Lipoprotein(a) levels in relation to diabetic complications in patients with non-insuIin-dependent diabetes

Abstract. The relationship between serum levels of lipoprotein(a) (Lp(a)) and the presence of chronic diabetic complications was studied in 194 patients with non-insulin-dependent diabetes mellitus (NIDDM; 75 males, 119 females; age 66±11 years; duration of diabetes, 11 (range 1–35) years). They were taking various treatments (diet alone, oral hypoglycaemic agents and/or insulin). Metabolic status and prevalence of diabetic complications were assessed by detailed history, physical examination, laboratory analysis and ECG. Average metabolic control was moderate (HbA_le, 8.2±1.7%). Median serum Lp(a) level was 183 U 1^--¹ (range 8–2600 U I^-1), which was significantly higher than in control subjects of comparable age (median 101; range 8–1747 U I^-1; P <0.05), while HDL-cholesterol levels were lower (1.14 ± 0.38 vs. 1.35 ± 0.35 mmol l^-1; P =0.001), and total cholesterol levels were comparable. No significant relation ships between diabetes treatment or metabolic control and Lp(a) levels were observed. In the quartile of patients with the highest Lp(a) levels. total cholesterol and triglycerides were slightly higher ( P < 0.05), where as HDL-cholesterol was not different. With increasing Lp(a) levels, higher prevalences of preproliferative retinopathy and of coronary artery disease (CAD) were observed, but not of the other complications. No relationship was found between the degree of albuminuria and Lp(a) levels. We conclude that in NIDDM patients, Lp(a) levels are elevated compared with non-diabetic subjects, and that higher Lp(a) levels are associated with higher prevalences of CAD and of retinopathy.     

938例糖尿病足病变严重程度与糖尿病肾病分期研究

目的探讨糖尿病足Wagner分级（1～5级）与糖尿病肾病分期（Ⅰ～Ⅴ）之间的相关性。方法 2001年1月至2008年6月期间在天津医科大学代谢病医院足病科住院的938例2型糖尿病合并糖尿病足病的患者为研究对象,根据Wagner分级分为足病较轻组（Wagner 1～2级组）和足病较重组（Wagner 3～5级组）,入院时留取24小时尿测量微量白蛋白（MAU）。结果糖尿病足病较重组与足病较轻组相比,糖化血红蛋白（HbA1c）和MAU水平明显增高,分别为HbA1c（9.63±2.37）%vs（9.12±2.05）%（P〈0.01）;MAU[43.85（90.40）]mg/d vs[27.50（59.35）]mg/d（P〈0.01）;足病较重组患有严重肾病（Ⅳ～Ⅴ期）的发生率明显高于糖尿病足病较轻组（30.8%vs 23.5%,P〈0.05）。结论糖尿病足病变严重程度较高者严重肾病发生率较高,MAU水平也较高。     

ACE基因插入缺失多态性与糖尿病肾病病情发展的关系

目的：探讨非胰岛素依赖型糖尿病（ＮＩＤＤＭ）肾病（ＤＮ）病情进展与血管紧张素转换酶（ＡＣＥ）基因插入缺失（ＩＤ）多态性的关系。方法：用ＰＣＲ方法分别检测了９２例不同程度蛋白尿的ＮＩＤＤＭ患者的ＡＣＥ基因型。结果：随着ＤＮ蛋白尿程度加重,ＤＤ型频率逐渐增高（微白蛋白尿期１７％,显性蛋白尿期２５％,肾功能不全期４６％）,而ＩＩ型频率逐渐下降（在３组分别为３３％、２９％和８％）,ＤＩ型在３组分布无显著性差异;在肾功能不全期组,ＤＤ型频率（４６％）显著高于肾功能正常期组（２０％）,Ｉ型频率（８％）显著低于肾功能正常期组（３２％）,ＤＩ型频率在２组无显著性差异。结论：ＤＤ型ＮＩＤＤＭ患者发生ＤＮ后,病情进展较快,ＤＤ型是ＤＮ恶化的促进因素;ＩＩ型为保护性因素。     

Angiotensin converting enzyme activity in the serum, lung and kidney of diabetic rats

