Plasma fatty acid-binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. METHODS: In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR <30 mL/min/1.73 m(2)) or albuminuria were not included. RESULTS: FABP4 concentrations were higher in diabetic patients with MDRD-GFR <60 mL/min/1.73 m(2) (P <0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P <0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = -0.511, P <0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P <0.001 and r = -0.510, P <0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8-30.7), P = 0.005 and 15.3 (3.1-76.4), P = 0.001; respectively], independent of microalbuminuria. CONCLUSIONS: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.     

Plasma lipoprotein composition in type 2 diabetic patients

In the present study lipoprotein fractions were studied in clinically well-characterized patients with type 2 diabetes. Apart from the usually isolated fractions (VLDL, LDL and HDL) a subfraction of VLDL was studied. This VLDL-subfraction (VLDL-2) has a similar chemical composition to beta-VLDL which has been suggested to be of importance in the development of atherosclerosis. The results shows that obese type 2 diabetic women carry substantial amounts of VLDL-2 (greater than 100% above the level of comparable non-diabetic women), (2p less than 0.01 for cholesterol and triglyceride amounts in VLDL-2). Furthermore obese diabetic women had total plasma cholesterol values 27% higher than non-diabetic obese women (2p less than 0.05). Total plasma triglyceride values were found to be significantly higher in diabetic women compared with non-diabetic women (2p less than 0.01). LDL-cholesterol was found significantly raised in obese diabetic women compared with the corresponding group of non-diabetic women (2p less than 0.05). HDL-cholesterol showed lower values in ideal-weight diabetic women than in ideal-weight non-diabetic women (2p less than 0.05). In summary, the results show that obese women with type 2 diabetes carry high concentrations of lipoprotein fractions which have been incriminated as being of importance in the development of atherosclerosis. This is in accordance with the sex ratio of atherosclerotic disease among diabetic patients compared to the sex ratio in non-diabetic patients.     

C-reactive protein,gamma-glutamyltransferase and type 2 diabetes in a Chinese population

BackgroundWe studied the association of C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and type 2 diabetes in Chinese.MethodA population-based cross-sectional study.ResultsCRP and GGT levels were significantly higher in participants with diabetes than in those without (P < 0.001). Higher CRP levels were positively associated with prevalent type 2 diabetes after adjustment for age, sex, smoking, alcohol consumption, physical activity, family history of diabetes, body mass index, waist circumference, waist/hip ratio, education, systolic blood pressure, triglycerides, high density lipoprotein cholesterol, use of antihypertensive drugs, aspirin and lipid-lowering agents, with multivariable odds ratios (OR) of 1.55 (95% confidence interval (CI), 1.05–2.27, P trend = 0.005, comparing quartile 4 to quartile 1). However, after further adjustment for GGT, the association was completely attenuated (fourth quartile OR 1.23, 95% CI, 0.83–1.82, P trend = 0.127). Moreover, the association of CRP and prevalent type 2 diabetes was stronger in subjects with GGT values above the median than in those with GGT values below the median. Increasing serum GGT quartiles were positively associated with prevalent type 2 diabetes after adjustment for potential confounding variables (P for trend < 0.001).ConclusionCRP may not be an independent risk factor for type 2 diabetes, at least in Chinese people.     

Plasma lipoprotein composition in type 2 diabetic patients

In the present study lipoprotein fractions were studied in clinically well-characterized patients with type 2 diabetes. Apart from the usually isolated fractions (VLDL, LDL and HDL) a subfraction of VLDL was studied. This VLDL-subfraction (VLDL-2) has a similar chemical composition to β-VLDL which has been suggested to be of importance in the development of atherosclerosis. The results shows that obese type 2 diabetic women carry substantial amounts of VLDL-2 (>100% above the level of comparable non-diabetic women), (2p<0.01 for cholesterol and triglyceride amounts in VLDL-2). Furthermore obese diabetic women had total plasma cholesterol values 27% higher than non-diabetic obese women (2p<0.05). Total plasma triglyceride values were found to be significantly higher in diabetic women compared with non-diabetic women (2p<0.01). LDL-cholesterol was found significantly raised in obese diabetic women compared with the corresponding group of non-diabetic women (2p<0.05). HDL-cholesterol showed lower values in ideal-weight diabetic women than in ideal-weight non-diabetic women (2p<0.05). In summary, the results show that obese women with type 2 diabetes carry high concentrations of lipoprotein fractions which have been incriminated as being of importance in the development of atherosclerosis. This is in accordance with the sex ratio of atherosclerotic disease among diabetic patients compared to the sex ratio in non-diabetic patients.     

Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.     

血、尿β痕迹蛋白检测对2型糖尿病肾损伤早期诊断价值研究

目的探讨血、尿β痕迹蛋白(βTP)检测在2型糖尿病肾损伤中的诊断价值。方法明确诊断为2型糖尿病患者178例,按照尿Alb/Cr比值将其分为三组:Alb/Cr正常组60例,微量白蛋白尿组65例,大量白蛋白尿组53例,另设健康对照组80名。采用胶乳增强散射免疫比浊法原理检测血、尿βTP,比较各组患者血、尿βTP水平,并与Scr、eGFR以及实验及临床相关指标进行相关性分析。结果尿Alb/Cr正常的2型糖尿病患者血清βTP为(0.70±0.36)mg/dl,较健康对照组[(0.59±0.12)mg/dl]显著升高(P<0.01)。微量白蛋白尿组血清βTP(0.82±0.30)mg/dl,较Alb/Cr正常组显著升高(P<0.05);大量白蛋白尿组血清βTP(1.79±1.19)mg/dl,与其他两组比较显著升高(P<0.01);三组2型糖尿病患者血清βTP阳性率分别为28.3%、60.0%和87.8%;尿液βTP/Cr阳性率分别为20%、84.6%和90.6%。相关分析结果表明,血清βTP与SC呈显著正相关,r为0.705 0(P<0.01),eGFR值与血β-TP呈显著负相关(r=-0.805 1,P<0.01)。尿βTP与Scr、HbA1c、收缩压、病程呈正相关(r分别为0.387 9、0.240 2、0.164 3、0.241 5,均P<0.05)。结论血清βTP对2型糖尿病患者早期肾损伤具有重要的诊断价值,可以早期反映肾小球滤过功能,而尿βTP/Cr可以作为评价2型糖尿病患者肾小管损伤的有效指标。     

Serum adiponectin and renal dysfunction in men with type 2 diabetes

OBJECTIVE: Inflammation is associated with both chronic kidney dysfunction and type 2 diabetes. Adiponectin, a novel circulating anti-inflammatory protein made by adipocytes, has been reported to be lower in diabetic than nondiabetic subjects. In contrast, serum levels of adiponectin are elevated in end-stage renal disease. We sought to investigate the relation between adiponectin and mild to moderate renal dysfunction in men with type 2 diabetes. RESEARCH DESIGN AND METHODS: Multivariate logistic regression was used to evaluate the relation between serum adiponectin concentrations and the presence of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m(2) by the four-variable Modification of Diet in Renal Disease equation) in participants with type 2 diabetes in the Health Professionals' Follow-Up Study. A total of 733 men were included in this cross-sectional analysis. RESULTS: Adiponectin was positively correlated with age (Spearman coefficient, r = 0.19, P < 0.001) and negatively correlated with weight (Spearman coefficient, r = -0.18, P < 0.001). Those with adiponectin in the second quartile or higher (>10 microg/ml) compared with those in the first quartile had a reduced odds for renal dysfunction (multivariate odds ratio 0.48 [95% CI 0.28-0.81]). These results were unchanged when serum lipids were included in the multivariate model. CONCLUSIONS: We conclude that a higher serum adiponectin concentration is associated with reduced odds of moderate renal dysfunction in men with type 2 diabetes.     

