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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 253 records · Page 14Linked to original sources
PubMed1997

Abnormal pulsatile secretion of growth hormone in non-insulin-dependent diabetes mellitus.

OBJECTIVE: Studies of GH secretion in patients with non-insulin dependent diabetes mellitus (NIDDM) have produced conflicting results. We aimed to differentiate the effects of obesity and metabolic control on pulsatile GH secretion in patients with NIDDM. DESIGN: Blood sampling every 15 min from 22.00 hours to 08.00 hours after a fasting period of at least 3 h. PATIENTS: 13 male NIDDM patients, 9 healthy control subjects matched for age and BMI, and 6 lean subjects matched for age. MEASUREMENTS: Measurement of GH by a novel ultrasensitive chemiluminescence assay. Analysis of concentration vs time profiles by a multiparameter deconvolution technique. RESULTS: GH burst frequency was increased in the NIDDM (0.82 +/- 0.28 h-1) compared with both control groups (lean: 0.6 +/- 0.11; obese: 0.56 +/- 0.19). GH burst mass was decreased in patients (1.57 +/- 0.98 micrograms/l.min) and in obese controls (1.46 +/- 1.44) compared to lean controls (3.71 +/- 3.88). These differences resulted in a significantly higher nocturnal pulsatile GH secretion rate in the lean compared to the obese controls, whereas in the patient group enhanced GH burst frequency compensated for reduced burst mass. The characteristics of GH secretion were not related to nocturnal or early morning blood glucose concentrations. However, GH secretion rate was correlated positively with HbA1c (r = 0.57; P = 0.04), and negatively with plasma C peptide concentrations. CONCLUSIONS: The specific increase in GH burst frequency previously described in insulin-dependent diabetes mellitus is also present in NIDDM. However, GH hypersecretion does not occur because GH burst mass is reduced in proportion to the degree of obesity. The effect of diabetes on the hypothalamic control of GH release appears to be determined by the quality of long-term glycaemic control.

Analysis of Variance↗
PubMed1997

No effect of calcitriol on insulin-mediated glucose uptake in healthy subjects.

Administration of active vitamin D (calcitriol) improves insulin sensitivity in uraemic patients. These patients have subnormal plasma calcitriol concentrations in parallel with increased intact parathyroid hormone (PTH) concentrations. It is therefore unclear whether the improvement in insulin sensitivity results from a direct effect of calcitriol or from amelioration of secondary hyperparathyroidism. So far, no evidence has been presented that insulin sensitivity is specifically affected by calcitriol in healthy subjects. We investigated the effect of (supra)therapeutic doses of calcitriol on insulin sensitivity in healthy volunteers. In a double-blind parallel group design, 18 healthy male subjects received in random order either placebo or 1.5 micrograms of calcitriol per day by mouth for 7 days. Insulin-mediated glucose uptake, i.e. insulin sensitivity, was assessed using the euglycaemic clamp technique. Mean glucose disposal rate, i.e. M-value, was not significantly affected by placebo or calcitriol treatment (placebo: 7.1 +/- 1.3 mg kg-1 min-1 before and 7.2 +/- 1.5 mg kg-1 min-1 after treatment; calcitriol 7.0 +/- 1.4 mg kg-1 min-1 and 7.2 +/- 1.4 mg kg-1 min-1). There were no significant changes in mean plasma glucose, insulin, phosphate, bicarbonate and ionized calcium concentrations after administration of placebo or calcitriol. Furthermore, platelet intracellular calcium concentration (assessed by fluorescence spectroscopy) and mean arterial blood pressure (24 h ambulatory measurement) did not change with placebo and calcitriol treatment. On the other hand, mean intact PTH concentration decreased significantly (P < 0.01) with calcitriol treatment, but not with placebo. In addition, mean 24 h urinary calcium excretion increased significantly (P < 0.05) with calcitriol administration but was unchanged with placebo. Administration of (supra)physiological doses of calcitriol has no effect on insulin sensitivity in healthy subjects, despite a significant decrease in PTH concentrations. These observations are compatible with the notion that the effect of calcitriol on insulin sensitivity is present only in uraemic calcitriol-depleted patients.

Administration, Oral↗
PubMed1997

Tissue factor antigen is elevated in patients with microvascular complications of diabetes mellitus.

