Biomedical subjects

G Jerums

Publications and source records attributed to G Jerums.

139 records · Page 8Linked to original sources

PubMedDate not supplied

Intermittent diabetic microalbuminuria: association with blood pressure, glycemic control, and protein intake.

The factors associated with intermittent microalbuminuria were studied over 7 years in 49 Type I and 53 Type II diabetics who had normal initial albumin clearance. Fasting plasma glucose, HbA1, 24 hour urinary glucose, blood pressure, protein intake (24 hour urinary urea), and the renal clearance of albumin, transferrin, and IgG, as well as total proteinuria, were assessed every 3-6 months. Fifteen Type I and 11 Type II diabetics had 40 and 31 episodes, respectively, of intermittent microalbuminuria, defined as an albumin clearance greater than 11 nl/sec, without progressing to persistent microalbuminuria. Rises in transferrin and IgG clearance paralleled albumin clearance in both Type I and Type II diabetics. There were no significant changes in blood pressure or glycemic control during episodes of intermittent microalbuminuria. However, in Type I diabetics, intermittent microalbuminuria was associated with higher levels of urinary urea excretion. This study raises the possibility that increased protein intake may participate in the development of nephropathy in Type I diabetes.

Adult↗

PubMedDate not supplied

Prediction of persistent microalbuminuria in patients with diabetes mellitus.

Persistent microalbuminuria [albumin excretion rate (AER): 30-300 micrograms/min] is predictive of clinical nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and cardiovascular mortality in addition to nephropathy in patients with non-insulin-dependent diabetes. The clinical significance of intermittent microalbuminuria, however, is unknown. We performed serial measurements of urinary albumin excretion at intervals of approximately 6 months in 139 diabetic patients who at entry did not have persistent microalbuminuria to determine whether intermittent microalbuminuria occurs more frequently in those patients who subsequently develop persistent microalbuminuria. The relative risk for the development of persistent microalbuminuria in diabetic patients with a greater proportion than 3 out of 20 determinations in the microalbuminuric range was 17.4 (95% confidence interval, 3.92-77.2) in those with IDDM and 2.78 (0.99-7.8) in those with non-insulin-dependent diabetes when compared with matched diabetic patients with fewer elevated measurements. These data suggest that frequent intermittent microalbuminuria predicts the future development of persistent microalbuminuria particularly in IDDM patients and that AER should be assessed by serial rather than single measurements.

Adolescent↗

PubMedDate not supplied

Extracellular matrix and its interactions in the diabetic kidney: a molecular biological approach.

Increased extracellular matrix (ECM) is the ultrastructural hallmark of diabetic microangiopathy. Its accumulation within the kidney is directly linked to the clinical manifestations of diabetic nephropathy, namely proteinuria and declining renal function. The pathogenesis of ECM changes in diabetes is not well understood, but is likely to involve interaction between cells, growth factors, structural proteins, and cell receptors for these molecules. Molecular biological techniques may offer the necessary tools for gaining insight into the pathogenetic processes that eventually lead to renal failure in diabetes.

Animals↗

PubMedDate not supplied

Angiotensin-converting enzyme (ACE) gene polymorphism in type II diabetic patients with increased albumin excretion rate.

Approximately one in three patients with diabetes is at risk of developing kidney disease, despite current methods of treatment. It has long been suspected that diabetic kidney disease has a genetic basis, but this has been difficult to prove. Polymorphisms of the angiotensin-converting enzyme (ACE) gene have been shown to be related to the occurrence of nephropathy in type I diabetic patients. This study showed that there was no association in the ACE genotype frequency and increased albumin excretion rate in type II diabetic patients.

Adult↗

PubMedDate not supplied

Natural history of early diabetic nephropathy: what are the effects of therapeutic intervention? Melbourne Diabetic Nephropathy Study Group.

Several studies have shown that lowering of blood pressure slows the rate of progression of diabetic renal disease. Some placebo-controlled studies have also shown that angiotensin-converting enzyme (ACE) inhibitors decrease or stabilize albuminuria in incipient nephropathy and slow the rate of progression of advanced nephropathy. However, it is not yet clear if prolonged treatment with ACE inhibitors or with other agents exerts a specific renoprotective effect in incipient diabetic nephropathy. It is proposed that such an effect should be independent from changes in systemic blood pressure and should be characterized by amelioration of the rate of rise of albumin excretion rate (AER) and the rate of fall of glomerular filtration rate (GFR) and independence from changes in other parameters known to influence AER (glycemic control, protein intake, sodium intake). In addition, there should be evidence that the potentially reversible effects of therapeutic intervention on AER and GFR are translated to long-term changes in renal function and structure. This paper reviews the evidence on which the concept of renoprotection is based, with particular reference to choice of end points, heterogeneity of study groups, and complexities of the disease process, and relates this evidence to the natural history of nephropathy in type I and type II diabetes. Based on the above, an assessment is made of the comparative effects of ACE inhibitors and other antihypertensive agents on AER and GFR. It is suggested that longitudinal intra-individual analysis of both variables may be necessary in order to determine whether ACE inhibitors exert greater renoprotection than calcium channel blockers or other antihypertensive agents.

