The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with C...The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.展开更多
Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations...Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.展开更多
MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identi...MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from cancer to inflammatory disease to obesity and diabetes. In many cell types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to play a role in some cancers, because mutations in Ras and B-Raf, which can activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2 signaling has also been found in polycystic kidney disease, and serious developmental disorders such as cardio-facio-cutaneous syndrome arise from mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well-differentiated cells and have been linked to long-term potentiation in neurons and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for insulin gene transcription in pancreatic beta cells, which produce insulin in response to increases in circulating glucose to permit efficient glucose utilization and storage in the organism. Nutrients and hormones that induce or repress insulin secretion activate and/or inhibit ERK1/2 in a manner that reflects the secretory demand on beta cells. Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders.展开更多
AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic seve...AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS： Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS： NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 （OR 20.98, 95% CI 3.22-136.62; P 〈 0.001） and visceral fat area 〉 158 cm^2 （OR 18.55, 95% CI 1.60-214.67; P = 0.019） were independent predictors for NASH. Advanced stage of NASH was found in 15 （50%） patients. HOMA-IR 〉 3.5 （OR 23.12, 95% CI 2.00-266.23; P = 0.012） and grading of portal inflammation （OR 7.15, 95% CI 1.63-31.20; P = 0.009） were determined as independent risk factors for advanced stage of NASH. CONCLUSION： Obesity （especially central obesity） and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.展开更多
AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS: We studied the association between DM2 and HCC in a large case-control study that e...AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS: We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC (78.3% males, mean age 68.5 ± 8.9 years) compared with an age and sex matched control group of 490 subjects. RESULTS: Prevalence of DM2 was significantly higher in HCC patients (31.2% vs 12.7%; OR = 3.12, 95% CI: 2.22-4.43) and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents (171.5 vs 118.7 mo). Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049). CONCLUSION: DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.展开更多
基金the Chinese High Tech Programs (863) from the Ministry of Science and Technology (No. 2002BA- 711A08)the National Natural Science Foundation of China (No. 30671155, and 39993420)+1 种基金Grant FMU-RT002 of Program for Innovative Research Team in Science and Technology in Fujian Province Universitythe Science Foundation from the Depart-ment of Education of Fujian Province (No. JA05251, and JB06215).
文摘The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.
文摘Objective: To explore the relationship between the insulin resistance and thedefects or mutations or mutations in insulin receptor (InsR)gene. Methods: Using the single-strandconformation polymorphism(SSCP), mutations and polymorphisms were detected in nine patients withacan-thosis nigricans (AN) and their first degree relatives in exon 17 and 20 of InsR gene. Thepolymorphisms and mutations were confirmed by DNA direct sequencing. Results: Fourteen variant SSCPpat-terns were detected. Direct sequencing revealed seven point mutations and six silentpolymorphisms. Five of the mutations appeared not to be mentioned in the previous literature. Thesemutations were all located within the domain of tyrokinase in InsR. Conclusion: It seem to us thatalmost all the AN patients with severe insulin resistance in this study have mutations in InsRtyrokinase domain.
文摘MAP kinases transduce signals that are involved in a multitude of cellular pathways and functions in response to a variety of ligands and cell stimuli. Aberrant or inappropriate functions of MAPKs have now been identified in diseases ranging from cancer to inflammatory disease to obesity and diabetes. In many cell types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to play a role in some cancers, because mutations in Ras and B-Raf, which can activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2 signaling has also been found in polycystic kidney disease, and serious developmental disorders such as cardio-facio-cutaneous syndrome arise from mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well-differentiated cells and have been linked to long-term potentiation in neurons and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for insulin gene transcription in pancreatic beta cells, which produce insulin in response to increases in circulating glucose to permit efficient glucose utilization and storage in the organism. Nutrients and hormones that induce or repress insulin secretion activate and/or inhibit ERK1/2 in a manner that reflects the secretory demand on beta cells. Disturbances in this and other regulatory pathways may result in the contribution of ERK1/2 to the etiology of certain human disorders.
文摘AIM： To examine whether visceral fat is associated with non-alcoholic steatohepatitis （NASH）, to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS： Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS： NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 （OR 20.98, 95% CI 3.22-136.62; P 〈 0.001） and visceral fat area 〉 158 cm^2 （OR 18.55, 95% CI 1.60-214.67; P = 0.019） were independent predictors for NASH. Advanced stage of NASH was found in 15 （50%） patients. HOMA-IR 〉 3.5 （OR 23.12, 95% CI 2.00-266.23; P = 0.012） and grading of portal inflammation （OR 7.15, 95% CI 1.63-31.20; P = 0.009） were determined as independent risk factors for advanced stage of NASH. CONCLUSION： Obesity （especially central obesity） and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance.
文摘AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS: We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC (78.3% males, mean age 68.5 ± 8.9 years) compared with an age and sex matched control group of 490 subjects. RESULTS: Prevalence of DM2 was significantly higher in HCC patients (31.2% vs 12.7%; OR = 3.12, 95% CI: 2.22-4.43) and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents (171.5 vs 118.7 mo). Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049). CONCLUSION: DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.
