2 型糖尿病伴脂肪肝患者血浆FGF21水平与肥胖、脂代谢及胰岛素抵抗的相关性

目的:研究2型糖尿病伴脂肪肝患者血浆成纤维细胞生长因子21(FGF21)水平与肥胖、脂代谢及胰岛素抵抗的相关性,为临床诊疗提供依据。方法:选取2013年5月到2015年11月我院收治的2型糖尿病伴脂肪肝患者100例为研究组,另选取同期单纯脂肪肝患者100例为脂肪肝组,健康体检者100例为对照组,比较各组入选次日清晨FGF21、谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、体重指数(BMI)、腰臀比(WHR)、空腹胰岛素(FINS)、空腹血糖(FBG)以及胰岛素抵抗指数(HOMA-IR)。结果:研究组TG、TC、AST、ALT、LDL-C、FFA、FBG、BMI、WHR、FINS、HOMA-IR以及FGF21均显著高于对照组,HDL-C显著低于对照组,比较差异具有统计学意义(P0.05);研究组FFA、TG、FINS、FBG、HOMA-IR以及FGF21显著高于脂肪肝组,BMI和WHR显著低于脂肪肝组,比较差异具有统计学意义(P0.05);相关性分析显示:FGF21与TG、FFA、BMI以及HOMA-IR呈正相关关系(P0.05)。结论:2型糖尿病合并脂肪肝患者FGF21水平会显著升高,且与脂肪代谢、肥胖以及胰岛素抵抗有关。     

血清成纤维细胞生长因子2、21、23与妊娠期糖尿病患者新生儿结局的关系

摘要 目的：探讨血清成纤维细胞生长因子2（FGF2）、成纤维细胞生长因子21（FGF21）、成纤维细胞生长因子23（FGF23）与妊娠期糖尿病（GDM）患者新生儿结局的关系。方法：选取2021年1月～2022年12月期间于我院产检的妊娠24～28周孕妇147例,均进行口服葡萄糖耐量试验（OGTT）,根据OGTT结果分为GDM组（n=86）和非GDM组（n=61）。其中GDM组根据新生儿结局分为不良组（n=21）和良好组（n=65）。对比非GDM组、GDM组的血清FGF2、FGF21、FGF23水平及新生儿结局情况。对比不良组和良好组的血清FGF2、FGF21、FGF23水平。单因素及多因素Logistic回归分析影响GDM患者新生儿结局的影响因素。结果：GDM组的血清FGF2、FGF21、FGF23水平均高于非GDM组（P<0.05）。GDM组的不良新生儿结局总发生率高于非GDM组（P<0.05）。不良组的血清FGF2、FGF21、FGF23水平均高于良好组（P<0.05）。单因素分析显示,GDM患者不良新生儿结局与年龄、孕前体质量指数（BMI）、分娩前BMI、空腹血糖（FPG）、餐后2 h血糖（2hPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）有关（P<0.05）。多因素分析结果显示,年龄偏高、FPG偏高、孕前BMI偏高、2hPG偏高、分娩前BMI偏高、HOMA-IR偏高、FGF2偏高、FINS偏高、FGF21偏高、FGF23偏高均是GDM患者不良新生儿结局的危险因素（P<0.05）。结论：GDM患者血清FGF2、FGF21、FGF23水平升高,其与年龄、孕前BMI、分娩前BMI、FPG、2hPG、FINS、HOMA-IR偏高均是导致GDM患者不良新生儿结局的危险因素。     

2型糖尿病患者血清Irisin水平与胰岛素抵抗的相关性研究

目的:探讨2型糖尿病患者血清Irision水平和胰岛素抵抗的相关性及其影响因素。方法:2型糖尿病患者50例,纳入健康人群30例为对照组。采用酶联免疫吸附法测定研究对象血清Irisin水平;同时测定糖尿病患者C肽、胰岛素抵抗指数、糖化血红蛋白水平。采用多元回归分析分析影响血清Irisin水平的因子。结果:病例组和对照组间BMI、腰围、血清Irisin、低密度脂蛋白间差异有统计学意义(p0.05)。血清Irisin水平和BMI、腰围、低密度脂蛋白、糖化血红蛋白、胰岛素抵抗指数、糖尿病病程呈负相关(r=-0.73,-0.68,-0.56,-079,-0.65,-0.73,均P0.05)。血清Irisin水平和C肽成正相关(r=0.62,P0.05)。胰岛素抵抗指数、糖尿病病程是影响血清Irisin水平的独立负影响因子。结论:糖尿病患者血清Irisin水平明显降低,和糖尿病患者胰岛素抵抗和病程密切相关。     