Abstract. Diabetes Mellitus in its early stages, is associated with kidney enlargement and increased glomerular filtration rate in humans and in rats. The present study was designed to clarify the direct effect of diabetes on serum and tissue angiotensin converting enzyme (ACE) activity in streptozotocin-induced diabetic rats. Serum ACE activity, as determined using a radiometric assay, was significantly increased in the diabetic rats ( n = 15) 14 days after induction of diabetes (670 ± 31 vs. 506±14 nmol ml^-1 min^-1). Lung ACE activity, but not renal, was significantly elevated at 7 and 14 days by 29 and 46%, respectively. Plasma renin activity in the diabetic rats was decreased at 7 and 14 days by 41 and 78%, respectively. Incubations of lung slices in the presence of glucose at different concentrations did not affect in-vitro release of the enzyme. Administration of insulin (8 units kg^-1) to diabetic rats ( n = 6) on the 4th day for 11 days reduced ACE activity to values below control. Thus, serum and lung ACE activity is increased in the diabetic rat and reduced upon insulin treatment.     

Effects of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and their combination on microalbuminuria in normotensive patients with type 2 diabetes

The goal of this study was to compare the effects of lisinopril, losartan, and their combination on microalbuminuria in normotensive patients with type 2 diabetes mellitus. Patients were randomly assigned to 3 groups: group 1 (n=9), group 2 (n=9), and group 3 (n=8) received 10 mg lisinopril, 50 mg losartan, and 10 mg lisinopril plus 50 mg losartan, respectively, each day. For 12 mo, the 24-h urine albumin excretion rate was assessed at 3-mo intervals. At study completion, the urine albumin excretion rate had been reduced significantly in each group (P=.001); however, no significant differences were noted among groups (P=.587). Investigators in the present study have concluded that lisinopril, losartan, and their combination have similar effects on microalbuminuria in normotensive patients with type 2 diabetes mellitus, and that combination therapy does not provide additional benefit.     

Associations of serum uric acid level with diabetic retinopathy and albuminuria in patients with type 2 diabetes mellitus

ObjectivesTo analyze the associations of serum uric acid (SUA) level with diabetic microvascular complications, including diabetic retinopathy (DR) and diabetic nephropathy (DN), in patients with type 2 diabetes mellitus (DM).MethodsThree hundred eighty-nine inpatients with type 2 DM were included in this retrospective analysis. Nonmydriatic fundus cameras were used to identify DR. Urinary albumin creatinine ratio was used to identify DN. Patients were divided into four groups according to SUA quartiles.ResultsThe prevalences of DR and albuminuria increased with increasing SUA level. Multivariate logistic regression analysis showed that, following adjustment for other risk factors, higher levels of SUA (Q3 and Q4) were associated with greater risk for DR, compared with the lower level (Q1) (odds ratio [OR]: 3.056, 95% confidence interval [CI]: 1.506–6.198; OR: 3.417, 95% CI: 1.635–7.139, respectively). Moreover, higher levels of SUA (Q2, Q3, and Q4) were associated with greater risk for albuminuria (OR: 2.418, 95% CI: 1.059–5.522; OR: 7.233, 95% CI: 3.145–16.635; and OR: 8.911, 95% CI: 3.755–21.147, respectively).ConclusionsSUA level was independently associated with DR and albuminuria in patients with type 2 DM. Elevated SUA level might be predictive for the occurrence of DR and DN.     

Prevalence,characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus patients in Jordan: a cross-sectional study

ObjectivesTo measure the prevalence of diabetic retinopathy in patients with type 2 diabetes, to define their characteristics, and identify the associated risk factors.MethodsWe performed a cross sectional study of 1316 adult patients with type 2 diabetes mellitus who attended an ophthalmology clinic. Demographic, clinical, and laboratory data were analyzed. Diabetic retinopathy (DR) was diagnosed using a complete ophthalmic evaluation, including a fundic examination. Two regression models were constructed to identify the risk factors associated with DR and the parameters associated with the stage of retinopathy.ResultsMen accounted for 774 (58.8%) of the participants. The prevalence of DR was 28.2% (371 participants). DR was significantly more common in participants who were ≥60 years old, were women, had had diabetes for >10 years, were taking insulin, were not taking metformin, had a body mass index >30 kg/m², were current smokers, or had a history of hypertension. Advanced stages of DR were more common in participants in the later stages of nephropathy and with albuminuria.ConclusionsPoor glycemic control, smoking, and advanced diabetic kidney disease are most closely associated with retinopathy. Further longitudinal studies are necessary to identify the mechanisms underlying these relationships and to guide community-based interventions.     

