Pedpheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diab...Pedpheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.展开更多
Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features ...Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.展开更多
AIM: To characterize changes in ghrelin levels in response to oral glucose tolerance test (OGTT) and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese childr...AIM: To characterize changes in ghrelin levels in response to oral glucose tolerance test (OGTT) and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner Ⅰ and Ⅱ stage with insulin resistance. METHODS: 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender: boys of Tanner Ⅰ (fir- Ⅰ ), boys of Tanner Ⅱ(BT-Ⅱ ), girls of Tanner Ⅰ (GT- Ⅰ ), girls of Tanner Ⅱ (GT-Ⅱ). Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 rain following OGTT. The control children with normal BMI were divided into control boys of Tanner Ⅰ (CBT- Ⅰ, n = 6), control boys of Tanner Ⅱ (CBT-Ⅱ, n = 5), control girls of Tanner Ⅰ (CGT- Ⅰ, n = 6), control girls of Tanner Ⅱ (CGT-Ⅱ, n = 5). Fasting serum ghrelin levels were analyzed. RESULTS: Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage (CGT- Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT- Ⅰ vs CBT- Ⅱ t = -4.794, P = 0.001). Basal ghrelin levels in fir-Ⅱ decreased more significantly than that in BT- Ⅰ group (t = 2.547, P = 0.029). Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT- Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in fir- Ⅰ (r = 0.898, P = 0.015). There wasn't a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance. CONCLUSION: In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance and insulin sensitivity.展开更多
AIM: To investigate the effects of different methylenetetrahydrofolate reductase(MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are co...AIM: To investigate the effects of different methylenetetrahydrofolate reductase(MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial.METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677 T and A1298 C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677 T is present independently of the negative effects of left ventricular hypertrophy, increased IntraRenal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.展开更多
AIM: To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents. METHODS: Transversal observational study included asymptomatic ado...AIM: To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents. METHODS: Transversal observational study included asymptomatic adolescents with central obesity from private and public schools in Salvador-Bahia, northeastern Brazil. The children answered a questionnaire that in- cluded age, gender, race, and medical history, and were submitted to a complete physical exam and abdominal ultrasound. Biochemical exams included: ALT, AST, GGT, C reactive protein (CRP), fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD included: the presence of steatosis in ultrasound and/or high level of ALT, negative or occasional historic of intake of alcohol (4 140 g/wk), negative investigation for hepatitis A, B, C, auto-immune hepatitis, Wilson disease and hemochro-matosis.RESULTS: From October, 2005 to October, 2006, the study included 1801 subjects between 11 and 18 years of age and a mean age of 13.7± 2.0 years. One hun- dred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%, most of whom were male and white. Insulin resistance (IR) was observed in 22.9% of them and had positive correlations with ALT and GGT (P 〈 0.05). Elevated CRP was observed in 6.9% of the cases; however, it was not associated with WC, IR or liver enzymes. CONCLUSION: The prevalence of NAFLD in Brazilian adolescents was low. The ethnicity may have influence this frequency in the population studied, which had a large proportion of African descendents.展开更多
AIM: To explore the association of serum insulin, insulin resistance, and β-cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We used a community-based study conducted between 1991 and 1993 ...AIM: To explore the association of serum insulin, insulin resistance, and β-cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We used a community-based study conducted between 1991 and 1993 in Kinmen, Taiwan to identify type 2 diabetics. A screening program for GSD was performed in 2001 by a panel of specialists who employed real-time ultrasound sonography to examine the abdominal region after the patient had fasted for at least 8 h. Screening was conducted in 2001 on 848 patients diagnosed with type 2 diabetes. The HOMA method was used to compare the profile differences