妊娠期糖尿病患者血清PGRN、FGF21、Vaspin水平与糖脂代谢及胰岛素抵抗的相关性分析

摘要 目的：研究妊娠期糖尿病（GDM）患者血清颗粒蛋白前体（PGRN）、成纤维细胞生长因子21（FGF21）及内脏脂肪组织源性丝氨酸蛋白酶抑制剂（Vaspin）水平与糖脂代谢及胰岛素抵抗（IR）的相关性。方法：选取2016年1月～2020年1月我院收治的300例GDM患者纳入研究,作为观察组,另取同期于我院进行体检的健康孕妇100例作为对照组。比较两组血清PGRN、FGF21、Vaspin水平、糖脂代谢以及IR相关指标水平,并通过Pearson相关性分析血清PGRN、FGF21及Vaspin水平与糖脂代谢、IR的关系。结果：观察组血清PGRN、FGF21及Vaspin水平均高于对照组（均P＜0.05）。观察组空腹血糖（FPG）、甘油三酯（TG）、总胆固醇（TC）及低密度脂蛋白胆固醇（LDL-C）均高于对照组（均P＜0.05）。观察组胰岛素抵抗指数（HOMA-IR）高于对照组,而胰岛素β细胞功能指数（HOMA-β）低于对照组（均P＜0.05）。经Pearson相关性分析可得：GDM患者血清PGRN、FGF21及Vaspin水平与FPG、TC、TG、LDL-C、HOMA-IR均呈正相关关系,而与HOMA-β呈负相关关系（均P＜0.05）。结论：GDM患者血清PGRN、FGF21及Vaspin水平均存在异常高表达,且和糖脂代谢及IR存在密切关系,可能成为临床上GMD诊治的潜在靶点。     

肥胖2型糖尿病患者神经肽Y水平与糖脂代谢的相关性分析

目的:探讨肥胖2型糖尿病患者神经肽Y(NPY)水平与糖脂代谢的相关性。方法:选择2017年7月至2019年7月我院接诊的134例肥胖2型糖尿病患者为本研究对象,设为观察组,并选择我院收治的2型糖尿病非肥胖患者100例作为对照组,分析腰围、腹围、臀围、BMI、腰臀比(WHR)、血清NPY、空腹血糖(FPG)、糖化血红蛋白(Hb Alc)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平变化情况,及其之间的相关性分析。结果:观察组腹围、腰围、臀围、腰臀比及BMI水平均显著高于对照组,差异显著(P0.05);观察组患者血清NPY、FPG、Hb Alc水平显著高于对照组,FINS水平显著低于对照组,差异显著(P0.05);观察组患者血清TC、TG、LDL-C水平显著高于对照组,HDL-C水平显著低于对照组,差异显著(P0.05);将FPG、Hb Alc、FINS、TC、TG、LDL-C、HDL-C作为因变量,将血清NPY作为自变量,在相关性分析结果中显示,血清NPY和FPG、Hb Alc、TC、TG、LDL-C之间均呈正相关(r=0.399,0.173,0.435,0.451,0.376,P均0.05),血清NPY和FINS、HDL-C之间均呈负相关(r=-0.566,-0.223,P均0.05)。结论:在肥胖2型糖尿病患者中NPY水平显著升高,且与腹部脂肪增加、糖脂代谢显著相关。     

