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K Hoogenberg

Publications and source records attributed to K Hoogenberg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Baroreflex sensitivity is depressed in microalbuminuric Type I diabetic patients at rest and during sympathetic manoeuvres.

AIMS/HYPOTHESIS: To evaluate baroreflex sensitivity (BRS) in microalbuminuric and normoalbuminuric Type I (insulin-dependent) diabetic patients without autonomic neuropathy and in healthy control subjects. METHODS: Microalbuminuric Type I diabetic patients (n = 15) were matched for age, sex, body mass index (BMI) and smoking habits with 15 normoalbuminuric patients and with 15 healthy control subjects. All subjects had a blood pressure less than 160/95 mmHg, a BMI less than 30 kg/m(2) and normal autonomic function on standard tests. Blood pressure and heart rate were measured non-invasively (Finapres) at rest and during sympathetic activation (handgrip, mental stress, standing). The baroreflex sensitivity was defined as the mean gain between blood pressure variability and heart rate variability in the 0.07-0.15 Hz frequency band. RESULTS: Resting baroreflex sensitivity was decreased in the microalbuminuric patients (3.5 +/- 0.4 ms/mmHg) compared with the normoalbuminuric patients and the healthy subjects (7.6 +/- 1.6 and 9.5 +/- 1.1 ms/mmHg, respectively, p < 0.001). The sympathetic tests reduced baroreflex sensitivity similarly in the groups without changing the between group differences. CONCLUSION/INTERPRETATION: Baroreflex sensitivity is reduced in Type I diabetic patients with microalbuminuria but without autonomic neuropathy. A prospective study should indicate whether this early abnormality in cardiovascular reflex function is a risk factor of cardiovascular mortality in these patients. [Diabetologia (1999) 42: 1345-1349]

Albuminuria↗
PubMed1999

Dopamine receptors--physiological understanding to therapeutic intervention potential.

There are two families of dopamine (DA) receptors, called D1 and D2, respectively. The D1 family consists of D1- and D5-receptor subtypes and the D2 family consists of D2-, D3-, and D4-receptor subtypes. The amino acid sequences of these receptors show that they all belong to a large superfamily of receptors with seven transmembrane domains, which are coupled to their intracellular signal transduction systems by G-proteins. The implications of DA receptors in neuropsychiatry and cardiovascular and renal diseases are discussed. Neuropsychiatry indications include Parkinson's disease, schizophrenia, migraine, drug dependence, mania and depression, and Gilles de la Tourette syndrome. The underlying dysfunction of dopaminergic systems and the potential benefits of dopaminergic therapy in these different indications are critically examined. With respect to the pharmacological treatment of Parkinson's disease, a range of DA agonists are in various stages of preclinical and clinical development. D2-receptor agonist activity is predominant in most effective antiparkinsonian DA agonists. However, in practice, it is difficult to treat patients for several years with DA agonists alone; therapeutic benefit is not sustained. Rather, the use of a combination of DA agonists and levodopa is considered preferable. Reports of the efficacy of DA partial agonists await confirmation, and recent clinical investigations also suggest the potential of D1 receptor agonists as antiparkinson drugs. Regarding migraine pathogenesis, clinical and pharmacological evidence suggests that DA is involved in this disorder. Most prodromal and accompanying symptoms may be related to dopaminergic activation. Several drugs acting on DA receptors are effective in migraine treatment. Furthermore, migraine patients show a higher incidence of dopaminergic symptoms following acute DA agonist administration, when compared with normal controls. In cardiology, the therapeutic benefits of DA agonists are noted in the treatment of heart failure. Low doses of DA are widely used for its specific dopaminergic effects on renal function, which are suggested to be beneficial, and for its alpha- and beta-adrenergic-mediated responses that occur with higher doses. However, studies have been unable to demonstrate that DA can prevent acute renal failure or reduce mortality. It appears that the significant progress that is being made in the molecular understanding of DA receptors will continue to have a tremendous impact in the pharmacological treatment of neuropsychiatric, cardiovascular, and renal diseases.

Animals↗
PubMed1999

Capillary permeability is increased in normo- and microalbuminuric type 1 diabetic patients: amelioration by ACE-inhibition.

BACKGROUND: Capillary leakage of sodium-fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes-associated microcirculatory abnormalities. DESIGN: We evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type 1 diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE-inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmol L-1. RESULTS: Transcapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P < 0.001) and was still further increased in microalbuminuric Type 1 diabetic patients (P < 0.01 compared to normoalbuminuric patients). Enalapril reduced NaF leakage (P < 0.05), mean arterial blood pressure (P < 0.05) and microalbuminuria (P < 0. 05). After treatment, NaF leakage was not different from that in normoalbuminuric patients. CONCLUSIONS: Capillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long-standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE-inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.