for insulin resistance (HOMA IR) and β-cell dysfunction (HOMA β-cell). RESULTS: We studied 440 type 2 diabetics who attended sonography check-ups. After excluding eight insulin-treated diabetics, the prevalence of GSD among the remaining 432 was 13.9% (26/187) among males and 14.7% (36/245) among females. After adjustment for other GSD-associated risk factors in addition to age and obesity, GSD risk increased among females with levels of serum insulin [4th vs 1st quartile odds ratios (OR) = 4.46 (95%CI: 1.71-11.66)] and HOMA IR [4th vs 1st quartile OR = 4.46 (95%CI: 1.71-11.66)]. Better HOMA β-cell function was significantly related to decreased risk of GSD [4th vs 1st quartile OR = 0.16 (95%CI: 0.03-1.70)]. Among males, age and central obesity were the most significant risk factors for GSD. No association of GSD with serum insulin, HOMA IR, and HOMA β-cell was observed among males. CONCLUSION: Serum insulin, insulin resistance, and β-cell dysfunction are risk factors for GSD in females, but not males with type 2 diabetes.展开更多
AIM: To identify the anthropometric, metabolic and mood state in hepatitis C virus (HCV)-infected patients from the west of Mexico and to evaluate the effect of 13reathwalk (13W), a combination of walking, synchr...AIM: To identify the anthropometric, metabolic and mood state in hepatitis C virus (HCV)-infected patients from the west of Mexico and to evaluate the effect of 13reathwalk (13W), a combination of walking, synchronized breathing and focussed attention, on those patients. METHODS: In an experimental study, 17 patients with serological and molecular diagnosis of HCV, not receiving pharmacological treatment, were studied. One hour sessions of 13W were practiced 3 times at week for six months. Body composition was assessed by electric impedance. Biochemical profiles and insulin resistance (IR) risk was assessed by conventional methods. Mood state was evaluated with specific and open questions at the beginning and at the end of the program. RESULTS: Seventy percent of patients were overweight or obese, and 77% of the patients presented with IR at the beginning of the study. Improvements were observed at the 3^rd mo, and statistically significant differences were recorded at the 6^th mo using the fitness score (76 vs 83, P 〈 0.01), in alanine aminotransferase (ALT)(106±93 U/L vs 59 ± 32 U/L, P 〈 0.01), total bilirubin (0.09 ± 1 mg/dL vs 0.62 ± 0.2 mg/dL, P 〈 0.01), ALT/ AST ratio (1.04 vs 0.70, P 〈 0.01), triglycerides (165 ± 86 mg/dL vs 124 ± 49 mg/dL, P 〈 0.01) and the IR risk (4.0 vs 2.7). Most patients (88%) indicated to feel better at the end of BW (P 〈 0.01).CONCLUSION: Breathwalk has an important effect on body composition, lipid profile and liver enzymes. It is also easy, inexpensive and has a beneficial effect on metabolic and mood state in HCV patients.展开更多
Dimethylarginine dimethylaminohydrolase 1(DDAH1)is an important regulator of plasma asymmetric dimethylarginine(ADMA)levels,which are associated with insulin resistance in patients with nonalcoholic fatty liver diseas...Dimethylarginine dimethylaminohydrolase 1(DDAH1)is an important regulator of plasma asymmetric dimethylarginine(ADMA)levels,which are associated with insulin resistance in patients with nonalcoholic fatty liver disease(NAFLD).To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD,we used hepatocyte-specific Ddah1-knockout mice(Ddah1HKO)to examine the progress of high-fat diet(HFD)-induced NAFLD.Compared to diet-matched flox/flox littermates(Ddah1f/f),Ddah1HKO mice exhibited higher serum ADMA levels.After HFD feeding for 16 weeks,Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice.On the contrary,overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice.RNA-seq analysis showed that DDAH1 affects NF-kB signaling,lipid metabolic processes,and immune system processes in fatty livers.Furthermore,DDAH1 reduces S100 calcium-binding protein A11(S100A11)possibly via NF-kB,JNK and oxidative stress-dependent manner in fatty livers.Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice.In summary,our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice.Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.展开更多
