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1.
Diabet Med ; 38(7): e14432, 2021 07.
Article in English | MEDLINE | ID: mdl-33078416

ABSTRACT

AIM: To measure skin autofluorescence in youth (<18 y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. METHODS: In a cross-sectional study (n = 383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. RESULTS: Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029 ± 0.003 arbitrary units per year (r = 0.76) and, for those without complications, it increased by 0.028 ± 0.002 arbitrary units (r = 0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022 ± 0.002 arbitrary units (r = 0.78) per year (p = 0.004). Mean ±se age-adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85 ± 0.04 vs 1.66 ± 0.02 arbitrary units) and people without diabetes (1.48 ± 0.03 arbitrary units; all P < 0.0001). Age-adjusted skin autofluorescence was higher in current smokers and recent ex-smokers vs non-smokers and longer-term ex-smokers (1.86 ± 0.06 vs 1.63 ± 0.02 arbitrary units; P = 0.0005). Skin autofluorescence area under the receiver-operating characteristic curve was 0.89 (95% CI 0.85-0.94) for retinopathy and 0.56 (95% CI 0.47-0.65) for nephropathy. CONCLUSIONS: Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.


Subject(s)
Diabetes Mellitus, Type 1/complications , Fluorescence , Luminescent Measurements , Skin/metabolism , Adult , Cross-Sectional Studies , Female , Glycation End Products, Advanced/metabolism , Humans , Male
3.
J Diabetes Complications ; 31(12): 1674-1680, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28941950

ABSTRACT

AIM: To examine the trajectory of small artery elasticity (SAE) and pulse pressure (PP) in people with Type 1 diabetes and non-diabetic controls across the lifespan, and explore associations with microvascular complications (CX+). METHODS: This cross-sectional study included 477 Type 1 diabetes patients (188 with CX+, 289 without CX-) and 515 controls. Relationships between SAE and PP and age were evaluated using segmented linear regression. Logistic regression was used to assess the associations between microvascular complications (retinopathy and/or nephropathy) and SAE and PP. RESULTS: SAE peaked significantly later among controls than diabetic patients CX- vs. CX+ (21.2 vs. 20.4 vs. 17.6 years respectively, p < 0.001). In adults, mean SAE was significantly lower in CX+ vs. CX- vs. controls (6.8 vs. 7.8 vs. 8.0 ml/mm Hg × 10; p < 0.0001), and mean PP was significantly higher in CX+ vs CX- and controls (60 vs. 55 vs. 53 mm Hg; p < 0.0001). CONCLUSION: Type 1 diabetes CX+ subjects have an earlier peak and decline in SAE relative to CX- and controls, who did not differ. Lower SAE and higher PP were associated with increased odds of Type 1 diabetes complications in adults. These clinically applicable techniques demonstrate an association between accelerated vascular aging and vascular complications in diabetes.


Subject(s)
Aging , Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/physiopathology , Vascular Stiffness , Adolescent , Adult , Aged , Aged, 80 and over , Child , Cohort Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/epidemiology , Disease Progression , Female , Humans , Male , Microvessels/physiopathology , Middle Aged , Pulse Wave Analysis , Regression Analysis , Risk , Victoria/epidemiology , Young Adult
4.
Diabet Med ; 34(4): 543-550, 2017 04.
Article in English | MEDLINE | ID: mdl-27770590

ABSTRACT

AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. RESULTS: Skin autofluorescence was significantly associated with age (R2 = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA1c (R2 = 0.32; P < 0.001) and HbA1c over the previous 2.5-10 years (R2 = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R2 = 0.11; P = 0.006). CONCLUSIONS: Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications.


Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/diagnostic imaging , Diabetic Retinopathy/diagnostic imaging , Microaneurysm/diagnostic imaging , Retinal Hemorrhage/diagnostic imaging , Skin/diagnostic imaging , Adolescent , Autonomic Nervous System Diseases/etiology , Autonomic Nervous System Diseases/physiopathology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/metabolism , Diabetic Angiopathies/etiology , Diabetic Angiopathies/physiopathology , Diabetic Retinopathy/etiology , Diabetic Retinopathy/physiopathology , Electrocardiography , Female , Fundus Oculi , Glycated Hemoglobin/metabolism , Heart Rate , Humans , Male , Microaneurysm/etiology , Microaneurysm/physiopathology , Multivariate Analysis , Optical Imaging , Retinal Hemorrhage/etiology , Retinal Hemorrhage/physiopathology , Skin/blood supply
5.
Diabet Med ; 33(11): 1544-1553, 2016 11.
Article in English | MEDLINE | ID: mdl-27472257

ABSTRACT

AIM: Insulin loses potency when stored at high temperatures. Various clay pots part-filled with water, and other evaporative cooling devices, are used in less-resourced countries when home refrigeration is unavailable. This study examined the cooling efficacy of such devices. METHODS: Thirteen devices used in Sudan, Ethiopia, Tanzania, Mali, India, Pakistan and Haiti (10 clay pots, a goat skin, a vegetable gourd and a bucket filled with wet sand), and two identical commercially manufactured cooling wallets were compared. Devices were maintained according to local instructions. Internal and ambient temperature and ambient humidity were measured by electronic loggers every 5 min in Khartoum (88 h), and, for the two Malian pots, in Bamako (84 h). Cooling efficacy was assessed by average absolute temperature difference (internal vs. ambient), and % maximal possible evaporative cooling (allowing for humidity). RESULTS: During the study period, mean ambient temperature and humidity were 31.0°C and 32.0% in Khartoum and 32.9°C and 39.8% in Bamako. All devices reduced the temperature (P < 0.001) with a mean (sd) reduction from 2.7 ± 0.5°C to 8.3 ± 1.0°C, depending on the device. When expressed as % maximal cooling, device efficacy ranged from 20.5% to 71.3%. On cluster analysis, the most efficacious devices were the goat skin, two clay pots (from Ethiopia and Sudan) and the suspended cooling wallet. CONCLUSIONS: Low-cost devices used in less-resourced countries reduce storage temperatures. With more efficacious devices, average temperatures at or close to standard room temperature (20-25°C) can be achieved, even in hot climates. All devices are more efficacious at lower humidity. Further studies are needed on insulin stability to determine when these devices are necessary.


Subject(s)
Aluminum Silicates , Drug Storage/methods , Drug Storage/standards , Hot Temperature , Insulin , Refrigeration/instrumentation , Refrigeration/methods , Clay , Climate , Cold Temperature , Drug Stability , Ethiopia , Haiti , Humans , Humidity , India , Mali , Pakistan , Sudan , Tanzania , Treatment Outcome
6.
Intern Med J ; 46(5): 550-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26909676

ABSTRACT

BACKGROUND: Concerns have been expressed 'that the physician-researcher is a dying breed'. As yet there are few Australian data. AIMS: To compare over time: (i) research progress of Sydney Medical School (SMS) medical practitioner - PhD awardees; (ii) National Health and Medical Research Council (NHMRC) project grant success rates for physician-researchers; and (iii) compare current NHMRC, NSW University and NSW Public Hospital pay scales for physician-researchers. METHODS: We evaluated 303 medical practitioners awarded a University of Sydney/SMS PhD in 1989-2012 and their publications. We assessed 1990-2014 NHMRC grants to physicians and non-physicians (nationally) and compared physician salaries from NHMRC, the University of Sydney and NSW public hospitals. RESULTS: SMS PhD completions by clinicians increased ≈2.4-fold since 1989, with a recent decline, whilst non-medical PhD awardees rose 10-fold. The median time of PhD award after medical degree completion was stable at 13 years. A lower percentage of the more recent physician-researchers had completed specialty training at PhD award (34% in 2011-2012 vs 71% in 1989-1990, P = 0.017). Publication rates were stable, but low. Although NHMRC funding increased >10-fold since 1990, national project grant success rates declined (35% in 1990, 17% in 2013 and 15% in 2014, P < 0.0001), with physician-led funded grants declining from 29% in 1989 to 21% in 2013, P = 0.002. Current NHMRC and University salaries are less than comparable-stage public hospital salaries. CONCLUSION: Since 1989, more medical graduates are completing SMS PhDs, although more often prior to completing clinical Fellowships, and many have ongoing, albeit low, research activity. Nationally NHMRC project grant success rates have declined significantly, as has the proportion of funded physician-led projects. Medical practitioner salaries from NHMRC and from Universities are less than in public hospitals. The Australian physician-researcher is at-risk. Knowledge and actions are needed to protect our medical research capacity.


