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PubMed2001

Activation of poly(ADP-ribose) polymerase in severe hemorrhagic shock and resuscitation.

This study examines activation of poly(ADP-ribose) polymerase (PARP) in the ileum during hemorrhage and resuscitation and determines if inhibition of PARP reduces organ dysfunction and metabolic acidosis. Awake, nonheparinized rats were hemorrhaged (40 mmHg, 60 min). Resuscitation used Ringer's solution (2 1/3 x shed volume) and packed red blood cells (2/3 shed volume). Ileal PARP activity was elevated at the end of hemorrhage (3.6-fold) and 10 min of resuscitation (5-fold). The subsequent decline in PARP activity observed after 60 min of resuscitation was not due to cleavage by caspase-3. Ileum permeability increased 10-fold and circulating liver enzymes increased 4- to 6-fold following 60 min of resuscitation in animals pretreated with 3-aminobenzoic acid, a structural analog that does not inhibit PARP. Pretreatment with 3-aminobenzamide (3-AB), a PARP inhibitor, reduced these changes, whereas posttreatment with a bolus of 3-AB was ineffective. Metabolic acidosis, accumulation of lactate, and base deficit was reduced by pretreatment with 3-AB. PARP is activated in the ileum by hemorrhage and by resuscitation. Activation of PARP contributes to organ dysfunction in the ileum and liver and appears to be central to the development of metabolic acidosis.

Acidosis↗
PubMed2003

Blood gas changes in the corpora cavernosa: metabolic and histomorphometric implications in the patient with erectile dysfunction.

PURPOSE: We evaluated corpora cavernosa metabolism in flaccidity and in erection, analyzing some blood gas analytical parameters and comparing them by histomorphometric examination to find a direct relation between biochemical-metabolic parameters and histological data. MATERIALS AND METHODS: We selected 33 patients with erectile dysfunction and divided them into 2 groups, including 1-those with congenital penile deviation who were responders to prostaglandin E1, and 2-those with severe organic erectile dysfunction who were not responders to prostaglandin E1. We evaluated O(2) and CO(2) pressure, pH and O(2) saturation in blood samples. We then made a histomorphometric study of cavernous tissue. We obtained specimens by cavernous biopsies and calculated O(2) and CO(2) exchange, the Haldane effect and the respiratory quotient into the corpora cavernosa. All data were evaluated by statistical analysis. RESULTS: Mean O(2) arterial pressure and saturation +/- SD were lower in group 2 than in group 1 (74.85 +/- 8.78 versus 96.43 +/- 14.87 and 94.98 +/- 1.4 versus 97.35 +/- 0.83, respectively). Mean CO(2) arterial pressure was 35.59 +/- 4.78 group 1 versus 38.8 +/- 2.71 in group 2 with borderline statistical significance. The Haldane effect was superior in flaccidity than in erection because of the influence of arterial-venous O(2) difference and the respiratory quotient, which was also an inverse ratio. Cavernous histomorphometry showed that in group 1 smooth muscle was a mean of 38.8 +/- 8.94% of cavernous tissue versus 24.9% in group 2. CONCLUSIONS: Our study shows that starting with blood gas analytical data we can completely study the metabolism of the corpora cavernosa and its relationships to erectile dysfunction. Cavernous histomorphometry can suggest the presence of smooth muscle into cavernous tissue, whereas our mathematical elaboration allowed us to evaluate all data in a more complete manner.

Alprostadil↗
PubMed1994

Activities of carbonic anhydrase in the cochleae of guinea pigs with early experimental endolymphatic hydrops.