2型糖尿病患者Pentraxin-3与尿白蛋白相关性的研究

目的:分析2型糖尿病患者Pentraxin-3(PTX3)与尿白蛋白的相关性,探讨PTX3在糖尿病肾病中的作用。方法:2型糖尿病患者115例,根据尿白蛋白排泄率(UAER)分成正常白蛋白尿组、微量白蛋白尿组与临床白蛋白尿组,分别检测3组PTX3、血糖、血脂、HS-CRP、γ-谷氨酰转移酶等。结果:微量白蛋白尿组PTX3水平显著高于正常白蛋白尿组(P<0.01),临床白蛋白尿组PTX3水平显著高于正常白蛋白尿组和微量白蛋白尿组(P<0.01),PTX3与UAER呈正相关(r=0.667,P<0.01)。各组间年龄、FPG、TG、GGT、HS-CRP比较差异有统计学意义(P<0.05)。结论:PTX3水平与白蛋白尿相关,PTX3有助于糖尿病肾病的早期诊断。2型糖尿病患者PTX3水平升高是一个重要的危险因素。     

中国人群中血糖波动与2型糖尿病视网膜病变关系的meta分析

目的 通过比较血糖波动在2型糖尿病伴视网膜病变（diabetic retinopathy, DR）与2型糖尿病不伴视网膜病变（non diabetic retinopathy, NDR）人群中的差异,探讨血糖波动与DR的关系。方法 全面检索数据库,纳入比较DR患者与NDR患者血糖波动的文献17篇,采用RevMan5.3软件和STATA12.0软件进行meta分析。结果 在纳入的17项研究中, DR组的平均血糖波动幅度（mean amplitude of glycemic excursion, MAGE）明显高于NDR组［加权均数差（weighted mean difference, WMD）及95%CI为2.12(1.66,2.58),P＜0.01］。在纳入的9项研究中,非增殖期糖尿病视网膜病变（non proliferative diabetic retinopathy, NPDR）组的MAGE明显低于增殖期糖尿病视网膜病变（proliferative diabetic retinopathy, PDR）组［WMD及95%CI为-1.09(-1.42,-0.77),P<0.01］。NPDR组的MAGE明显高于NDR组［WMD及95%CI为1.52（1.25,1.79）,P<0.01］。结论 从NDR组到NPDR组再到PDR组,平均血糖波动幅度呈逐步增大趋势。     

Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy

To determine correlations among the levels of urinary MMP-9 and type-IV collagen, hyperglycemia, urinary protein excretion, and renal injuries in patients with type 2 diabetic nephropathy, we measured levels of urinary MMP-9 and protein, blood urea nitrogen (BUN), serum creatinine (s-Cr), fasting plasma glucose (FPG), and glycohemoglobin A1c (HbA1c) in 47 diabetic patients and 14 healthy adults. Urinary type-IV collagen was also measured in 28 diabetic patients and seven healthy adults. Patients with diabetic nephropathy were divided into two groups: 1). patients with normoalbuminuria or microalbuminuria (0-299 mg/g.Cr; n=27), and 2). patients with macroalbuminuria (>300 mg/g.Cr; n=20). The mean level of urinary MMP-9 in group 2 was significantly higher than those in healthy adults (P<0.05), and the levels of urinary MMP-9 in patients with diabetic nephropathy increased in accordance with the clinical stage of the disease. The levels of urinary MMP-9 tended to be correlated with HbA1c in these patients, but the correlation was not statistically significant. The mean level of urinary type-IV collagen in group 2 of patients with diabetic nephropathy was significantly higher than that in group 1 and healthy adults. Levels of urinary type-IV collagen in patients with diabetic nephropathy also increased in accordance with the clinical stage of the disease. The results suggest that measurements of urinary MMP-9, as well as urinary type-IV collagen, may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy, especially in the early stage.     

尿NGAL、L-FABP及RBP与老年2型糖尿病肾病的相关性研究

目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肝型脂肪酸结合蛋白(L-FABP)及视黄醇结合蛋白(RBP)在老年2型糖尿病肾病(DKD)患者中的变化,及与尿微量清蛋白/肌酐比值(UACR)和估算的肾小球滤过率(eGFR)的相关性。方法选取2017年1月至2018年3月该院收治的老年2型DKD患者184例,根据UACR分为尿蛋白正常组(n=68)、微量清蛋白尿组(n=66)及大量清蛋白尿组(n=50),另选取同期体检健康者60例作为健康对照组。采用酶联免疫吸附测定检测各组尿NGAL、L-FABP及RBP水平。Pearson相关分析尿NGAL、L-FABP及RBP水平与UACR、eGFR的相关性。结果尿蛋白正常组、微量清蛋白尿组和大量清蛋白尿组尿NGAL、L-FABP及RBP水平明显高于健康对照组(P<0.05),微量清蛋白尿组尿NGAL、L-FABP及RBP水平明显高于尿蛋白正常组(P<0.05),大量清蛋白尿组尿NGAL、L-FABP及RBP水平明显高于尿蛋白正常组和微量清蛋白尿组(P<0.05)。相关性分析显示,老年2型DKD患者尿NGAL、L-FABP及RBP水平与UACR均呈正相关(r=0.542、0.826、0.706,P<0.01),尿NGAL、L-FABP及RBP水平与eGFR均呈负相关(r=-0.483、-0.607、-0.635,P<0.01)。结论尿NGAL、L-FABP及RBP水平在老年2型DKD患者中明显升高,与2型DKD患者的发生、发展密切相关。     

Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease

OBJECTIVE

There is now growing evidence that magnesium (Mg) deficiency is implicated in type 2 diabetes and its complications. However, it has not been fully elucidated whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in type 2 diabetic nephropathy.

RESEARCH DESIGN AND METHODS

This retrospective cohort study included 455 chronic kidney disease (CKD) patients (144 with type 2 diabetic nephropathy and 311 with nondiabetic CKD) who were hospitalized at Osaka General Medical Center for a CKD educational program between April 2001 and December 2007. The primary outcome was progression to renal replacement therapy. Participants were categorized based on serum Mg level into Low-Mg (serum Mg level ≤1.8 mg/dL) and High-Mg (serum Mg level >1.8 mg/dL) groups with the previously published normal lower limit chosen as the cutoff point.

RESULTS

Of the subjects with type 2 diabetic nephropathy, 102 progressed to ESRD during follow-up (median, 23 months). A multivariate Cox proportional hazards model showed that after adjustment for various demographic factors and laboratory data, the Low-Mg group had a 2.12-fold higher risk of ESRD than the High-Mg group (95% CI 1.28–3.51; P = 0.004). In contrast, 135 of the nondiabetic CKD subjects progressed to ESRD during follow-up (median, 44 months). No significant difference in outcome was found between the Low- and High-Mg groups of this population (adjusted hazard ratio, 1.15; 95% CI 0.70–1.90; P = 0.57).

CONCLUSIONS

Hypomagnesemia is a novel predictor of ESRD in patients with type 2 diabetic nephropathy.Magnesium (Mg) is the fourth most abundant cation in the human body and plays a key role in many fundamental biological processes, including energy metabolism and DNA synthesis. Mg deficiency has been shown to cause endothelial cell dysfunction, inflammation, and oxidative stress, which are major contributors to atherosclerosis (1–3). Some epidemiologic studies have reported associations between low Mg intake or serum Mg level and hypertension, coronary artery disease, and ischemic stroke (4–6).Mg and type 2 diabetes have a close relationship. Approximately one-third of patients with type 2 diabetes have hypomagnesemia, mainly caused by enhanced renal excretion (7). Mg deficiency is associated with poor glycemic control, and Mg supplementation improves insulin sensitivity (8). Moreover, there is substantial evidence of associations between hypomagnesemia and various complications of type 2 diabetes, including neuropathy, retinopathy, foot ulcers, and albuminuria (9–12). The relationship between Mg deficiency and advanced type 2 diabetic nephropathy, however, remains to be fully elucidated. Pham et al. (13) reported that serum Mg level was significantly associated with the slope of inverse serum creatinine (SCr) in type 2 diabetes with near-normal renal function. However, they failed to show a significant association between hypomagnesemia and hard renal outcome (doubling of SCr and initiation of renal replacement therapy [RRT]), probably due to low statistical power (14). Therefore, the aim of the current study was to determine whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in patients with advanced type 2 diabetic nephropathy. We also compared the impact of hypomagnesemia on renal outcome in type 2 diabetic nephropathy with that in nondiabetic chronic kidney disease (CKD).     