2型糖尿病患者脂联素、8-OHdG表达及其与认知功能的相关性

本研究旨在探究老年2型糖尿病患者血浆脂联素、8-羟基脱氧鸟苷(8-OHdG)表达变化及其与认知功能的相关性,通过选取本院2016年2月至2017年2月收治的2型糖尿病患者作为研究对象,根据有无认知功能损害分为2组,并选取同期100名健康体检者。检查入组人群血浆脂联素、8-OHdG水平,并对临床资料进行分析。结果发现糖尿病患者血浆脂联素、8-OHdG水平高于健康人群(p0.05);糖尿病伴认知功能障碍患者血浆脂联素、8-OHdG水平高于糖尿病患者(p0.05)。糖尿病患者MMSE评分、MoCA评分、数字广度测验得分低于健康人群,连线测验完成时间高于人群(p0.05);糖尿病伴认知功能障碍患者MMSE评分、MoCA评分、数字广度测验得分低于糖尿病患者无认知功能障碍者,连线测验完成时间高于糖尿病患者无认知功能障碍者(p0.05)。经Spearman相关性分析,发现2型糖尿病患者MoCA评分与年龄、BMI、糖尿病病程、空腹血糖、HBA1c、血浆脂联素水平、血浆8-OHdG水平呈负相关,与受教育年限呈正相关(p0.05)。结果说明2型糖尿病伴认知功能障碍患者血浆脂联素、8-OHdG水平升高,且与患者认知功能呈负相关;临床中可通过检测血浆脂联素、8-OHdG水平,对糖尿病患者认知功能进行初步评估,以指导后续治疗。     

2 型糖尿病患者血浆成纤维细胞生长因子-21 水平的变化及意义

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血浆成纤维细胞生长因子-21(fibroblast growth factor 21,FGF-21)水平变化以及观察短期胰岛素强化治疗对FGF-21水平的影响。方法:选择我院2013年1月至2015年1月收治的T2DM患者64例,其中初诊T2DM患者32例(T2DM组),T2DM合并大血管病变患者32例(合并大血管病变组),并选择同期体检健康者30例(对照组)。采用酶联免疫法测定三组血浆FGF-21水平以及胰岛素强化治疗前后的变化,分析血浆FGF-21水平与体质量指数(BMI)、腰臀比(WHR)、血脂、血糖、空腹血浆胰岛素(FINS)和糖化血红蛋白(Hb A1C)等水平的关系。结果:T2DM组及T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于对照组(P0.05),T2DM合并大血管病变组患者空腹血浆FGF-21水平明显高于T2DM组和对照组(P0.05)。空腹血浆FGF-21水平与T2DM患者FPG、Hb A1C水平呈明显正相关,WHR、舒张压、Hb A1C是影响血浆FGF-21水平的独立相关因素。经胰岛素强化治疗后,血浆FGF-21水平较治疗前明显下降(P0.05)。结论:T2DM患者血浆FGF-21水平明显升高,可能参与了T2DM及其大血管病变的发生和发展,胰岛素强化治疗可明显降低T2DM患者血浆FGF-21水平,血浆FGF-21可能作为T2DM病情和疗效评估的参考指标。     

基于主成分分析法探讨人体测量学参数与青少年血糖关系的研究

目的:调查分析人体测量学参数包括体重指数(BMI)、腰围(WC)、臀围(HC)、腰围/臀围比(WHR)及腰围/身高比(WHtR)对南昌地区青少年空腹血糖的影响。方法:在南昌地区进行随机抽样检查731例12-18岁之间的青少年,测量身高、体重、BMI、WC、HC、WHR、WHtR和空腹血糖,用SAS软件进行统计分析。结果:男女性的五项人体测量学指标和空腹血糖间均呈显著正相关,相关系数为0.14-0.38;通过主成分分析得到四个主成分,多重回归分析结果表明联合四个主成分比单独使用其中任何一个更能解释空腹血糖的变异。结论:BMI、WC、HC、WHR、WHtR与男性和女性空腹血糖都有一定相关性,并且联合这五项测量学指标比单独使用其中任何一个能更精确预测空腹血糖。     

