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Biomedical subjects

R W Bilous

Publications and source records attributed to R W Bilous.

At least 19 recordsLinked to original sources
PubMed1992

Cell and matrix components of the glomerular mesangium in type I diabetes.

In a cross-sectional study, glomerular basement membrane (GBM) width, the volume fractions of the mesangium (VvMes), its cell (VvCell) and matrix (VvMatx) components, and surface density of the peripheral capillary surface (SvPGBM) were measured in renal biopsies from 187 nondiabetic living related and cadaveric donors of kidneys for transplantation and from 150 patients with insulin-dependent (type I) diabetes mellitus of 1-41 yr duration. In the diabetic patients, the matrix was the major factor in the expansion of the mesangium. However, both VvCell (0.11 +/- 0.04) and VvMatx (0.20 +/- 10) in diabetic patients exceeded the same measurements in nondiabetic subjects (0.07 +/- 0.02 for each component) (P less than 0.001 in each case). Linear regression analysis demonstrated significant correlations (P less than 0.001 for all) between GBM width, VvMes, VvCell, VvMatx, or SvPGBM and either urinary albumin excretion and creatinine clearance, with the higher correlation coefficients in all cases with albuminuria. Of the structural parameters, VvMatx correlated best with either functional measure by stepwise regression, with GBM as an added factor only with albuminuria. Therefore, although models of diabetic glomerulopathy must consider enlargement of both mesangial cells and matrix, the predominant factor in the progression of structural and functional renal disease is mesangial matrix expansion.

Adult↗
PubMed1991

Global glomerular sclerosis and glomerular arteriolar hyalinosis in insulin dependent diabetes.

We studied the lesions of global glomerular sclerosis and arteriolar hyalinosis in 43 (29 females) insulin-dependent diabetes mellitus (IDDM) patients whose creatinine clearance (CCr) was greater than or equal to 45 ml/min/1.73 m2 and whose renal biopsies had at least 20 glomeruli available for study. These patients, ages 17 to 55 years, had IDDM for 7 to 32 (20 +/- 6, means +/- SD) years. CCr ranged from 47 to 139 (91 +/- 25) ml/min/1.73 m2 and urinary albumin excretion (UAE) from 5 to 3386 (median = 127) mg/24 hrs. Eighteen patients were hypertensive. Thus, these patients represented a broad clinical range from normal renal function through overt diabetic nephropathy. The percent of glomeruli which were globally sclerosed was strongly correlated with CCr (r = -0.64, P less than 0.0001) and log UAE (r = +0.67, P less than 0.001). Hypertension was more common in patients with more than 10% sclerosed glomeruli (chi square = 9.5, P less than 0.002). Percent sclerosed glomeruli was highly significantly correlated with the index of severity of the arteriolar hyalinosis lesion (r = +0.66, P less than 0.0001) and mesangial volume fraction (r = +0.61, P less than 0.0001). We hypothesize that arteriolar hyalinosis could contribute to global glomerular sclerosis through severe compromise of glomerular blood flow. Alternately, global glomerular sclerosis may result from marked mesangial expansion and capillary occlusion. However, in this broad range of patients it appeared that global glomerular sclerosis and mesangial expansion were not infrequently independent diabetic renal lesions which could contribute separately to the ultimate development of overt diabetic nephropathy.

Adolescent↗
PubMed1989

The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes.

The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up, no progression could be detected in any structural measure in the glomerulus. Furthermore, the recipients of pancreas transplants had smaller glomerular volumes than 13 matched diabetic patients who were recipients of renal allografts but who did not undergo pancreas transplantation (mean +/- SD, 1.80 +/- 0.55 vs. 2.47 +/- 0.73 x 10(6) microns 3; P = 0.02) and showed markedly less mesangial expansion (mesangial-volume fraction, 0.19 +/- 0.07 vs. 0.31 +/- 0.10 microns 3 per cubic micrometer; P = 0.004). We conclude that successful pancreas transplantation is associated with significantly less severe diabetic glomerulopathy in kidneys previously transplanted into diabetic patients. These data support the hypothesis that normoglycemia can prevent the progression of diabetic glomerulopathy in humans.

