Relationship of Glycosylated Haemoglobin to C-Peptide Secretory Status and Antibody Binding of Insulin in Insulin-Dependent Diabetes

Abstract

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.

Correlation between HbA1c, Purified Insulins, Diabetic Control, and Insulin Antibodies in Diabetic Children

“…8, 24], Dixon el al. [9] and others [25] proposed that insulin antibodies may exert a favorable effect on metabolic control by acting as a reservoir that binds and releases insulin according to a reversible equilibrium between the free and bound pools of hormone. Using HbAlc as an objec tive indicator of metabolic control, we have shown significantly higher HbAlc values in children with relatively higher insulin anti bodies.…”

Disappearance rate of insulin antibodies after discontinuing insulin treatment in 42 Type 2 (non-insulin-dependent) diabetic patients

“…In addition to their wellrecognized adverse effects, the presence of insulin antibodies has often been considered to have some beneficial effects, at least under certain circumstances [2,3]. Regardless of the clinical significance of circulating insulin antibodies, assessment of their kinetics is of considerable interest [1,[4][5][6][7][8].…”

The bioavailability of circulating antibody-bound insulin following insulin withdrawal in Type I (insulin-dependent) diabetes

“…With low levels of antibody, and only small amounts of bound insulin, the dissociation of insulin from the antibody becomes rate limiting because the amount of insulin delivered into the free insulin pool equals the dissociation rate constant multiplied by the amount of bound insulin: during insulin withdrawal the insulin will be 'stripped' from the antibody leaving residual insulin on the most slowly dissociating antibodies and resulting in a rapid fall in the free insulin concentration. The potential clinical advantage of insulin availability from the antibody bound pool which we have demonstrated during insulin withdrawal may well be of significance and is most likely to benefit patients on once-daily insulin regimens [3]. However, the effectiveness of some of the newer methods of insulin administration, such as continuous subcutaneous infusion, might well be impaired by insulin antibodies, which would be expected to damp down and prolong the meal-time peaks of insulin concentration produced by this technique [14].…”

“…A correlation between the level of insulin binding by serum and diabetic control as judged by the haemoglobin A1 percentage has been demonstrated in C-peptide negative patients on a once-daily insulin regimen [3], but this association was not observed when the patients were changed to a twice-daily insulin regimen. The problem of whether antibody-bound insulin is available for biological action, and the extent to which it might be clinically useful, is of particular interest because over recent years there has been a reduction in both the prevalence of insulin antibodies and the insulin-binding levels found in those who do form antibodies.…”

“…Little is known about the effect of the more modest levels of antibodies that exist in most Type 1 (insulin-dependent) diabetic patients. In these patients, it is evident from measurement of antibody-bound insulin that substantial quantities of insulin may be present in the plasma and it has been suggested that this source of insulin could act as a buffer to fluctuations in insulin levels [2].A correlation between the level of insulin binding by serum and diabetic control as judged by the haemoglobin A1 percentage has been demonstrated in C-peptide negative patients on a once-daily insulin regimen [3], but this association was not observed when the patients were changed to a twice-daily insulin regimen. The problem of whether antibody-bound insulin is available for biological action, and the extent to which it might be clinically useful, is of particular interest because over recent years there has been a reduction in both the prevalence of insulin antibodies and the insulin-binding levels found in those who do form antibodies.…”