老年2 型糖尿病患者血清中25- 羟维生素D水平 与胰岛beta细胞功能的关系

目的：探讨老年2 型糖尿病患者血清中25- 羟维生素D水平与其胰岛素beta细胞功能的相关性,为老年2 型糖尿病的预防和 治疗提供理论基础。方法：选取2013 年6 月至2014 年6 月在我院接受治疗的老年2 型糖尿病患者300 例作为研究对象,另选取 同期在我院参加体检的健康志愿者300 例作为对照组。采用酶联免疫吸附法测定和比较两组研究对象血清中25-羟维生素D 的 含量,采用稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(IAI)、胰岛beta细胞的功能指数(HBCI)以及空腹胰岛beta细胞的功 能指数(FBCI)评估老年2 型糖尿病患者的胰岛beta细胞功能,并分析老年2 型糖尿病患者血清中25- 羟维生素D 水平与上述参数 的相关性。结果：老年2 型糖尿病患者血清中25-羟维生素D水平为(10.2± 0.9)ng/mL,显著低于正常对照人群(P<0.05);老年2 型 糖尿病患者血清中25- 羟维生素D 水平与HOMA-IR 呈显著正相关(r=0.438,P=0.019),与IAI 呈显著负相关(r=-0.392,P=0.023), 与HBCI和FBCI无明显相关性(P>0.05)。结论：老年2 型糖尿病患者血清中的25- 羟维生素D 水平较低,与其胰岛素beta细胞功能 障碍有关,补充25-羟维生素D 可能有助于老年2 型糖尿病的治疗和预防。     

血清GDF-15、FGF21与非酒精性脂肪性肝病患者肝纤维化和代谢综合征的关系研究

摘要 目的：研究血清生长分化因子15（GDF-15）、成纤维细胞生长因子21（FGF21）与非酒精性脂肪性肝病（NAFLD）患者肝纤维化和代谢综合征（MS）的关系。方法：选取我院2019年1月～2021年2月收治的102例NAFLD患者记作研究组。另选取同期健康体检志愿者100例作为对照组。比较两组血清GDF-15、FGF21与肝纤维化指标水平，并采用Pearson相关性分析明确血清GDF-15、FGF21与肝纤维化指标水平的关系。此外，将研究组患者按照是否并发MS分为MS组以及非MS组，比较MS组以及非MS组血清GDF-15、FGF21水平以及基线资料。采用多因素Logistic回归分析NAFLD并发MS的影响因素。结果：研究组血清GDF-15、FGF21水平高于对照组（均P＜0.05）。研究组血清透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原（PCⅢ）以及Ⅳ型胶原（ⅣC）水平高于对照组（均P＜0.05）。经Pearson相关性分析发现，血清GDF-15、FGF21水平与血清HA、LN、PCⅢ、ⅣC水平均呈正相关关系（均P＜0.05）。经单因素分析发现，血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、GDF-15、FGF21水平以及体质量指数、空腹血糖（FPG）、餐后2小时血糖（2hPG）、收缩压（SBP）、舒张压（DBP）、甘油三酯（TG）均和MS有关（均P＜0.05）。经多因素Logistic回归分析发现，血清AST、ALT升高是NAFLD并发MS的保护因素，而体质量指数、GDF-15、FGF21、FPG、2hPG、SBP、DBP、TG升高均是NAFLD并发MS的危险因素（均P＜0.05）。结论：血清GDF-15、FGF21与NAFLD患者肝纤维化以及MS均密切相关，可作为预测NAFLD患者肝纤维化以及MS的辅助性生物学指标。     

Circulating FGF21 levels are progressively increased from the early to end stages of chronic kidney diseases and are associated with renal function in Chinese

Background

Fibroblast growth factor 21 (FGF21) is a hepatic hormone involved in the regulation of lipid and carbohydrate metabolism. This study aims to test the hypothesis that elevated FGF21 concentrations are associated with the change of renal function and the presence of left ventricular hypertrophy (LVH) in the different stages of chronic kidney disease (CKD) progression.

Methodology/Principal Findings

240 subjects including 200 CKD patients (146 outpatients and 54 long-term hemodialytic patients) and 40 healthy control subjects were recruited. All CKD subjects underwent echocardiograms to assess left ventricular mass index. Plasma FGF21 levels and other clinical and biochemical parameters in all subjects were obtained based on standard clinical examination methods. Plasma FGF21 levels were significantly increased with the development of CKD from early- and end-stage (P<0.001 for trend), and significantly higher in CKD subjects than those in healthy subjects (P<0.001). Plasma FGF21 levels in CKD patients with LVH were higher than those in patients without LVH (P = 0.001). Furthermore, plasma FGF21 level correlated positively with creatinine, blood urea nitrogen (BUN), β2 microglobulin, systolic pressure, adiponectin, phosphate, proteinuria, CRP and triglyceride, but negatively with creatinine clearance rate (CCR), estimated glomerular filtrate rate (eGFR), HDL-c, LDL-c, albumin and LVH after adjusting for BMI, gender, age and the presence of diabetes mellitus. Multiple stepwise regression analyses indicated that FGF21 was independently associated with BUN, Phosphate, LVMI and β2 microglobulin (all P<0.05).

