Limited Joint Mobility in Insulin-dependent Diabetes: Relationship to Retinopathy, Peripheral Nerve Function and HLA Status

Eighty-eight (43 per cent) of 204 patients with insulin-dependentdiabetes had limited joint mobility affecting mainly the smalljoints of the hands. The presence of limited joint mobilitycorrelated with duration of diabetes and with the presence ofretinopathy. Patients with longstanding diabetes were approximately25 times more likely to have proliferative retinopathy if limitedjoint mobility was present than if it was absent, although therisk for non-proliferative or background retinopathy was notincreased. In patients with longstanding diabetes and limited joint mobilitynerve conduction velocity and vibration perception thresholdwere significantly reduced compared with patients having similarduration of diabetes but normal joints. The association betweeninsulin-dependent diabetes and HLA-DR3 and HLA-DR4 was confirmed,but there was no difference, between patients with and withoutlimited joint mobility, in the frequency of the various HLAtypes. Limitation of joint mobility appears to be another ‘chroniccomplication’ of diabetes, developing in parallel withretinopathy and deteriorating peripheral nerve function, andpossibly of similar aetiology.     

Regulation of sterol synthesis in human intestinal mucosa

Abstract The effect of dietary factors and experimental manipulations designed to perturb the entero-hepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects.
Fasting significantly reduced the rate of sterol synthesis from [¹⁴C] acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [^l4C] acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects.
These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.     

Prediction of Outcome in Graves' Disease after Carbimazole Treatment

In a prospective study to determine which factors would predictremission or relapse, 65 patients with hyperthyroid Graves'disease were treated for six months with a blocking replacementregimen of carbimazole, 40 mg daily, and triiodothyronine (T3).They were followed for one year after stopping treatment, bywhich time 32 (49 per cent) had relapsed. Although the treatmentprotocol, relapse rate and frequency of the HLA-DR3 antigenin this population were similar to those of a regionally separateGraves' population investigated previously, the predictive valueof HLA-DR3 status together with thyroid stimulating antibody(TSAB) levels was strikingly different. In the present studythere was no significantly abnormal distribution of any HLAantigen in the relapse group compared with those patients whoachieved remission. Thyroid stimulating antibodies were detectedin 62 patients (95 per cent) and fell significantly (p<0.05)after carbimazole treatment, irrespective of DR3 status or outcome;TSAB levels only became undetectable in nine patients (28 percent) who subsequently relapsed and in nine patients (30 percent) who maintained remission. T3-suppressed 20 min ¹²³I uptakefell equally after treatment in the relapse and remission groupsbut continued to fall thereafter in the group which maintainedremission. In these patients, ¹²³I uptake was significantlylower at the end of the study period than at the end of treatment(p<0.05). Serum free T4 levels were higher before treatmentin the patients who later relapsed than in those whose diseaseremitted (p<0.02). This proved the only significant markerassociated with outcome but was of little predictive value inany patient. This study highlights the problem in predictingthe outcome of antithyroid drug treatment, since even withinthe same country under similar conditions, divergent resultshave been obtained. It appears that the loci controlling theimmune response in Graves' disease are likely to include geneslying outside the HLA-DR region. The results also suggest thatthe immunological effects of antithyroid drugs are maintainedafter stopping treatment in those patients whose disease remits.     

IgG SUBCLASS DISTRIBUTION OF THYROID AUTOANTIBODIES: A ''FINGERPRINT'' OF AN INDIVIDUAL''S RESPONSE TO THYROGLOBULIN AND THYROID MICROSOMAL ANTIGEN

The IgG subclass distribution of autoantibodies to thyroglobulin and thyroid microsomal antigen was studied in 21 patients with Graves' disease during fluctuations in total IgG class autoantibody levels induced by various forms of therapy. In addition, changes in autoantibody subclass distributions were investigated during the natural course of Hashimoto's disease in seven patients taking thyroxine. The autoantibodies were principally of subclasses IgG1 and/or IgG4 in Graves' patients although IgG2 contributed significantly to thyroglobulin antibodies in 5/7 Hashimoto sera. In Graves' disease the distribution of microsomal and thyroglobulin antibodies among the IgG subclasses remained essentially unchanged over periods of 6 months-2 years whether autoantibody levels decreased during carbimazole therapy or increased transiently following 131Iodine treatment or subtotal thyroidectomy. Similar observations were made for thyroglobulin antibodies in Hashimoto patients studied over 2 1/2-4 years; furthermore, the IgG subclass distribution of microsomal antibodies was usually different from that of thyroglobulin antibodies in the same patient. These observations suggest that the microsomal and/or thyroglobulin antibody subclass distribution is characteristic for a particular individual and may be regarded as the 'fingerprint' of an individual's response to these thyroid autoantigens.