Albuminuria↗
PubMed1998

Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in Type 1 diabetic patients with elevated urinary albumin excretion.

The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 microg min(-1). Apo E genotype was characterized by polymerase chain reaction and restriction isotyping. In 11 IDDM patients with at least one epsilon4 allele (apo E4 group), baseline serum total and low density lipoprotein (LDL) cholesterol were higher (p < 0.05 for both) than in 25 patients without an epsilon4 allele and with at least one epsilon3 allele (apo E3 group). Dietary counselling resulted in a similar decrease in cholesterol intake in both groups, whereas linoleic acid did not change. In the apo E4 group, serum total and LDL cholesterol at follow-up fell (p < 0.01 for both) to levels that were not different from those in the apo E3 group, and the changes in these parameters were greater (p < 0.02) than those in the apo E3 group. We conclude that the apo E4 allele is associated with atherogenic lipoprotein abnormalities in Type 1 DM patients with minor elevations in albuminuria when they use their habitual diet. Apo E4 carrying patients respond better to a low cholesterol diet.

Adult↗
PubMed1998

High-density lipoprotein cholesterol is related to the TaqIB cholesteryl ester transfer protein gene polymorphism and smoking, but not to moderate alcohol consumption in insulin-dependent diabetic men.

In non-diabetic subjects, the high-density lipoprotein (HDL) cholesterol level is increased by alcohol and decreased by smoking. The biallelic B1B2 polymorphism of the cholesteryl ester transfer protein (CETP) gene is a genetic determinant of HDL cholesterol. We evaluated the effect of moderate alcohol consumption, the CETP gene polymorphism and clinical variables on HDL cholesterol and other lipoprotein parameters in insulin-dependent diabetic (IDDM) men. Thirteen moderate alcohol using IDDM men (median alcohol consumption 17 g/d) and 13 abstainers, individually matched for the CETP gene polymorphism and clinical factors including smoking, were studied. HDL cholesterol, serum apo AI and serum CETP activity levels were very similar in alcohol users compared to abstainers (1.36 +/- 0.28 vs 1.36 +/- 0.36 mmol l-1, 1.71 +/- 0.31 vs 1.75 +/- 0.33 g l-1 and 134 +/- 27 vs 138 +/- 53 nmol l-1h-1, respectively, n.s. for all). No significant differences in apo B-containing lipoproteins were observed. Multiple regression analysis (multiple r = 0.68) showed that HDL cholesterol was positively associated with the presence of the B2 allele (0.23 mmol l-1 higher for each B2 allele present, p = 0.004) and negatively with smoking (0.15 mmol l-1 lower per 10 cigarettes smoked daily, p = 0.011), but not with alcohol consumption (p = 0.66). This study suggests that moderate alcohol consumption has no beneficial effect on the lipoprotein profile in IDDM men. HDL cholesterol is adversely influenced by smoking, whereas considerable variation in its level appears to be explained by the CETP gene polymorphism.

Adult↗
PubMed1998

Norepinephrine-induced blood pressure rise and renal vasoconstriction are not attenuated by enalapril treatment in microalbuminuric IDDM.

BACKGROUND: In non-diabetic subjects, an attenuated systemic norepinephrine (NE) responsiveness may contribute to the mechanisms of action of angiotensin-converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor treatment influences systemic and renal haemodynamic responsiveness to exogenous NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin-dependent diabetic (IDDM) patients, representing a patient category that benefits by strict blood pressure control. METHODS: In seven microalbuminuric IDDM patients, systemic and renal responsiveness to NE, infused at individually determined threshold [deltamean arterial pressure (MAP)=0 mmHg], 20% pressor (deltaMAP=4 mmHg) and pressor (deltaMAP=20 mmHg) doses, were compared before and after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at 5 mmol/l and insulin was infused at 30 mU/kg/h. RESULTS: Enalapril decreased MAP (P<0.05) and microalbuminuria (P<0.05), whereas effective renal plasma flow (ERPF) increased (P<0.01) and glomerular filtration rate remained unaltered. The filtration fraction tended to decline (P=0.09). The ACE inhibitor-induced fall in MAP disappeared at NE pressor dose, and the overall mean increase in MAP in response to NE was even higher with than without enalapril (P<0.05). After enalapril, the ERPF remained higher at all NE doses (P<0.05), but the magnitude of the NE-induced fall in ERPF was not altered by ACE inhibition treatment. Overnight urinary albumin excretion fell with ACE inhibition (P<0.05), but this effect was not seen during NE infusion. The angiotensin II/active renin ratio and serum aldosterone levels remained lower with enalapril at all NE doses (P<0.05). CONCLUSIONS: Enalapril does not attenuate systemic and renal vascular responsiveness to exogenous NE in microalbuminuric IDDM despite adequate inhibition of the renin-angiotensin-aldosterone system. These findings suggest that the effect of NE on vasoconstriction is not counteracted effectively by ACE inhibition treatment alone.

