Diagnosis, Follow-up Study And Pioglitazone Intervention In Metabolic Syndrome (MS)

The term metabolic syndrome (MS) refers to a cluster of cardiovascularrisk factors and it has become a hot spot around the world. During the pastdecade, there have been various attempts to standardize the definition of themetabolic syndrome as a diagnostic category, with several institutionsproposing various criteria. The definitions of the metabolic syndrome thathave most often been used in the literature were proposed by the World HealthOrganization (WHO) and the National Cholesterol Education Program's AdultTreatment PanelⅢ(ATPⅢ). The Chinese Diabetes Society (CDS) proposeda definition of the metabolic syndrome according to the research in Chinesepeople in 2004. However, efforts continue to integrate the individual metabolicsyndrome traits into an overall diagnosis and in 2005 the InternationalDiabetes Federation (IDF) established a worldwide consensus definition of themetabolic syndrome. Still this consensus definition of the metabolic syndromewill not be the final definition and further studies are needed to confirm itsvalue when used in Chinese people. Thus we compared the four workingdefinitions of the metabolic syndrome in the same population to investigatethe difference of the underlying etiology of the metabolic syndrome amongthese definitions. Obesity and abnormal glucose metabolism are two important elements inthe metabolic syndrome and strong predictors of incident metabolic syndrome.With the current obesity and type 2 diabetes (T2DM) epidemic, one wouldexpect a prevalence increase in the metabolic syndrome. Although mostinvestigations did report the increased trend of the prevalence of the metabolicsyndrome year by year, discrepancies still existed in the reports. Until now, nodata are available on the trend of the prevalence of the metabolic syndrome inChina. For this reason we performed a follow-up study in the same naturalpopulation and intended to investigate the features of the changes of themetabolic syndrome and its components.At present, no authoritative and integrative guideline on the managementof the metabolic syndrome. Thiazolidinediones have multiple effects on thecomponents of the metabolic syndrome such as increasing insulin sensitivity,improving the metabolism of glucose and blood lipid, ameliorating obesityand decreasing blood pressure. No well-designed experiments are available onthe therapy of metabolic syndrome with thiazolidiones in China at present. Wetherefore made an open, parallel randomized trial and aimed at investigatingthe effects of pioglitazone on the metabolic syndrome and its components inmetabolic syndrome patients with T2DM on the basis of lifestyle change.In summary, we examined the diagnosis, tumover and medicalintervention of the metabolic syndrome in this report. The protocol was asfollow: (1) Comparison of the application of the four working definitions of metabolic syndrome in male medical examinees; (2) Two-year follow-upstudy of the changes of the metabolic syndrome in medical examinees; (3)Metabolic effects of pioglitazone in metabolic syndrome patients with T2DM. Part 1 Comparison of the Application of the Four Working Definitionsof Metabolic Syndrome in male Medical ExamineesOBJECTIVE: To compare the prevalence of the metabolic syndrome(MS) by four working definitions.DESIGN: Cross-sectional study.METHODS: MS was diagnosed in 739 medical examinees by the fourworking definitions respectively: one proposed by the World HealthOrganization (WHO), one by the Third Report of the National CholesterolEducation Program Expert Panel on Detection, Evaluation, and Treatment ofHigh Blood Cholesterol in Adults (Adult Treatment PanelⅢ[ATPⅢ]), oneby the Chinese Diabetes Society (CDS) and one by International DiabetesFederation(IDF). Then the prevalences of MS detected by the four workingdefinitions were compared among each other.RESULTS: (1) Among 739 participants the prevalence of MS was37.5% using WHO definition, 11.6% using ATPⅢdefinition, 24.8% usingCDS definition and 23.4% using IDF definition. (2) Among all the testee64.1% were classified as either having or not having the metabolic syndromeunder the four definitions. The agreement in the diagnosis of MS using WHOdefinition and ATPⅢdefinition was 72.8%, 82.7% using WHO and CDSdefinitions, 78.1% using WHO and IDF definitions, 82.3% using ATPⅢandCDS definitions, 80.6% using ATPⅢand IDF definitions, and 85.1% using CDS and IDF definitions. (3) The fasting insulin and insulin resistance index(HOMA-IR) were both significantly higher in MS subjects than that innon-MS subjects. (4) The prevalences of hypertention were the highest amongall the components in the four definitions respectively. The prevalence ofmicroalbuminuria was the lowest among that of all the components in WHOdefinition while central obesity had the lowest prevalence in ATPⅢdefinition.