2型糖尿病肾病患者C-反应蛋白及代谢指标临床分析

目的比较2型糖尿病（T2DM）肾病患者血清C-反应蛋白（CRP）水平变化并探讨其与代谢指标的关系。方法将148例T2DM患者设为糖尿病组（DM组）,并根据24 h尿微量白蛋白分为三组：无肾病组55例（B组）、早期肾病组58例（C组）、临床肾病组35例（D组）,30例健康体检者为对照组（A组）。测定血清CRP水平,同时检测血压、体质量指数（BM I）、空腹血糖（FPG）、血脂、尿酸（UA）、空腹胰岛素,计算胰岛素抵抗指数（HOMA-IR）,观察各组间CRP变化并进行相关分析。结果①DM组与A组相比,收缩压（SBP）、FPG、HOMA-IR、甘油三酯（TG）、低密度脂蛋白-胆固醇（LDL-C）升高、UA升高（P〈0.01或P〈0.05）,高密度脂蛋白-胆固醇（HDL-C）降低（P〈0.05）;D组与B组相比,SBP、UA升高（P〈0.05）,HDL-C降低（P〈0.05）;②B、C、D组CRP高于A组（P〈0.01）,C、D组CRP高于B组（P〈0.01）,D组CRP高于C组（P〈0.05）;③相关分析显示CRP与BM I、SBP、TG、LDL-C、HOMA-IR、UA存在显著正相关。结论 CRP与糖尿病肾病（DN）的发生相关,且随着DN进展而逐渐增高,可预测DN的进展;CRP水平升高与BM、ITG、LDL-C、UA、HOMA-IR等代谢指标密切相关,可作为T2DM患者心血管并发症的临床预测指标。     

Serum calcineurin activity in relation to oxidative stress and glycemic control in type II diabetes mellitus

OBJECTIVES: In view of the well-recognized prevalence of oxidative stress in diabetes mellitus and the susceptibility of calcineurin (Ca(2+)-calmodulin dependent protein phosphatase 2 B) to free radicals, calcineurin was assayed in the sera of type II diabetic patients. DESIGN AND METHODS: Serum contents of thiobarbituric acid reactive substances, calcineurin and calmodulin, as well as activities of calcineurin and superoxide dismutase were measured in 81 diabetic patients and compared with age-matched controls. RESULTS: Oxidative stress in diabetic subjects was evidenced by increased thiobarbituric acid reactive substances, decreased superoxide dismutase activity concomitant with decreased calcineurin activity in sera. The observed decrease in calcineurin activity had a reciprocal correlation with fasting blood sugar, thiobarbituric acid reactive substances, and glycosylated hemoglobin. CONCLUSION: The inverse correlation observed between serum calcineurin activity and glycosylated hemoglobin levels suggests that an assay of serum calcineurin activity may be useful in simultaneous assessment of oxidative stress and glycemic control in type II diabetes mellitus.     

脂联素与1型糖尿病肾病及可溶性血管细胞黏附分子-1的关系

目的:探讨1型糖尿病患者血清脂联素与肾小球滤过率之间的关系。方法:用酶联免疫法对75例1型糖尿病患者和40例对照组血清脂联素和可溶性血管细胞黏附分子-1水平进行测定。结果:1型糖尿病患者血清脂联素水平明显高于对照组[(17.47±6.36)μg/mL vs(13.98±5.63)μg/mL,P<0.01)],且脂联素与肾小球滤过率呈负相关,与可溶性血管细胞黏附分子-1呈正相关。结论:1型糖尿病患者血清脂联素与患者的肾功能减退密切相关,并与内皮和血管损伤有关。     

Arterial stiffness and vascular complications in patients with type 1 diabetes: The Finnish Diabetic Nephropathy (FinnDiane) Study

Abstract

Introduction/aims. While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D.

Methods. This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.7 versus 41.6 ± 1.2 years; P = NS)). Arterial stiffness was measured by pulse wave analysis from each participant. Furthermore, information on diabetic retinopathy, nephropathy, and CVD was collected. The renal status was verified from at least two out of three urine collections.

Results. Patients with T1D without signs of diabetic nephropathy had stiffer arteries measured as the augmentation index (AIx) than age-matched control subjects (17.3% ± 0.6% versus 10.0% ± 1.2%; P < 0.001). Moreover, AIx (OR 1.08; 95% CI 1.03–1.13; P = 0.002) was associated with diabetic laser-treated retinopathy in patients with normoalbuminuria in a multivariate logistic regression analysis. The same was true for AIx and diabetic nephropathy (1.04 (1.01–1.08); P = 0.004) as well as AIx and CVD (1.06 (1.00–1.12); P = 0.01) in patients with T1D.

