Angiotensin converting enzyme (ACE) activity levels in insulin-independent diabetes mellitus and effect of ACE levels on diabetic patients with nephropathy

Involvement of complications is considered to be one of the major factors in the prognosis of diabetes mellitus (DM). Recent studies indicate that most diabetic complications such as nephropathy and hypertension are vascular-originated. Renin-angiotensin involvement, especially changes in ACE activity level, is considered to be a key factor since ACE converts angiotensin I to angiotensin II which is a potent vasoconstrictor and plays a vital role in the regulation of blood pressure. Our present study focused on ACE activity levels along with blood glucose and HbA(1c) levels in diabetic patients with (n=18) or without (n=25) nephropathy as compared to control subjects (n=25). Blood glucose levels were significantly higher in both diabetic groups compared to controls (p<0.001). On the other hand, compared to controls, blood HbA(1c) levels were slightly higher in DM patients without complications whereas they were significantly increased in nephropatic DM patients (p<0.001). There was a very strong increase (p<0.001) at the level of ACE activity in both of the diabetic groups (with nephropathy: 47.11+/-3.70 U l(-1); without complications: 43.72+/-2.93 U l(-1); controls: 25.15+/-2.30 U l(-1)). ACE activity levels were also significantly higher in diabetic patients with nephropathy than in type II DM patients without complication (p<0.01). Our results demonstrate that ACE activity levels are increased in diabetic patients. Additional significant increase in ACE activity levels in diabetic patients with complications such as nephropathy supports the hypothesis that ACE activity has an essential role in the development of complications in diabetes.     

Selected metals status in patients with noninsulin-dependent diabetes mellitus

In order to investigate the relationships between metals zinc [Zn], copper [Cu], magnesium [Mg], or Calcium [Ca] and noninsulin-dependent diabetes mellitus, 65 patients of newly diagnosed noninsulin-dependent diabetes mellitus and 54 nondiabetic healthy controls were studied. The concentrations of selected metals in fasting blood samples and 24-h urine collections were determined. Hyperzincuria and hypermagnesuria were detected in diabetic patients (p<0.01). The diabetics also had lower Zn and Mg, and higher Cu, and Ca levels in their plasma than those of the controls, but the statistical differences in Ca and Mg were not significant.Significantly lower Zn and higher Ca levels in erythrocytes were found in diabetic patients (p<0.01). There is evidence of a significant difference in metals status between diabetic patients with or without the specific complications. This study further indicates that patients with NIDDM on Taiwan also have distinct changes in their metals status, and these perturbations are associated with some diabetic complications.     

2型糖尿病骨密度与冠状动脉钙化积分相关性研究

目的:探讨2型糖尿病患者冠脉钙化积分与骨密度的关系。方法:入选在2015年6月至2017年6月我科住院的2型糖尿病患者98例,按照性别以及糖化血红蛋白8%、低密度脂蛋白2.6 mmol/L、身高体重指数24 kg/m2为切点分为两组,进行冠脉动脉CT检查,计算冠脉动脉总钙化积分,依照钙化积分等于0为阴性组,大于0为阳性组。同时检测患者的骨密度、骨代谢指标、血钙、血磷等水平。比较冠脉钙化积分和骨代谢指标及骨密度的相关性。结果:1)男性患者中:阳性组糖化血红蛋白和颈部血管斑块形成明显高于阴性组,差异有统计学意义。女性患者中:阳性组年龄、颈部血管内膜厚度、高血压病史明显高于阴性组,差异有统计学意义。2)阳性、阴性两组之间骨代谢指标差异无统计学意义。3)男性患者中:阳性组腰椎骨密度明显高于阴性组,差异有统计学意义。女性患者中阳性组的腰椎骨密度明显低于阴性组,差异有统计学意义,在控制混杂因素以后,两组间差异无统计学意义。4)分别在男性和女性患者中按照年龄为60岁分为两组,两组间阳性组与阴性组的骨代谢指标及骨密度差异无统计学意义。结论:在2型糖尿病患者中,冠脉钙化积分和骨代谢以及骨密度之间无明显相关性。     

Soluble LDL-immune complexes in type 2 diabetes and vascular disease.