Patients with late diabetic complications have increased levels of parameters indicating activation of coagulation (Takakashi et al., 1989; Ceriello, 1993; Murakami et al., 1993; Kario et al., 1995; Shimizu et al., 1995; Yokoyama et al., 1996), endothelial cell damage (Jensen, 1989; Iwashima et al., 1990; Sernau et al., 1995; Gabath et al., 1996). TF is believed to activate the coagulation mechanism in patients with late complications of diabetes. We studied the TF antigen plasma levels in 72 patients with diabetes mellitus (36 type I, 36 type II) with respect to its relevance as a marker of microvascular diabetic complications. TF levels did not correlate with macrovascular disease, diabetes type or age. Sixty patients with decreased renal function not due to diabetes were studied for evaluation of the contribution of renal failure to TF antigen plasma levels. We did not find a significant correlation of TF with s-creatinine in non diabetic patients (r = 0.27, p > 0.05). However, TF levels were elevated in diabetic patients with microvascular disease. Patients with retinopathy had higher TF levels than without (0.30 ng/ml vs 0.11 ng/ml, p < 0.007). When patients were divided into subgroups according to the urine albumin concentration, TF antigen of patients without albuminuria (0.019 ng/ml, n = 25) did not differ from patients with microalbuminuria (0.095 ng/ml, n = 19 p > 0.05). However, TF levels were significantly higher in patients with macroalbuminuria (n = 28; 0.215 ng/ml, p < 0.005). Thus activation of coagulation in patients with microvascular complications of diabetes may be triggered by tissue factor.

Adult↗
PubMed1997

Nephropathy in type II diabetes.

The incidence and prevalence of endstage renal failure from renal involvement in patients with type II diabetes has recently increased in the Western world and in Asia. Interesting differences of prevalence are found between different nations. The reasons for the recent increase in the frequency of nephropathy in type II diabetes include (i) an increasing prevalence of type II diabetes, (ii) aging of the population and (iii) improved survival of patients with type II diabetes. Today patients more frequently live long enough to experience diabetic nephropathy. In contrast to previous opinion, no major differences with respect to renal involvement are found between type I and type II diabetes. This concerns renal hemodynamics as well as renal histology, although non-specific changes presumably of an ischemic nature are more frequently found in patients with type II diabetes. The renal risk appears to be similar in type II diabetes, i.e. cumulative prevalence of proteinuria and the same is true for the rate of progression to renal failure.

Diabetes Mellitus, Type 2↗
PubMed1997

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects.

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.

Adult↗
PubMed1997

Excess of DD homozygotes in haemodialysed patients with type II diabetes. The Diabetic Nephropathy Study Group.

The role of the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene in the genesis of diabetic nephropathy has been controversial. It has recently been proposed that progression occurs more rapidly in individuals with diabetic and non-diabetic renal disease who are homozygous for the D allele. We studied 658 patients with type II diabetes, 347 without diabetic nephropathy and 311 with various stages of diabetic nephropathy, and determined the I/D polymorphism of the ACE gene. Patients at the extremes of renal risk, i.e. normotensive patients without antihypertensive treatment and without nephropathy (n = 144), vs patients on dialysis (n = 61), differed with respect to genotype (DD 36.8% vs 57.4%; P = 0.007) and allele frequencies (D 0.59 vs 0.76; P < 0.001). In contrast, patients with and without presumed nephropathy as assessed by albuminuria did not differ with respect to DD genotype. In conclusion, in this study, which was limited by sample size, patients with the highest renal risk more frequently had the DD genotype. This would be compatible with a greater risk of (or rate of) progression to end-stage renal failure.

Adult↗
PubMed1997

Subacute infusion of physiological doses of parathyroid hormone raises blood pressure in humans.

BACKGROUND: Acute administration of parathyroid hormone (PTH) causes vasodilation and blood pressure decrease in experimental animals. This effect contrasts with the putative role of secondary hyperparathyroidism in the pathogenesis of hypertension of patients with renal failure. Uraemia is characterized by insulin resistance and hyperinsulinaemia. We therefore investigated whether subacute administration of physiological doses of human 1,34-PTH affects blood pressure under conditions of controlled insulin levels (euglycaemic clamp technique) in humans. METHODS: In a double-blind cross-over design 10 healthy male subjects received, on two occasions, in random order, for 2 h, either a sham infusion or an infusion of 200 units of 1,34-PTH. RESULTS: Mean ionized calcium concentration increased significantly (P < 0.01) within the normal range during euglycaemic hyperinsulinaemia, both with sham infusion (from 1.25 +/- 0.04 to 1.29 +/- 0.02 mmol/l) and with infusion of 1,34-PTH, but the increase was more marked with 1,34-PTH administration (from 1.26 +/- 0.05 to 1.33 +/- 0.07). In addition, mean platelet intracellular calcium concentration (by fluorescence spectroscopy) was unchanged with sham infusion (49.9 +/- 4.1 versus 50.3 +/- 5.0 nmol), but increased significantly (P < 0.05; paired t-test) after 1,34-PTH infusion (from 49.8 +/- 5.0 to 52.8 +/- 5.8). The infusion of 1,34-PTH resulted in a significant (P < 0.01) increase in mean MAP (from 84 +/- 5 to 88 +/- 5 mmHg) as compared with sham infusion (85 +/- 4 versus 86 +/- 4). The intra-individual changes in intracellular calcium concentration (delta[Ca2+]i) were significantly correlated to the changes in mean MAP (delta MAP) (r = 0.87, P < 0.001). In contrast to blood pressure, insulin sensitivity was not affected by 1,34-PTH infusion (M-value: 7.2 +/- 1.6 mg/kg per min) as compared with sham infusion (7.3 +/- 1.4). CONCLUSION: Subacute administration of physiological doses of parathyroid hormone under hyperinsulinaemic conditions significantly affects intracellular calcium and blood pressure in healthy subjects, but does not affect the action of insulin.

