We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patien...We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.展开更多
Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide vari...Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of 【 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.展开更多
Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is l...Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.展开更多
Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary...Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.展开更多
Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a...Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.展开更多
The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase ...The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase and protein tyrosine phosphatase 1B(PTP1B)inhibitory activity have been reported from the middle-polarity part of A.tsao-ko,whereas the antidiabetic potency of the low-polarity constituents is still unclear.In this study,three new hydroxytetradecenals,(2E,4E,8Z,11Z)-6R-hydroxytetradeca-2,4,8,11-tetraenal(1),(2E,4E,8Z)-6R-hydroxytetradeca-2,4,8-trienal(2)and(2E,4E)-6R-hydroxytetradeca-2,4-dienal(3)were obtained from the volatile oils of A.tsao-ko.The structures of compounds 1–3 were determined using spectroscopic data involving 1D and 2D nuclear magnetic resonance(NMR),high-resolution mass spectra(HRMS),and specific rotation([α]D).Their hypoglycemic activity was evaluated against glycogen phosphorylase(GPa)and PTP1B.Compounds 1 and 2 displayed moderate activity against PTP1B with inhibition rates of 33.8%−50.3%at 100 and 200μM.Moreover,compound 1 exhibited an obvious inhibitory effect on GPa(IC50=31.7μM),whereas compound 2 was inactive.This study demonstrates hydroxytetradecenals as the characteristic components of A.tsao-ko with therapeutic potential in diabetes.展开更多
Background Non-high-density lipoprotein cholesterol （non-HDL-C） and Apolipoprotein B （apoB） increase car- diovascular disease （CVD） risk, but few studies have explored the correlations of non-HDL-C and apoB with...Background Non-high-density lipoprotein cholesterol （non-HDL-C） and Apolipoprotein B （apoB） increase car- diovascular disease （CVD） risk, but few studies have explored the correlations of non-HDL-C and apoB with cor- onary atherosclerosis in non-diabetes acute coronary syndrome （ACS）. Methods The study enrolled 443 sub- jects with non-diabetic ACS, and all subject check coronary angiography, and coronary atherosclerosis were eval- uated using Gensini Score （GS） scale including small （GS 1-15）, middle （GS16-43）, and severe （GS≥44）. All sub- jects were classified into 4 groups： High apoB （≥90 mg/dL） and High non-HDL-C （≥130 mg/dL）, High non-HDL -C alone, High apoB alone, and normal apoB and non-HDL-C. Results After adjusted for risk factors, non-HDL -C and apoB were positively correlated with GS （ r = 0.075, P = 0.002 and r = 0.092, P 〈 0.001）. In the GS 0-15, high non-HDL-C ＋ high apoB group 29.3% and high apoB alone group 28.2% were significantly lower than nor- mal non-HDL-C＋ normal apoB group 48% （p = 0.010）. In the GS 16-43, high non-HDL-C alone group 50.4% and high apoB alone group 47.6% were significantly more than high non-HDL-C＋ high apoB group 34.1% （P = 0.036）. In the GS ≥44, high non-HDL-C＋ high apoB group 36.6% was significantly higher than high non-HDL- C alone group 16% and normal non-HDL-C＋ normal apoB 14.2%（P 〈 0.001）. Conclusions The high non-HDL- C and apoB are the risk factors for coronary artery atherosclerosis in non-diabetic ACS.展开更多
文摘We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.
文摘Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of 【 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.
基金This work was supported by the Health Commission of Hubei Province Scientific Research Project(No.WJ2021M129)the National Key Research and Development Program of China(No.2021YFC2701502)。
文摘Melatonin receptor 1B(MT2,encoded by the MTNR1B gene),a high-affinity receptor for melatonin,is associated with glucose homeostasis including glucose uptake and transport.The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus(GDM);however,the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood.This article aims to investigate the relationship between rs10830963 variants and GDM development,as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts.TaqMan-MGB(minor groove binder)probe quantitative realtime polymerase chain reaction(qPCR)assays were used for rs10930963 genotyping.MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence,western blot,and qPCR.The relationship between MT2 and glucose transporters(GLUTs)or peroxisome proliferator-activated receptorγ(PPARγ)was established by western blot,and glucose consumption of trophoblasts was measured by a glucose assay kit.The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women(P<0.05).The fasting,1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers(P<0.05).Besides,the protein and messenger RNA(mRNA)expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women(P<0.05).Melatonin could stimulate glucose uptake and GLUT4 and PPARγprotein expression in trophoblasts,which could be attenuated by MT2 receptor knockdown.In conclusion,the rs10830963 variant was associated with an increased risk of GDM.The MT2 receptor is essential for melatonin to raise glucose uptake and transport,which may be mediated by PPARγ.