BACKGROUND AND AIMS: The oxidative modification of LDL has been shown to affect its clearance and to exert cytotoxic and immunogenic effects. The objective of our study was to analyse markers of LDL oxidation-soluble LDL containing immune complexes (LDL-ICs) in type 2 diabetes with micro- and macrovascular disease. PATIENTS AND METHODS: The study included 69 diabetic patients with coronary artery disease (DM + CAD), 78 non-diabetics with CAD, 47 controls, and 27 diabetics with nephropathy and 36 free from complications. OxLDL antibodies and advanced glycated end-products were measured by ELISA, and LDL-IC apo B content after PEG precipitation. RESULTS: Determination of a broad range of oxLDL antibody activity in all study groups showed no significant differences. In contrast, the content of apo B, a component of the antigen moiety of oxLDL-ICs, was higher in CAD and diabetes (+ CAD) than in LDL-ICs isolated from controls (p < 0.001). LDL-ICs did not differ between patients with CAD + DM and CAD patients free from diabetes. LDL-IC levels in diabetic patients with or without microangiopathy were significantly higher than in healthy volunteers (PEG-apo B 0.278 +/- 0.107 vs. 0.165 +/- 105 g/l, p < 0.002; PEG-IgG 151.7 +/- 76 vs. 115.4 +/- 62 g/l, p < 0.05). However, there was no significant difference in the level of circulating LDL-ICs between the subgroup of diabetic patients with nephropathy/retinopathy and patients free of microvascular disease (Ab-oxLDL 27.7 +/- 10.4 vs. 27.1 +/- 9.3 AU, NS; PEG-apo B 0.324 +/- 0.111 vs. 0.287 +/- 0.124 g/l, NS; PEG-IgG 1.68 +/- 0.68 vs. 1.42 +/- 0.80 g/l, NS). There was a statistically significant positive correlation between AGE content and LDL-ICs (r = 0.35, p < 0.009). A significant but inverse correlation was recorded between triglyceride concentration and level of LDL-ICs in DM + CAD (r = - 0.32, p < 0.016) and CAD patients (r = - 0.35, p < 0.002). A highly significant negative correlation between triglycerides and circulating LDL-ICs (r = - 0.54, p < 0.039) was observed in patients with early nephropathy, but not in those with physiological proteinuria. It is known that at a high triglyceride level in type 2 diabetes, the majority of LDL are small and dense, thus being more susceptible to oxidative modification. This could be a possible mechanism explaining why more LDL-ICs, with a level inversely correlating with triglyceride concentration, are generated in diabetes. CONCLUSION: The increased level of circulating LDL-ICs is a risk factor for the general population, including those with diabetes. Our results suggested the contribution of LDL-ICs to the development of atherosclerosis to probably be more significant than the direct contribution of oxLDLAb itself.     

Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes

INTRODUCTION: Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease. MATERIALS AND METHODS: CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression. RESULTS: SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction). DISCUSSION: Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.     

Relationship among coronary plaque compliance, coronary risk factors and tissue characteristics evaluated by integrated backscatter intravascular ultrasound

ABSTRACT: BACKGROUND: The purpose of the present study was to evaluate the mechanical properties of coronary plaques and plaque behavior, and to elucidate the relationship among tissue characteristics of coronary plaques, mechanical properties and coronary risk factors using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: Non-targeted plaques with moderate stenosis (plaque burden at the minimal lumen site: 50-70%) located proximal to the site of the percutaneous coronary intervention target lesions were evaluated by IB-IVUS. Thirty-six plaques (less calcified group: an arc of calcification [less than or equal to]10) in 36 patients and 22 plaques (moderately calcified group: 10< an arc of calcification [less than or equal to]60) in 22 patients were evaluated. External elastic membrane volume (EEMV) compliance, lumen volume (LV) compliance, plaque volume (PV) response (difference between PV in systole and diastole), EEM area stiffness index were measured at the minimal lumen site. Relative lipid volume (lipid volume/internal elastic membrane volume) was calculated by IB-IVUS. Results: In the less calcified group, there was a significant correlation between EEMV compliance and the relative lipid volume (r=0.456, p=0.005). There was a significant inverse correlation between EEM area stiffness index and the relative lipid volume (p=0.032, r =-0.358). The LV compliance and EEM area stiffness index were significantly different in the diabetes mellitus (DM) group than in the non-DM group (1.32 +/- 1.49 vs. 2.47 +/- 1.79 %/10 mmHg, p =0.014 and 28.3 +/- 26.0 vs. 15.7 +/- 17.2, p =0.020). The EEMV compliance and EEM area stiffness index were significantly different in the hypertension (HTN) group than in the non-HTN group (0.77 +/- 0.68 vs. 1.57 +/- 0.95 %/10 mmHg, p =0.012 and 26.5 +/- 24.3 vs. 13.0 +/- 16.7, p =0.020). These relationships were not seen in the moderately calcified group. Conclusion: The present study provided new findings that there was a significant correlation between mechanical properties and tissue characteristics of coronary arteries. In addition, our results suggested that the EEMV compliance and the LV compliance were independent and the compliance was significantly impaired in the patients with DM and/or HTN. Assessment of coronary mechanical properties during PCI may provide us with useful information regarding the risk stratification of patients with coronary heart disease.     

