Growth-onset Diabetics Research Articles

Human C-peptide: radioimmunologic assay and physiopathological applications

SummaryThe use of the C-peptide radioimmunoassay has become possible due to the availability of synthetic antigen and improvement in antisera production.Proinsulin cross-reactivity can be avoided and C-peptide specifically determined by extraction of proinsulin with sepharose-bound insulin antibodies. In insulin treated diabetics, proinsulin insulin antibody complexes can be precipitated with polyethylene glycol (PEG) or concentrated ethanol. C-peptide immunoassay is leasable even in presence of exogenous insulin.With this assay it has been shown that1) almost half of the growth-onset diabetics have a residual insulin secretion, 2) residual β-ceil activity is associated with a better diabetic control and 3) perhaps a lesser degree of degenerative complications.Finally, hypoglycemic conditions can be better documented by simultaneous determination of Cpeptide and insulin in blood.

Differential volumetry of A,B and D cells in the pancreatic islets of diabetic and nondiabetic subjects.

The percentile volumes vA, vB and vD of A, B and D cells in the islets of Langerhans were histometrically estimated in the pancreases from 59 autopsy cases including maturity- and growth-onset diabetics and nondiabetics. Volumetry was performed microscopically by point counting method using a square-lattice eyepiece, then the total A, B and D cell volumes VA, VB, and VD were calculated from the total islet volume Vi of the pancreas in VB between the three groups. Namely, it was only 0.156 and 0.388 cm3 in the growth- and maturity-onset diabetics, much smaller values than 0.636 cm3 in nondiabetics. The simultaneous investigation on clinical records revealed a negative correlation between VB and the maximum blood sugar of the individual. The smaller VB in diabetes was attributed to the diminution of Vi because vA, vB and vD were almost the same regardless of the presence or absence of diabetes. These results strongly suggested a failure of insulin production in diabetes due to quantitative deficiency of B cells.

Islet Morphometry in the Diabetic Pancreas of Man

Quantitative changes of the pancreatic islets in diabetes mellitus were analyzed by a stereological method. 26 maturity-onset and 5 growth-onset diabetics, and 37 nondiabetics including 9 hypertensives were selected from autopsy materials and the pancreases were subjected to histometry. The total islet volume Vi was 0.974 cm3 in the control, whereas it was only 0.596 and 0.255 cm3 in the maturity-onset and growth-onset diabetic groups, respectively. The hypertensive group gave almost the same value as the control. There was an obvious negative correlation between Vi and the maximum blood sugar level during glucose tolerance test, whether the case was diabetic or not. Moreover, in the diabetic group Vi diminished with descending age of onset. These findings indicate the importance of VI in the pathophysiology of diabetes and support the classical concept of insulin deficiency as the primary pathogenetic role. On the other hand, the total islet number Ni decreased with increasing mean radius r, and the diabetic and control cases shared a common regression of Ni on r. The diabetic pancreas was not characterized by Ni, r or by the distribution pattern of r.

Levodopa-Stimulated Growth Hormone Secretion and Diabetic Retinopathy

Since growth hormone has been implicated as a possible etiologic factor in the development of diabetic retinopathy, we examined growth hormone levels in two groups of growth-onset diabetics matched for age and duration of disease. The experimental group had definite proliferative diabetic retinopathy; the control group of growth-onset diabetics had no significant retinopathy. Basal and levodopa-stimulated levels of growth hormone were determined for each group. Growth hormone response could not be correlated with the presence or absence of diabetic retinopathy (P less than .05).

Endophthalmitis After Vitrectomy

A 29-year-old white man with growth-onset diabetes developed fulminant endophthalmitis after vitreous lavage. The only significant symptom was severe pain 36 hours after surgery. The endophthalmitis rapidly became more severe. Despite systemic antibiotics, therapeutic vitrectomy and lensectomy, followed by the intraocular injection of antibiotics 48 hours postoperatively, the eye was lost.

Oral contraceptives and carbohydrate metabolism

Oral contraceptives and carbohydrate metabolism

Hepatic glycogen studies in Indian diabetics

Twenty normal, 35 growth-onset (GO), and 15 maturity-onset (MO) diabetics were studied. The mean glycogen content in 20 healthy controls was 1755 ± 752.6 mg 100 g dry liver tissue and 3865 ± 1466.7 mg and 3130 ± 1525 mg 100 g in 35 GO and 15 MO diabetics, respectively. Hepatomegaly was seen often in GO diabetics (31%), especially in the ketotic patients (50%). Mean hepatic glycogen content in 13 hepatomegalic patients was 4559.2 ± 1882.5 mg 100 g . In 37 without liver enlargement it was 3296.8 ± 1290.2 mg 100 g . The difference was statistically significant ( P < 0.02). Hepatomegaly in diabetics has been attributed to excessive glycogen infiltration rather than to fatty deposition in the liver cells. The fasting blood sugar level and the fasting glycogen content in the liver tissue showed a positive statistically significant relationship in the diabetics. Adequate control of hyperglycaemia in 19 diabetics (16 with insulin and three with tolbutamide) showed a definite decrease in the glycogen content of the liver.

