-
1.
Expression of mitochondrial superoxide dismutase in polymorphonuclear leukocytes from patients with type 1 diabetes with and without microvascular complications.
Wegner, M, Rawłuszko-Wieczorek, AA, Araszkiewicz, A, Pioruńska-Stolzmann, M, Zozulińska-Ziółkiewicz, D, Wierusz-Wysocka, B, Jagodziński, PP
Polskie Archiwum Medycyny Wewnetrznej. 2014;(5):239-46
Abstract
INTRODUCTION One of the causes of impaired antioxidant response in patients with type 1 diabetes might be decreased expression of mitochondrial manganese superoxide dismutase (MnSOD). OBJECTIVES The aim of this study was to evaluate the expression of MnSOD on transcript and protein levels in polymorphonuclear leukocytes (PMNLs) from patients with type 1 diabetes and analyze its association with microvascular complications. PATIENTS AND METHODS The MnSOD expression was assessed in PMNLs from 46 patients with type 1 diabetes and 12 age- and sex -matched healthy subjects. The study group was divided into 2 subgroups: with and without microvascular complications. The MnSOD expression on the transcript level was evaluated by real -time quantitative polymerase chain reaction, while that on the protein level by Western blot analysis. RESULTS A significant increase in the MnSOD transcript level was observed in all patients with diabetes with and without microvascular complications (P = 0.01, P = 0.02, respectively). The MnSOD protein level was higher in patients without microvascular complications compared with those with complications and the control group (P = 0.05, P = 0.03, respectively). The MnSOD expression was positively correlated with fasting plasma glucose and total cholesterol levels both at the transcript level (r = 0.4, P <0.05 for both correlations) and at the protein level (r = 0.3 and r = 0.4, respectively, P <0.05). CONCLUSIONS Although an increased MnSOD transcript level in patients with type 1 diabetes suggests enhanced antioxidant mobilization in all diabetic patients, decreased levels of the MnSOD protein in PMNLs from patients with microvascular complications compared with those without complications indicates that patients with microvascular complications may have impaired antioxidant response.
-
2.
The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes.
Monnier, VM, Sell, DR, Strauch, C, Sun, W, Lachin, JM, Cleary, PA, Genuth, S, ,
Journal of diabetes and its complications. 2013;(2):141-9
-
-
Free full text
-
Abstract
PURPOSE We determined the association between novel and acid-labile skin collagen-linked advanced glycation endproducts (AGEs) and the progression of microvascular and neuropathic complications from baseline to near study closeout in the Diabetes Control and Complications Trial (DCCT). METHODS From a skin biopsy obtained near the close of the DCCT, proteolytic collagen digests were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane (GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the glycation product fructose-lysine (FL) using isotope dilution method. RESULTS GSPNE and MG-H1 correlated with age and diabetes duration (P<0.02), while GSPNE and FL correlated with the history of glycemia expressed as mean A1c (P≤0.003). Age and duration-adjusted GSPNE and FL levels were lower in intensive (INT) vs. conventional (CONV) treatment subjects in the primary prevention DCCT cohort (P<0.0001), and FL was lower in INT in the secondary intervention cohort (P<0.0001). GSPNE was associated with increased incidence of retinopathy progression (odds ratio (OR) / unit increase in GSPNE 2.5 for 3 step progression on the ETDRS scale, P=0.003) and sustained≥3 microaneurysms (MA) (OR=4.8, P<0.0001) from DCCT baseline up to the time of the biopsy, and prevalence of microalbuminuria or AER>40mg/24h (OR=5.3, P<0.0001), and confirmed clinical neuropathy (OR=3.4, P=0.015) at the time of the biopsy. GSPNE adjusted for mean A1c remained significant for ≥3 MA (P=0.0252) and AER (P=0.0006). The strong association of complications with A1c was reduced or eliminated when adjusted for GSPNE. CONCLUSIONS Glucosepane is a novel AGE marker of diabetic complications that is robustly associated with nephropathic, retinopathic and neuropathic outcomes despite adjustment for A1c, suggesting that it could be one mediator of these complications with possible diagnostic implications.
-
3.
[Primary preventive effect of metformin upon atherosclerosis in patients with type 2 diabetes mellitus].