Objective: To investigate the expression pattern of resistin (RSTN) in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury (TBI). Methods: Seventy-eight SD rats were ...Objective: To investigate the expression pattern of resistin (RSTN) in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury (TBI). Methods: Seventy-eight SD rats were randomly divided into traumatic group (n=36), RSTN group (n=36) and sham operation group (n=6). Fluid percussion TBI model was developed in traumatic and RSTN groups and the latter received additional 1 mg RSTN antibody treatment for each rat. At respectively 12 h, 24 h, 72 h, 1 w, 2 w, and 4 w after operation, venous blood was collected and the right hind leg skeletal muscle tissue was sampled. We used real-time PCR to determine mRNA expression of RSTN in skeletal muscles, western blot to determine RSTN protein expression and ELISA to assess serum insulin as well as fasting blood glucose (FBG) levels. Calculation of the quantitative insulin sensitivity check index (Q value) was also conducted. The above mentioned indicators and their correction were statistically analyzed. Results: Compared with sham operation group, the RSTN expression in the skeletal muscle as well as serum insulin and FBG levels revealed significant elevation (P〈0.05), and reduced Q value (P〈0.05) in traumatic group. Single factor linear correlation analysis showed a significant negative correlation between RSTN expression and Q values (P〈0.001) in traumatic group. Conclusion: The expression of RSTN has been greatly increased in the muscular tissue of TBI rats and it was closely related to the index of glycometabolism. RSTN may play an important role in the process of insulin resistance after TBI.展开更多
Objective To analyze the efficacy and safety of drugs on reverse of atypical endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). Methods Seventeen patients with PCOS complicated by atypical en...Objective To analyze the efficacy and safety of drugs on reverse of atypical endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). Methods Seventeen patients with PCOS complicated by atypical endometrial hyperplasia (9 patients who were treated with progestin but not reversed were considered as group A; 8 patients who were untreated were considered as group B) were retrospectively analyzed Both groups received oral glucose tolerance test (OGTT) and insulin release test, to check whether the patients had insulin resistance (IR) or hyperinsulinemia. The 17 patients were treated with oral contraceptives combined with metformin. Results After the 17 patients with PCOS complicated by IR and hyperinsulinemia received drug treatment for 3 -6 cycles, atypical endometrial hyperplasia was success- fully reversed Conclusion Oral contraceptives combined with metformin is a clinically practical and effective method for treatment of PCOS complicated by atypical insulin-resistant endometrial hyperplasia.展开更多
基金Supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases, No. DK067248
文摘Pedpheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.
基金Supported by Department of Science and Technology,Government of India to Iqra Hameed,No.Wos-A LS 509/2012
文摘Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.
基金Supported by Research Award (2005c24001) from Department of Science and Technology, Zhejiang Province, China
文摘AIM: To characterize changes in ghrelin levels in response to oral glucose tolerance test (OGTT) and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner Ⅰ and Ⅱ stage with insulin resistance. METHODS: 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender: boys of Tanner Ⅰ (fir- Ⅰ ), boys of Tanner Ⅱ(BT-Ⅱ ), girls of Tanner Ⅰ (GT- Ⅰ ), girls of Tanner Ⅱ (GT-Ⅱ). Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 rain following OGTT. The control children with normal BMI were divided into control boys of Tanner Ⅰ (CBT- Ⅰ, n = 6), control boys of Tanner Ⅱ (CBT-Ⅱ, n = 5), control girls of Tanner Ⅰ (CGT- Ⅰ, n = 6), control girls of Tanner Ⅱ (CGT-Ⅱ, n = 5). Fasting serum ghrelin levels were analyzed. RESULTS: Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage (CGT- Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT- Ⅰ vs CBT- Ⅱ t = -4.794, P = 0.001). Basal ghrelin levels in fir-Ⅱ decreased more significantly than that in BT- Ⅰ group (t = 2.547, P = 0.029). Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT- Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in fir- Ⅰ (r = 0.898, P = 0.015). There wasn't a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance. CONCLUSION: In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance and insulin sensitivity.
文摘AIM: To investigate the effects of different methylenetetrahydrofolate reductase(MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial.METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677 T and A1298 C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677 T is present independently of the negative effects of left ventricular hypertrophy, increased IntraRenal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.