The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

Background

Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population.

Methods

The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows.

Results

Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels).

Conclusion

In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease.     

Urinary excretion of glucagon-like peptide 1 (GLP-1) 7-36 amide in human type 2 (non-insulin-dependent) diabetes mellitus.

The urinary excretion of insulinotropic glucagon-like peptide 1 (GLP-1) was investigated as an indicator of renal tubular integrity in 10 healthy subjects and in 3 groups of type 2 diabetic patients with different degrees of urinary albumin excretion rate. No significant difference emerged between the groups with respect to age of the patients, known duration of diabetes, metabolic control, BMI, or residual beta-cell pancreatic function. Endogenous creatinine clearance was significantly reduced under conditions of overt diabetic nephropathy, compared with normo and microalbuminuric patients (p < 0.01). Urinary excretion of GLP-1 was significantly higher in normoalbuminuric patients compared to controls (490.4 +/- 211.5 vs. 275.5 +/- 132.1 pg/min; p < 0.05), with further increase under incipient diabetic nephropathy conditions (648.6 +/- 305 pg/min; p < 0.01). No significant difference resulted, in contrast, between macroproteinuric patients and non-diabetic subjects. Taking all patients examined into account, a significant positive relationship emerged between urinary GLP-1 and creatinine clearance (p = 0.004). In conclusion, an early tubular impairment in type 2 diabetes would occur before the onset of glomerular permeability alterations. The tubular dysfunction seems to evolve with the development of persistent microalbuminuria. Finally, the advanced tubular involvement, in terms of urinary GLP1 excretion, under overt diabetic nephropathy conditions would be masked by severe concomitant glomerular damage with the coexistence of both alterations resulting in a peptide excretion similar to control subjects.     

Fetomaternal adrenomedullin levels in diabetic pregnancy.

We investigated whether maternal and fetoplacental adrenomedullin, a newly discovered hypotensive peptide involved in the insulin regulatory system, is modified in diabetic pregnancy. We studied its correlation with pregnancy complications associated with this disease. Thirty-six pregnant women with diabetes (13 with type I and 23 with gestational diabetes mellitus) and in 40 uncomplicated pregnancies were included. 10 out of 36 diabetic pregnancies were complicated by gestational hypertension. In each woman, adrenomedullin concentration in maternal and fetal plasma and in amniotic fluid was assessed by specific radioimmunoassay. We found that overall mean amniotic fluid adrenomedullin concentration was higher (p < 0.05) in diabetic (14.7 +/- 1.6 fmol/ml) than in uncomplicated pregnancies (10.8 +/- 0.9 fmol/ml), whereas no differences were present in maternal and fetal plasma adrenomedullin levels between diabetic and uncomplicated pregnant women. High levels of amniotic fluid adrenomedullin were found in both type I and gestational diabetes mellitus pregnancies (13.7 +/- 1.4 and 15.6 +/- 2.2 fmol/ml, respectively). Diabetic pregnancies complicated by gestational hypertension showed lower (p < 0.05) amniotic fluid adrenomedullin concentrations than normotensive diabetic patients. These findings suggest that placental adrenomedullin production is upregulated in diabetic pregnancy, and it may be important to prevent excessive vasoconstriction of placental vessels.     

Serum beta-glycosidases in diabetes mellitus

Levels of fasting blood glucose, serum beta-glucuronidase and beta-N-acetylglucosaminidase in 47 Libyan diabetic patients were determined. The respective mean values were 254.5 +/- 11 mg/dl, 74 +/- 5.7 Sigma units/ml and 171.8 +/- 25.5 microM PNP/dl. The mean body mass index and duration of diabetes of the patients were 30.5 +/- 0.91 kg/m2 and 7.5 +/- 1.16 years, respectively. Statistically significant correlations were found between fasting blood glucose and serum beta-glucuronidase levels (r = 0.65; p less than 0.001) and also between fasting blood glucose and beta-N-acetylglucosaminidase levels (r = 0.58; p less than 0.001). The activities of these two enzymes increase in serum with increasing fasting blood glucose levels. Patients with positive family history of diabetes have higher activities of these two enzymes than those without positive history of diabetes in the family. Patients with secondary complications have both enzymes elevated as compared with patients without secondary complications. Female patients have higher beta-N-acetylglucosaminidase activity and lower beta-glucuronidase activity than males. Age and duration of diabetes do not appear to have any effect on the activities of these enzymes.     