(5) The detection rate of abnormal glucose metabolism was the lowestaccording to ATPⅢdefinition (all P＜0.001, compared with other threedefinitions). More patients with hypertention could be detected by ATPⅢandIDF definitions than by WHO and CDS definitions (P＜0.001 for all thecomparisons).There were no differences of the detection rates of abnormalserum lipid among the four definitions. As to the detection of obesity, WHOdefinition could achieve the highest detection rate which was not significantlyhigher than that by CDS definition (P=0.131) whereas ATPⅢdefinition hadthe lowest one (P＜0.001 for all the comparisons).CONCLUSIONS: (1) The prevalences of metabolic syndrome in thenatural male population were 11.6%～37.5%。(2) Although there was a highconcordance among the four working definitions for metabolic syndrome,differences in the prevalences of metabolic syndrome in the same populationstill existed. Part 2 Two-Year Follow-up Study of the Changes of the MetabolicSyndrome in Medical ExamineesOBJECTIVE: To evaluate the changes in the features and componentsof the metabolic syndrome (MS) during the two-year follow-up study in 430medical examinees. Definitions by WHO, ATPⅢ, CDS, and IDF are used todetermine metabolic syndrome respectively.DESIGN: Prospective cohort study.METHODS: Health examinations were carried out in the employees of acollege in 2003 and 2005 respectively. Baseline data are from 2003, andfollow-up data from 2005. A total of 430 subjects were included in the study,who participated in both health examinations and had the complete medicaldata. WHO, ATPⅢ, CDS and IDF definitions for Metabolic Syndrome wereused to compare the changes in the features and components of the metabolicsyndrome in all subjects.RESULTS: (1) Among all 430 subjects, four working definitions (WHO,ATPⅢ, CDS and IDF) for MS were used to diagnose MS and its components.Compared with the baseline, the prevalences of hyperglycemia by all fourworking definitions significantly increased in 2005 (51.2% vs 27.9%, 38.1%vs 17.9%, 51.2% vs 27.9%, 64.4% vs 35.3%, respectively; P=0.000 for allthe comparisons). The prevalences of MS detected by CDS and ATPⅢdefinitions were both kept rising during follow-up (30.2% vs 25.3%,P=0.019; 16.0% vs 11.9%, P=0.028). The prevalences of MS determined either by WHO or by IDF definitions didn't change significantly during thetwo years (P=0.142, P=0.073). Similarly, we compared the changes of theprevalences of hyper-glycemia and MS according to the four workingdefinitions among 310 subjects who were normoglycemic at baseline and gotthe same results. (2) Waist circumference, diastolic blood pressure, serumtriglyceride, serum total cholesterol, fasting insulin and HOMA-IR alldecreased significantly after 2-year follow-up (P＜0.05 for all thecomparisons). HOMA-IS was also lower in 2005 than baseline afteradjustment for insulin resistance (P＜0.001). The fasting plasma glucose,postprandial plasma glucose and serum low density lipoprotein levels were allhigher than the baseline (P＜0.05 for all the comparisons). (3) The fastingplasma glucose and postprandial plasma glucose were higher in elderly people(equal to or more than 60 years of age) than in younger ones (P=0.000 for allthe comparisons). The plasma glucose levels all increased during thefollow-up in all people no matter young or old (P=0.000 for all thecomparisons). The islet function in the elderly people was lower than that inyounger people, and islet functions decreased during the follow-up in allpeople (P=0.000 for all the comparisons). (4) Among the subjects who tookactive exercises, waist circumference, diastolic blood pressure, serumtriglyceride levels and HOMA-IR were all significantly lower in follow-upthan the baseline (P＜0.001, 0.014, 0.008, 0.000, respectively).CONCLUSIONS: (1) Both prevalences of MS detected by either CDS or ATPⅢdefinition increased after follow-up. (2) Islet function decreasedwhile blood glucose increased with age, resulting the higher prevalence of MS.