Adult↗
PubMed1989

Glomerular lesions and urinary albumin excretion in type I diabetes without overt proteinuria.

Since several studies have suggested that a slight increase in urinary albumin excretion (microalbuminuria) is predictive of nephropathy in patients with diabetes mellitus, we studied the relation of albumin excretion to renal structure in patients with insulin-dependent (Type I) diabetes. Renal biopsy specimens were evaluated with light- and electron-microscopical morphometric techniques in 48 patients who had had diabetes for 5 to 40 years and who excreted less than 200 mg of urinary albumin per 24 hours. Patients in Group I (n = 26) had normal urinary albumin excretion, creatinine clearance, and blood pressure; those in Group II (n = 10) had increased urinary albumin excretion but normal creatinine clearance and blood pressure; those in Group III (n = 12) had increased urinary albumin excretion and hypertension, decreased creatinine clearance, or both. Glomerular structure varied similarly, ranging from normal to abnormal in Groups I and II, but was consistently abnormal in Group III. The thickness of the glomerular basement membrane, the fractional volume of the mesangium, and the mesangial volume per glomerulus in Group III exceeded the corresponding values in the other groups significantly. Thus, microalbuminuria, when present with hypertension, decreased creatinine clearance, or both, indicates established abnormalities of glomerular structure. Normal albumin excretion, or microalbuminuria without these other functional abnormalities, does not accurately predict the severity of the underlying glomerular lesions in patients with Type I diabetes.

Adolescent↗
PubMed1989

The predictive value of microalbuminuria.

An elevated urinary albumin excretion (termed microalbuminuria) has been proposed as a predictor for later development of clinical diabetic nephropathy (hypertension, falling glomerular filtration rate [GFR], and urinary albumin excretion greater than 300 mg/24 h). However, review of the original reports on the predictability of microalbuminuria revealed a concomitant presence of elevated BP and a propensity to falling GFR. Thus, the predictability of microalbuminuria rests on the added evaluation of BP and GFR. Additional investigation is needed to address the possibility that microalbuminuria and either a rising BP or a falling GFR or both indicates established diabetic nephropathy rather than predicting its development.

Albuminuria↗
PubMed1989

Mean glomerular volume and rate of development of diabetic nephropathy.

We studied kidney glomerular structure and function in two groups of type I (insulin-dependent) diabetic subjects with 14-16 yr (group 1, n = 16) and 24-26 yr (group 2, n = 13) duration of diabetes and compared them to a group of 18 nondiabetic subjects with similar age ranges. Within each diabetic group, subjects were selected for normal kidney function (urinary albumin excretion less than 40 mg/24 h, normal blood pressure, creatinine clearance greater than 90 ml.min-1.1.73 m-2) or for nephropathy (urinary albumin excretion greater than 200 mg/24 h). Morphometric analysis of glomeruli revealed a significantly larger mean glomerular volume in subjects with nephropathy (group 2). Mesangial volumes were significantly greater in the nephropathic than the normoalbuminuric diabetic subjects in each group, but filtration surface per glomerulus was constant among all subjects. The percentage of sclerosed glomeruli was also significantly increased in the nephropathic subjects compared with the subjects with normal kidney function, in whom sclerosed glomeruli did not exceed 8%. In addition, there was a significant correlation between percentage of globally sclerosed glomeruli and glomerular volume in group 2 (rs = .79, P less than .01) but not group 1 (rs = -.20, NS) subjects. Thus, glomerular size or individual capacity for glomerular expansion may determine the rate of progression of the loss of kidney function in subjects destined to develop diabetic nephropathy.

Adolescent↗
PubMed1989

The relationship between glomerular structure and function in insulin-dependent diabetes.

Diabetic nephropathy affects up to 40% of insulin dependent patients for reasons that are unclear. This review briefly describes the methodology of histological quantitative morphometry as applied to the human renal glomerulus and what the results tell us about the glomerular structural determinants of GFR. A case is made for the use of renal biopsy as an important part of studies of the diabetic kidney.

Anthropometry↗
PubMed1988

The epidemiology of hypothyroidism--an update.

