Lipoprotein(a) as a predictor of cardiovascular disease in a prospectively followed cohort of patients with type 1 diabetes.
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Cardiovascular Diseases↗
Biomedical subjects
Martin Auinger
Publications and source records attributed to Martin Auinger.
Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?
OBJECTIVE: In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones. RESEARCH DESIGN AND METHODS: Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT). RESULTS: PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004). CONCLUSIONS: After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.
Adult↗
Prevalence of LADA and frequency of GAD antibodies in diabetic patients with end-stage renal disease and dialysis treatment in Austria.
BACKGROUND: The prevalence of individuals with latent autoimmune diabetes in adults (LADA) among diabetic patients with end-stage renal disease is unknown. Furthermore, there are no references in the literature about the persistence of glutamic acid decarboxylase antibodies (GADA) in uraemic LADA patients. The aim of the study, therefore, was to evaluate the prevalence of LADA, classified according to special features, in diabetic patients undergoing dialysis therapy as well as to find out the frequency of GADA in these patients. In addition, we investigated vascular risk factors and the prevalence of vascular diseases in each type of diabetes. METHODS: 538 patients undergoing chronic dialysis therapy from 37 Austrian dialysis centres were analysed in the study. Patients were divided into three groups: patients with type 1 or type 2 diabetes and patients with LADA. The classification of the different types of diabetes was based on the guidelines of the German Diabetes Society. We measured GADA and estimated the baseline data with reference to body mass index (BMI), age at onset of diabetes and at initiating dialysis therapy, the actual values of haemoglobin (Hb) A1c and cholesterol and the prevalence of vascular diseases by using a structured questionnaire. RESULTS: Type 1 diabetes was classified in 52 patients, type 2 diabetes in 434 and LADA in 52 (9.7%). The prevalence of positive GADA was 17.3% in the type 1 diabetic patients and 26.9% in the LADA patients. There was no positive GADA in the type 2 diabetic subjects. Age at the onset of diabetes and age at the start of dialysis were approximately the same in the LADA and the type 2 diabetic patients, while the age of the subjects with type 1 diabetes was significantly lower (P<0.001). BMI was significantly lower (25+/-3 vs 27+/-5 kg/m2) in the LADA patients than in the type 2 diabetic patients. The mean HbA1c value in the LADA patients was significantly higher than in the subjects with type 2 diabetes (P<0.01). Blood pressure (BP) was similar between LADA and type 1 or type 2 diabetes, though diastolic BP tended to be lower in the LADA patients than in the type 1 diabetics. The cholesterol levels were comparably high in each type of diabetes. In the LADA patients, the prevalence of retinopathy was lower than in the type 1 diabetics and the prevalence of stroke and angina pectoris was lower than in the type 2 diabetic patients, but the differences were not significant. CONCLUSIONS: The prevalence of LADA in diabetic patients on maintenance dialysis was 9.7%. This value is comparable to the frequency of LADA at onset of diabetes. The frequency of persisting GAD autoantibodies was 27% in the LADA patients and 17% in the type 1 diabetic patients. BMI was significantly lower in the LADA patients than in the type 2 diabetic patients, while diastolic BP only tended to be lower in the LADA patients than in the type 1 diabetics. The prevalence of vascular diseases was not significantly different between LADA and types 1 or 2 diabetes. According to our data it can be assumed that only a few uraemic patients with LADA are suitable for simultaneous pancreas-kidney transplantation.
Adult↗
[Peritoneal dialysis in patients with diabetic nephropathy].
Since the introduction of peritoneal dialysis (PD) into clinical nephrology at the end of the 1970s, many improvements have led to acceptance of this method as renal replacement therapy equivalent to hemodialysis. It is unclear whether the diabetic patient is the ideal candidate for PD and if this procedure should be the preferred method of treatment of renal failure in these patients, especially when kidney transplantation cannot be performed. PD may provide several advantages for diabetic patients with end-stage renal failure; for example, better hemodynamic stability is achieved during peritoneal ultrafiltration and vascular access surgery becomes unnecessary. On the other hand, the continuous glucose absorption may lead to increased insulin requirements, obesity and hyperlipidemia. Furthermore, peritoneal protein loss may aggravate malnutrition, which is frequently present in these patients. However, for a differentiated assessment of outcome in PD, the individual history (diabetes type 1 or type 2) and accompanying comorbidity of diabetic patients have to be considered. Nowadays nephrologists have to be aware of the concept of individualized therapy, which is integrated into an overall plan and takes into account the different conditions of diabetic patients and their treatment options. By improving removal of sodium and water, as well as improving quality of metabolic control, new dialysis solutions (icodextrin, neutral-pH solutions) and automated PD could have a positive impact on outcome in diabetic patients. In contrast, from retrospective studies on PD there is evidence of higher long-term mortality rates in elderly women with diabetes and in patients with cardiac insufficiency than in those on hemodialysis. Further research is necessary in order to optimize individualized therapy for diabetic patients with end-stage renal disease in the future.