Adult↗
PubMed1998

Effects of low-dose dopamine on renal and systemic hemodynamics during incremental norepinephrine infusion in healthy volunteers.

OBJECTIVES: To assess the effects of low-dose dopamine on norepinephrine-induced renal and systemic vasoconstriction in normotensive healthy subjects. DESIGN: On separate days, either a low-dose dopamine (4 microg/kg/min) or a placebo (5% glucose) infusion was added in a single, blinded, randomized order to incremental norepinephrine infusions of 40, 80, and 150 ng/kg/min over a 60-min period each. SETTING: Outpatient clinic of a university-affiliated hospital. SUBJECTS: Normotensive healthy volunteers. INTERVENTIONS: Infusions of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: Blood pressure and heart rate were measured with a semiautomated device, and glomerular filtration rate and effective renal plasma flow were determined with constant infusions of 125I-iothalamate and 131I-hippurate, respectively. Norepinephrine alone progressively increased mean arterial pressure to pressor levels, whereas this effect was attenuated by the addition of dopamine (p < .05 vs. norepinephrine alone). Glomerular filtration rate increased during lower norepinephrine doses and did not decrease at the highest norepinephrine dose. Addition of dopamine further increased glomerular filtration rate. Effective renal plasma flow decreased with each norepinephrine alone infusion step, but this decrease was completely prevented by concomitant dopamine infusion (p < .01 vs. norepinephrine). Sodium excretion tended to decrease with norepinephrine, but increased two- to three-fold after addition of dopamine (p < .01 vs. norepinephrine alone). CONCLUSIONS: In healthy man, norepinephrine causes a large decrease in renal plasma flow but not in glomerular filtration rate. Concomitant dopamine administration prevents this decrease in renal plasma flow, increases sodium excretion, and also attenuates the norepinephrine-induced systemic blood pressure increase. These findings warrant further clinical evaluation of the effect of concomitant low-dose dopamine and norepinephrine administration in critically ill patients.

Adrenergic alpha-Antagonists↗
PubMed1998

Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus.

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.

Adult↗
PubMed1997

Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin:cholesterol acyltransferase and lipid transfer protein activity levels.

Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) cholesterol associated with moderate alcohol consumption. We measured plasma LCAT, CETP and PLTP activities with exogenous substrate assays, as well as lipoproteins and HDL lipids in 6 alcohol-abstaining men, 18 matched men who used < or = 1 and 18 men who used > or = 1 alcohol-containing drinks per day. Plasma cholesterol and triglycerides were similar in the three groups. HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol and HDL triglycerides were higher in the alcohol drinkers compared to the abstainers (all P < 0.05). No differences in plasma LCAT, CETP and PLTP activity levels were observed between the three groups. Analysis of covariance also demonstrated that the use of alcohol was associated with higher HDL cholesterol (P < 0.04), whereas plasma LCAT, CETP and PLTP activity levels were not related to alcohol consumption. Furthermore, HDL cholesteryl ester was positively associated with LCAT activity (P < 0.001), PLTP activity (P < 0.01) and alcohol intake (P < 0.04) and negatively with plasma triglycerides (P < 0.001) and CETP activity (P < 0.03); indicating that alcohol influenced HDL cholesteryl ester independently from these biochemical parameters. The higher HDL cholesterol associated with moderate alcohol consumption is, therefore, unlikely to be caused by and effect on plasma LCAT, CETP or PLTP activity levels.

Adolescent↗
PubMed1997

Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.

Adult↗
PubMed1996

Increased urinary IgG/albumin index in normoalbuminuric insulin-dependent diabetic patients: a laboratory artefact.