Normal auditory function depends on maintenance of the unique ion composition in the endolymph. Carbonic anhydrase in the inner ear has been suggested to play an important role in maintaining the ion concentration and regulating fluids of the inner ear. Cochlear dysfunction may indicate changes in the biochemical components and osmotic pressure of the inner ear fluids as well as inadequate generation of intracellular metabolic energy. Dysfunction of the inner ear was investigated in the early stages of endolymphatic hydrops. Normal adult albino guinea pigs were operated on to obliterate the endolymphatic ducts and sacs of the right ears to induce endolymphatic hydrops. The auditory function of experimental guinea pigs was assessed according to the difference between the preoperative and postoperative hearing thresholds of the auditory brainstem response (ABR). Vibratome sections of the hydropic cochlea (right) and control cochlea (left) were stained histochemically for the activities of carbonic anhydrase in this study. Decreased activity of this enzyme was not shown consistently in the stria vascularis and organ of Corti of the hydropic cochlea in the early stage of endolymphatic hydrops whereas auditory dysfunction in the hydropic ear was noted from the ABR threshold for the experimental animals with 2 months survival. The results of the present study suggest that further investigation concerning the role of carbonic anhydrase in the cochlear auditory function is necessary.

Animals↗
PubMed1993

Reduced Na(+)-K(+)-ATPase activities in the cochleae of guinea pigs with experimental endolymphatic hydrops.

Normal auditory function depends on the maintenance of the unique ion composition in the endolymph. The Na(+)-K(+)-ATPase in the lateral wall of the cochlear duct has been suggested to play an important role in maintaining the endolymphatic ion concentration and in generating a positive endocochlear potential. Cochlear dysfunction may indicate changes in the biochemical components and osmotic pressure of the inner ear fluids as well as inadequate generation of intracellular metabolic energy. Dysfunction of the stria vascularis and spiral prominence was investigated in the early stages of endolymphatic hydrops. Vibratome sections of hydropic and normal cochleae were stained histochemically for Na(+)-K(+)-ATPase activity in this study. Decreased activity of this enzyme was shown in the stria vascularis and spiral prominence of the hydropic cochlea in the early stage of endolymphatic hydrops. The results coincide with those of studies of electrophysiologic changes in cochlear function in hydropic animals by others. The results of the present study provide further information concerning a possible deficit in ion transport activity and decreased enzymatic activity in the cochlea.

Animals↗
PubMed1996

Formate-induced alterations in retinal function in methanol-intoxicated rats.

Formic acid is the toxic metabolite in methanol poisoning. Permanent visual damage in methanol-intoxicated humans and non-human primates has been associated with prolonged exposures (> 24 hr) to blood formate concentrations in excess of 7 mM; however, little information is available on the toxicity associated with chronic low-level or repeated exposure to methanol. The present studies compared the effects on retinal function and structure of rapidly increasing formate concentrations typical of acute methanol intoxication with low-level plateau formate concentrations more likely to be generated by subacute or chronic methanol exposure. Rats that accumulated formate concentrations of 8-15 mM developed metabolic acidosis, retinal dysfunction, and retinal histopathologic changes. Retinal dysfunction was measured as reductions in the a- and b-waves of the electroretinogram that occurred coincident with blood formate accumulation. Histopathologic studies revealed vacuolation in the retinal pigment epithelium and photoreceptor inner segments. Rats exposed to formate concentrations ranging from 4 to 6 mM for 48 hr showed evidence of retinal dysfunction in the absence of metabolic acidosis and retinal histopathology. These data indicate that formic acid generated from methanol oxidation acts as a direct retinal toxin. Formate-induced retinal dysfunction in methanol-intoxicated rats can be produced by steadily increasing concentrations of formate and importantly can also be produced by prolonged exposure to lower concentrations of formate. Our findings substantiate evidence based on clinical case reports and a small number of epidemiological studies and support the hypothesis that the visual system toxicity produced by acute, subacute, or chronic methanol poisoning share a common mechanism.

Animals↗
PubMed2001

[Comparison of dobutamine echocardiography and rest-redistribution 201-thallium SPECT in the assessment of myocardial viability taking PET as gold standard].