吡格列酮对2型糖尿病肾病患者骨桥蛋白和尿微量白蛋白的影响

目的:探讨吡格列酮对2型糖尿病(T2DM)早期肾病患者血清骨桥蛋白(OPN)及尿微量白蛋白/尿肌酐比值(UMA/Cr)的影响.方法:90例T2DM患者按照2009年ADA糖尿病指南以UMA/Cr分为单纯糖尿病组(DM,UMA/Cr＜ 30 μg/mg)30例、糖尿病肾病组(DN,UMA/Cr:30 ～ 299 μg/mg)60例,同时选择30名体检正常者为正常对照组.再将DN组随机分为吡格列酮组30例(吡格列酮30 mg/d+胰岛素,n=30)和安慰剂组30例(安慰剂+胰岛素,n=30),随访治疗3个月.所有对象均测定血糖、血脂、肾功能、C反应蛋白(CRP)、OPN和UMA/Cr等.结果:吡格列酮组治疗3个月后,UMA/Cr[(35.02±6.38) μg/mg vs(86.30±12.21) μg/mg、P＜0.01]、OPN[(394.24±19.43)ng/mL vs (457.00±15.21) ng/mL、P＜0.01]及HbA1c、TG、CRP与安慰剂组比较均显著降低,差异有统计学意义.相关性分析显示△UMA/Cr(△:治疗前-治疗后的差值)与血清△OPN(r=0.673,P=0.000)呈显著正相关.结论:T2DM肾病患者血清OPN水平升高.吡格列酮能减少UMA/Cr水平.其部分可能是通过降低血清OPN水平实现的.     

初发2型糖尿病患者并发勃起功能障碍的病例对照分析

目的：探讨初发2型糖尿病(T2DM)患者并发勃起功能障碍(ED)的多种影响因素。方法：应用1：1配对病例对照研究，顺序收集57例初发T2DM合并ED的患者作为病例组，同期初发T2DM未合并ED的患者57例作为对照组，一对内年龄相差不超过2岁。对体重指数(BMI)、空腹血糖(FPG)、口服葡萄糖耐量实验(OGTT)2h血糖(2hPG)、空腹血胰岛素(INS)、空腹C-肽、糖化血红蛋白(HbAlc)、血清睾酮(T)、雌二醇(E2)、睾酮／雌二醇(T／E2)、血清一氧化氮(NO)、红细胞醛糖还原酶(AR)、吸烟、酗酒、伴发疾病(包括高血压、高脂血症、高尿酸血症、心脏疾病、肝脏疾病等)、其他慢性并发症(糖尿病神经病变、糖尿病视网膜病变、糖尿病肾病等)、药物使用(包括B受体阻滞剂、钙通道阻滞剂、血管紧张素转换酶抑制剂及利尿剂等可影响勃起功能的药物)等进行分析。结果：BMI、FPG、2hPG、INS、HbAlc、AR、NO、伴发疾病、并发症以及药物使用在两组间差异有显著性(P<0．05)。结论：初发T2DM患者并发勃起功能障碍是多种因素作用的结果。     

Plasma uric acid and the risk of type 2 diabetes in a Chinese community

BACKGROUND: Previous cross-sectional studies have shown hyperuricemia to be prevalent among individuals with metabolic syndrome, but the evidence from prospective studies of an association between uric acid and diabetes risk is limited. We prospectively investigated the association between plasma concentrations of uric acid and the incidence of type 2 diabetes in Chinese individuals. METHODS: We conducted a community-based prospective cohort study of 2690 participants (age range, 35-97 years) in the Chin-Shan Community Cardiovascular Cohort Study, who were found to be free of diabetes and cardiovascular disease during baseline assessment at study entry in 1990. During a median 9.0-year follow-up, 548 participants developed type 2 diabetes. RESULTS: High plasma uric acid concentrations were associated with a higher prevalence of metabolic syndrome. After adjustment for age, sex, body mass index, and other covariates, the relative risks (RR) of diabetes according to uric acid quintile were 1.11, 1.29, 1.40, and 1.63 [95% confidence interval (CI), 1.20-2.23; P for trend <0.001]. After additional adjustment for metabolic syndrome, the RR for comparing the participants in the fifth and first uric acid quintiles was 1.40 (95% CI, 1.02-1.92; P for trend = 0.027). In joint analyses, participants who were in the highest uric acid quintile and also had metabolic syndrome had a 3.3-fold greater risk of diabetes (95% CI, 2.27-4.94) than those in the lowest uric acid quintile and without metabolic syndrome. CONCLUSIONS: These findings suggest a modest positive association between plasma uric acid concentration and the incidence of type 2 diabetes in Chinese individuals. The association between hyperuricemia and diabetes was partly mediated through the metabolic syndrome.