Reversibility of autonomic nerve function in relation to rapid improvement of glycemic control.

To determine the reversibility of autonomic nerve function in relation to the rapid improvement of glycemic control, we studied 54 patients with type 2 diabetes mellitus (33 men and 21 women; mean age, 49+/-8 years; mean duration of diabetes, 10+/-7 years). For 4 weeks of admission, the subjects were placed on strict dietary therapy, and 10 of them were under dietary therapy, 16 initially continued treatment with oral hypoglycemic agents, while 28 were treated with insulin. We measured the dark-adapted pupillary area (DAPA) by infrared photography, an indicator of diabetic autonomic neuropathy, on the second and 28th day after hospitalization. The change in FPG (delta FPG = - 111+/-49 mg/dl; mean +/- SD, p<0.001) and the change in HbA1c (delta HbA1c = -1.3+/-0.3%, p<0.001) were significantly improved. We observed significant improvements in the change in DAPA (delta DAPA) of all patients (25.1+/-11.0 vs. 25.7+/-11.6 mm2, delta DAPA = 0.6+/-1.4 mm2, p<0.01) and in those of patients without retinopathy (delta DAPA = 1.0+/-0.6 mm2, p<0.01). No change was observed in those of patients with retinopathy (delta DAPA= -0.02+/-0.3 mm2, NS). The delta DAPA was related to the delta HbA1c (r = -0.479, p<0.001) and also to the diabetic duration (years, r = -0.517, p<0.001). These findings suggest that a rapid improvement of glycemic control improves autonomic nerve function observed in type 2 diabetes with shorter duration. Particular attention should be paid to maintaining strict glycemic control at the stage of diabetic patients without retinopathy and those with shorter duration.     

A method for early diagnosis of reduced mobility of hand joints in diabetes mellitus type I

The study aimed at elaborating the technique of an early diagnosis of cheiroarthropathy. The study involved 170 patients with diabetes mellitus type I aged between 16 and 45 years and disease duration ranging from 1 year to 33 years. Advanced cheiroarthropathy with shining waxy skin was diagnosed in 41 patients (group I). No lesions characteristic for cheiroarthropathy was diagnosed in 122 patients (group II) while in 7 patients (group III) only skin lesions without contractures were noted. Proliferative retinopathy was significantly more frequent (p less than 0.001) in the group with cheiroarthropathy--39% to 8%. Mean age of patients of group I is 31.5 +/- 5.9 years, in group II--31.0 +/- 6.6 years. Duration of diabetes mellitus is 17.8 +/- 6.2 and 9.6 +/- 7.2 years respectively (p less than 0.05). An angle of metacarpophalangeal joint of the V finger extension was measured in all patients with goniometer. A significant difference was noted in both groups: 34.4 +/- 8.08 degrees and 56.5 +/- 7.1 degrees, respectively (p less than 0.01). Mathematic models were designed basing on the value of measured angle and duration of the disease. These models facilitate possible risk of cheiroarthropathy. Systematic measurements of metacarpophalangeal joint extension seems valuable means of early diagnosis of diabetic cheiroarthropathy and follow-up of such patients.     

老年主动脉瓣钙化与冠心病合并心律失常的相关性探讨

目的:探讨老年患者主动脉瓣钙化与冠心病合并心律失常的相关性。方法:纳入解放军总医院疑诊为冠心病的老年住院患者276例,行冠状动脉造影,同期行超声心动图和24 h动态心电图检查,详细记录患者病史。根据超声结果,将患者分成主动脉瓣钙化(AVC)组和非主动脉瓣钙化(NAVC)组,比较两组冠心病合并心律失常的检出率,评价老年患者主动脉瓣钙化对冠心病合并心律失常的预测价值。结果:AVC组和NAVC组的年龄、吸烟史、高血压史、糖尿病史存在显著性差异(P0.05);AVC组冠心病的确诊率为93.7%,而NAVC组为80.6%,两组差异有统计学意义(P=0.002);AVC组冠心病合并心律失常检出率也显著性高于NAVC组(59.2%vs 35.1%,P=0.043)。结论:主动脉瓣钙化与冠心病合并心律失常密切相关,有望作为冠心病合并心律失常的高危患者有效的筛查指标。     

