OBJECTIVE--To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN--Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING--Hertfordshire, England. SUBJECTS--468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES--Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS--93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS--Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.

https://www.bmj.com/content/bmj/303/6809/1019.full.pdf

Fetal and infant growth and impaired glucose tolerance at age 64.

Catalyzed reporter deposition, a novel method of signal amplification application to immunoassays

Calcitonin (CT) is a hormone that received its name because of its secretion in response to induced hypercalcemia and its hypocalcemic effect (1). It was shown to originate from the thyroid gland (2). More specifically, the hormone was revealed to be located within the thyroidal parafollicular cells, interspersed within and about the follicular epithelium (3–5). Subsequently termed C cells, they occur primarily in the central region of each lobe of the human thyroid gland (6, 7). These cells, which have CT-containing secretion granules, are neuroendocrine. Embryologically, they originate from the neural crest and migrate to the ultimobranchial glands (8). In mammals, the ultimobranchial glands fuse with the thyroid gland. It was the demonstration that medullary thyroid cancer (MTC) was a malignancy of the C cells (5, 9) that eventually led to the isolation of human CT from this tumor and the determination of its structure (10, 11). Simultaneously, the amino acid sequence of porcine CT was determined (12). Later, the development of immunoassays of serum CT in humans led to the observation that the level of this hormone was increased in the serum of patients with MTC (13–15) and to the demonstration that these levels were further augmented after iv calcium and/or pentagastrin administration (13, 16, 17). These findings had a great impact on the clinical diagnosis, the evaluation of efficacy of surgical extirpation, and the follow-up monitoring of MTC. Although RET germline mutation testing has replaced CT for the purpose of determining the presence of carriers of this tumor associated with multiple endocrine neoplasia type 2 (18, 19), the measurement of serum CT has become and has remained the classical clinical marker for MTC. Immature and mature CT

/pdf/clinical-review-167-procalcitonin-and-the-calcitonin-gene-1g397io4e7.pdf

Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors.

(2000). Enzyme-Linked Immunosorbent Assay. Journal of Immunoassay: Vol. 21, No. 2-3, pp. 165-209.

Enzyme-Linked Immunosorbent Assay

Enzyme immunoassay techniques: an overview

Enzyme amplification--a general method applied to provide an immunoassisted assay for placental alkaline phosphatase.

Enzyme amplification can enhance both the speed and the sensitivity of immunoassays

A fast highly sensitive colorimetric enzyme immunoassay system demonstrating benefits of enzyme amplification in clinical chemistry.

A highly sensitive, specific and rapid two-site enzyme-immunometric assay (EIA) for the measurement of immunoreactive (ir) human calcitonin (hCT) in human plasma was developed using high-affinity monoclonal antibodies. The assay was validated in terms of sensitivity, specificity and reproducibility and its performance compared with that of a radioimmunoassay (RIA) employing a polyclonal antiserum. The sensitivity of the overnight EIA (2 pmol/l) was comparable with the long-incubation (7 days) RIA. The overnight RIA had a sensitivity of 10 pmol/l. The inter- and intra-assay variations of the EIA were less than 12%. Some related and non-related peptides were compared with synthetic hCT for cross-reactivity in the assay and were found to be negative. The mean recovery of added synthetic hCT from plasma of normal volunteers was 96%. Both RIA and EIA have been applied to the measurement of ir-hCT in normal volunteers and in patients with medullary carcinoma of the thyroid. In both groups, the level of ir-hCT measured by EIA was found to be lower than that measured by RIA, presumably due to the ability of the more specific EIA to detect only the 'mature' form of the hormone. EIA offers an attractive alternative to the more cumbersome and lengthy RIA in current usage, with the added advantage of employing a non-isotopic label.

A sensitive and specific two-site enzyme-immunoassay for human calcitonin using monoclonal antibodies.

A new sensitive and fast peptide immunoassay based on enzyme amplification used in the determination of CGRP and the demonstration of its presence in the thyroid

Colin H. Self

Papers

Enzyme amplification--a general method applied to provide an immunoassisted assay for placental alkaline phosphatase.

Enzyme amplification can enhance both the speed and the sensitivity of immunoassays

A fast highly sensitive colorimetric enzyme immunoassay system demonstrating benefits of enzyme amplification in clinical chemistry.

A sensitive and specific two-site enzyme-immunoassay for human calcitonin using monoclonal antibodies.

A new sensitive and fast peptide immunoassay based on enzyme amplification used in the determination of CGRP and the demonstration of its presence in the thyroid