Subject(s)
Biomedical Research , Education, Medical, Continuing/statistics & numerical data , Physicians/statistics & numerical data , Research Personnel/statistics & numerical data , Australia , Biomedical Research/economics , Education, Medical, Continuing/trends , Financing, Government , Humans , Logistic Models , Publications/statistics & numerical data , Publications/trends , Workforce
7.
Intern Med J ; 46(4): 412-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26692102

ABSTRACT

BACKGROUND: Given the concerns that physician-researchers are 'at risk', and ≈50% of Australian medical students are female, the evaluation of female physician-researchers is important. AIMS: To compare over time (i) research-related metrics of male and female physician-researchers from Sydney Medical School; and (ii) National Health and Medical Research Council (NHMRC) Project grant leadership by gender. METHODS: The Sydney Medical School (SMS) PhD award lists from 1989 to 2012 were cross-referenced with the Australian Health Practitioner Regulation Agency database, and registered medical practitioners were searched for in the Scopus database for publications and H-indexes. The gender of medical-practitioner Chief Investigator A (CIA) in Australia on funded NHMRC Project grants in 1990 to 2014 was also compared. RESULTS: Of the medical practitioners awarded University of Sydney PhD, females increased from 14 to 55% in 1989-1990 and 2009-2010 and decreased to 38% in 2011-2012 (overall increase, P = 0.047). PhD award timings relative to MBBS and clinical fellowship completions were similar for both genders (P > 0.05). Post-PhD, as many women as men publish and have similar H-indexes, but women publish fewer papers (0.7 vs 1.0 publications per year, P = 0.028). On medical practitioner-led, funded NHMRC project grants between 1999 and 2014, female CIA increased from 7.5 to 19.5%, P < 0.0001. For the 17% of project grant applications funded to commence in 2014, 21% were medical practitioner-led, of whom 19.5% were female. CONCLUSIONS: Since 1989, more female medical practitioners are completing SMS PhD at similar times in their careers to males. However, relative to their male peers, they publish less. Fewer female than male medical practitioner-researchers hold NHMRC Project Grant CIA status nationally, although the rates are increasing. In addressing physician-researcher workforce issues, including retention, attention should be given to factors impacting females.


Subject(s)
Biomedical Research/trends , Physicians/trends , Research Personnel/trends , Australia , Fellowships and Scholarships/trends , Female , Humans , Male , Time Factors
9.
Diabet Med ; 29(6): 726-33, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22211881

ABSTRACT

OBJECTIVE: To determine if ocular and skin autofluorescence, reflecting advanced glycation end-products, and vascular stiffness correlate in non-diabetic and Type 1 diabetic subjects and if levels differ by diabetes status. RESEARCH DESIGN AND METHODS: Patients with Type 1 diabetes (n = 69, 19 with and 50 without vascular complications) and 60 subjects without diabetes (control) had ocular and skin autofluorescence and pulse-wave analysis performed in the fasted state. Correlations between measures within groups used the Pearson or Spearman correlation-coefficient and measures between groups were compared by ANOVA. RESULTS: Lens and skin autofluorescence correlated in control (r = 0.58, P = 0.0001) and in Type 1 diabetes (r = 0.53, P = 0.001). Corneal autofluorescence correlated with lens (r = 0.53, r = 0.52, P = 0.0001) and skin autofluorescence (r = 0.34, P = 0.01 and r = 0.49, P = 0.00001) in control and Type 1 diabetes respectively. In Type 1 diabetes, small and large artery elasticity correlated inversely and systemic vascular resistance correlated positively with skin autofluorescence (all P = 0.001), and with lens and corneal autofluorescence (all P < 0.03). In Type 1 diabetes tissue advanced glycation end-products correlated with C-reactive protein and inversely with the estimated glucose disposal rate and with circulating advanced glycation end-product levels. Relative to non-diabetic subjects, lens, corneal and skin fluorescence were increased (all P < 0.001) and small artery elasticity was decreased in diabetes (P = 0.04). Lens, corneal and skin autofluorescence were greater (all P = 0.0001) in patients with Type 1 diabetes with complications compared to those without complications, but small artery elasticity did not differ significantly. CONCLUSIONS: Ocular and skin autofluorescence and vascular stiffness correlate in non-diabetic and Type 1 diabetes subjects and are increased in Type 1 diabetes. Tissue advanced glycation end-products correlate with vascular risk factors, including circulating advanced glycation end-products.


