Juxtaglomerular body abnormalities in youth-onset diabetic subjects.

Abnormal microalbuminuria in insulin-dependent diabetic subjects (IDDS) is significantly associated with pre-clinical nephropathy. In youth-onset IDDS declining plasma renin activity is significantly associated with improved albumin excretion, while persistently elevated renin activity is associated with continued abnormal microalbuminuria. To determine if these changes are reflected in changes in cell count in the juxtaglomerular body and if biopsy findings correlate with abnormal microalbuminuria, renal tissue of 20 IDDS (Study IDDS) ages 16 to 31 years, evaluated concurrently for plasma renin activity and microalbuminuria, were examined by light microscopy. Biopsy or autopsy specimens from 21 normal subjects and 32 IDDS (Non-Study IDDS), ages 2 to 25, were also examined. Specimens from the majority of prepubertal and all pubertal and postpubertal Non-Study IDDS and all Study IDDS independently of status of microalbuminuria had morphologic abnormalities. Normal or mesangially expanded glomeruli were found in association with expanded juxta-glomerular bodies and increased cell number, or with sclerotic bodies and decreased cell number. Sclerosis of juxtaglomerular bodies occurred independently of glomerular sclerosis. The highest percentage of glomeruli with expanded juxtaglomerular bodies and high cell count was present in specimens of Study IDDS with the most abnormal levels of microalbuminuria. T lymphocytes, noted within juxtaglomerular bodies, were present in specimens of 62% of the 52 Study and Non-Study IDDS. Abnormalities of the juxtaglomerular body are distinctive features of renal pathology in IDDS. T lymphocytes in the endocrine juxtaglomerular body suggest the presence of an autoimmune process. Confirmatory studies are necessary.

Some characteristics of spontaneous platelet aggregation in young insulin-dependent diabetic subjects.

Spontaneous platelet aggregation (SPA), a phenomenon observed in vitro, was noted in 29 of 74 (39%) children and adolescents with insulin-dependent diabetes. Its occurrence was independent of age of onset, duration of diabetes, HbAI levels or presence of background retinopathy but varied between normal and abnormal in given individuals tested repeatedly over some time. Plasma beta-thromboglobulin, the platelet protein specific for Phase II of the release reaction, was elevated in the diabetic subjects but was independent of the occurrence of SPA. SPA in the diabetic children and adolescents, in contrast to SPA in other conditions, was not suppressed by either acute or chronic administration of aspirin adequate to suppress ADP induced second wave aggregation. SPA was uniformly suppressed by addition to the in vitro system of EDTA, adenosine, antisera to human fibrinogen or vitamin E. The data suggest that SPA is ADP induced and reflects either abnormal platelet membrane permeability to the nucleotide or its abnormal release, or abnormal platelet sensitivity to normal plasma levels of ADP.

Insulin resistance caused by massive degradation of subcutaneous insulin.

Severe resistance to subcutaneous insulin but sensitivity to intravenous insulin persisted for 15 months in a 17-year-old diabetic girl. Heat-labile insulin-degrading activity was present in the patient's ketotic sera and in the 100,000 g fraction (soluble fraction) of adipose tissue. Serum-degrading activity was not inhibited by N-ethylmaleimide. The soluble fraction also degraded glucagon and B chain but not growth hormone or myoglobin. It was inhibited by incubation with the patient's nonketotic sera, normal sera, or Trasylol. Glutathione-insulin-transhydrogenase (GIT) activity was 66% of normal. The biopsy of adipose tissue at remission showed a normal level of insulin- and glucagon-degrading activity. The activity was eluted from Sephadex G200 as a single peak and had properties consistent with those of the insulin-specific protease (ISP). The increased degrading activity present during insulin resistance had properties not shared with ISP, suggesting the presence of an uncharacterized protease.

Hemoglobin AIc levels in insulin-dependent and -independent diabetes mellitus.

Unusual increases in the minor hemoglobin components (Hb AIa, b, c) known to be elevated in diabetes mellitus were found in states of relative or absolute insulinopenia: diabetic ketoacidosis, steroid-induced diabetes, insulin-dependent diabetes in cystic-fibrosis patients, and cystic fibrosis occurring in infants who have a marked suppression of insulin secretion. In ketoacidotic diabetics, it required at least a month for high Hb AI levels (16.9 +/- 2.6 per cent) to stabilize at nonacidotic levels (12.8 +/- 0.3 per cent), suggesting that decreases occur only as new red cells form under conditions less favorable to Hb AI synthesis. Abnormal amounts os Hb A and Hb AI resisted removal from diabetic red-cell membranes by low ionic buffers but yielded to hypotonic Tris buffer. Their removal resulted in simultaneous elution of peripheral and integral membrane proteins. It is suggested that Hb so firmly bound could reduce membrane elasticity and cell deformability, characteristics so vital to normal red cell movement through the microvasculature.