Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p <0.01). 86 of the patients had first morning urine albumin concentration < 30 mg/L (normoalbuminuria = NA), 16 patients 30–200 mg/L (microalbuminuria = MA) and ten patients < 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p > 0.5). No significant difference in median Lp(a) concentration was found between patients with IDDM, NIDDM treated with insulin, or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p > 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 umol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p < 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.     

Serum fructosamine correlates with gingival index in children with insulin-dependent diabetes mellitus (IDDM)

Abstract Fructosamine assay, which is used in diagnosing and monitoring diabetic patients, is compared with the hemoglobin and plasma glucose assays in children and adolescent insulin-dependent diabetes mellitus patients. We demonstrated that the gingival index scores were correlated with fructosamine values in insulin-dependent diabetes mellitus patients but not in non-diabetic controls. We also found that there was no correlation between gingivitis scores and fasting plasma glucose and HbAlc values. Periodontitis was found to be rare in diabetic children and adolescents.     

Oxygen-Dependent Processes in Monocytes and Metabolic Risk Factors for Atherogenesis

Oxygen-dependent processes in peripheral blood monocytes were intensified in patients with metabolic cardiovascular syndrome. This was manifested in increased production of O(2)(*-) and NO. Among metabolic factors (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, glucose, etc.), products of glycosylation (fructosamine) and plasma triacylglycerols were most potent in modulating generation of O(2)(*-) and NO by monocytes.     

Enzymatic kinetics regarding reversible metabolism of CS-0777, a sphingosine 1-phosphate receptor modulator,via phosphorylation and dephosphorylation in humans

1.?CS-0777, a candidate compound for autoimmune diseases, becomes phosphorylated active metabolite, M1, by fructosamine 3-kinase (FN3K), FN3K-related protein (FN3K-RP); and M1 is reverted back to CS-0777 by alkaline phosphatase (ALP) in the body. We performed enzyme kinetic analysis of phosphorylation of CS-0777 by FN3K, FN3K-RP, human erythrocytes and human platelets; and dephosphorylation of M1 by various ALP isozymes and human liver, kidney, lung and small intestine microsomes.

2.?The Michaelis constants of human FN3K, FN3K-RP and erythrocytes for CS-0777 phosphorylation were in the range from 498?μM to 1060?μM. FN3K inhibitor, 1-deoxy-1-morpholinofructose, suppressed only about 20% of CS-0777 phosphorylation activity in human erythrocyte lysate. Immunodepletion of FN3K and FN3K-RP decreased M1 formation activity by about 25% and 50%, respectively, in human erythrocyte lysate.

3.?The Michaelis constants of four human ALPs and microsomes were in the range from 10.9?μM to 32.1?μM. The ALP inhibitor, levamisole, suppressed over 50% of M1 dephosphorylation activity in liver, kidney and lung microsomes.

4.?FN3K-RP is expected to take a prominent role in the phosphorylation of CS-0777 in human erythrocytes; dephosphorylation of M1 was observed in all ALPs and human tissue microsomes examined, with a similar affinity towards M1 among them.     

Effects of 4 weeks’ administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations

Summary The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 μg four times per day (breakfast, lunch, dinner, and evening snack), 30 μg three times per day (breakfast, lunch and dinner [BLD]), 30 μg three times per day (breakfast, dinner and evening snack [BDS]), and 60 μg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 μg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (– 1.4 ± 0.5 vs 0.3 ± 0.5 μmol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 ± 10 μmol/l in the pramlintide 30 mg four times per day group, 43 ± 7 μmol/l in the pramlintide 30 μg three times per day (BLD) group, 47 ± 6 μmol/l in the pramlintide 30 μg three times per day (BDS) group, 46 ± 7 μmol/l in the pramlintide 60 μg twice per day group, and 29 ± 8 μmol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA_1c as the measurement of glycaemic control are warranted. [Diabetologia (1997) 40: 1278–1285] Received: 3 January 1997 and in revised form: 2 May 1997     

