No abstract

In a group of 34 adult and child subjects a high correlation (r = 0.988) was found between lean body mass, as determined by potassium-40 counting, and urinary creatinine excretion. The effect of technical errors was reduced by averaging the results of two or three 40K assays on each subject, and by making consecutive 3-day collections of urine. It appears that one can make a reasonable estimate of lean body mass from urinary creatinine excretion.

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since Il)DM seems to develop after a prodromal period of,8-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered (3-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDIM, whereas 1 patient progressed to a high 64,000 M, immunoreactivity, at a time where a commencement of a decline in (3-cell function was detected. 64,000 M, antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of (-cell autoimmunity and may be useful to predict a later development of IDDM.

Killer cell immunoglobulin-like receptors (KIRs) modulate natural killer cell and T-cell function by interacting with HLA class 1 ligands on target cells. Both KIR and HLA are highly polymorphic. We studied the influence of KIR and HLA class 1 genes on the susceptibility to develop type 1 diabetes. The results showed increased numbers of activating KIR genes in patients compared with control subjects (P ‫؍‬ 0.049). The combination of the activating KIR2DS2 gene, together with its putative HLA ligand, was present more frequently in patients than in diabetes high-risk HLA-matched control subjects (P ‫؍‬ 0.030). Moreover, our results imply that an increase in activating KIR2DS2-HLA ligand pairs combined with a lack of inhibitory KIR-HLA ligand pairs is associated with an additional risk to develop type 1 diabetes in individuals with diabetes high-risk HLA alleles (P ‫؍‬ 0.035). We propose that the genetic imbalance between KIR and their HLA class 1 ligands may enhance the activation of T-cells with a low affinity for pancreatic self-antigens, thereby contributing to the pathogenesis of type 1 diabetes.

No abstract

Aims/hypothesis Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the K ATP channels in pancreatic beta cells are a common cause of neonatal diabetes. One-third of patients also have developmental delay, which probably results from mutated K ATP channels in muscle, nerve and brain. Sulfonylureas, which bind to the sulfonylurea receptor 1 subunit of the K ATP channel, can replace insulin injections in patients with KCNJ11 mutations. The aim of this study was to investigate the long-term outcome and impact on neurological features of sulfonylurea treatment.

No abstract

No abstract