(3) Intensive lifestyle intervention could decrease waist circumference, lowerdiastolic blood pressure and serum triglyceride and improve insulin sensitivityand finally favour the control of MS. Part 3 Metabolic Effects of Pioglitazone in Metabolic SyndromePatients with Type 2 DiabetesOBJECTIVE: To evaluate the effects of pioglitazone on metabolicsyndrome and its component parameters.DESIGN: Randomized, open, controlled clinical trial.METHODS: Type 2 Diabetic Patients were enrolled if they met theadjusted WHO definition of MS (criterium of obesity was defined as WHR＞0.9(male) or＞0.85 (female) and/or BMI≥25kg/m~2; microalbuminuria wasnot included in the definition). Seventy-eight patients were enrolled. Theywere randomized to receive oral pioglitazone (30 mg once daily) on the basisof the original regimen for 6 months. Thus we divided the patients into controlgroup (keeping on the original regimen, n=39) and trial group (pluspioglitazone, n=39). All the patients were required to carry out diet control andproper exercises for at least 3 months before the study. All the patients wererequired to receive a fixed doses of all the agents for hyperglycemia,hypertension or abnormal serum lipoproteins and keep the lifestyle as beforeduring the 6 months' observation. Blood was drawn every 3 months todetermine fasting plasma glucose and insulin, 2-h plasma glucose after taking75g glucose, glycosylated hemoglobin(HbAlc) and serum lipoproteins.HOMA-IS and HOMA-IR were used to assess the islet function and insulinresistance respectively. Additionally, retrospective studies were performed by analyzing the patients according to CDS and IDF definitions. Patients of MSdetected by CDS and IDF definitions respectively were screened out andcomparisons were made to find out the effects of pioglitazone on MS and itscomponents.RESULTS: (1) Comparisons among 75 patients who met the adjustedWHO definition:①There was no difference in WHR between the two groups.But WHR had a tendency to decrease during the observation in the trial groupand WHR at the second and third follow-up were both lower than that atbaseline (P=0.019, 0.009 respectively).②Plasma glucose did not changeduring the study in the control group (P＞0.05). Fasting plasma glucosedecreased to the nadir at the second follow-up and at the same time the fastingplasma glucose was lower in the trial group than that in the control group (P=0.027). As to 2-h plasma glucose, it reached the nadir at the second follow-upand the glucose levels during the observation were both lower than that atbaseline (P＜0.001 for both comparisons). The level of HbAlc in the trialgroup was lower than that in the control group at the end of the study(P=0.003).③There was no change of insulin resistance during the follow-upin the control group. And insulin sensitivity was higher in the trial group thanthat in the control group (P＜0.05). Insulin resistance began to improve at thesecond follow-up and the improvement retained till the end of the study in thetrial group. After adjustment for insulin resistance, there was no difference inthe islet function between the two groups and no difference during the follow-up in both groups (P＞0.05 for all the comparisons).④The levels ofdiastolic blood pressure during the follow-up were higher than that at baselinein the control group (P＜0.05 for both comparisons). But there was a tendencyto decrease during the follow-up in the trial group and the level at the end ofthe study was lower than that at baseline (P=0.015) and that at the secondfollow-up (P=0.027).⑤TG tended to decrease during the follow-up in thetrial group (P=0.098, 0.088 respectively). The levels of HDL-c during thefollow-up were higher than that at baseline (P=0.001, 0.010 respectively). (2)All the 75 patients met the IDF definition, thus the effect of pioglitazone onMS and its components among these patients were the same as the resultsabove. (3) Among all the participants, 63 patients met the CDS definition.Similar results were achieved.CONCLUSIONS: Treatment with pioglitazone led to positivemetabolic effects in metabolic syndrome patients with type 2 diabetes.