Adult↗
PubMed1997

Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset.

OBJECTIVE: Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity. DESIGN AND METHODS: Twelve healthy volunteers (aged 43+/-9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45+/-9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively. RESULTS: In volunteers the mean M-value after Ang II infusion (10.1+/-1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2+/-0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1+/-1.3 mg/kg per min) and sham infusion (5.5+/-1.2 mg/kg per min). The difference in the mean absolute increase in the M value (deltaM) between groups was significant (P< 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0+/-3.5 to 15.5+/-3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8+/-3.3 to 19.1+/-3.7 ml/100 ml per min, P< 0.01). Again, the difference between the mean absolute increases in MBF (deltaMBF) in the groups was significant (P < 0.01). A significant correlation was found between deltaMBF and deltaM (r= 0.62, P<0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients. CONCLUSIONS: In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.

Adult↗
PubMed1997

Progression of renal failure after subtotal nephrectomy in transgenic rats carrying an additional renin gene [TGR(mREN2)27].

OBJECTIVE: To study the evolution of glomerulosclerosis after renal ablation in a model with abnormal regulation of the renin gene. METHODS: Four-month-old female ovariectomized hypertensive heterozygous transgenic rats (TGR) harbouring the murine REN-2 gene were compared with pressure-matched, pair-fed, stroke-prone, spontaneously hypertensive rats (SHRsp). Both groups were followed for 6 weeks after 70% subtotal nephrectomy (SNX) or sham operation. RESULTS: Blood pressures in the SNX group at the end of the experiment were 193 +/- 3 mmHg in TGR and 199 +/- 5 mmHg in SHRsp. The final C(in) was 306 +/- 68 microliters/min per 100 g body weight in TGR that had undergone SNX and 550 +/- 93 microliters/min per 100 g body weight in SHR that had undergone SNX (P < 0.02), whereas inulin clearance (C(in)) in sham-operated pair-fed TGR and SHRsp controls did not differ from each other. The glomerulosclerosis index was 1.75 +/- 0.08 in perfusion-fixed TGR that had undergone SNX versus 1.21 +/- 0.03 in SHR that had undergone SNX (P < 0.005). In addition, the media thickness of preglomerular vessels was significantly greater in TGR that had undergone SNX (7.48 +/- 0.79 microns) than it was in SHRsp that had undergone SNX (5.27 +/- 1.38 microns, P < 0.02). Rat renal renin messenger RNA (mRNA) expression and, in parallel, mouse REN-2 gene expression were lower in TGR after SNX. Plasma renin and angiotensin II (ANG II) concentrations were reduced to a similar extent in both SNX groups, but plasma prorenin was higher in TGR that had undergone SNX than it was in SHRsp that had undergone SNX. The angiotensin II:I ratio in the kidney was significantly higher in TGR (P < 0.01). There was no significant difference between sham-operated or subtotally nephrectomized TGR and SHRsp with respect to angiotensin type 1 mRNA and angiotensinogen mRNA. The renal angiotensin converting enzyme activity, however, was significantly higher in sham operated and subtotally nephrectomized TGR than it was in sham operated SHRsp and in SHRsp that had undergone SNX. CONCLUSION: Deterioration of renal function is accelerated in subtotally nephrectomized transgenic rats [TGR(mREN2)27] compared with that in comparably hypertensive SHRsp despite suppressed circulating active mRNA and decreased renal renin mRNA. Although alternative explanations are possible, this observation is consistent with a role for local ANG II in the genesis of glomerulosclerosis.

Angiotensins↗
PubMed1997

A polymorphism in the gene for the angiotensin II type 1 receptor is not associated with hypertension.

BACKGROUND: A mutation in the gene for the angiotensin II type 1 (AT1) receptor (A1166C) has been reported to be associated with primary hypertension. OBJECTIVE: To determine whether this observation could be confirmed with a different population sample. DESIGN: We examined 414 individuals with primary hypertension and 172 normotensive controls. METHODS: The mutation in the gene for the AT1 receptor was detected using restriction polymerase chain reaction. CONCLUSIONS: We detected no association of the AT1 receptor polymorphism with hypertension, but a trend towards a decreased prevalence of the 1166C allele among hypertensive patients with a late age at diagnosis (> or = 50 years) was observed.

Adult↗