:787-794.
(15)Raz I,Eldor R,Cernea S,et al.Diabetes:insulin resistance and derangements in lipid metabolism.Cure through intervention in fat transport and storage.Diabetes Metab Res Rev 2005,21:3-14.
(16)Chandran M,Phillips SA,Ciaraldi T,et al.Adiponectin:more than just another fat cell hormone? Diabetes Care 2003,26:2442-50.
(17)Xu H,Barnes GT,Yang Q,et al.Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.J Clin Invest 2003,112:1821-30.
(18)Natali A,Toschi E,Baldeweg S,et al.Clustering of insulin resistance with vascular dysfunction and low-grade inflammation in type 2 diabetes.Diabetes 2006,55:1133-40.
(19)Matsuzawa Y.Therapy Insight:adipocytokines in metabolic syndrome and related cardiovascular disease.Nat Clin Pract Cardiovasc Med 2006,3:35-42.
(20)Knobler H,Benderly M,Boyko V,et al.Adiponectin and the development of diabetes in patients with coronary artery disease and impaired fasting glucose.Eur J Endocrinol 2006,154:87-92.
(21)Pan XR,Hu YH,Li GW,Liu PA,Bennett PH,Howard BV.Impaired glucose tolerance and its relationship to ECG-indicated coronary heart disease and risk factors among Chinese.Da Qing IGT and diabetes study.Diabetes Care 1993,16:150-156.
(22)Pan XR,Li GW,Hu YH,Wang TX,Yang WY,An ZX et al.Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance.The Da Qing IGT and Diabetes Study.Diabetes Care 1997,20:537-544.
(23)Tuomilehto J,Lindstrom J,Eniksson JG,et al.Prevention of type diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med 2001,344:1343-1350.
(24)Knowlez WC,Barrett-Connor E,Fowter SE,et al.Reduction in the incidence of type 2 diabeteswith lifestyle intervention or metformin.N Engl J Med 2002,346:393-403.
(25)Hamman RF,Wing RR,Edelstein SL,Lachin JM,Bray GA,Delahanty L,Hoskin M,Kriska AM,Mayer-Davis EJ,Pi-Sunyer X,Regensteiner J,Venditti B,Wylie-Rosett J.Effect of weight loss with lifestyle intervention on risk of diabetes.Diabetes Care.2006,29:2102-7.
(26)Chiasson JL,Josse RG,Gormis R,et al.Acarbose for prevention of type 2 diabetes mellitus:the STOP-NIDDM randomized trial.Lancet,2002,359:2072-2077..
(27)Lehmann JM,Moore LB,Smith-Oliver TA,Wilkison W0,Willson TM,Kliewer SA.An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).J Biol Chem.1995,270:12953-6.
(28)Miyazaki Y,Mahankali A,Matsuda M,Mahankali S,Hardies J,Cusi K,Mandarino LJ,DeFronzo RA.Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients.J Clin Endocrinol Metab.2002,87:2784-91.
(29)Knowler WC,Hamman RF,Edelstein SL,et al.Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program.Diabetes,2005,54:1150-6.
(30)Buchanan TA,Xiang AH,Peters RK,et al.Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic Women.Diabetes 2002,51:2796-2803.
(31)Gerstein HC,Yusuf S,Bosch J,et al.Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose:a randomised controlled trial.Lancet,2006,368:1096-105.
(32)Saloranta C,Guitard C,Pecher E,De Pablos-Velascc P,Lahti K,Brunel P,Groop L.Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population.Diabetes Care.2002,25(12):2141-6.
(33)Califf RM,Boolell M,Haffner SM,Bethel MA,McMurray J,Duggal A,Holman RR;NAVIGATOR Study Group.Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance:rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR)Trial.Am Heart J 2008,156(4):623-32.
(34)Torgerson JS,Hauptman J,Boldrin MN,et al.XENical in the prevention of diabetes in obese subjects (XENDOS)study:a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.Diabetes Care,2004,27:155-61.
(35)Scheen AJ.Renin-angiotensin system inhibition prevents type 2 diabetes mellitus.Part 1.A meta-analysis of randomised clinical trials.Diabetes Metab 2004,30:487-96.
