Cardiovascular Risk Management in Type 1 Diabetes.

PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is associated with increased mortality, with premature cardiovascular disease (CVD) a major factor. To date, research has identified multiple risk factors for this excess CVD liability. However, gaps remain in our understanding of the underlying mechanisms. RECENT FINDINGS: T1DM is generally diagnosed at a young age. Since cardiovascular complications often only manifest at a later stage of life, there is generally less focus in earlier years on reducing CVD risk for affected individuals. This is an area that requires improvement as risk factors might be managed from earlier age to reduce later development of CVD. In this review, we discuss the evidence for cardiovascular risk factors, risk prediction models, candidate surrogate measurements and CVD risk management.

Synthesis of procollagen by matrix-free cells from embryonic-chick arteries.

Cells were isolated from the major arteries of 17-day chick embryos by digestion of the tissue with collagenase and trypsin. The cells, when examined immediately after isolation, exhibited a high degree of viability and they were shown to synthesize and secrete procollagen at a high and constant rate for several hours when incubated in suspension in modified Krebs medium. Continuous labelling of the cells with [(14)C]proline demonstrated a lag of about 30min between the time at which the synthesis of non-diffusible peptide-bound hydroxy[(14)C]proline became linear and the time at which its secretion into the medium became linear. This lag time compares with that of 18min observed for freshly isolated matrix-free cells from embryonic-chick tendon, which synthesize and secrete the same type of collagen. Gel-filtration chromatography and polyacrylamide-gel electrophoresis indicated that the collagenous polypeptides secreted into the medium were in the precursor form, known as procollagen, and that the constituent pro-alpha-chains were linked by interchain disulphide bonds and were also in a triple-helical conformation. Characterization of the secreted procollagen by gel-filtration chromatography, polyacrylamide-gel electrophoresis, DEAE-agarose chromatography, and polyacrylamide-gel electrophoresis of peptides obtained by CNBr cleavage, indicated that the predominant form was type-I procollagen. This work extends the range of freshly isolated matrix-free cell systems, which have been characterized for use in studies on the biosynthesis and secretion of procollagen, and it indicates differences in the rates of secretion of procollagen in different cell types secreting the same type of procollagen.

Collagen biosynthesis in normal and hypertrophic scars and keloid as a function of the duration of the scar.

The rates of collagen biosynthesis and the tissue concentrations of collagen in normal scar, hypertrophic scar and keloid were determined as a function of the duration of the lesions. The rate of collagen synthesis in normal scar was approximately constant between 6 months and 20 years after the initial wounding, but in both hypertrophic scar and keloid the rate was initially approximately twice that in normal scar, and 2-3 years after wounding it fell to approximately the same level as in normal scar. The tissue concentration of collagen appeared to be relatively constant in normal scar with respect to the time elapsed after wounding, but in both types of abnormal scar it was initially somewhat lower than normal scar and then rose to values higher than in normal scar after about 2-3 years. Since similar results were obtained for both types of abnormal scar in terms of the rates of collagen biosynthesis with respect to the time elapsed after wounding and also in terms of the tissue concentrations of collagen, this may indicate that the events in the pathogenesis of both abnormal scar types are similar. The results also raise the possibility that the formation of both types of abnormal scar may occur in two phases: an initial phase characterized by abnormally high rates of collagen biosynthesis and a later phase characterized by essentially normal rates of collagen biosynthesis.

The isolation, and amino acid and carbohydrate composition, of polymeric collagens prepared from various human tissues.

1. Insoluble polymeric collagens from various human tissues were prepared by the EDTA method. Almost all of the collagen from simple soft tissues such as dermis, tendon, submucosa, sclera and cornea could be extracted, whereas the more complex tissues such as intercostal cartilage and intervertebral disc yielded only small amounts of collagen. Amino acid and carbohydrate analysis indicated that most of the preparations were highly purified on the basis of their tyrosine, hexosamine, mannose, xylose and fucose contents. 2. Wide variation in the total hexose content was observed, the lowest being 8.5 residues/3000 amino acid residues for collagen from dermis and the highest being 42.1 residues/3000 in corneal collagen. The molar ratios of sugars also varied, submucosal collagen having a galactose/glucose ratio of 1.0 and corneal collagen having a ratio of 2.3. 3. The presence of glucosylgalactosylhydroxylysine was confirmed in submucosal collagen by compositional and chromatographic analysis of this component after its isolation from alkaline hydrolysates of the collagen. Evidence was also obtained for the presence of galactosylhydroxylysine. 4. Determination of the hydroxylysyl glycosides was carried out and it was observed that the amounts of these components varied widely from tissue to tissue. Corneal collagen contained 19.1 hydroxylysine-linked carbohydrate units/3000 amino acid residues, whereas tendon collagen contained only 4.1 units/3000. Variation in the ratio disaccharide unit/monosaccharide unit was also observed, the ratio being 1.2 in intercostal cartilage collagen and 4.1 in submucosal collagen. The proportion of the total hydroxylysine that was substituted by carbohydrate also varied from tissue to tissue.