Austria↗
Results of a nationwide screening for Anderson-Fabry disease among dialysis patients.
Anderson-Fabry disease is possibly underdiagnosed in patients with end-stage renal disease. Nationwide screening was therefore undertaken for Anderson-Fabry disease among dialysis patients in Austria. Screening for alpha-galactosidase A (AGAL) deficiency was performed by a blood spot test. In patients with a positive screening test, AGAL activity in leukocytes was determined. Individuals with decreased leukocyte AGAL activity were subjected to mutation testing in the GLA gene. Fifty (90.9%) of 55 Austrian hemodialysis centers participated in this study; 2480 dialysis patients (80.1% of the Austrian dialysis population) were screened. In 85 patients, the screening test was positive (85 of 2480, 3.42%; women, 3.32%; men, 3.50%). Among these 85 patients, 4 men (in 3 of whom Anderson-Fabry disease was already known before screening) had a severely decreased and 11 subjects had a borderline low AGAL activity. Genetic testing revealed mutations associated with Fabry disease in all four men with severely decreased AGAL activity resulting in a prevalence of 0.161% for the entire study population. A nationwide screening of dialysis patients permitted detection of a hitherto unknown man with Anderson-Fabry disease. The overall prevalence among dialysis patients was at least ten times higher as compared with recent registry data. Screening programs among patients with end-stage renal disease, especially men, should be put in place to identify families with Anderson-Fabry disease who probably may benefit from specific clinical care, and perhaps from enzyme replacement therapy. In dialysis patients, however, there is no evidence to support enzyme replacement therapy at present.
Aged↗
[Diabetic nephropathy].
Diabetes mellitus is the leading single cause for renal replacement therapy. Its development and progression, however, can be ameliorated by adequate therapy. The present article represents the recommendations of the Austrian Diabetes Association for the prevention and treatment of diabetic nephropathy.
Albuminuria↗
Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patients.
BACKGROUND: Dyslipidemic factors obviously contribute to the high cardiovascular risk in dialysis patients but are often an underestimated problem. Therefore, we determined the prevalence of dyslipidemic factors in a large group of unselected hemodialysis (N = 564) and CAPD (N = 168) patients. METHODS: We used the recently published recommendations of the Medical Experts Group concerning cardiovascular risk factors for the categorization of dyslipidemic factors. These were total cholesterol>200 mg/dL, low-density lipoprotein (LDL) cholesterol>100 mg/dL, high-density lipoprotein (HDL) cholesterol <40 mg/dL, triglycerides>180 mg/dL, and Lp(a)>30 mg/dL. RESULTS: CAPD patients had, in sum, a markedly worse lipid profile when compared with HD patients. They had higher frequencies of elevated total cholesterol (67% vs. 34%), triglycerides (47% vs. 28%), and Lp(a) concentrations (37% vs. 30%) when compared with HD patients. In both patient groups, about two thirds of the patients had LDL cholesterol above 100 mg/dL and HDL cholesterol below 40 mg/dL. When we analyzed the total frequency of dyslipidemic factors, we observed that the CAPD group included a markedly higher number of patients with three or four concurrent dyslipidemic factors than HD patients (P < 0.001). Furthermore, we analyzed apolipoprotein A-IV (apoA-IV), which was recently shown to be associated with cardiovascular disease, and which was about twice as high in both patient groups when compared with controls (P < 0.001). CONCLUSIONS: Dyslipidemic risk factors are highly prevalent in dialysis patients, and the concomitant occurrence of several risk factors in a given patient is more often observed in CAPD than HD patients.
Adult↗
Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: results of the Vienna multicenter study.
Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.
Analysis of Variance↗