基金the traditional Chinese medicine(TCM)clinical research base contribution subject of the State Administration of TCM of China(JDZX2012039)special scientific research of Chinese Medicine Industry of the State Administration of TCM of China(201207001)
文摘Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.
基金supported by the National Natural Science Foundation of China(grant Nos.30972531 and 81320108026)a project of the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.
基金the Yunnan Major Scientific and Technological Program(202202AE090035)Xingdian Yingcai Project(YNWR-QNBJ-2018-061)+2 种基金the Yunnan Fundamental Research Projects(202201AV070010,202301AS070069)Yunnan Province Science and Technology Department(202305AH340005)the Fund of State Key Laboratory of Phytochemistry and Plant Resources in West China(P2022-KF12).
文摘The fruits of Amomum tsao-ko(Cao-Guo)were documented in Chinese Pharmacopoeia for the treatment of abdominal pain,vomiting,and plague.In our previous study,a series of diarylheptanes and flavonoids withα-glucosidase and protein tyrosine phosphatase 1B(PTP1B)inhibitory activity have been reported from the middle-polarity part of A.tsao-ko,whereas the antidiabetic potency of the low-polarity constituents is still unclear.In this study,three new hydroxytetradecenals,(2E,4E,8Z,11Z)-6R-hydroxytetradeca-2,4,8,11-tetraenal(1),(2E,4E,8Z)-6R-hydroxytetradeca-2,4,8-trienal(2)and(2E,4E)-6R-hydroxytetradeca-2,4-dienal(3)were obtained from the volatile oils of A.tsao-ko.The structures of compounds 1–3 were determined using spectroscopic data involving 1D and 2D nuclear magnetic resonance(NMR),high-resolution mass spectra(HRMS),and specific rotation([α]D).Their hypoglycemic activity was evaluated against glycogen phosphorylase(GPa)and PTP1B.Compounds 1 and 2 displayed moderate activity against PTP1B with inhibition rates of 33.8%−50.3%at 100 and 200μM.Moreover,compound 1 exhibited an obvious inhibitory effect on GPa(IC50=31.7μM),whereas compound 2 was inactive.This study demonstrates hydroxytetradecenals as the characteristic components of A.tsao-ko with therapeutic potential in diabetes.
基金supported by the Natural Science Foundation of China(No.81070182)the Natural Science Foundation of Guangdong Province(No.10151008901000224)
文摘Background Non-high-density lipoprotein cholesterol （non-HDL-C） and Apolipoprotein B （apoB） increase car- diovascular disease （CVD） risk, but few studies have explored the correlations of non-HDL-C and apoB with cor- onary atherosclerosis in non-diabetes acute coronary syndrome （ACS）. Methods The study enrolled 443 sub- jects with non-diabetic ACS, and all subject check coronary angiography, and coronary atherosclerosis were eval- uated using Gensini Score （GS） scale including small （GS 1-15）, middle （GS16-43）, and severe （GS≥44）. All sub- jects were classified into 4 groups： High apoB （≥90 mg/dL） and High non-HDL-C （≥130 mg/dL）, High non-HDL -C alone, High apoB alone, and normal apoB and non-HDL-C. Results After adjusted for risk factors, non-HDL -C and apoB were positively correlated with GS （ r = 0.075, P = 0.002 and r = 0.092, P 〈 0.001）. In the GS 0-15, high non-HDL-C ＋ high apoB group 29.3% and high apoB alone group 28.2% were significantly lower than nor- mal non-HDL-C＋ normal apoB group 48% （p = 0.010）. In the GS 16-43, high non-HDL-C alone group 50.4% and high apoB alone group 47.6% were significantly more than high non-HDL-C＋ high apoB group 34.1% （P = 0.036）. In the GS ≥44, high non-HDL-C＋ high apoB group 36.6% was significantly higher than high non-HDL- C alone group 16% and normal non-HDL-C＋ normal apoB 14.2%（P 〈 0.001）. Conclusions The high non-HDL- C and apoB are the risk factors for coronary artery atherosclerosis in non-diabetic ACS.
