Whole body capillary exchange of albumin. Alterations in diabetic microangiopathy.

Until the mid eighties most conceptual knowledge of peripheral transcapillary plasma protein transport has been based on experiments with the lymph collection methods, picturing macromolecular exchange as a slow, mainly unidirectional flux from plasma to lymph. All sieving or restriction is assumed to occur at the capillary membrane level reducing interstitial as well as lymphatic plasma protein concentrations. However, in newer experiments using rapidly resolving tracer techniques, transcapillary albumin fluxes are found 10 to 20 times higher than the lymphatic return.

Hip and distal arm fracture rates in peri- and postmenopausal insulin-treated diabetic females.

Objectives: Hip and distal arm fractures are associated with osteoporosis in the postmenopausal female. In diabetic patients, bone mass has been found to be reduced leading to the hypothesis that diabetes is a risk factor for osteoporosis. Whether this has any clinical implication has only been sparsely elucidated.

Plasma disappearance and distribution volume of polyfructosan in type 1 (insulin-dependent) diabetes mellitus.

The simultaneous plasma disappearance curves of the extracellular marker polyfructosan and 125I-fibrinogen were recorded for 3 h in 24 male long-term diabetic patients. Eight normal subjects served as a control group. The patients were divided into three groups according to their urinary albumin excretion: Group 1 had normal albumin excretion (< 30 mg/24 h), Group 2 had microalbuminuria (30-300 mg/24 h), and Group 3 had clinical nephropathy (> 300 mg/24 h).

The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy.

We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsy-proven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.

Increased urinary loss of high density lipoproteins in albuminuric insulin-dependent diabetic patients.

The pathophysiological mechanisms resulting in hyperlipidaemia in albuminuric insulin-dependent diabetic patients are largely unknown. Increased non-specific hepatic protein synthesis as a response to urinary protein loss, has been proposed. However in that case it is unexplained why the plasma concentration of the high density lipoprotein (HDL) subfraction, in contrast to all other lipoprotein subfractions, is normal or even reduced in albuminuric patients.

The prevalence of hypercholesterolaemia and its relationship with albuminuria in insulin-dependent diabetic patients: an epidemiological study.

To assess the prevalence of hypercholesterolaemia and its relationship with metabolic control and urinary albumin excretion in Type 1 diabetic patients, all 1577 insulin-dependent patients attending the outpatient clinic at the Steno Memorial Hospital were studied. None had previously received lipid-lowering drugs. Hypercholesterolaemia, defined as plasma concentration of cholesterol above 6.

Micro-albuminuria and large vessel disease in diabetes.

Background: Atherosclerosis is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. Recent studies have shown that albuminuria is a predictor of cardiovascular disease in these patients and there is a particularly high incidence of coronary heart disease in the early stages of albuminuria.

Available Evidence: A number of established cardiovascular risk factors, such as elevated blood pressure, atherogenic changes in the plasma concentrations of lipids and lipoproteins, elevated plasma levels of fibrinogen and, probably, hyper-reactivity of platelets are present in patients with diabetic nephropathy.

Effects of isradipine in Type 1 (insulin-dependent) diabetic patients with albuminuria and normal blood pressure.

The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin excretion (more than 30 mg/24h) based on several 24 h urine collections, and BP was normal (below 140/90 mmHg).

Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients.

A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%).

Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy.

The urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n = 45), normal UAE less than 30 mg/24 h; group 2 (n = 27), microalbuminuria (UAE 30-300 mg/24 h); and group 3 (n = 29), clinical diabetic nephropathy (UAE greater than 300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3.

Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients.

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased.

Inhibition of N-acetylheparosan deacetylase in diabetic rats.

The effects on N-acetylheparosan deacetylase (N-deacetylase) activity exerted by poorly and well-regulated diabetes and variation of genetic background were investigated in insulin-treated streptozocin-induced diabetic rats of two different strains (H and U). N-deacetylase plays a key role in heparan sulfate biosynthesis, because N-deacetylation is a prerequisite for N- and further O-sulfation. Specific activity of the enzyme was reduced by 50% in poorly regulated diabetic rats compared with nondiabetic rats (P less than 0.

Nocturnal electroencephalogram registrations in type 1 (insulin-dependent) diabetic patients with hypoglycaemia.

Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications were studied overnight for two consecutive and one subsequent night with continuous monitoring of electroencephalogram and serial hormone measurements. The aims were: 1) to evaluate the influence of spontaneous and insulin-induced hypoglycaemia on nocturnal electroencephalogram sleep-patterns and, 2) to evaluate counter-regulatory hormone responses. Spontaneous hypoglycaemia occurred on six nights (38%) with blood glucose concentrations less than 3.

Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-1 beta content but not monokine secretion in healthy and insulin-dependent diabetic individuals.

The effects of dietary supplementation with omega-3-polyunsaturated fatty acids (omega-3-PUFA) on the proliferative response of PBMC and on the secretion of monokines and arachidonic acid metabolites from PBMC and monocytes (Mo) from healthy subjects and patients with recent-onset insulin-dependent diabetes mellitus (IDDM) were examined. Three groups of eight to nine healthy individuals were randomized to either 2.0 g/day or 4.

Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy.

The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of [2H] glucosamine and [35S] sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of [3H] glucosamine into HA, CS + DS, and HS and [35S] sulfate into CS + DS and HS were not significantly different between the three groups.

Effects of insulin on renal haemodynamics and sodium handling in normal subjects.

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order.

Is hypertension a major independent risk factor for retinopathy in type 1 diabetes?

Hypertension is an established risk factor for retinopathy. Whether it is an independent risk factor or acts only by association with nephropathy is not known. Therefore, we studied 273 Type 1 diabetic patients.

Albuminuria--a marker of renal and generalized vascular disease in insulin-dependent diabetes mellitus.

Atherosclerotic vascular disease is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. The frequent coexistence in these patients of microangiopathy and coronary artery disease was observed more than 30 years ago and later verified in large epidemiological studies. Thus, the subgroup (30-40%) of patients who develop clinical nephropathy, also are at extremely high risk of early cardiovascular death.

Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats.

Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance in vivo. Normal Wistar Kyoto rats were injected ip with a single injection of 4 micrograms/kg of the mature form of recombinant IL-1 beta (amino acids 117-269) or once daily on 5 consecutive days.