基金Supported by Fundao de Amparo a Pesquisa do Estado da Bahia
文摘AIM: To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease (NAFLD) among asymptomatic Brazilian adolescents. METHODS: Transversal observational study included asymptomatic adolescents with central obesity from private and public schools in Salvador-Bahia, northeastern Brazil. The children answered a questionnaire that in- cluded age, gender, race, and medical history, and were submitted to a complete physical exam and abdominal ultrasound. Biochemical exams included: ALT, AST, GGT, C reactive protein (CRP), fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD included: the presence of steatosis in ultrasound and/or high level of ALT, negative or occasional historic of intake of alcohol (4 140 g/wk), negative investigation for hepatitis A, B, C, auto-immune hepatitis, Wilson disease and hemochro-matosis.RESULTS: From October, 2005 to October, 2006, the study included 1801 subjects between 11 and 18 years of age and a mean age of 13.7± 2.0 years. One hun- dred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%, most of whom were male and white. Insulin resistance (IR) was observed in 22.9% of them and had positive correlations with ALT and GGT (P 〈 0.05). Elevated CRP was observed in 6.9% of the cases; however, it was not associated with WC, IR or liver enzymes. CONCLUSION: The prevalence of NAFLD in Brazilian adolescents was low. The ethnicity may have influence this frequency in the population studied, which had a large proportion of African descendents.
基金Supported by the grants from the National Science Council, Nos.NSC-91-2320-B-010-102 and NSC-92-2320-B-010-102
文摘AIM: To explore the association of serum insulin, insulin resistance, and β-cell dysfunction with gallstone disease (GSD) in type 2 diabetics. METHODS: We used a community-based study conducted between 1991 and 1993 in Kinmen, Taiwan to identify type 2 diabetics. A screening program for GSD was performed in 2001 by a panel of specialists who employed real-time ultrasound sonography to examine the abdominal region after the patient had fasted for at least 8 h. Screening was conducted in 2001 on 848 patients diagnosed with type 2 diabetes. The HOMA method was used to compare the profile differences for insulin resistance (HOMA IR) and β-cell dysfunction (HOMA β-cell). RESULTS: We studied 440 type 2 diabetics who attended sonography check-ups. After excluding eight insulin-treated diabetics, the prevalence of GSD among the remaining 432 was 13.9% (26/187) among males and 14.7% (36/245) among females. After adjustment for other GSD-associated risk factors in addition to age and obesity, GSD risk increased among females with levels of serum insulin [4th vs 1st quartile odds ratios (OR) = 4.46 (95%CI: 1.71-11.66)] and HOMA IR [4th vs 1st quartile OR = 4.46 (95%CI: 1.71-11.66)]. Better HOMA β-cell function was significantly related to decreased risk of GSD [4th vs 1st quartile OR = 0.16 (95%CI: 0.03-1.70)]. Among males, age and central obesity were the most significant risk factors for GSD. No association of GSD with serum insulin, HOMA IR, and HOMA β-cell was observed among males. CONCLUSION: Serum insulin, insulin resistance, and β-cell dysfunction are risk factors for GSD in females, but not males with type 2 diabetes.
文摘AIM: To identify the anthropometric, metabolic and mood state in hepatitis C virus (HCV)-infected patients from the west of Mexico and to evaluate the effect of 13reathwalk (13W), a combination of walking, synchronized breathing and focussed attention, on those patients. METHODS: In an experimental study, 17 patients with serological and molecular diagnosis of HCV, not receiving pharmacological treatment, were studied. One hour sessions of 13W were practiced 3 times at week for six months. Body composition was assessed by electric impedance. Biochemical profiles and insulin resistance (IR) risk was assessed by conventional methods. Mood state was evaluated with specific and open questions at the beginning and at the end of the program. RESULTS: Seventy percent of patients were overweight or obese, and 77% of the patients presented with IR at the beginning of the study. Improvements were observed at the 3^rd mo, and statistically significant differences were recorded at the 6^th mo using the fitness score (76 vs 83, P 〈 0.01), in alanine aminotransferase (ALT)(106±93 U/L vs 59 ± 32 U/L, P 〈 0.01), total bilirubin (0.09 ± 1 mg/dL vs 0.62 ± 0.2 mg/dL, P 〈 0.01), ALT/ AST ratio (1.04 vs 0.70, P 〈 0.01), triglycerides (165 ± 86 mg/dL vs 124 ± 49 mg/dL, P 〈 0.01) and the IR risk (4.0 vs 2.7). Most patients (88%) indicated to feel better at the end of BW (P 〈 0.01).CONCLUSION: Breathwalk has an important effect on body composition, lipid profile and liver enzymes. It is also easy, inexpensive and has a beneficial effect on metabolic and mood state in HCV patients.