BACKGROUND AND AIM: To compare Tl-201 SPECT and dobutamine stress echocardiography for the detection of myocardial viability in patients with severe left ventricular dysfunction using metabolic imaging by positron emission tomography as the standard reference. MATERIAL AND METHODS: We studied 25 consecutive patients with severe coronary artery disease and left ventricular dysfunction that underwent two different diagnostic modalities for evaluating myocardial viability: stress echocardiography with incremental doses of dobutamine from 5 up to 40 g/kg/min in 3 min stages, and 201 Tl SPECT using a rest-redistribution protocol with delayed images obtained at 4 hours. Fluorodeoxyglucose uptake by PET was used as the gold standard. Viability criteria were as follows, for 201Tl SPECT imaging: normal uptake at rest and presence of redistribution in the delayed images, for dobutamine stress echocardiography: sustained improvement and biphasic response. RESULTS: Sensitivity of thallium redistribution was 46%, for normal uptake, plus redistribution 82%, 34% for dobutamine biphasic response and 58% for sustained improvement plus biphasic response. Specificity of biphasic response was 82% and that of redistribution 67%. Stepwise logistic regression indicated that biphasic wall motion response during dobutamine stress echocardiography (2.01 CI 95%; 1.10 to 3.99) and the presence of redistribution plus normal uptake at rest with thallium imaging (2.68 CI 95%; 1.42 to 5.13) were the best predictors of viability. These results were the same when both techniques were analyzed together. CONCLUSIONS: Biphasic wall motion response during dobutamine stress echocardiography and the normal uptake plus presence of redistribution with thallium imaging were the best pre

Cardiotonic Agents↗
PubMed2026

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals↗
PubMed2005

Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study.

BACKGROUND: The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome. METHODS AND RESULTS: We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups. CONCLUSIONS: Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.

Adult↗
PubMed2006

The role of glycosaminoglycans and sulodexide in the treatment of diabetic nephropathy.

Diabetic nephropathy occurs in 20-40% of diabetic patients, making it one of the most important causes of end-stage renal disease (ESRD). It has a large impact in terms of associated morbidity and mortality for the individual patient and in terms of costs for healthcare. Several studies have demonstrated that micro- and macroalbuminuria predict cardiovascular morbidity and mortality in patients with diabetes mellitus.Current nephroprotective therapies for diabetic nephropathy include the pursuit of normoglycemia and normotension, and a consensus is emerging that there is a necessity to also achieve as low a level of albuminuria as possible. However, the search for innovative and ancillary approaches to the prevention and treatment of this diabetic complication is warranted since strict metabolic control can be difficult, and sometimes dangerous, to achieve and even diabetic patients responding to ACE inhibitors (ACEIs) or angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and metabolic control show progressive renal damage and eventually ESRD. A number of drugs are currently being investigated; glycosaminoglycans are particularly interesting since, in theory, they target the generalized endothelial dysfunction and metabolic defect in matrix and basement membrane synthesis which, according to the Steno hypothesis, are responsible for diabetic nephropathy and macroangiopathy.Treatment with glycosaminoglycans, and with sulodexide in particular, significantly improves albuminuria in type 1 and type 2 diabetic patients with micro- or macroalbuminuria. The albuminuria-lowering effect of sulodexide enhances the effect of ACEI/ARB therapy. Most studies have shown that the effect of sulodexide on albuminuria is sustained, strongly suggesting that favorable chemical and anatomic remodeling is induced by exogenous glycosaminoglycans in renal tisues, as observed in the experimental model.

Albuminuria↗
PubMed2001

Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy.

Diabetes mellitus is a major cause of peripheral neuropathy, commonly manifested as distal symmetrical polyneuropathy. This review examines evidence for the importance of vascular factors and their metabolic substrate from human and animal studies. Diabetic neuropathy is associated with risk factors for macrovascular disease and with other microvascular complications such as poor metabolic control, dyslipidaemia, body mass index, smoking, microalbuminuria and retinopathy. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. Investigations on biopsy material from patients with mild to severe neuropathy show graded structural changes in nerve microvasculature including basement membrane thickening, pericyte degeneration and endothelial cell hyperplasia. Arterio-venous shunting also contributes to reduced endoneurial perfusion. These vascular changes strongly correlate with clinical defects and nerve pathology. Vasodilator treatment in patients and animals improves nerve function. Early vasa nervorum functional changes are caused by the metabolic insults of diabetes, the balance between vasodilation and vasoconstriction is altered. Vascular endothelium is particularly vulnerable, with deficits in the major endothelial vasodilators, nitric oxide, endothelium-derived hyperpolarising factor and prostacyclin. Hyperglycaemia and dyslipidaemia driven oxidative stress is a major contributor, enhanced by advanced glycation end product formation and polyol pathway activation. These are coupled to protein kinase C activation and omega-6 essential fatty acid dysmetabolism. Together, this complex of interacting metabolic factors accounts for endothelial dysfunction, reduced nerve perfusion and function. Thus, the evidence emphasises the importance of vascular dysfunction, driven by metabolic change, as a cause of diabetic neuropathy, and highlights potential therapeutic approaches.