Zhang, XY, Du, JL, Jia, YJ, Bai, R, Yang, Y, Ba, Y, Xing, Q, Men, LL
Zhonghua yi xue za zhi. 2009;(30):2134-7
Abstract
OBJECTIVE To investigate the preventive action of metformin for atherosclerosis (AS) in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 140 cases with T2DM were assigned to 2 groups taking metformin (n = 75) or not (n = 65). All cases received intensive control of blood glucose, blood pressure and blood lipids for 100 weeks. The data before and after intensive control were recorded and statistically analyzed. Common carotid intima-media thickness (CC-IMT) was the efficacy endpoint of AS. RESULTS Diastolic blood pressure (DBP), fasting blood glucose, post 2-hour blood glucose, glycated hemoglobin A1c, triglyceride (TG) and total cholesterol (TC) decreased in both groups after intensive metabolic control for 100 weeks (P < 0.05). Body mass index (BMI), HOMA insulin resistance index (HOMA-IR) and CC-IMT decreased in metformin group (P < 0.05) while high-density lipoprotein cholesterol (HDL-C) increased (P < 0.05). BMI (23.1 +/- 0.98) kg/m2, HOMA-IR (1.68 +/- 0.20) and CC-IMT (0.55 +/- 0.13) mm in metformin group were lower than those in non-metformin group [(24.1 +/- 0.05) kg/m2, 2.03 +/- 1.38, (0.70 +/- 0.15) mm)] at 100 week (P < 0.05). CC-IMT was positively correlated with BMI (r = 0.489, P < 0.05) , TC (r = 0.429, P < 0.05), low-density lipoprotein cholesterol (LDL-C) (r = 0.426, P < 0.05) and HOMA-IR (r = 0.428, P < 0.05). CONCLUSION Metformin attenuates CC-IMT of patients with T2DM and it has the primary preventive effect upon AS in patients with T2DM.
-
4.
Telmisartan reduced blood pressure and HOMA-IR with increasing plasma leptin level in hypertensive and type 2 diabetic patients.
Usui, I, Fujisaka, S, Yamazaki, K, Takano, A, Murakami, S, Yamazaki, Y, Urakaze, M, Hachiya, H, Takata, M, Senda, S, et al
Diabetes research and clinical practice. 2007;(2):210-4
Abstract
Telmisartan, a new angiotensin II type 1 receptor blocker (ARB), was recently reported to stimulate PPARgamma, and stronger effects of Telmisartan on insulin sensitivity has been expected than the class effect of ARB. In the present study, we examined the effects of Telmisartan on insulin sensitivity and adipokine levels in hypertensive and type 2 diabetic patients. Outpatients with both hypertension and type 2 diabetes mellitus (n=36; male 23, female 13), received 20-40mg Telmisartan orally once daily for 6 months. Physical examinations and blood or urine tests were performed before and 3 or 6 months after starting Telmisartan treatment. Results were statistically compared using Wilcoxon analysis. Telmisartan treatment for 3 or 6 months reduced systolic and diastolic blood pressure and urinary albumin excretion. Fasting plasma glucose, HbA1c, total and HDL-cholesterol, triglyceride, body weight, BMI and waist length were not changed. Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment, suggesting the improved insulin sensitivity. Total and high molecular adiponectin were not changed. Interestingly, serum leptin was significantly increased by 3 months Telmisartan treatment, suggesting a possible involvement of leptin in improved insulin sensitivity. In conclusion, Telmisartan improved insulin resistance with increased serum leptin level in hypertensive and type 2 diabetic patients.
-
5.
Effects of irbesartan on intracellular antioxidant enzyme expression and activity in adolescents and young adults with early diabetic angiopathy.
Chiarelli, F, Di Marzio, D, Santilli, F, Mohn, A, Blasetti, A, Cipollone, F, Mezzetti, A, Verrotti, A
Diabetes care. 2005;(7):1690-7
Abstract
OBJECTIVE Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy. RESEARCH DESIGN AND METHODS This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l). RESULTS At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan. CONCLUSIONS Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.
-
6.
The Diabetes Prevention Program.
Muniyappa, R, El-Atat, F, Aneja, A, McFarlane, SI
Current diabetes reports. 2003;(3):221-2
-
7.
[Transcapillary filtration of plasma proteins in patients with diabetes type II microangiopathy complications].