Conclusion

Plasma FGF21 levels are significantly increased with the development of early- to end-stage CKD and are independently associated with renal function and adverse lipid profiles in Chinese population. Understanding whether increased FGF21 is associated with myocardial hypertrophy in CKD requires further study.     

Serum Concentrations of Fibroblast Growth Factors 19 and 21 in Women with Gestational Diabetes Mellitus: Association with Insulin Resistance,Adiponectin, and Polycystic Ovary Syndrome History

Background

Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters.

Method

Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters.

Results

Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history.

Conclusions

Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.     

Aging is associated with increased FGF21 levels but unaltered FGF21 responsiveness in adipose tissue

Fibroblast growth factor 21 (FGF21) has been proposed to be an antiaging hormone on the basis of experimental studies in rodent models. However, circulating FGF21 levels are increased with aging in rodents and humans. Moreover, despite the metabolic health‐promoting effects of FGF21, the levels of this hormone are increased under conditions such as obesity and diabetes, an apparent incongruity that has been attributed to altered tissue responsiveness to FGF21. Here, we investigated serum FGF21 levels and expression of genes encoding components of the FGF21‐response molecular machinery in adipose tissue from healthy elderly individuals (≥70 years old) and young controls. Serum FGF21 levels were increased in elderly individuals and were positively correlated with insulinemia and HOMA‐IR, indices of mildly deteriorated glucose homeostasis. Levels of β‐Klotho, the coreceptor required for cellular responsiveness to FGF21, were increased in subcutaneous adipose tissue from elderly individuals relative to those from young controls, whereas FGF receptor‐1 levels were unaltered. Moreover, total ERK1/2 protein levels were decreased in elderly individuals in association with an increase in the ERK1/2 phosphorylation ratio relative to young controls. Adipose explants from aged and young mice respond similarly to FGF21 “ex vivo”. Thus, in contrast to what is observed in obesity and diabetes, high levels of FGF21 in healthy aging are not associated with repressed FGF21‐responsiveness machinery in adipose tissue. The lack of evidence for impaired FGF21 responsiveness in adipose tissue establishes a distinction between alterations in the FGF21 endocrine system in aging and chronic metabolic pathologies.     

Dual actions of fibroblast growth factor 19 on lipid metabolism

Elevated triglyceride (TG) and cholesterol levels are risk factors for cardiovascular disease and are often associated with diabetes and metabolic syndrome. Recent reports suggest that fibroblast growth factor (FGF)19 and FGF21 can dramatically improve metabolic dysfunction, including hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. Due to their similar receptor specificities and co-receptor requirements, FGF19 and FGF21 share many common properties and have been thought to be interchangeable in metabolic regulation. Here we directly compared how pharmacological administration of recombinant FGF19 or FGF21 proteins affect metabolism in B6.V-Lep^ob/J leptin-deficient mice. FGF19 and FGF21 equally improved glucose parameters; however, we observed increased serum TG and cholesterol levels after treatment with FGF19 but not with FGF21. Increases in serum TGs were also observed after a 4-day treatment with FGF19 in C57BL6/J mice on a high-fat diet. This is in contrast to many literature reports that showed significant improvements in hyperlipidemia after chronic treatment with FGF19 or FGF21 in high-fat diet models. We propose that FGF19 has lipid-raising and lipid-lowering actions mediated through different FGF receptors and target tissues, and the results described here provide a potential mechanism that may explain the inconsistency in the reported effects of FGF19 on lipid metabolism.     

Serum levels of FGF-21 are increased in coronary heart disease patients and are independently associated with adverse lipid profile

Background

Fibroblast growth factor 21 (FGF-21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and lipid metabolism in animal models. The relationship between plasma levels of FGF-21 and coronary heart disease (CHD) in unknown.