(36)Bosch J,Yusuf S,Gerstein HC,et al.Effect of ramipril on the incidence of diabetes,N Engl J Med 2006,355:1551-62.
(37)Scheen AJ.Renin-angiotensin system inhibition prevents type 2 diabetes mellitus.Part 2.Overview of physiological and biochemical mechanisms.Diabetes Metab,2004,30:498-505.
(38)Park H,Hasegawa G,Obayashi H,et al.Relationship between insulin resistance and inflammatory markers and anti-inflammatory effect of losartan in patients with type 2 diabetes and hypertension.Clin Chim Acta 2006,374:129-34.
(39)Sharma AM.The obese patient with diabetes mellitus:from research targets to treatment options.Am J Med 2006,119:S17-23.
(40)Drucker DJ.The biology of incretin hormones.Cell Metab 2006,3:153-65.
(41)Wang Q,Brubaker PL.Glucagon-like peptide-1 treatment delays the onset ef diabetes in8 Week-old db/db mice.Diabetologia 2002,45:1263-73.
(42) Stoffers DA,Desai BM,DeLeon DD,et al.Neonatal exendin-4 prevents the development of diabetes in the intrauterinegrowth retarded rat.Diabetes 2003,52:734-40,
(43) Buse JB,Henry RR,Han J,et al.Effects of exenatide(exendin-4)on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes.Diabetes Care 2004,27:2628-35.
(44) DeFronzo RA,Ratner RE,Han J,et al.Effects of exenatide(exendin-4)on g]ycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes.Diabetes Care 2005,28:1092-100.
(45) Kendall DM,Riddle MC,Rosenstock J,et al.Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea.Diabetes Care 2005,28:1083-91.
(46) Poston WS,Foreyt JP.Sibutramine and the management of obesity.Expert Opin Pharmacother 2004,5:633-42.
(47) Arterburn DE,Crane PK,Veenstra DL.The efficacy and safety of sibutramine for weight loss:a systematic review.Arch Intern Med,2004,164:994-1003.
(48) Vettor R,Serra R,Fabris R,et al.Effect of sibutramine on weight management and metabolic control in type 2 diabetes:a meta-analysis of clinical studies.Diabetes Care 2005,28:942-9.
(49) Scheen AJ,Finer N,Hollander P,et al.Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes:a randomised controlled study.Lancet,2006,368:1660-1672.
(50) Rosenstock J.The potential of rimonabant in prediabetes:Pooled 1-year results from the RIO-Lipids,RIO-Europe and RIO-North American studies[abstract].Presented at the 65th Annual Meeting of the American Diabetes Association,2005.Abstract 13-LB.
(51) Sjostrom L,Lindroos AK,Peltonen M,et al.Lifestyle,diabetes and cardiovascular risk factors 10 years after bariatric surgery.N Engl J Med,2004,351:2683-2693.
(52)Li GW,Zhang P,Wang JP,et al.The long-term effect of lifestyle intervention to prevent diabetes in the China Da Qing Diabetes Prevention Study:a 20-year follow-up study.Lancet.2008,371:1783-1789.
(53)Morrish NJ,Wang SL,Stevens LK,Fuller JH,Keen H:Mortality and causes of death in the WHO multinational study of vascular disease in diabetes.Diabetologia 2001,44 (Suppl.2):S14-S21.
(54)Beckman JA,Creager MA,Libby P:Diabetes and atherosclerosis:epidemiology,pathophysiology,and management.JAMA 2002,287:2570-2581.
(55)Creager MA,Luscher TF,Cosentino F,Beckman JA:Diabetes and vascular disease:pathophysiology,clinical consequences,and medical therapy:part I.Circulation 2003,108:1527-1532.
(56)Morrish NJ,Wang SL,Stevens LK,Fuller JH,Keen H:Mortality and causes of death in the WHO multinational study of vascular disease in diabetes.Diabetologia 2001,44 (Suppl.2):S14-S21.