Comparison of studies of the prevalence and incidence of hypothyroidism is hampered by differing definitions and population samples. Using a uniform set of diagnostic criteria, the prevalence of previously undiagnosed, spontaneous, overt hypothyroidism in community-based studies has been estimated between 2-4/1000 total population world-wide. If all cases of previously diagnosed hypothyroidism, previous thyroid surgery and radioiodine treatment are included, this prevalence rises to approximately 10/1000, and if subclinical cases are included, then the prevalence is probably over 50/1000 total population. The annual incidence of overt hypothyroidism is between 1-2/1000 for female and around 2/10,000 for males, with individuals having previously elevated TSH and positive circulating thyroid autoantibodies, being particularly at risk. The question of widespread population screening for hypothyroidism is unsettled, but it is probably not cost-effective unless incorporated as part of a screening programme for other conditions such as cervical cancer, or targeted at high risk groups such as post-menopausal women. The combination of serum TSH estimation and a high clinical index of suspicion should detect most patients with thyroid dysfunction, although detailed studies on the use of the more sensitive assays in the detection of both hyper- and hypothyroidism have yet to be published.

Female↗
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Recruitment, Randomization, and baseline characteristics of the treatment groups.

The general and ophthalmologic eligibility criteria were applied in the course of formal screening of selected members of clinic populations at the six treatment centers between August 1980 and November 1981. Patients eligible on the grounds of the history and general physical examination underwent a detailed ophthalmologic examination and determination of C-peptide status. Initial rates of recruitment were slow, which occasioned modifications of the eligibility criteria and a prolongation of the recruitment phase. All six clinics approached their goal of at least six patients in each of the continuous subcutaneous insulin infusion (CSII) and conventional insulin treatment (CIT) groups, with a final total of 70 randomized subjects. The method of paired randomization was acceptable, but led to some delay during periods of slow recruitment activity. Data from two patients who chose to drop out of the study shortly after randomization are included in the baseline characteristics. There was no difference between treatment groups with respect to age or duration of known diabetes, body weight, systolic blood pressure, proportion of cigarette smokers, retinopathy level as assigned by analysis of stereofundus photographs, or microaneurysm counts performed on fluorescein angiograms. A trend toward milder retinopathy in the CIT group proved to be statistically insignificant. Subsequent assessment of stereofundus photographs at the Fundus Photograph Reading Center indicated that six patients were misclassified by treatment center ophthalmologists with respect to ophthalmologic eligibility. We conclude that recruitment goals were met and randomization was successful.

Adolescent↗
PubMed1985

Eight-month correction of hyperglycemia in insulin-dependent diabetes mellitus is associated with a significant and sustained reduction of urinary albumin excretion rates in patients with microalbuminuria.

Persistent Albustix-positive proteinuria and subsequent chronic renal failure are frequently encountered in insulin-dependent diabetes mellitus (IDDM). Rates of decline of renal function may be modified by treatment of accompanying hypertension, but studies of the effects of long-term continuous subcutaneous insulin infusion (CSII) on deterioration of renal function provide no statistically significant evidence of benefit of near-normoglycemia. However, short-term studies in IDDM subjects with negative Albustix tests but subclinically raised levels of albumin excretion rate (AER) have shown that treatment with CSII significantly reduces this microalbuminuria. The prospective, controlled 8-mo Kroc Collaborative Study therefore offered the opportunity of examining more protracted effects of CSII-induced metabolic correction upon microalbuminuria. Twenty-four-hour urine collections obtained at baseline, 4, and 8 mo were available from 59 Albustix-negative patients. Beta 2-microglobulin excretion was normal. The 39 normoalbuminuric (AER less than 12 micrograms/min) patients did not differ from the 20 microalbuminuric (AER elevated between 13.2 and 192.6 micrograms/min) with respect to distributions of age, sex, and duration of diabetes. In both the normoalbuminuric and the microalbuminuric groups studied at 4 and 8 mo, percent glycosylated hemoglobin (%HbA1) and mean blood glucose were significantly decreased during CSII compared with baseline values, whereas no change occurred in the group continuing their conventional insulin therapy (CIT). AER did not differ between CIT and CSII treatments in the normoalbuminuric group. AER fell significantly in the CSII-treated microalbuminuric patients at 4 (P less than 0.05) and 8 (P less than 0.01) mo but showed no consistent change in the CIT microalbuminuric group.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1984

Metabolic effects of physical exercise in insulin-dependent diabetics controlled by continuous subcutaneous insulin infusion or conventional injection therapy.