The previous observation that urinary IgG excretion is increased in normoalbuminuric insulin-dependent (IDDM) patients is unexplained and could possibly be related to a laboratory phenomenon. When untreated urine samples were stored -20 degrees C for 2 to 4 weeks, the IgG/albumin Index (IgG clearance divided by albumin clearance) was higher in normoalbuminuric IDDM patients than in control subjects (0.91 (0.68-1.54), n = 27 vs 0.72 (0.55-0.79), n = 15 (median (interquartile range)), p < 0.05). In normo- and microalbuminuric IDDM patients the IgG/albumin index was higher in urine samples with glucose than without glucose (1.16 (0.93-1.68), n = 11 vs 0.73 (0.50-0.91), n = 16, p < 0.05, and 0.33 (0.23-0.60), n = 17 vs 0.15 (0.10-0.26), n = 14, p < 0.02 for normo- and microalbuminuric patients, respectively). We, therefore, evaluated the preserving effects of glucose and bovine serum albumin (BSA) on urinary IgG after 1 h to 16 weeks of freezing at -20 degrees C in 4 non-diabetic subjects (proteinuria ranging from 0.05 to 8.0 g 24 h-1). Urine samples were either stored without precautions or treated with addition of phosphate buffer, BSA (1%) and glucose 100 and 300 mM). The weekly decline from 1 to 16 weeks of IgG in the urine aliquots diluted 1:1 with buffered glucose 300 mM and glucose 300 mM + BSA 1% was insignificant, whereas urinary IgG declined with all other storage regimes (p < 0.05). These results suggest that glucose in urinary specimens of IDDM patients prevents at least in part the loss of urinary IgG and may thus explain the higher urinary IgG/albumin index when unprocessed urine is stored frozen before assay. Laboratory precautions are necessary when urinary IgG cannot be measured immediately.

Adult↗
PubMed1995

Triiodothyronine rapidly lowers plasma lipoprotein (a) in hypothyroid subjects.

BACKGROUND: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). METHODS: The effect of short-term hypothyroidism on plasma Lp(a) was studied in 14 patients who had undergone a total thyroidectomy because of a well-differentiated thyroid carcinoma. They were studied 2 weeks after withdrawal of triiodothyronine (T3) therapy and 7 (5-9) weeks after resumption of T3 treatment (75-100 micrograms T3 daily). Fourteen euthyroid subjects served as controls. RESULTS: In the hypothyroid phase the athyreotic patients had higher levels of Lp(a) (105 [12-536] vs. 42 [1-321] mg/l, p < 0.05), apo-B (p < 0.001) and LDL cholesterol (p < 0.001) as compared with the euthyroid control subjects. T3 therapy lowered Lp(a) by 29% to 50 (12-535) mg/l, p < 0.01. Apo B and LDL cholesterol fell by 42% (p < 0.001) and by 53% (p < 0.001), respectively. After resumption of T3 therapy the levels of Lp(a), apo-B and LDL cholesterol were not different from those of the control subjects. The mean percentual decreases in Lp(a) and in apo-B were similar, although the individual changes in Lp(a) were more variable. CONCLUSIONS: Short-term hypothyroidism increases plasma Lp(a) and T3 therapy rapidly lowers Lp(a) together with apo-B and LDL cholesterol. Our findings support the hypothesis that thyroid hormone regulates plasma Lp(a) and apo-B in a parallel manner. Elevated concentrations of Lp(a) in combination with LDL cholesterol may be involved in the increased risk of cardiovascular disease assumed to be associated with hypothyroidism.

Adult↗
PubMed1995

Chronic mesenteric ischaemia: diagnostic challenges and treatment options.

OBJECTIVES: A description of the clinical presentation, diagnostic procedure and mode of therapy in three patients suffering from chronic mesenteric ischaemia. DESIGN AND INTERVENTIONS: In all cases, the diagnosis was made on the basis of abdominal complaints in combination with angiographic findings. The primary treatment objective was restoration of blood flow via a revascularization procedure, for the patient in whom this could not be accomplished an enteral feeding programme was undertaken. RESULTS: One patient had a panmalabsorption syndrome which was treated with an aortomesenteric bypass operation, the second one presented with multiple gastric ulcerations which only improved after a percutaneous transluminal angioplasty. In the third patient, neither surgery or angioplasty were feasible and a tentative enteral feeding programme was given, after which the ability to consume a normal oral diet without abdominal distress was regained. CONCLUSIONS: These three cases illustrate the diverse clinical pictures by which chronic mesenteric ischaemia may present itself. This diagnosis should be kept in mind when other more common causes of a patient's abdominal complaints cannot be found, hence giving consideration to abdominal angiography as the next diagnostic procedure. With respect to therapy, restoring blood flow through surgery or angioplasty is the primary form of treatment. However, if neither of these therapeutic options is feasible, it is suggested that such patients may benefit from a nutritional training programme.