Animals↗
PubMed2005

[Metabolic syndrome: limited significance for clinical practice].

The risk factors for diabetes and cardiovascular disease are clustered in the 'metabolic syndrome'. The introduction of working definitions of this syndrome, all including dyslipidaemia (high triglycerides and low HDL cholesterol level), hypertension, hyperglycaemia and a measure of fat distribution or obesity, has enabled descriptive studies. Prospective population studies report an approximately two-fold increased risk of cardiovascular disease in subjects with the metabolic syndrome, with a linear increase in risk with increasing number of risk factors. So far, there is no solid evidence that insulin resistance is the main cause of the syndrome. A number of alternative or contributing mechanisms have been proposed, including cortisol metabolism and microvascular dysfunction. The concept of the metabolic syndrome has improved public awareness. Its utility in clinical practice, however, is under debate. Reduction of obesity by life-style changes and treatment of individual risk factors is still the best line of action.

Cardiovascular Diseases↗
PubMedDate not supplied

Role of exercise and metabolism in heart failure with normal ejection fraction.

Left ventricular dysfunction associated with metabolic disorders has a number of features that might shed light on the integrity of heart failure with normal ejection fraction. First, although these patients may be dyspneic and have a normal ejection fraction, their diastolic dysfunction is not isolated. Both experimental models and sensitive new parameters in humans have shown abnormal systolic function, even though the less sensitive parameters (such as ejection fraction) become abnormal only with stress. Moreover, the mechanistic contributors to myocardial dysfunction, including structural changes and metabolic influences on the cardiac myocyte, interstitial fibrosis, vascular disease, and altered loading, are likely to influence systolic as much as diastolic function. The responses of systolic and diastolic heart failure to exercise training show analogies, particularly with respect to the importance of peripheral adaptation, as well as a similar training response. Together, these features are more supportive of a continuum of pathophysiology between systolic and diastolic heart failure, rather than the 2 representing discreet phenomena.

Animals↗
PubMed1998

Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein.

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

Adult↗
PubMed2002

[Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury: a study by the positron emission tomography in twenty subjects with normal MRI findings].

Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerbral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with 15O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO2 in all regions. Then we compared rCBF, OEF, and CMRO2 between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO2 along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO2 of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of "relative luxury perfusion". Comparison of rCBF, OEF and CMRO2 between normal group and impaired group revealed that CMRO2 of the impaired group was significantly lower than that of the normal group in the bilateral frontal, temporal, and occipital lobe. After 9.3 months, FIQ scores of 13 subjects were significantly increased. CMRO2 was significantly increased in the bilateral frontal and temporal lobe, as well as in the right occipital lobe, along with the improvement of FIQ score. It was concluded that higher brain dysfunction caused by chronic MTBI was related to malfunction of neuronal networks based on the generalized decrease of brain oxygen metabolism in all brain regions. Damage to neuronal networks in the bilateral frontal and temporal lobe appeared to play the most important role in higher brain dysfunction.

Adolescent↗
PubMed2004

Pathogenesis and consequences of HIV-associated wasting.