Conclusions. Arterial stiffness was associated with microvascular and macrovascular complications in patients with T1D.     

Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus

Objectives

The aim of this study was to examine the relationship between serum levels of uric acid (UA) and 1,5-anhydroglucitol (1,5-AG) in elderly subjects (60 years or older; mean age, 73.0 ± 7.2 years) with and without type 2 diabetes mellitus (DM).

Methods

Subjects with DM (n = 97) and without DM (n = 360) were recruited from among our outpatients (estimated glomerular filtration rate ≥ 45 mL min^− 1 1.73 m^− 2 , and urine protein equivalent to < 1.0 g/L), and a cross-sectional study was performed with simple linear regression and stepwise multiple linear regression analyses.

Results

The mean serum UA levels of men were significantly higher than those of women in both groups. The mean serum 1,5-AG levels of men were significantly higher than those of women in the non-DM group. There were positive correlations (indicated by Pearson's correlation coefficients) between serum UA levels and 1,5-anhydroglucitol levels in all patients and in both men and women. Simple linear regression and multiple linear regression analyses showed that the serum 1,5-AG levels were significantly and positively correlated with the serum UA level in both the non-DM group and the DM group. In the non-DM group, HbA1c levels, as well as 1,5-AG levels, were positively correlated with serum UA levels. Furthermore, the correlation between 1,5-AG and UA levels was stronger in subjects with DM than in subjects without DM.

Conclusions

These results suggest that the serum 1,5-AG level is an independent factor associated with serum UA levels in the nondiabetic state, as in DM.     

Serum N-acetyl-beta-D-glucosaminidase profiles in type 1 diabetes secondary complications: causes of changes and significance of determination

The connection between changes in the activity of serum N-acetyl-beta-D-glucosaminidase (NAG, E.C.3.2.1.30) and iso-enzymes and degree of secondary complications was analyzed in four groups of type 1 diabetic patients (n=69): without complications (n=22); with retinopathy (n=16); with retinopathy and polyneuropathy (n=13), and with retinopathy, neuropathy, and nephropathy (n=18). In all groups statistically significant higher (P<0.001) percent fraction of A form (83.84+/-6.09, 84.37+/-5.74, 81.76+/-6.02, 76.37+/-7.38%, resp.) and lower (P<0.001, P<0.01) fraction of B form (15.87+/-5.65, 15.66+/-5.74, 18.33+/-5.98, 23.63+/-7.38, resp.) in total NAG compared with the control (A=69.38+/-4.79%, B=30.61+/-4.78%) were found. The differences in A as well as B forms between diabetic groups were not statistically significant. Significant strong positive correlations between total NAG and glycemia (0.494-0.623), total NAG and A form (0.934-0.966), and A form and glycemia (0.512-0.638) were found in all groups. No correlation was found between the fractions of B and A forms, except in the fourth group. The A form of diabetic patients in the fourth group was more acidic compared with the control and other diabetic groups. It was concluded that the changes in serum NAG and iso-enzymic profiles in diabetes are the consequence of its increased exocytose, especially of the A form, in hyperglycemia and posttranslational modifications of iso-enzymes. The total activity of serum NAG and iso-enzymic profiles cannot be used for monitoring the development and distinction of type 1 diabetes secondary complications.     

Serum prolidase enzyme activity and its relation to histopathological findings in patients with non‐alcoholic steatohepatitis

The aim of this study was to investigate serum prolidase enzyme activity and to find out its association with liver biopsy specimens' histopathological findings in patients with nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. Thirty‐six patients with biopsy‐proven NASH and 29 healthy controls were enrolled. Serum prolidase enzyme activity was measured spectrophotometrically. Serum prolidase enzyme activity was significantly higher in patients with NASH thancontrols (P=0.016). A significant correlation was observed between serum prolidase enzyme activity and fibrosis score in patients with NASH (r=0.661, P<0.001). Serum prolidase activity seems to be correlated with the level of fibrosis. Monitoring serum prolidase activity may be a useful adjunctive tool in predicting liver fibrosis, especially in the absence of advanced fibrosis and other conditions, which may affect the interpretation of prolidase activity. J. Clin. Lab. Anal. 24:207–211, 2010. © 2009 Wiley‐Liss, Inc.     