(57)Stamler J,Vaccaro 0,Neaton JD,Wenteorth D.Diabetes,other risk factors,and 12-yr cardiovascular morality for men screened in the Multiple Risk Factor intervention Trial.Diabetes Care.1993;16:434-444.
(58)Manson JE,Colditz GA,Stampfer MJ,et al.A prospective study study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women.Arch Intern Med.1991,151:1141-1147.
(59)Laakso M.Hyperglycemia and cardiovascular disease in type 2 diabetes.Diabetes,1999,48:937-942.
(60)Saydah SH,Loria CM,Eberhardt MS,Brancati FL:Subclinical states of glucose intolerance and risk of death in the U.S.Diabetes Care,2001,24:447-453.
(61)Consequences of the new diagnostic criteria for diabetes in older men and women:DECODE Study (Diabetes Epidemiology:Collaborative Analysis of Diagnostic Criteria in Europe).Diabetes Care 1999,22:1667-1671.
(62)DECODE Study Group,European Diabetes Epidemiology Group:Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 2003,26:688-696.
(63)DECODE Study Group,European Diabetes Epidemiology Group:Glucose tolerance and cardiovascular mortality:comparison of fasting and 2-hour diagnostic criteria.Arch Intern Med 2001,161:397-405.
(64)Andersson DK,Svardsudd K.Long-term glycemic control relates to mortality in type Ⅱ diabetes.Diabetes Care.1995,18:1534-43.
(65)Wei M,Gaskill SP,Haffner SM,Stern MP.Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality.The San Antonio Heart Study.Diabetes Care.1998,21:1167-72.
(66)Stratton IM,Adler AI,Neil HAW,Matthews DR,Manley SE,Cull CA,Hadden D,Turner RC,Holman RR,the UK Prospective Diabetes Study Group:Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35):prospective observational study.BMJ 2000,321:405-412.
(67)de Vegt F,Dekker JM,Ruhe HG,Stehouwer CDA,Ni jpels GBLM,Heine RJ.Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population:the Hoorn Study.Diabetologia 1999,42:926-931.
(68)Donahue RP,Abbott RD,Reed DM,Yano K.Post challenge glucose concentration and coronary heart disease in men of Japanese ancestry:Honolulu Heart Program.Diabetes 1987,36:689-692.
(69)Lowe LP,Liu K,Greenland P,Metzger BE,Dyer AR,Stamler J:Diabetes,asymptomatic hyperglycemia,and 22-year mortality in black and white men:the Chicago Heart Association Detection Project in Industry study.Diabetes Care 1997,20:163-169.
(70)The DECODE Study Group,the European Diabetes Epidemiology Group:Glucose tolerance and mortality:comparison of WHO and American Diabetes Association diagnostic criteria.Lancet 1999,354:617-621.
(71)Coutinho M,Gerstein HC,Wang Y,Yusuf S:The relationship between glucose and incident cardiovascular events:a meta regression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years.Diabetes Care 1999,22:233-240.
(72)Abdul-Ghani MA,Tripathy D,DeFronzo RA.Contributions of b-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose.Diabetes Care 2006;29:1130-9.
(73)Meyer C,Pimenta W,Woerle HJ,Haeften TV,Szose E,Mitrakou A,et al.Different mechanisms for Impaired fasting Glucose and Impaired postprandial glucose tolerance in humans.Diabetes Care 2006;29:1909-14.
(74)Mitrakou A,Kelley D,Mokan M,Veneman T,Pangburn T,Reilly J,et al.Role of reduced suppression of glucose production and diminished early insulin release in Impaired glucose tolerance.N Engl J Med 1992;326:22-9.
(75)Diwadkar VA,Anderson JW,Bridges SR,Gowri MS,Oelgten PR:Postprandial low density lipoproteins in type 2 diabetes are oxidized more extensively than fasting diabetes and control samples.Proc Soc Exp Biol Med 1999,222:178-184.
(76)Jorgensen RG,Russo L,Mattioli L,Moore WV:Early detection of vasculardysfunction in type I diabetes.Diabetes 1988,37:292-296.