Subject(s)
C-Reactive Protein/metabolism , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/physiopathology , Diabetic Retinopathy/physiopathology , Fluorescence , Glycated Hemoglobin/metabolism , Glycation End Products, Advanced/blood , Vascular Resistance , Adult , Blood Pressure , Body Mass Index , Cornea/blood supply , Cross-Sectional Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/blood , Diabetic Angiopathies/etiology , Diabetic Retinopathy/blood , Diabetic Retinopathy/etiology , Female , Humans , Lens, Crystalline/blood supply , Male , Risk Factors , Skin/blood supply
10.
Diabet Med ; 24(12): 1345-51, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17971181

ABSTRACT

AIMS: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. METHODS: Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. RESULTS: PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). CONCLUSIONS: In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.


Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetic Nephropathies/blood , Diabetic Retinopathy/blood , Eye Proteins/blood , Nerve Growth Factors/blood , Protease Inhibitors/blood , Serpins/blood , Adult , Biomarkers/blood , Body Mass Index , C-Reactive Protein/analysis , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/physiopathology , Enzyme-Linked Immunosorbent Assay , Female , Glycated Hemoglobin , Humans , Male , Middle Aged , Oxidative Stress/physiology
11.
Diabetologia ; 50(3): 643-53, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17216278

ABSTRACT

AIMS/HYPOTHESIS: Hyperglycaemia, one of the main features of diabetes, results in non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA-I), the most abundant apolipoprotein in HDL. The aim of this study was to determine how glycation affects the structure of apoA-I and its ability to activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport. MATERIALS AND METHODS: Discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the cholate dialysis method and glycated by incubation with methylglyoxal. Glycation of apoA-I was quantified as the reduction in detectable arginine, lysine and tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by immunoblotting. (A-I)rHDL size and surface charge were determined by non-denaturing gradient gel electrophoresis and agarose gel electrophoresis, respectively. The kinetics of the LCAT reaction was investigated by incubating varying concentrations of discoidal (A-I)rHDL with a constant amount of purified enzyme. The conformation of apoA-I was assessed by surface plasmon resonance. RESULTS: Methylglyoxal-mediated modifications of the arginine, lysine and tryptophan residues in lipid-free and lipid-associated apoA-I were time- and concentration-dependent. These modifications altered the conformation of apoA-I in regions critical for LCAT activation and lipid binding. They also decreased (A-I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol esterification in (A-I)rHDL varied according to the level of apoA-I glycation and progressively decreased as the extent of apoA-I glycation increased. CONCLUSIONS/INTERPRETATION: It is concluded that glycation of apoA-I may adversely affect reverse cholesterol transport in subjects with diabetes.