Albuminuria↗

PubMedDate not supplied

Lack of effect of gliclazide on early diabetic nephropathy and retinopathy: a two-year controlled study.

This study has attempted to document a specific haemovascular action of gliclazide on the reversal of early diabetic microangiopathy. A prospective double-blind controlled study was performed over 2 years, comparing gliclazide versus placebo in insulin-treated and gliclazide versus glibenclamide in non-insulin-treated diabetic subjects, after a 1-year run-in period. Glycaemic control was not significantly different in gliclazide- and non-gliclazide-treated subjects before or after the commencement of active therapy. Following treatment with gliclazide in 17/32 insulin-treated and 8/17 non-insulin-treated subjects with Albustix-negative proteinuria, there was no difference in retinopathy score, total proteinuria or the renal clearance of creatinine, albumin, transferrin and immunoglobulin G. In the insulin-treated group, progression of retinopathy was observed in approximately one-third of subjects, but no parameter of proteinuria progressed over 2 years. Thus, this study did not detect a reversal of the parameters measured and does not support an action of gliclazide on diabetic microangiopathy, independent of its hypoglycaemic action.

Blood Pressure↗

PubMedDate not supplied

Effects of intranasal insulin in non-obese type II diabetics.

The comparative effects of intranasal and subcutaneous insulin on blood glucose and insulin levels are described in non-obese type II diabetics, in the fasting state and following a standard meal. In the fasting studies, intranasal insulin (30 units) produced a single early insulin peak. Elevated insulin levels and their hypoglycaemic effect persisted for less than 2 h whereas with subcutaneous insulin (8 units) elevated insulin levels and evidence of hypoglycaemic action were still present at 4 h. By contrast, in the meal studies both forms of insulin had similar effects on serum insulin levels and blood glucose. Moreover elevated insulin levels and evidence of reduction in post-prandial hyperglycaemia were now present at 4 h with both intranasal and subcutaneous insulin administration. Intranasal insulin in combination with a test meal now produced a biphasic insulin profile more closely resembling the normal insulin response to a meal, and reflecting the combined effects of endogenous and exogenous insulin.

Administration, Intranasal↗

PubMedDate not supplied

Long-term intraindividual variability of serum lipids in patients with type I and type II diabetes.

The objective of this study was to estimate the long-term intraindividual variability of lipid levels in adult type I and type II diabetic patients. Total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and hemoglobin A1c were measured every 3-6 months in 135 patients attending the Austin Hospital diabetes clinic. Analysis was performed on 60 diabetic patients (33 type I and 27 type II) who had not been treated with lipid lowering drugs and who met the inclusion criteria of at least five measurements [mean +/- standard error of the mean (SEM), 9.5 +/- 0.4; range, 5-17] collected over a minimum of 4 years (5.1 +/- 0.1; 4-6.5 years). Total variability, expressed as coefficient of variation, was 8.8 +/- 0.4% for total cholesterol, 23.9 +/- 1.5% for triglycerides, 10.2 +/- 0.5% for HDL cholesterol, and 12.0 +/- 0.5% for LDL cholesterol. Biological variability, derived from total and analytical variability, was higher than previous estimates in nondiabetic subjects for total cholesterol and HDL cholesterol but similar for triglycerides and LDL cholesterol. No relationship was observed between total lipid variability and diabetes type, age, baseline or mean lipid levels, duration of follow-up, or the number of samples per patient. Men demonstrated greater variability than women for total cholesterol (men 9.5 +/- 0.5%, n = 34, women 7.9 +/- 0.5%, n = 26, p < 0.01) and triglycerides (men 26.5 +/- 2.2%, women 20.4 +/- 1.4%, p = 0.03). Total lipid variability was also unrelated to baseline or mean hemoglobin A1c or to the change in hemoglobin A1c during the study as a whole. However, the change in hemoglobin A1c was associated with the change in total cholesterol (r = 0.30, p < 0.03) and the change in LDL cholesterol (r = 0.27, p < 0.05). In conclusion, long-term intraindividual lipid variability in adult diabetic subjects is higher for total and HDL cholesterol than previously published values in nondiabetic subjects. Variability of triglycerides is at least double that of total cholesterol, HDL cholesterol and LDL cholesterol. Biological variability, not measurement error, accounts for the greatest proportion of total variability for all lipid parameters. Confidence levels calculated from these data have implications for the initiation of lipid lowering therapy and in monitoring the effects of intervention.

Adult↗

PubMedDate not supplied

Diabetic vascular complications.

1. Diabetic vascular complications can be arbitrarily divided into micro- and macrovascular complications, the major microvascular complications being nephropathy, retinopathy and neuropathy. Macrovascular complications are due to accelerated atherosclerosis and include ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. 2. It is postulated that metabolic and haemodynamic factors interact leading to the development of diabetic vascular complications. 3. Advanced glycation appears to be an important pathway in the pathogenesis of diabetic complications with evidence that the inhibitor of this process, aminoguanidine, attenuates the development of a range of diabetic vascular complications. 4. The results of experimental studies have led to large-scale clinical trials of various therapeutic agents that act to interfere with the metabolic and haemodynamic pathways implicated in the progression of diabetic complications.