Weight loss is a negative prognostic indicator in patients infected with HIV. Mortality rates rise measurably with as little as 3-5% weight loss over 6 months. The sensitivity of this measure is at least partly due to the correlation between weight loss and a metabolic cachexia that has been observed with other infections, trauma, and some cancers. However, the cachexia in patients with HIV, commonly termed wasting, may also be due to, or exacerbated by, reduced caloric intake, gastrointestinal dysfunction, or metabolic abnormalities independent of abnormal energy expenditure. In patients with HIV wasting, therapies should be directed both at reversing the underlying source of protein energy malnutrition and at other factors that may be contributing to weight loss.

Antiretroviral Therapy, Highly Active↗
PubMed1999

[Systemic inflammatory response syndrome in critical patients - an analysis of 1,292 cases].

OBJECTIVE: To study the significance of the occurrence and the development of systemic inflammatory response syndrome (SIRS) in critical patients. METHODS: The clinical data of 1292 patients accepted by our hospital in ten months from October 1995 to July 1996 were analyzed. The patients met at least two of the criteria for SIRS such as fever, hypothermia, tachycardia, tachypnea or abnormal white blood cell count. RESULTS: 1292 (67.7%) of the 1909 patients investigated met two or more of the criteria for SIRS. In the 1292 cases, those who met two, three or four of the criteria were respectively 467 (36.1%), 526 (40.7%) and 299 (23.1%). 149 patients (11.5%) in the 1292 cases died of multiple organ dysfunction syndrome (MODS). In which 33 (7.1%), 57 (10.8%) and 59 (19.7%) respectively in patients with two, three and four of the criteria for SIRS. The proportion of patients suffering from acute respiratory distress syndrome, metabolic function dysfunction, disseminated intravascular coagulation and acute renal failure increased with the increase in the number of SIRS criteria that the patients met and with the increase in the proportion of patients progressing from SIRS to septic shock. The mortality rate of the patients also gradually increased while the patients with SIRS were developing sepsis, severe sepsis and septic shock, but there was no statistical significance (P > 0.05). CONCLUSION: It is suggested that bacterial infection, severe trauma and acute pancreatitis might cause SIRS and compensatory anti-inflammatory response syndrome might play an important role in the maintenance of internal environment of the body. A comprehensive understanding of SIRS might be of help to the management of critical diseases.

Adolescent↗
PubMed1992

Tubular secretion of Tamm-Horsfall protein in type 1 (insulin-dependent) diabetes mellitus using a simplified enzyme linked immunoassay.

The relationship between glomerular and tubular dysfunction and metabolic control in type 1 diabetes was studied. To that end the urinary excretion rates of albumin and Tamm-Horsfall protein as well as HbA1c levels were measured in 58 patients with different degrees of diabetic nephropathy and in 76 apparently healthy subjects matched for sex and age. The urinary Tamm-Horsfall protein levels were measured by a simplified enzyme linked immunoassay. The intra- and interassay variations were 8.9% and 13.6%, respectively. The intraindividual variation was 41% and the sensitivity of the assay was 4 micrograms/l. The Tamm-Horsfall protein excretion rate was 42.1 x/2.0 micrograms/min (geometric mean x/tolerance factor) in the diabetic patients compared to 34 x/1.9 micrograms/min in the control subjects (NS). The diabetic patients had higher albumin excretion rate (38.5 x/7.3 micrograms/min) than the control subjects (4.7 x/2.3 micrograms/min; P less than 0.001). By using multivariate analysis of variance, HbA1c level was found to be the only independent variable associated with Tamm-Horsfall protein excretion rate in diabetic patients (r = -0.28; P = 0.04), while no relationship was found between Tamm-Horsfall protein excretion rate and age, age at onset and duration of diabetes, gender, serum creatinine, diuresis, urinary albumin excretion rate, systolic and diastolic blood pressure levels and antihypertensive treatment. The urinary albumin excretion rate was associated with diastolic blood pressure (r = 0.34; P = 0.02) but not with HbA1c levels when testing the above variables by multivariate analysis of variance. In conclusion, these results may indicate a lack of relationship between glomerular and tubular dysfunction. The former was influenced only by diastolic blood pressure levels and the latter only by the degree of metabolic control. However, the correlations were weak and do not provide any insight into what is actually responsible for glomerular and tubular dysfunction.

Adult↗