BNP及NT-proBNP与2型糖尿病关系的研究进展

BNP及NT-proBNP是诊断心衰的重要指标。近年来BNP及NT-proBNP与2型糖尿病关系的研究有了新的进展。我们收集近年来国内外关于2型糖尿病中BNP及NT-proBNP的相关文献并进行研究。结果显示2型糖尿病合并冠心病、高血压、糖尿病肾病患者BNP或NT-proBNP有升高趋势。单纯2型糖尿病及糖尿病视网膜病变患者以及低血糖患者BNP或NT-proBNP差异无统计学意义。高血压、年龄、性别、体重指数、肾功能及心脏结构功能改变是2型糖尿病患者BNP及NT-proBNP的影响因素。降糖药物对2型糖尿病患者BNP及NT-proBNP水平的研究尚少,糖尿病病程、FPG以及HbA1c对BNP及NT-proBNP的影响尚存在争议。BNP及NT-proBNP升高对2型糖尿病合并冠心病、高血压、糖尿病肾病患者病情评估,预后判断及诊治具有非常重要的意义。降糖药物、糖尿病病程、FPG以及HbA1c对BNP及NT-proBNP的影响需要进一步研究。     

The prevalence, type and severity of cardiovascular disease in diabetic and non-diabetic patients: a matched-paired retrospective analysis using coronary angiography as the diagnostic tool

People with diabetes mellitus have a 2-8-fold excess in cardiovascular mortality than people without diabetes. This study compared angiographically determined cardiovascular disease in 79 patients with diabetes mellitus and an equal number of matched controls without diabetes under the age of 55 years. Seventy-nine diabetic patients coming to coronary angiography during a 12-month period were reviewed retrospectively along with 79 control patients matched for age (+/- 3 years), sex, ethnic origin and risk factors (hyperlipidemia, body mass index and smoking history). The angiographic features of a consecutive series of 62 European and 17 Asian patients and their matched-paired controls were assessed. In all study subjects had undergone elective coronary angiography and ventriculography. Angiographic findings were graded to describe severity and extent of coronary atherosclerosis. Left ventricular systolic function was assessed by ejection fraction. The diabetic group had a significantly higher arterial systolic pressure than the non-diabetic group (p < 0.008) and they were clinically obese with a body mass index of >30. Detailed analysis of the angiograms showed that prevalence and severity of coronary artery disease in diabetic patients was greater. The mean 'severity score' was 11.66 for the diabetic group against 8.49 for the non-diabetic group (p < 0.037). Multivessel disease was more common in diabetic patients than in the controls, with three-vessel disease being the most common. Furthermore, 38 of 79 diabetic patients had three-vessel disease compared to 29 of 79 controls. Diabetic patients were also more likely to have more segments diseased in one vessel. Systolic function was reduced in the diabetic group, with a significantly lower (p < 0.05) mean ejection fraction. The present study supports the evidence that diabetic patients have more extensive coronary artery disease than non-diabetic patients and a poorer prognosis, and that the coronary arteries of the Asian patients were affected more adversely than those of the European group irrespective of the diabetic state.     

Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus

Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11+/-1.15 x 10(3) AU/g vs controls 4.08+/-0.71 x 10(3) AU/g, p<0.001, vs DM1 4.14+/-0.86 x 10(3) AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50+/-75.15 micromol/l vs healthy subjects 79.80+/-23.72 micromol/l, p<0.001, vs DM1 97.50+/-30.91 micromol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products.     

Monitoring of early and advanced glycation in relation to the occurrence of microvascular complications in children and adolescents with type 1 diabetes mellitus