基金supported by grants from National Natural Science Foundation of China(82070250,32200631)Beijing Natural Science Foundation(5222029,China)+1 种基金China Postdoctoral Science Foundation(2022T150640)the Fundamental Research Funds for the Central Universities。
文摘Dimethylarginine dimethylaminohydrolase 1(DDAH1)is an important regulator of plasma asymmetric dimethylarginine(ADMA)levels,which are associated with insulin resistance in patients with nonalcoholic fatty liver disease(NAFLD).To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD,we used hepatocyte-specific Ddah1-knockout mice(Ddah1HKO)to examine the progress of high-fat diet(HFD)-induced NAFLD.Compared to diet-matched flox/flox littermates(Ddah1f/f),Ddah1HKO mice exhibited higher serum ADMA levels.After HFD feeding for 16 weeks,Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice.On the contrary,overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice.RNA-seq analysis showed that DDAH1 affects NF-kB signaling,lipid metabolic processes,and immune system processes in fatty livers.Furthermore,DDAH1 reduces S100 calcium-binding protein A11(S100A11)possibly via NF-kB,JNK and oxidative stress-dependent manner in fatty livers.Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice.In summary,our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice.Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.
文摘Objective: To investigate the expression pattern of resistin (RSTN) in skeletal muscle tissue and its influence on glycometabolism in rats with traumatic brain injury (TBI). Methods: Seventy-eight SD rats were randomly divided into traumatic group (n=36), RSTN group (n=36) and sham operation group (n=6). Fluid percussion TBI model was developed in traumatic and RSTN groups and the latter received additional 1 mg RSTN antibody treatment for each rat. At respectively 12 h, 24 h, 72 h, 1 w, 2 w, and 4 w after operation, venous blood was collected and the right hind leg skeletal muscle tissue was sampled. We used real-time PCR to determine mRNA expression of RSTN in skeletal muscles, western blot to determine RSTN protein expression and ELISA to assess serum insulin as well as fasting blood glucose (FBG) levels. Calculation of the quantitative insulin sensitivity check index (Q value) was also conducted. The above mentioned indicators and their correction were statistically analyzed. Results: Compared with sham operation group, the RSTN expression in the skeletal muscle as well as serum insulin and FBG levels revealed significant elevation (P〈0.05), and reduced Q value (P〈0.05) in traumatic group. Single factor linear correlation analysis showed a significant negative correlation between RSTN expression and Q values (P〈0.001) in traumatic group. Conclusion: The expression of RSTN has been greatly increased in the muscular tissue of TBI rats and it was closely related to the index of glycometabolism. RSTN may play an important role in the process of insulin resistance after TBI.
文摘Objective To analyze the efficacy and safety of drugs on reverse of atypical endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). Methods Seventeen patients with PCOS complicated by atypical endometrial hyperplasia (9 patients who were treated with progestin but not reversed were considered as group A; 8 patients who were untreated were considered as group B) were retrospectively analyzed Both groups received oral glucose tolerance test (OGTT) and insulin release test, to check whether the patients had insulin resistance (IR) or hyperinsulinemia. The 17 patients were treated with oral contraceptives combined with metformin. Results After the 17 patients with PCOS complicated by IR and hyperinsulinemia received drug treatment for 3 -6 cycles, atypical endometrial hyperplasia was success- fully reversed Conclusion Oral contraceptives combined with metformin is a clinically practical and effective method for treatment of PCOS complicated by atypical insulin-resistant endometrial hyperplasia.