(77)Giugliano D,MarfellaR,Coppola L,Verrazzo G,Acampora R,Giunta R,Nappo F,Lucarelli C,D' Onofrio F:Vascular effects of acute hyperglycemia in humans are reversed by L-arginine:evidence for reduced availability of nitric oxide during hyperglycemia.Circulation 95:1783-1790,1997
(78)Jones RL,Peterson CM:Reduced fibrinogen survival in diabetes mellitus a reversible phenomenon.J Clin Invest 1979,63:485-493.
(79)Ceriello A,Taboga C,Tonutti L,Giacomello R,Stel G,Motz E,Pirisi M:Post-meal coagulation activation in diabetes mellitus:the effect of acarbose.Diabetologia 1996,39:469-473.
(80)Ruosladti E:Integrins.J Clin Invest 1991,187:1-5.
(81)Lopes-Virella MF,VirellaG:Immune mechanism of atherosclerosis in diabetes mellitus (Review).Diabetes 1992,41 (Suppl.2):86-91.
(82)Ceriello A,Falleti E,Motz E,Taboga C,Tonutti L,Ezsol Z,Gonano F,Bartoli E:Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus:the possible role of oxidative stress.Horm Me tab Res 1998,30:-146-149.
(83)Marfe]la R,.Esposito K,Giunta R,Coppola G,De Angelis L,Farzati B,Prolisso G,Giugliano D:Circulating adhesion molecules in humans:role of hyperglycemia and hyperinsulinemia.Circulation 2000,101:2247-2251.
(84)Plutzky J:Inflammation in atherosclerosis and diabetes mellitus.Rev Endocr Me tab Disord 2004,5:255-259.
(85)Nappo F,Esposito K,Cioffi M,Giugliano G,Molinari AM,Paolisso G,Marfella R,Giugliano D:Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients:role of fat and carbohydrate meals.J Am Coll Cardiol 2002,39:1145-1150.
(86)Brownlee M:Biochemistry and molecular cell biology of diabetic complications.Nature 2001,414:813-820.
(87)Ceriello A:New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy.Diabetes Care 2003,26:1589-1596.
(88)Beckman JS,Koppenol WH:Nitric oxide,superoxide,and peroxynitrite:the good,the bad,and ugly.Am J Physiol 1996,271:.C1424-C1437.
(89)Shishehbor MH,Aviles RJ,Brennan ML,Fu X,Goormastic M,Pearce GL,Gokce N,Keaney JF Jr,Penn MS,Sprecher DL,Vita JA,Hazen SL;Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy.JAMA 2003,289:1675-1680.
(90)Title LM,Cummings PM,Giddens K,Nassar BA:Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes:a effect prevented by vitamin C and E.J Am Coll Cardiol 2000,36:2185-2191.
(91)Beckman JA,Goldfine AB,Gordon MB,Creager MA:Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans.Circulation 2001,103:1618-1623.
(92)Chiasson JL,Josse RG,Gomis R,Hanefeld M,Karasik A,Laakso M,the STOP-NIDDM Trial Research Group:Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance:the STOP-NIDDM trial.JAMA 2003,290:486-494.
(93)Hanefeld M,Chiasson JL,Koehler C,Henkel E,Schaper F,Temelkcva-Kurktschiev T:Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance.Stroke 2004,35:1073-1078.
(94)Hanefeld M,Cagatay M,Petrowitsch T,Neuser D,Petzinna D,Rupp M:Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients:meta-analysis of seven long-term studies.Eur Heart J 2004,25:10.-16.
(95)Esposito K,GiuglianoD,Nappo F,MarfellaR:Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus.Circulation 2004,29:2978-2984.
(96)McGarry JD.What if Minkowski had been ageusic? An alternative angle on diabetes.Science 1992,258:766-70.
(97)Ginsberg HN.REVIEW:efficacy and mechanisms of action of statins in the treatment of diabetic dyslipidemia.J Clin Endocrinol Metab 2006,91:383-92.
(98)Adiels M,Boren J,Caslake M J,et al.Overproduction of VLDLl driven by hyperglycemia is a dominant feature of diabetic dyslipidemia.Arterioscler Thromb Vase Biol 2005,25:1697-703.
(99)Sparks JD,Sparks CE.Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion.Biochim Biophys Acta 1994,1215:9-32.