Angiography↗
PubMed1995

Alterations in cortisol metabolism in insulin-dependent diabetes mellitus: relationship with metabolic control and estimated blood volume and effect of angiotensin-converting enzyme inhibition.

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the interconversion of cortisol and its inactive metabolite, cortisone, and protects the mineralocorticoid receptor from activation by cortisol. Sodium and fluid retention is a well documented phenomenon in insulin-dependent diabetes mellitus (IDDM), but it is not known whether diabetes-associated alterations in cortisol metabolism contribute to its pathogenesis. Therefore, we evaluated some aspects of cortisol metabolism by measuring urinary metabolites of cortisol and cortisone in eight microalbuminuric and eight normoalbuminuric IDDM patients and eight matched control subjects. In both IDDM groups, the overnight excretion of tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), and tetrahydrocortisone (THE) was lower than that in the control group (P < 0.05 to P < 0.01). Both the allo-THF/THF ratio, a parameter of 5 alpha/5 beta-reduction of cortisol, and the cortisol to cortisone metabolite ratio (THF+allo-THF/THE), which reflects the overall direction of the cortisol to cortisone interconversion, were lower in the IDDM groups (P < 0.05 to P < 0.01). In the combined subjects (n = 24), allo-THF, allo-THF/THF, and THF+allo-THF/THE were inversely correlated with hemoglobin A1c (r = -0.69, P < 0.001; r = -0.61, P < 0.01; and r = -0.58, P < 0.01, respectively). Upper arm segmental blood volume, estimated by an electrical impedance technique, was positively correlated with the cortisol to cortisone metabolite ratio in both the control subjects (r = 0.77; P < 0.05) and the IDDM patients in whom it was measured (r = 0.56; P < 0.05; n = 13), whereas the regression line was shifted leftward in IDDM (i.e. a lower ratio at the same blood volume; P < 0.03, by analysis of covariance). In seven microalbuminuric IDDM patients, the angiotensin-converting enzyme inhibitor, enalapril (10 mg daily for 6-12 weeks), resulted in a moderate further lowering of the cortisol to cortisone metabolite ratio (P < 0.05). The present data suggest a chronic hyperglycemia-related impairment in the reduction of corticoids to tetrahydro metabolites and an imbalance in 11 beta HSD. Altered 11 beta HSD activity is unlikely to be primarily responsible for the sodium and fluid retention in IDDM. Moreover, an additional mechanism of action of angiotensin-converting enzyme inhibition might be provided by an effect on 11 beta HSD activity.

Adrenal Cortex Hormones↗
PubMed1995

Influence of ambient plasma noradrenaline on renal haemodynamics in type 1 (insulin-dependent) diabetic patients and healthy subjects.

Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal experiments have shown that noradrenaline (NA) infusion increases the intraglomerular pressure by predominantly efferent arteriolar vasoconstriction. The relationships between ambient plasma NA levels and renal haemodynamics were studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic patients (group D1) (albumin excretion rate (Ualb V) < 20 micrograms min-1), and in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20-200 micrograms min-1), all patients being without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml min-1 1.73 m-2)) and effective renal plasma flow (ERPF (ml min-1 1.73 m-2)) were determined over a 2-h period using constant infusions of 125I-iothalamate and 131I-hippuran, respectively. The subjects were studied in the fasting state. The diabetic patients were investigated during near normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126 +/- 15 and 538 +/- 89, respectively) were elevated as compared with controls (108 +/- 15 and 478 +/- 73; p < 0.01 and p < 0.05, respectively). In group D2, GFR (124 +/- 25, p < 0.05) but not ERPF (515 +/- 104) was higher than in the controls. GFR and ERPF were negatively correlated with venous plasma NA in group C (r = -0.61, p < 0.005 and r = -0.64, p < 0.001, respectively), in group D1 (r = -0.54, p < 0.03 and r = -0.63, p < 0.005, respectively) and in group D2 (r = 0.53, p < 0.03 and r = -0.60, p < 0.01, respectively). Multiple regression analysis disclosed that diabetes per se, independent from plasma NA, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are inversely related to venous plasma NA levels, both in healthy and in diabetic subjects, supporting the hypothesis that plasma NA is a vasoconstrictive substance. The independent positive effect of diabetes as a categorial variable on GFR, suggests that concomitant vasodilating mechanisms play a role in the renal haemodynamic alterations in Type 1 diabetes mellitus.

Adult↗