Methodology/Principal Findings

This study aimed to investigate the correlation of serum FGF-21 levels and lipid metabolism in the patients with coronary heart disease. We performed a logistic regression analysis of the relation between serum levels of FGF-21 and CHD patients with and without diabetes and hypertension. This study was conducted in the Departments of Endocrinology and Cardiovascular Diseases at two University Hospitals. Participants consisted of one hundred and thirty-five patients who have been diagnosed to have CHD and sixty-one control subjects. Serum FGF-21 level and levels of fasting blood glucose; triglyceride; apolipoprotein B100; HOMA-IR; insulin; total cholesterol; HDL-cholesterol; LDL-cholesterol; and C-reactive protein were measured. We found that median serum FGF-21 levels were significantly higher in CHD than that of control subjects (P<0.0001). Serum FGF-21 levels in CHD patients with diabetes, hypertension, or both were higher than that of patients without these comorbidities. Serum FGF-21 levels correlated positively with triglycerides, fasting blood glucose, apolipoprotein B100, insulin and HOMA-IR but negatively with HDL-C and apolipoprotein A1 after adjusting for BMI, diabetes and hypertension. Logistic regression analysis demonstrated that FGF-21 showed an independent association with triglyceride and apolipoprotein A1.

Conclusions/Significance

High levels of FGF-21 are associated with adverse lipid profiles in CHD patients. The paradoxical increase of serum FGF-21 in CHD patients may indicate a compensatory response or resistance to FGF-21.     

Glucose Control and Lipid Metabolism in African American Patients with Type 2 Diabetes Mellitus and Chronic Hepatitis C Viral Infection

ObjectiveTo compare lipid profiles and glucose control in African American patients with type 2 diabetes mellitus with and without chronic hepatitis C viral (HCV) infection.MethodsThis retrospective study conducted in an academic outpatient setting included African American patients with both type 2 diabetes and HCV, patients with HVC only, and patients with type 2 diabetes only. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values were compared among all 3 patient groups.ResultsThe study population included 283 patients, of whom 111 had type 2 diabetes and HCV, 68 had HCV only, and 104 had type 2 diabetes only. Chronic HCV was associated with lower total cholesterol and LDL-cholesterol levels in patients with or without type 2 diabetes. In contrast, elevated serum triglyceride levels associated with diabetes were not reduced in patients with chronic HCV, although diabetes control was better in the diabetes group with HCV than in the diabetes group without HCV (mean hemoglobin A_1c [standard error of the mean]: 7.1% [1.8%] vs 8.8% [2.1%], P < .001). HDL cholesterol was higher in the patients with earlier stages of HCV when compared with HDL cholesterol in the other 2 groups.ConclusionsChronic HCV infection in type 2 diabetic patients decreases serum levels of total and LDL cholesterol, but has no such protective effect on triglyceride levels. HCV infection may alter the cellular pathways of cholesterol and triglyceride metabolism in patients with type 2 diabetes. (Endocr Pract. 2011;17:363-368)     

LY2405319, an Engineered FGF21 Variant,Improves the Metabolic Status of Diabetic Monkeys

Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that represents a promising target for the treatment of several metabolic diseases. Administration of recombinant wild type FGF21 to diabetic animals leads to a dramatic improvement in glycaemia and ameliorates other systemic measures of metabolic health. Here we report the pharmacologic outcomes observed in non-human primates upon administration of a recently described FGF21 analogue, LY2405319 (LY). Diabetic rhesus monkeys were treated subcutaneously with LY once daily for a period of seven weeks. The doses of LY used were 3, 9 and 50 mg/kg each delivered in an escalating fashion with washout measurements taken at 2, 4, 6 and 8 weeks following the final LY dose. LY therapy led to a dramatic and rapid lowering of several important metabolic parameters including glucose, body weight, insulin, cholesterol and triglyceride levels at all doses tested. In addition, we observed favorable changes in circulating profiles of adipokines, with increased adiponectin and reduced leptin indicative of direct FGF21 action on adipose tissue. Importantly, and for the first time we show that FGF21 based therapy has metabolic efficacy in an animal with late stage diabetes. While the glycemic efficacy of LY in this animal was partially attenuated its lipid lowering effect was fully preserved suggesting that FGF21 may be a viable treatment option even in patients with advanced disease progression. These findings support continued exploration of the FGF21 pathway for the treatment of metabolic disease.     

Fibrates, dyslipoproteinaemia and cardiovascular disease

Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.