Lack of predictive value of islet cell antibodies, insulin antibodies, and HLA-DR phenotype for remission in cyclosporin-treated IDDM patients. The Canadian-European Randomized Control Trial Group.

The effect of immunosuppression on the humoral immune response to islet autoantigens and exogenously administered insulin and the predictive value of islet cell cytoplasmic antibodies (ICAs), insulin antibodies (IAs), and HLA-DR phenotype for remission during immunosuppression were studied in a prospective randomized double-blind trial of cyclosporin administration in 98 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients. HLA-DR phenotype and glycosylated hemoglobin were determined at study entry, and insulin requirement, glucagon-stimulated C-peptide, ICAs, and IAs were measured at entry and after 1, 3, 6, 9, and 12 mo of follow-up. Cyclosporin therapy caused significant suppression of the prevalence and serum concentrations of ICAs and IAs.

Monitoring of blood glucose concentration in subjects with hypoglycaemic symptoms during everyday life.

Objective: To study the persistence of hypoglycaemic symptoms, changes in blood glucose concentrations, and the relation between reported symptoms and measured blood glucose values in functional hypoglycaemia.

Design: Re-evaluation of symptoms in patients admitted consecutively with suspected hypoglycaemia followed by a case-control study.

Setting: The Steno Memorial Hospital in Gentofte, Denmark, which specialises in the diagnosis and treatment of and research on endocrine disorders, including hypoglycaemia.

Functional and morphological effects of interleukin-1 beta on the perfused rat pancreas.

We recently reported a potentiating effect of recombinant human interleukin-1 beta on glucose-stimulated insulin release from the isolated perfused pancreas. With the aim of determining whether the stimulatory effect of recombinant interleukin-1 beta on the B cell in the intact gland was modulated by varying the concentration, time of exposure to recombinant interleukin-1 beta or B-cell activity, and to elucidate a possible mechanism of action, we measured in the perfused rat pancreas the release of insulin, glucagon and/or prostaglandin E2 according to the following three different protocols: (1) perfusion with 20 ng/ml of recombinant interleukin-1 beta for 92 min at 5 and 20 mmol/l D-glucose (2) perfusion with varying concentrations of recombinant interleukin-1 beta ranging from 0.1 x 10(-3) ng/ml to 100 ng/ml at 5 and 20 mmol/l D-glucose (3) perfusion with 20 ng/ml of recombinant interleukin-1 beta at 5, 11 or 20 mmol/l D-glucose.

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of type 1 (insulin-dependent) diabetes mellitus.

An increased proinsulin to C-peptide molar ratio at the onset of Type 1 (insulin-dependent) diabetes mellitus has been suggested. We studied fasting proinsulin levels and proinsulin/C-peptide ratios in the newly diagnosed diabetic subjects participating in the Canadian/European placebo controlled cyclosporin study at entry, during the one year treatment period and six months of follow-up. Available entry data from 176 out of the 188 allocated patients were compared to 60 age and weight matched control subjects.

Intra-peritoneal administration of interleukin-1 beta induces impaired insulin release from the perfused rat pancreas.

Previous studies have demonstrated a stimulatory effect of interleukin-1 beta (IL-1 beta) on insulin and glucagon release from the perfused rat pancreas, accompanied by selective lysis of 20% of beta-cells as assessed by electronmicroscopy. However, we have not observed an inhibitory action of IL-1 beta on insulin release from the perfused pancreas as shown for isolated islets. To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4 micrograms IL-1 beta/kg or saline for 5 days.

Yersinia enterocolitica and thyroid autoimmunity.

The concordance rate of Graves' disease in pairs of identical twins of 30 to 60% points to the influence of environmental factors, and infections have often been incriminated in the pathogenesis. More than 15 years ago we demonstrated an increased frequency of antibodies to Yersinia enterocolitica (Y. ent.

Partial normalization by dietary cod-liver oil of increased microvascular albumin leakage in patients with insulin-dependent diabetes and albuminuria.

In a double-blind crossover study, we compared the effects of eight weeks of dietary supplementation with cod-liver oil with the effects of supplementation with olive oil on endothelial permeability, blood pressure, and plasma lipid levels in 18 patients with insulin-dependent diabetes mellitus and albuminuria. When the patients received the cod-liver-oil supplement, the mean (+/- SEM) transcapillary escape rate of albumin (as compared with the base-line rate) decreased from 8.7 +/- 0.

Improved survival in patients with diabetic nephropathy.

The effect of early antihypertensive treatment on survival of patients with diabetic nephropathy was evaluated by studying two cohorts of Type 1 (insulin-dependent) diabetic patients developing persistent proteinuria in I: 1957-1973 (late treatment group n = 49) and II: 1979-1983 (early treatment group n = 71). At onset of nephropathy, the two cohorts were comparable with regard to age (29(8) vs 30(8) years, mean (SD], duration of diabetes (16(6) vs 18(7) years), blood pressure (132(16)/85(11) vs 134(16)/86(8) mm Hg), proteinuria (0.8(0.