The authors aimed to evaluate if the monitoring of serum advanced glycation end-products (s-AGEs) could help to predict a development of diabetic complications. Clinical and biochemical parameters including fructosamine (FAM), glycated hemoglobin (HbA1c) and serum AGEs were investigated in children and adolescents with 1 type diabetes with (+DC) and without (-DC) complications. FAM levels (in mmol/l) were significantly elevated in +DC diabetic group compared to -DC one (3.043+/-0.459 vs. 2.614+/-0.430; p<0.001) or to controls (3.043+/-0.459 vs. 1.620+/-0.340; p<0.001) as well as in -DC compared to controls (2.614+/-0.430 vs. 1.620+/-0.340; p<0.001). HbA1c (in %) were significantly elevated in +DC diabetic group compared to -DC one (10.48+/-1.83 vs. 8.41+/-1.19; p<0.001) or to controls (10.48+/-1.83 vs. 5.0+/-0.38, p<0.001) and also in -DC compared to controls (8.41+/-1.19 vs. 5.0+/-0.38; p<0.001). Serum AGEs levels (in A. U.) were significantly higher in +DC group than in -DC (73.0+/-14.09 vs. 65.8+/-9.05; p<0.05) and in group +DC than in controls (73.0+/-14.09 vs. 60.17+/-13.78; p<0.05), whereas there was no difference between -DC and controls. FAM correlated with HbA1c in both diabetic groups (+DC: r=0.374; p<0.05; -DC: r=0.719; p<0.001), but not in controls. Serum AGEs were correlated with HbA1c (r=0.478; p=0.003) in +DC, but not in -DC or controls. Enhanced serum AGEs levels show that they could be not only an attendant phenomenon of microangiopathies, but also a predictor of their development.     

Lipoperoxidation in hepatic subcellular compartments of diabetic rats

It is known that an accumulation of lipoperoxidative aldehydes malondialdehyde (MDA) and 4-hydroxynonenal (HNE) takes place in liver mitochondria during aging. The existence and role of an increased extra- and intra-cellular oxidative stress in diabetes, an aging-accelerating disease, is currently under discussion. This report offers evidence that lipoperoxidative aldehydes accumulate in liver microsomes and mitochondria at a higher rate in spontaneously diabetic BB/WOR rats than in control non-diabetic animals (HNE content, diabetes vs. control: microsomes 80.6+/-19.9 vs. 25.75+/-3.6 pmol/mg prot, p = .024; mitochondria 77.4+/-15.4 vs. 26.5+/-3.5 pmol/mg prot, p = .0103). Liver subcellular fractions from diabetic rats, when exposed to the peroxidative stimulus ADP/Fe, developed more lipoperoxidative aldehydes than those from non diabetic rats (HNE amount, diabetes vs. control: microsomes 3.60+/-0.37 vs. 2.33+/-0.22 nmol/mg prot, p = .014; mitochondria 3.62+/-0.26 vs. 2.30+/-0.17 nmol/mg prot, p = .0009). Liver subcellular fractions of diabetic rats developed more fluorescent chromolipids related to HNE-phospholipid adducts, either after in vitro peroxidation (microsomes: p = .0045; mitochondria: p = .0023) or by exposure to exogenous HNE (microsomes: p = .049; mitochondria: p = .0338). This higher susceptibility of diabetic liver membranes to the non-enzymatic attack of HNE may be due to an altered phospholipid composition. Moreover, a decreased activity of the HNE-metabolizing systems can be involved: diabetic liver mitochondria and microsomes were unable to consume exogenous HNE at the same rate as non-diabetic membranes; the difference was already significant after 5' incubation (microsomes p<.001; mitochondria p<.001). These data show an increased oxidative stress inside the hepatocytes of diabetic rats; the impairment of the HNE-metabolizing systems can play a key role in the maintenance and propagation of the damage.     

Periodontal disease status of pregnant women with diabetes mellitus

The aim of the present study was to evaluate the association between type I diabetes mellitus (DM) and periodontal disease in pregnant women. Fifty-two pregnant women aged 27.9 +/- 6.9 years with type I DM participated in the present study. Forty-two non-pregnant type I female diabetics (mean age: 27.9 +/- 6.1 years) and 121 healthy non-pregnant women (mean age: 29.1 +/- 5.7 years) without diabetes formed the control group. All subjects were given a clinical periodontal examination including probing pocket depth (PPD), probing attachment level (PAL), assessment of plaque and gingivitis scores (SBI). Blood parameters included levels of hemoglobin, glycosylated hemoglobin, total cholesterol, triglyceride and leukocytes. The pregnant diabetic subjects showed despite a good metabolic control significantly higher values for the SBI compared to the controls. Pregnant diabetic subjects displayed a significant correlation between the dose of insulin per day and PPD (p < or = 0.05) as well as the PAL (p < or = 0.05). In conclusion, the results of the study indicate that pregnant diabetics demonstrate a higher degree of periodontal inflammation and destruction compared to non-pregnant diabetics and healthy non-pregnant patients.