Response of large and small vessels to α and β adrenoceptor stimulation in heart failure: effect of angiotensin converting enzyme inhibition

Summary— The increased sympathetic drive in chronic heart failure (CHF) might provoke vascular adrenoceptor desensitization, which, together with endothelial dysfunction, could contribute to the altered vasomotor tone seen in CHF. We investigated 1) whether CHF alters the responses mediated by α and β adrenoceptors in small and large peripheral arteries, and 2) the effect of angiotensin-converting enzyme (ACE) inhibition. Rats with CHF (coronary artery ligation) were treated with placebo or the ACE inhibitor lisino-pril (10 mg/kg/d) starting 7 days after ligation. Responses to phenylephrine (α, agonist), salbutamol (β₂ agonist) as well as acetylcholine (endothelium-dependent), were assessed after 3 months in isolated and pressurized segments of the abdominal aorta, the femoral and the mesenteric arteries. In animals with hemodynamic signs of CHF, neither the vasoconstrictor responses to phenylephrine nor the vasodilator response to salbutamol were affected. In contrast, the dilator response to acetylcholine of both small arteries, but not that of the aorta, was impaired. Furthermore, CHF did not modify vessel structure. While lisinopril did not modify the responses to adrenergic agonists, it normalized the response to acetylcholine. Furthermore, ACE inhibition reduced vascular media cross sectional area and collagen density. Thus, the unchanged arterial responsiveness to adrenoceptor agonists does not indicate any vascular adrenoceptor desensitization, while endothelial dependent vasodilation of small arteries is impaired in CHF. ACE inhibition does not modify the response to adrenergic stimuli, prevents endothelial dysfunction and induces both cardiac and vascular remodeling, which probably contribute to the effect ACE inhibitors have on exercise tolerance and survival.     

Assessing telehealth interventions for physical activity and sedentary behavior self‐management in adults with type 2 diabetes mellitus: An integrative review

Type 2 diabetes is a chronic disease, requiring lifestyle management to prevent chronic complications. Increasing physical activity and reducing sedentary behavior are integral to maintaining glycemic control. The purpose of this study was to (1) appraise and synthesize the literature about physical activity and sedentary behavior intervention delivery via telehealth strategies in adults with type 2 diabetes mellitus and (2) to evaluate what is known about the effectiveness of such interventions on physical activity, sedentary behavior, and glycemic control. An integrative literature review was carried out, including the electronic databases PubMed, CINAHL, and PsychInfo, searching for articles published within the past 10 years, meeting specified inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement guidelines. Seventeen studies were included. Significant improvements in physical activity and sedentary behavior were identified in web and mobile phone‐based interventions. Modest improvements in glycemic control were reported. Theoretical framework use and integration was limited, and intervention length and follow‐up varied greatly in the studies reviewed. Outcomes were measured using both self‐report and objective measures, but objective measures were used less frequently. Further, few studies have been conducted in the United States or in rural populations. Web and mobile phone‐based telehealth interventions to increase physical activity, reduce sedentary behaviors, and improve glycemic control have been supported by the literature. A need exists for future studies that are theory‐driven, include dose‐specific measures, self‐report and objective measures, and long‐term follow‐up. Examining intervention effects in rural populations is needed.     

Susceptibility of glutatione and glutathione-related antioxidant activity to hydrogen peroxide in patients with type 2 diabetes: effect of glycemic control

OBJECTIVES: The aim of the present study was to examine the susceptibility of glutathione (GSH) and glutathione related antioxidant enzymes to oxidation in type 2 diabetic patients with and without glycemic control. DESIGN AND METHODS: Erythrocyte glutathione level and activities of glutathione peroxidase (G-Px), glutathione reductase (G-Red) and glutathione S-transferase (GST) in controls, well controlled and poorly controlled type 2 diabetics were measured by spectrophotometric assays before and after the incubation in vitro with H2O2. RESULTS: GSH level, G-Px and G-Red activities decreased but GST activity increased in the erythrocytes from all the groups after the incubation with H2O2. Percentage of decrease in GSH was independent from glycemic control, whereas the percentage of decreases in G-Px and G-Red was related to glycemic control. The percentage of increase in GST was found to be independent from diabetes. CONCLUSIONS: GSH and GSH-related antioxidant enzymes in human erythrocytes are susceptible to oxidation, particularly, G-Px and G-Red which were found to be more susceptible to oxidation in erythrocytes from poorly controlled type 2 diabetic patients.