Muszyńska-Lachota, I
Annales Academiae Medicae Stetinensis. 2002;:255-69
Abstract
UNLABELLED This study presents the results of the research on transcapillary filtration of plasma proteins in patients with non-insulin dependent diabetes mellitus (NIDDM). The aims of the study were as follows: (a) Examination of transcapillary filtration of plasma proteins in patients with NIDDM; (b) Search for correlations between metabolic status of diabetes, severity of diabetic microangiopathy and penetration of individual protein fractions into the blister fluid; (c) Examination of the influence of nonenzymatic glycation on albumin fragmentation and its transcapillary filtration. It was also decided to check whether changes in the blister fluid would appear earlier than fundal fluorescein angiography or microalbuminuria, two markers of diabetic microangiopathy. The study enrolled 34 patients with type II diabetes mellitus, aged 35-78 years, with a mean disease duration of 12.5 years (SD = 7.8). The control group included 10 non-diabetic volunteers aged 31-76 years. The mean age in both groups did not differ significantly. The cantharidin blister method was used to study the permeability of capillary vessels. The following laboratory tests were done: concentrations of serum urea, creatinine, glucose, fructosamine, glycated hemoglobin, cholesterol, and triglycerides. Electrophoretic separation of proteins in plasma and blister fluid was performed and the concentration of fructosamine in fluid was measured. Routine urinalysis was supplemented with microalbuminuria. The eye fundus was inspected and fundal fluorescein angiography was done. The influence of nonenzymatic glycation on protein fragmentation and its possible impact on the permeability of capillary vessels was determined with in vitro glycation of human serum albumin. In patients without diabetic retinopathy the Cb:Cs ratio for beta-globulin turned out to be significantly lower than in patients with proliferative retinopathy. Patients with normoalbuminuria had the Cb:Cs ratio for alpha 2-globulin significantly lower than patients with urinary albumin concentrations > or = 165 mg/L. When the group was divided with regard to serum fructosamine concentrations, the subgroup with fructosamine concentrations lower than 3 mmol/L revealed a significantly higher Cb:Cs ratio for fructosamine than the subgroup with fructosamine > or = 3 mmol/L. Concentrations of total protein, albumin, beta-globulin and gamma-globulin in blister fluid correlated positively with glycemia in the control group. Blister fluid concentration of beta-globulin correlated positively with HbAIC concentration. In the study group, total protein content in blister fluid correlated negatively with duration of diabetes and level of glycosuria. Concentrations of blister fluid alpha 1-globulin and gamma-globulin correlated negatively with glycosuria. Concentrations of blister fluid beta-globulin correlated negatively with duration of diabetes. Electrophoretic separation of in vitro SDS glycosylated human serum revealed no additional fraction in the incubated samples. Electrophoretic separation of in vitro glycosylated albumin disclosed co-migration of albumin monomers incubated for varying times with glucose. CONCLUSIONS 1. Glycation of human serum and albumin does not cause fragmentation of the proteins, but decreases transcapillary filtration of albumin due to change of molecular electric charge. 2. Patients with non-insulin dependent diabetes and microangiopathic complications reveal increased transcapillary transport of alpha 2- and beta-globulin in skin. 3. Increased permeability of skin capillary vessels for alpha 2- and beta-globulin in diabetic microangiopathy reflects an advanced stage of the disease and may facilitate progression.
-
8.
Effect of pregnancy on microvascular complications in the diabetes control and complications trial. The Diabetes Control and Complications Trial Research Group.
,
Diabetes care. 2000;(8):1084-91
-
-
Free full text
-
Abstract
OBJECTIVE To assess the effect of pregnancy on the development and progression of retinopathy and microalbuminuria in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted longitudinal analyses of the Diabetes Control and Complications Trial (DCCT), a multicenter controlled clinical trial that compared intensive treatment with conventional diabetes therapy and studied 180 women who had 270 pregnancies and 500 women who did not become pregnant during an average of 6.5 years of follow-up. Women assigned to the conventional treatment group were changed to intensive therapy if they were planning pregnancy or as soon as possible after conception. Fundus photography was performed every 6 months, and the urinary albumin excretion rate (AER) was measured annually. RESULTS Compared with nonpregnant women, pregnant women had a 1.63-fold greater risk of any worsening of retinopathy from before to during pregnancy (P < 0.05) in the intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not pregnant women in the conventional group (P < 0.001). In the conventional group, the odds of > or =3-step progression from the baseline retinopathy level was >2.9-fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR) peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during pregnancy in the intensive group, but not in the conventional group, was significantly elevated from the level at baseline, albeit in the normal range. Although individual patients had transient worsening of retinopathy during pregnancy, even to the proliferative level, at the end of the DCCT, mean levels of retinopathy and albuminuria in subjects who had become pregnant were similar to those in subjects who had not become pregnant within each treatment group. CONCLUSIONS Pregnancy in type 1 diabetes induces a transient increase in the risk of retinopathy; increased ophthalmologic surveillance is needed during pregnancy and the first year postpartum. The long-term risk of progression of early retinopathy and albumin excretion, however, does not appear to be increased by pregnancy.