(100)Bansal S,Buring JE,Rifai N,et al.Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.JAMA 2007,298:309-16.
(101)Nordestgaard BG,BennM,Schnohr P,et al.Nonfasting triglycerides and risk of myocardial infarction,ischemic heart disease,and death in men and women.JAMA 2007,298:299-308.
(102)Sattar N,Williams K,Sniderman AD,et al.Comparison of the associations of apolipoprotein B and non-high-density lipoprotein cholesterol with other cardiovascular risk factors in patients with the metabolic syndrome in the Insulin Resistance Atherosclerosis Study.Circulation 2004,110:2687-93.
(103)Rashid S,Watanabe T,Sakaue T,et al.Mechanisms of HDL lowering in insulin resistant,hypertriglyceridemic states:the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity.Clin Biochem 2003,36:421-9.
(104)Lau DC,DhillonB,Yan H,et al.Adipokines:molecular links between obesity and atheroslcerosis.Am J Physiol Heart Circ Physiol 2005,288:H2031-41.
(105)Roytblat L,Rachinsky M,Fisher A,et al.Raised interleukin-6 levels in obese patients.Obes Res 2000,8:673-5.
(106)Hotamisligil GS,Arner P,Caro JF,et al.Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance.J Clin Invest 1995,95:2409-15.
(107)Esposito K,Pontillo A,Di Palo C,et al.Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women:a randomized trial.JAMA 2003,289:1799-804.
(108)Festa A,D' Agostino R Jr,Tracy RP,et al.Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes:the Insulin Resistance Atherosclerosis Study.Diabetes 2002,51:1131-7.
(109)Christiansen T,Richelsen B,Bruun JM.Monocyte chemoattractant protein-1 is produced in isolated adipocytes,associated with adiposity and reduced after weight loss in morbid obese subjects.Int J Obes (Lond)2005,29:146-50.
(110)J.Amar,L.Perez,R.Burcelin,and B.Chamontin,“Arteries,inflammation and insulin resistance,” Journal of Hypertension,2006,24:S18-S20.
(111)P.Theuma and V.A.Fonseca,“Inflammation,insulin resistance,and atherosclerosis,“ Metabolic Syndrome and Related Disorders,2004,2:105-113
(112)F.Montecucco,G.Bianchi,M.Bertolotto,G.Viviani,F.Dallegri,and L.Ottonello,“Insulin primes human neutrophils for CCL3-induced migration:crucial role for JNK 1/2,”Annals of the New York Academy of Sciences,2006,1090:399-407.
(113) K.Kappert,H.Meyborg,M.Clemenz,et al.,"Insulin facilitates monocyte migration:a possible link to tissue inflammation in insulin-resistance," Biochemical and Biophysical Research Communications,2008,365:503-508.
(114) C.K.Roberts,D.Won,S.Pruthi,et al.,"Effect of a short term diet and exercise intervention on oxidative stress,inflammation,MMP-9,and monocyte chemotactic activity in men with metabolic syndrome factors," Journal of Applied Physiology,2006,100:1657-1665.
(115) B.Glowin ska-Olszewska and M.Urban,"Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1in obese children and adolescents," Metabolism,2007,56:799-805.
(116) G.Boden,W.Song,L.Pashko,and K.Kresge,"In vivo effects of insulin and free fatty acids on matrix metalloproteinases in rat aorta," Diabetes 2008,57:476-483.
(117) P.J.Grant,"The genetics of atherothrombotic disorders:a clinician' s view," Journal of Thrombosis and Haemostasis 2003,1:1381-1390.
(118) G.Anfossi,I.Russo,and M.Trovati,"Platelet resistance to the anti-aggregating agents in the insulin resistant states,"Current Diabetes Reviews 2006,2:409-430.
(119) Dormandy JA,Charbonnel B,Eckland DJ,et al.PROactive investigators.Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study(PROspective pioglitAzone Clinical Trial In macroVascular Events):a randomised controlled trial.Lancet,2005,366:1279-89.
(120) Nissen SE,Wolski K.Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.N Engl J Med 2007,356:2457-71.