Glycogen storage disease: type I.

To the Editor .—I read with interest Dr. Richard Fine's article inThe Journal(Amer J Dis Child115:238-331 [March] 1968). I would like to make some comments with regard to the author's statement: Retinal changes have not been previously described in patients with GSD Type I. Newer mentioned Von Gierke's disease among conditions in which lipemia retinalis occurs. To quote from his book 1 : Lipemia retinalis occurs most commonly in diabetic acidosis, usually in growth onset diabetes. It may occur also in essential familial hyperlipidemia, secondary hyperlipidemias of the nephrotic syndrome, pancreatitis, Von Gierke's disease, or other conditions with increased triglyceride concentration of the blood. Dr. Fine and his associates described: Multiple bilateral symmetrical, yellowish, nonelevated discrete paramacular lesions in the occular fundi of their cases and found them most striking in patients with the highest serum triglyceride levels. These changes are not consistent with the classical description of

SOME PHYSICAL-CHEMICAL VARIABLES AFFECTING INSULIN MIGRATION IN VITRO. I. ELECTROPHORESIS.

Summary and conclusionsIn confirmation of our previous studies(4), it is again noted that TRIS in this in vitro system does not function as an inert buffer, and that physical-chemical interaction with insulin does occur on Whatman 3 mm paper. The degree of interaction is greater in the buffer system containing the greater concentration of TRIS. The beta-gamma globulin binding of radioinsulin in the growth-onset diabetics is not as completely dissociated by TRIS as that observed in the maturity-onset or insulin-resistant diabetic patients. This observation suggests that insulin is more tightly bound to the beta-gamma globulins appearing in the serum of growth-onset diabetics as compared to more freely dissociated binding by the beta-gamma globulins of the maturity-onset or insulin-resistant diabetic patients in this study. An alternative suggestion is that a difference in the nature of the chemical bond which is dissociated by the TRIS occurs in the sera of growth-onset diabetics. Since displacement of rad...

EXHAUSTION OF INSULOGENIC RESERVE IN MATURITY-ONSET DIABETIC PATIENTS DURING PROLONGED AND CONTINUOUS HYPERGLYCEMIC STRESS.

Solutions of 15 per cent glucose were administered by continuous intravenous infusion for five to seven days to six normal subjects, seven tolbutamide-responsive adult diabetics, and six tolbutamide-nonresponsive adult diabetics. Blood glucose concentration, plasma insulin activity, and net assimilation of carbohydrate were determined daily. An “insulogenic index,” relating level of circulating insulin activity to magnitude of glycemic stimulus, enabled comparison of the insulin-secreting capacity of respective groups. In nondiabetic subjects, mean daily blood glucose levels remained normal, and carbohydrate loads averaging 717 gm. per day were wholly retained. In both diabetic groups, increasing blood glucose and glycosuria permitted net glucose uptakes of only 88 per cent in tolbutamide-responders and 56 per cent in tolbutamide-nonresponders. Plasma insulin activity increased significantly in all groups. In both normal subjects and tolbutamide-responsive diabetics, enhanced levels appeared on the first day, were sustained at high titers each day thereafter, and exhibited mean maximal value on the last day of infusion. Conversely, in tolbutamide-nonresponsive diabetics, average maximal insulin activity was achieved on the second day, whereafter it declined progressively and sometimes disappeared completely. Compared to an insulogenic index of 100 per cent to represent the greatest secretory response of normal subjects, the corresponding maximal index was 49 per cent for tolbutamide-responders and 17 per cent for tolbutamide-nonresponders. On the last day of infusion, capacity for sustained insulin release was reflected by insulogenic indexes of 55 per cent, 32 per cent and 0.1 per cent in the respective groups. The data indicate that unremitting hyperglycemia tends to exhaust insulogenic reserve in adult-onset diabetics, and that betacytotropic collapse occurs most rapidly in patients with severest clinical intolerance to carbohydrate. This demonstration strengthens the view that maturity-onset diabetes and growth-onset diabetes represent different stages of the same disease. The findings suggest that the fundamental lesion in hereditary human diabetes is either primary beta cell deficiency or impaired responsiveness of peripheral tissues to the action of insulin—or, quite possibly, a combination of both.