Animals↗

PubMedDate not supplied

Progression of proteinuria in type 1 and type 2 diabetes.

A longitudinal study evaluating the time course of the transition from normal to microalbuminuria, and then on to macroalbuminuria, was made over a mean period of 7 years in a cohort of 52 patients with Type 1 diabetes and 61 patients with Type 2 diabetes. Transient episodes of micro- and macroalbuminuria were often observed before the ultimate development of persistent Albustix-positive proteinuria. The transition from normal to microalbuminuria and from micro- to macroalbuminuria was characterized by rises in renal albumin clearance accompanied by lesser rises in total proteinuria. Seven patients with Type 1 and 12 with Type 2 diabetes showed evidence of progression, the interval for the transition from normal to macroalbuminuria varying from 3 to 5 years. In Type 1 diabetic patients, the development of micro- and macroalbuminuria was associated with a decline in renal function and a rise in systolic blood pressure without a significant change in blood glucose control. In Type 2 diabetic patients, the development of microalbuminuria was associated with a small decline in renal function but no change in blood pressure or blood glucose control. It is concluded that the transition from normal to micro- and on to macroalbuminuria may be more rapid then previously reported and varies considerably among individuals.

Adult↗

PubMedDate not supplied

Microalbuminuria: prognostic and therapeutic implications in diabetes mellitus.

Thirty years following the development of the first radioimmunoassay for albumin, microalbuminuria is widely acknowledged as an important predictor of overt nephropathy in patients with Type 1 diabetes and of cardiovascular mortality in Type 2 diabetes. In addition, there is accumulating evidence to suggest that diabetic patients with microalbuminuria may have more advanced retinopathy, higher blood pressure, and worse dyslipidaemia than patients with normal albumin excretion rates. Recent studies have focused on the role of intervention, principally with antihypertensive therapy and intensive glycaemic control, in reducing microalbuminuria. While successful in reducing urinary albumin excretion it remains to be established whether such therapies will be translated into a reduction in renal failure and decreased cardiovascular morbidity and mortality.

Albuminuria↗

PubMedDate not supplied

Spectrum of proteinuria in type I and type II diabetes.

We prospectively investigated the evolution of proteinuria in 52 type I diabetics over 7.8 +/- 0.3 (mean +/- SE) yr and in 61 type II diabetics over 6.4 +/- 0.3 yr. Measurements of renal protein clearance were performed serially, and the time course of proteinuria was classified in each subject based on a threshold albumin clearance of 11 nl/s, equivalent to a urinary albumin excretion rate of 30 micrograms/min. The classification based on this threshold yielded four distinct patterns of albuminuria: minimal, intermittent, progressing, and established. These patterns occurred in both type I and type II diabetics independently of the duration of follow-up. This study has identified a pattern of intermittent microalbuminuria that is also associated with transient elevations of transferrin and IgG clearances. The relationship of clinical and biochemical parameters to proteinuria patterns was evaluated. No relationship was detected between proteinuria patterns and glycemic control in either type I or type II diabetics. In type I but not type II diabetics, established proteinuria was associated with higher systolic blood pressure and decreased creatinine clearance. The phase of intermittent proteinuria detected in this study may represent a reversible stage in the development of diabetic nephropathy, but the factors that trigger the transition to progressing proteinuria remain obscure.

Adult↗

PubMedDate not supplied

Long-term use of intranasal insulin in insulin-dependent diabetic patients.

This study, in 3 phases, compared the long-term acceptability and efficacy of insulin administered by nasal spray with an intensified subcutaneous regimen in nine type I (insulin-dependent) diabetic subjects on baseline therapy with ultralente insulin. In phase 1, patients were begun and stabilized on a regimen of ultralente daily and Actrapid insulin three times daily. Phase 2 consisted of 4 mo of this intensified subcutaneous regimen. In phase 3, intranasal administration of insulin, with 1% (wt/vol) sodium glycocholate, replaced Actrapid insulin for 4 mo. Glycemic control was compared in each of the three phases. It was possible to maintain the dose of ultralente insulin relatively constant in only six of the nine subjects during the intranasal phase of the study. The six subjects showed a significant rise in glycosylated hemoglobin during the intranasal phase (10.4 +/- 0.6% intranasal vs. 9.1 +/- 0.3% subcutaneous, P less than .05) but not in plasma or urinary glucose levels. There was no significant change in the incidence of hypoglycemic episodes during intranasal insulin therapy in this group. The other three subjects were considered treatment failures. Six of the nine original subjects expressed a preference for intranasal insulin, and one subject complained of mild nasal irritation insufficient to cease treatment. The intranasal route of administration of insulin has the potential to replace short-acting insulin as an adjunct to longer-acting insulin in some insulin-treated diabetic patients.

Administration, Intranasal↗