Subject(s)
Apolipoprotein A-I/chemistry , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Apolipoprotein A-I/blood , Apolipoprotein A-I/physiology , Enzyme Activation , Glycosylation , Humans , Hyperglycemia/blood , Hyperglycemia/enzymology , Lipoproteins, HDL/blood , Lipoproteins, HDL/isolation & purification , Pyruvaldehyde/pharmacology
12.
Ann N Y Acad Sci ; 1043: 655-61, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16037289

ABSTRACT

Characteristic tissue fluorescence is associated with advanced glycation end product (AGE) accumulation in experimental diabetes models, but its utility in patients with type 1 diabetes remains to be established. We studied 148 patients with type 1 diabetes and 77 healthy age-matched control subjects. Low-molecular weight (LMW) fluorophore levels were estimated in plasma samples obtained after an overnight fast. Intra- and interassay coefficients of variation were 4.7% and 6.4%, respectively. LMW fluorophore levels were significantly higher in patients with diabetes than in control subjects (6.3 +/- 0.6 AU/mL vs. 4.1 +/- 0.3; P = 0.007). However, all of this difference came from patients with microvascular complications (n = 67, 7.5 +/- 1.3). There was no significant difference in LMW fluorescence between complication-free patients (4.4 +/- 0.2) and control subjects (P > 0.05). On multivariate analysis, LMW fluorophores correlated with measures of renal function (P < 0.05) but not with diabetes per se. In addition, there was no correlation between LMW fluorophores and the markers of oxidative stress or systemic inflammation. Longitudinal and interventional studies are required to determine whether the association between LMW fluorophores and nephropathy is cause or effect.


Subject(s)
Diabetes Mellitus, Type 1/blood , Glycation End Products, Advanced/metabolism , Adult , Body Mass Index , C-Reactive Protein/metabolism , Creatinine/blood , Female , Glycated Hemoglobin/analysis , Glycation End Products, Advanced/analysis , Humans , Kidney Function Tests , Lipids/blood , Male , Molecular Weight , Reference Values , Spectrometry, Fluorescence
13.
Diabetologia ; 47(8): 1385-95, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15309289

ABSTRACT

AIMS/HYPOTHESIS: This study was designed to determine whether inhibition of formation of AGE and advanced lipoxidation end-products (ALE) is a mechanism of action common to a diverse group of therapeutic agents that limit the progress of diabetic nephropathy. We compared the effects of the ACE inhibitor enalapril, the antioxidant vitamin E, the thiol compound lipoic acid, and the AGE/ALE inhibitor pyridoxamine on the formation of AGE/ALE and protection against nephropathy in streptozotocin diabetic rats. METHODS: Renal function and AGE/ALE formation were evaluated in rats treated with the agents listed above. Plasma was monitored monthly for triglycerides, cholesterol, creatinine and TNF-alpha, and 24-h urine samples were collected for measurement of albumin and total protein excretion. After 29 weeks, renal expression of mRNA for extracellular matrix proteins was measured, and AGE/ALE were quantified in skin and glomerular and tubular collagen. RESULTS: Diabetic animals were both hyperglycaemic and dyslipidaemic, and showed evidence of early nephropathy (albuminuria, creatinaemia). All interventions limited the progression of nephropathy, without affecting glycaemia. The order of efficacy was: pyridoxamine (650 mg.kg(-1).day(-1)) > vitamin E (200 mg.kg(-1).day(-1)) > lipoic acid (93 mg.kg(-1).day(-1)) approximately enalapril (35 mg.kg(-1).day(-1)). Pyridoxamine also significantly inhibited AGE/ALE accumulation in tissues; effects of other agents were mixed, but the degree of renoprotection was consistent with their effects on AGE/ALE formation. CONCLUSIONS/INTERPRETATION: All interventions inhibited the progression of nephropathy at the doses studied, but the maximal benefit was achieved with pyridoxamine, which also limited dyslipidaemia and AGE/ALE formation. These experiments indicate that the more effective the renoprotection, the greater the inhibition of AGE/ALE formation. For optimal protection of renal function, it would be beneficial to select drugs whose mechanism of action includes inhibition of AGE/ALE formation.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antioxidants/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/prevention & control , Animals , Blood Glucose/metabolism , DNA Primers , Diabetes Mellitus, Experimental/blood , Disease Progression , Female , Fibronectins/genetics , Kidney Function Tests , Lipids/blood , Polymerase Chain Reaction , Pyridoxamine/therapeutic use , Rats , Rats, Sprague-Dawley , Thioctic Acid/therapeutic use , Vitamin E/therapeutic use
14.
Biochem Soc Trans ; 31(Pt 6): 1413-6, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14641077