The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion. Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P less than 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.

Adult↗
PubMed1983

Severe diabetic microangiopathy with normal glucose tolerance and pituitary infarction.

Blood glucose concentrations in a woman with severe retinopathy, nephropathy, and neuropathy were found to be within the normal range. A high random blood glucose concentration was recorded only once, six months before her initial presentation. At necropsy the anterior lobe of the pituitary gland showed old, extensive infarction. Occult pituitary hypofunction may explain severe diabetic microangiopathy in patients with normal glucose tolerance.

Adult↗
PubMed1983

Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes.

The effect of long term correction of hyperglycaemia on the rate of deterioration of renal function was studied in six insulin dependent diabetics with proteinuria due to diabetic nephropathy. After a planned run in observation period of 10 to 24 months patients entered a programme of continuous subcutaneous insulin infusion for up to 24 months. Glycaemic control was promptly and significantly improved and optimal glycaemic values sustained throughout the study. Blood pressure was maintained stable. A control group of six nephropathic diabetics was studied receiving conventional insulin injection treatment but also with blood pressure control over the same period.Despite greatly improved metabolic control in the infusion treated group no significant change in the rate of decline of glomerular filtration rate could be shown, the plasma creatinine concentrations continued to increase, and the fractional clearance of albumin and IgG rose progressively, indicating progression of glomerular damage. The conventionally treated control group behaved similarly. In a single patient receiving the continuous infusion the rate of decline of the glomerular filtration rate slowed considerably, suggesting that the response to strict diabetic control may differ in some patients.These findings suggest that by the time glomerular function has started to fail in diabetic nephropathy the process culminating in end stage renal failure has become self perpetuating and is little influenced by the degree of metabolic control. A new definition of potential clinical diabetic nephropathy is proposed that will permit identification of patients at risk and earlier intervention by glycaemic correction in an attempt to arrest diabetic renal disease.

Adult↗
PubMed1983

Monitoring glomerular function in diabetic nephropathy. A prospective study.

Glomerular function was monitored prospectively in 13 patients with insulin-dependent diabetes and diabetic nephropathy for up to 51 months. Glomerular filtration rate, measured by 51Cr-EDTA clearance, showed a linear decline in all patients. Rates of fall ranged between 0.63 and 2.4 ml/minute per month (mean +/- SEM 1.2 +/- 0.16). Plasma creatinine concentration proved to be an insensitive marker of glomerular function, especially in the early phase of nephropathy. A good correlation was found between the rate of change of 51Cr-EDTA glomerular filtration rate and that of inverse creatinine levels when plasma creatinine concentrations exceeded 200 mumol/liter. Inverse plasma beta 2-microglobulin concentrations, however, showed a highly significant correlation (r = 0.93; p less than 0.001) with 51Cr-EDTA glomerular filtration rate over the whole range of values, making it sensitive in screening for early impairment of renal function. A significant relationship (r = 0.85; p less than 0.01) was found between the rates of change of the 51Cr-EDTA glomerular filtration rate and of inverse beta 2-microglobulin levels for plasma beta 2-microglobulin concentrations above 3 mg/liter. A progressive increase in the fractional clearance of albumin, IgG, and beta 2-microglobulin was noted as the glomerular filtration rate fell, indicating an evolving defect in the renal handling of proteins. The rate of decline of the glomerular filtration rate was unrelated to age, sex, duration of diabetes, duration of diabetes before onset of proteinuria, glomerular filtration rate, initial albumin clearance, blood glucose control, and arterial pressure, when diastolic values were below 100 mm Hg. The effect of therapeutic intervention (e.g., blood glucose, blood pressure, or diet) on the progression of diabetic nephropathy can be reliably evaluated by precise measures of rate of decline of glomerular filtration rate and changes in fractional clearance of plasma proteins. The factor(s) determining the individual rate of decline of renal function still remain obscure.

Adult↗