Characterization of PPD-specific T-cell lines generated in type I (insulin-dependent) diabetic and healthy individuals.

The particular susceptibility to insulin-dependent diabetes mellitus (IDDM) conferred by HLA-DR3,4 heterozygosity has been suggested to be an effect of transcomplementation of HLA class II molecules. To test this hypothesis of special IDDM-specific hybrid determinants and to evaluate the T-cell repertoire towards a specific antigen in IDDM patients we generated a total of 352 PPD-specific T-cell lines by the soft-agar cloning technique and studied their restriction by HLA class II molecules. Of these lines, 227 were from nine IDDM patients, of whom six were DR3,4 heterozygotes, and 125 from 10 healthy controls.

Normal urinary albumin excretion in recently diagnosed type 1 diabetic patients.

The urinary excretion of albumin and retinol binding protein were measured in 51 recently diagnosed Type 1 diabetic patients and 48 control subjects, matched for age and sex. The diabetic patients, admitted consecutively to the Steno Memorial Hospital, were all studied 3 to 6 months after the onset of diabetes. Urinary albumin excretion (median and 95% confidence interval) was similar in the diabetic patients and normal control subjects (8 (6-11) vs 8 (6-11) mg 24-h-1, NS).

Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity.

Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes.

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients.

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.

Diabetic ketoacidosis in Denmark: epidemiology, incidence rates, precipitating factors and mortality rates.

The epidemiology of uncontrolled diabetes mellitus was studied in an 11.2% sample of the Danish population (574,696 inhabitants) during a 24-month period. Some 175 admissions in ketoacidosis (heavy ketonuria and plasma bicarbonate below 21 mmol/l) were recorded.

Modulation of calcium flux influences interleukin 1 beta effects on insulin release from isolated islets of Langerhans.

The controlled flux of calcium across the cell membrane is intimately linked to the release of insulin from pancreatic beta-cells, but the uncontrolled influx of calcium is a common final denominator of cell death. Because interleukin 1 has been shown to be cytotoxic to beta-cells in isolated rat islets of Langerhans and since interleukin 1 has a calcium ionophore effect on other cell types, this study was designed to test whether alterations of the calcium flux across the beta-cell membrane would influence the effects of interleukin 1 on isolated rat and mouse islets. Further, the cytosolic free Ca2+ concentration was measured by the fura-2 method in rat islets during acute interleukin 1 exposure.

Limb salvage in diabetics with foot ulcers.

The healing results in 491 ulcers in 272 diabetic patients are reported. Soft moulded insoles and shoe corrections were the main part of the therapy. There were 329 (67%) neuropathic, 87 (17%) traumatic, 44 (9%) ischaemic and 31 (6%) ulcers of other various pathogenesis.

Initial plasma disappearance and distribution volume of [131I]albumin and [125I]fibrinogen in man.

The simultaneous plasma disappearance curves of albumin and fibrinogen were recorded in eight normal subjects from 10 to 60 min following intravenous injection. Additional samples were taken at 3, 4, 5, 6 and 7 min. The initial distribution volume (IDV) of albumin calculated by semilogarithmic extrapolation to zero time was 5.

Plasma zinc concentrations during the first 2 years after diagnosis of insulin-dependent diabetes mellitus: a prospective study.

Studies of zinc status in insulin-dependent diabetes mellitus (IDDM) have shown contradictory results. Zinc is essential for many enzymes involved in the human metabolism and may play a role in the biosynthesis and storage of insulin in the B-cell. We therefore prospectively followed 26 patients (14 males and 12 females) with newly diagnosed IDDM in order to determine the plasma zinc variation at the time of diagnosis and after 1, 3, 6, 12 and 24 months.

Interleukin 1 induces new protein formation in isolated rat islets of Langerhans.

It is hypothesized that interleukin 1 induces toxic free radical formation in pancreatic beta-cells leading to beta-cell degeneration and destruction. Therefore, isolated rat pancreatic islets were examined for interleukin 1 and heat shock induced proteins. Afer exposure to human interleukin 1 beta (0.

Elevated albumin excretion and retinal changes in children with type 1 diabetes are related to long-term poor blood glucose control.

All diabetic children (n = 113) under 19 years old and with more than 2 years of diabetes attending the Steno Memorial Hospital in 1987 were studied. Normal urinary albumin excretion (less than 30 mg 24 h-1) was found in 96 patients (85%), 15 had microalbuminuria (30-300 mg 24 h-1) (13%), and 2 patients were proteinuric (greater than 300 mg 24 h-1) (2%). Retinal morphology was evaluated by colour fundus photography.

Albuminuria reflects widespread vascular damage. The Steno hypothesis.

Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.

Features of endothelial dysfunction in early diabetic nephropathy.

The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls.

Micro-ELISA for the quantitation of human urinary and serum retinol-binding protein.

A highly sensitive enzyme linked immunoadsorbent assay for determining retinol-binding protein in urine and serum is described. Commercially available reagents are used. The standard curve ranges from 1.