ABSTRACT

Hyperglycaemia is the major risk factor for the development of complications in both Type I and Type II diabetes; however, there is growing evidence from several clinical trials that dyslipidaemia, including hypertriglyceridaemia, is a significant and independent risk factor for diabetic complications. In this paper, we propose that chemical modification of proteins by lipids may be a underlying pathogenic mechanism linking dyslipidaemia to diabetic complications. Thus the major AGEs (advanced glycation end-products) in tissues, such as carboxymethyl-lysine, carboxyethyl-lysine and hydroimidazolones, may, in fact, be ALEs (advanced lipoxidation end-products), derived from lipids. Increased lipid peroxidation and accelerated ALE formation, possibly catalysed by hyperglycaemia and oxidative stress, may be the mechanistic link between dyslipidaemia and diabetic complications. If correct, this proposal would suggest that inhibition or reversal of glycation, which is a central theme of this symposium, may not be sufficient for protection against diabetic complications.


Subject(s)
Diabetes Mellitus/metabolism , Lipids/physiology , Proteins/metabolism , Diabetes Complications , Humans , Hyperlipidemias/complications , Hyperlipidemias/metabolism , Lipid Peroxidation
15.
Wiad Lek ; 52(1-2): 35-41, 1999.
Article in Polish | MEDLINE | ID: mdl-10335123

ABSTRACT

The aim of the study was to assess thyroid gland function in non-insulin dependent diabetes mellitus patients under different therapeutic regimens. There were examined 75 patients with type II diabetes mellitus, age range 33-80 years (average 65.24 +/- 14.32 years) including 46 women and 29 men. Group I was treated with insulin, group II--with diet, and group III--with sulfonylurea derivatives oral antidiabetic agents. Control group consisted of 91 healthy persons in appropriate age. The highest glucose levels were in insulin treated group--174.17 +/- 40.31 mg%, and were significantly higher from the values observed in oral antidiabetic agents treated group (169.89 +/- 41.34 mg%), and in diet treated group, where glucose levels were the lowest--134.57 +/- 25.06 mg%. In both groups--patients treated with insulin and with oral antidiabetic agents a positive correlation between fT4 and glycated hemoglobin levels were observed. Performed experiments and investigations suggest: 1. There are no differences in thyroid gland function in patients with non-insulin dependent diabetes mellitus. 2. Different therapies (diet, insulin therapy, oral antidiabetic agents) have no influence on thyroid gland function.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Thyroid Function Tests , Thyroid Gland/physiology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
16.
Folia Morphol (Warsz) ; 57(3): 257-62, 1998.
Article in English | MEDLINE | ID: mdl-9857574

ABSTRACT

The aim of the work was to estimate the health state and physical efficiency of children from rural area of Lubin-Glogów Copper-Basin in correlation with lead levels in blood. Lead concentration in blood showed increase tendency together with age of the children. In both sexes together with rise in lead concentration in blood enlargement of palatine tonsils was observed. In children with a higher lead concentration in blood lower values of physical fitness parameters are recorded.


Subject(s)
Copper , Lead/blood , Mining , Physical Fitness , Population Surveillance , Rural Health , Adolescent , Child , Evaluation Studies as Topic , Female , Humans , Male , Poland
17.
Postepy Hig Med Dosw ; 52(3): 269-81, 1998.
Article in Polish | MEDLINE | ID: mdl-9789436

ABSTRACT

This article present a review on the physiological activity and possible mechanism of action of C-peptide and clinical significance of using this hormone in the treatment of diabetes mellitus. The present results might suggest that, contrary to the prevailing view, C-peptide possesses biological activity and plays an important part in the attenuating or preventing from diabetic complications. It is important to realize that this discovery might someday revolutionize diabetes treatment, however further studies will be required to define and confirm the exact mechanism of C-peptide activity.