血清果糖胺测定作为糖尿病诊断单一指标可行性的研究

目的通过对糖尿病确诊患者(测试组)及非糖尿病患者(对照组)进行血清果糖胺水平检测,评价该指标作为糖尿病单一诊断指标的可行性。方法采用自动生化分析仪对30例糖尿病患者及30例非糖尿病患者进行空腹血糖、餐后2h血糖及果糖胺测定,比较两组患者空腹血糖、餐后血糖及果糖胺结果差异有无统计学意义。结果测试结果表明,测试组果糖胺异常率达94.3%,数值范围(2.51±0.37)mmol/L,与对照组比较差异有统计学意义(P0.05),测试组、对照组空腹血糖及餐后2h血糖差异均有统计学意义(P0.05)。结论开展果糖胺试验可以反映患者测定前2～3周前的平均血糖水平,可作为糖尿病诊断筛查的灵敏指标。     

Binding of mannose‐binding lectin to fructosamines: a potential link between hyperglycaemia and complement activation in diabetes

Background

Complement activation via the MBL pathway has been proposed to play a role in the pathogenesis of diabetic complications. As protein glycation is increased in diabetes, we tested the possibility that the glycation product fructoselysine is a ligand for MBL and that its interaction with this protein may initiate complement activation.

Methods

We investigated the binding of MBL to fructoselysine by chromatography of human serum on fructoselysine‐Sepharose, followed by Western blot and mass spectrometry analysis. We also performed enzyme‐linked immunosorbent assays using purified MBL and fructoselysine‐derivatized (binding assay) or mannan‐coated plates (inhibition assay). Complement activation was determined by the fixation of C3d following incubation of fructoselysine‐derivatized plates with serum from subjects with different levels of MBL.

Results

MBL and its associated proteases were selectively purified from serum by chromatography on fructoselysine‐Sepharose. Competition experiments indicated that MBL had a similar affinity for mannose, fructose and fructoselysine. MBL bound, in a highly cooperative manner, to fructoselysine‐derivatized plates. This binding was associated with complement activation and was much lower with serum from subjects with low‐MBL genotypes.

Conclusions

MBL binding to fructoselysine and the ensuing complement activation may provide a physiopathological link between enhanced glycation and complement activation in diabetes. The cooperative character of this binding may explain the high sensitivity of diabetic complications to hyperglycaemia. Copyright © 2010 John Wiley & Sons, Ltd.     

糖尿病人血清果糖胺测定的临床意义

应用自制的DMF为标准品,建立一种测定糖化血清蛋白(GSP)的新方法——血清果糖胺(SFA)测定法。应用此方法对37名健康人和52例糖尿病人进行SFA测定,二者间差别显著。糖尿病患者的SFA与空腹血糖(FBG)及糖化血红蛋白(HbA_1)显著相关,与测定前3周的FBG均值相关性最好,17例无微血管并发症的糖尿病患者和15例有微血管并发症的糖尿病患者SFA之间无显著差异。本文提示SFA可以反映糖尿病患者的高血糖状态,对了解近期血糖控制情况有实用价值。     

黄连解毒汤对体内外晚期糖基化终产物形成的影响

目的探讨黄连解毒汤对体内外晚期糖基化终产物(AGEs)形成的影响。方法链脲佐菌素(ip给药)建立糖尿病大鼠模型,以不同剂量(0.5、1.0 g/kg)黄连解毒汤ig给药90 d后,检测血糖、糖化血红蛋白,血浆和肾组织中的果糖胺和AGEs水平。将不同浓度的黄连解毒汤与葡萄糖和牛血清白蛋白孵育21 d,用荧光光度法测定AGEs的荧光值。结果黄连解毒汤能明显降低糖尿病大鼠的血糖和糖化血红蛋白水平(P<0.01),抑制血浆和肾组织的果糖胺和AGEs的生成(P<0.01),并呈明显的剂量依赖性。黄连解毒汤对体外AGEs的生成也有明显的抑制作用,并有一定的剂量依赖性。结论黄连解毒汤对体内外AGEs的生成均有明显的抑制作用,这可能是黄连解毒汤治疗糖尿病并发症的机制之一。