Subject(s)
Diabetes Mellitus/physiopathology , Peptides/physiology , Animals , Blood Glucose/metabolism , Diabetes Mellitus/drug therapy , Humans , Kidney/metabolism , Muscle, Skeletal/metabolism , Peptides/therapeutic use , Reference Values
19.
Med Pr ; 47(3): 217-25, 1996.
Article in Polish | MEDLINE | ID: mdl-8760505

ABSTRACT

UNLABELLED: The aim of the work was to assess te effect of chronic occupational exposure to organic solvents, hydrogen cyanide, and harmful physical factors (noise, vibration and electromagnetic fields) on intra- and extracellular concentration of magnesium, zinc, copper and calcium. The study converted 83 persons (25 males and 57 females), aged 20-58 years (median: 37.8 +/- 8.64), employed in the MERA PAFAL SA Factory of Measuring Equipment, Swidnica, for 0.42 +/- 34 years (median: 11.84 +/- 9.28). The subjects were divided into four groups: Group A-25 persons exposed to organic solvents; Group B-24 persons exposed to hydrogen cyanide; Group C-19 persons exposed to noise and vibration; and Group D-8 persons exposed to electromagnetic fields. Blood samples (10 ml) were collected from each person. Intra- and extracellular concentrations of magnesium, zinc, copper and calcium were estimated. CONCLUSIONS: exposure to 1) organic solvents induces depletion of calcium and zinc from the body and intracellular cumulation of magnesium; 2) to hydrogen cyanide induces depletion of intracellular zinc and intracellular cumulation of magnesium and zinc; 3) to noise and vibration induces depletion of calcium, zinc and copper and intracellular cumulation of magnesium; and 4) electromagnetic fields does not induce any significant changes in ionic concentrations.


Subject(s)
Chemical Industry , Environmental Monitoring , Hydrogen Cyanide/adverse effects , Metals/blood , Occupational Exposure , Solvents/adverse effects , Adult , Calcium/blood , Copper/blood , Electromagnetic Fields/adverse effects , Female , Humans , Magnesium/blood , Male , Middle Aged , Noise/adverse effects , Vibration/adverse effects , Zinc/blood
20.
Pol Arch Med Wewn ; 93(4): 305-13, 1995 Apr.
Article in Polish | MEDLINE | ID: mdl-7479254

ABSTRACT

The aim of the work was evaluation of activity of angiotensin converting enzyme (ACE) in non-insulin dependent diabetes mellitus depending on evidence of hypertonia, duration of diabetes and possibility of fat metabolism disturbances. 20 patients were studied (16 women and 4 men, average age 57.5 years). Average time of duration of diabetes was approximately 9 years (from 1 year to 25 years). The control group included 68 people (34 women and 34 men) in age of 19 to 67 years. Convertase activity was determined by Friedland and Silverstein's spectrofluorometric assay. Average ACE activity values in diabetic patient (44.45 +/- 13.14 mmol/ml/min) were close up to control group values and were not significantly different. Similar significant difference was not ascertain between average ACE activity values in patients with more than and less than 10 years of diabetes, in patients with hypercholesterolemia over and less 300 mg%, in patients with and without hypertonia and in patients with and without LDL hypercholesterolemia over and less 200 mg%. Positive correlation was observed between ACE activity values and triglyceride levels in patients with less than 10 years of diabetes (r = 0.88, p < 0.01) and in patients with hypercholesterolemia over 300 mg% (r = 0.75, p < 0.01). In this last group, in addition, the positive correlation was present between ACE activity values and total cholesterol levels (r = 0.86, p < 0.001). Correlation between ACE activity and total cholesterol level was ascertained in patients with LDL hypercholesterolemia over 200 mg% too (r = 0.81, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Peptidyl-Dipeptidase A/metabolism , Aged , Case-Control Studies , Female , Humans , Hypercholesterolemia/metabolism , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/metabolism , Lipoproteins, VLDL/metabolism , Male , Middle Aged , Triglycerides/blood
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