Aims/hypothesis Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ( cf PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness. Methods cf PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age-and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n=570, mean age 59.1, 56% male). Results After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted cf PWV±SE: NGM, 9.15±0.12 m/s; IGR 9.76±0.11 m/s, p<0.001; diabetes, 9.89±0.12 m/s, p< 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71±0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82±0.24 m/s) categories had similar cf PWV (p=0.83). Modelled predictors of cf PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (β=0.10; 95% CI 0.05, 0.18; p=0.003), 2 h post-challenge glucose (β=0.14; 95% CI 0.02, 0.23; p<0.001) and HOMA-IR (β=0.20, 95% CI 0.05, 0.53; p<0.001) were independently related to cf PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication. Conclusions/interpretation IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.

The higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in US blacks as compared with whites may be due to a higher frequency of NIDDM risk factors in blacks, a higher inherent susceptibility to NIDDM among blacks, or the risk factors' having a greater effect in blacks. The authors evaluated 4,379 subjects from the Second National Health and Nutrition Examination Survey (1976-1980) for whom NIDDM was ascertained by medical history and oral glucose tolerance test, and for whom data on a number of risk factors were available. The prevalence of NIDDM was 60% higher in blacks than in whites (p < 0.001) and was highest in black women. Although most risk factors for NIDDM were more common in blacks, this higher frequency did not completely explain the racial disparity in the prevalence of NIDDM. After adjustment for all risk factors by logistic regression, an elevated risk of NIDDM was particularly evident at higher obesity levels in blacks as compared with whites; the odds were 70% higher for blacks at a percentage of desirable weight of 150 (95% confidence interval 1.1-2.8). The risk of NIDDM associated with obesity was greatest in black women: The odds in this group were sevenfold higher at a percentage of desirable weight of 150 versus 100 (95% confidence interval 2.6-18.8). The possibility of racial differences in metabolic adaptation to obesity highlights the importance of preventing this condition in blacks, particularly in black women.

Sedimentation velocity analyses of the isolated subunits of mouse 7s nerve growth factor (NGF) and their binary complexes have been performed. The 2.5s (p) form of NGF binds 2 a subunits independent of the presence of y subunits. Two y subunits are also complexed by 2.5s NGF; however, this interaction is dependent on the presence of a carboxyl terminal arginine residue on the p polypeptide chain. The partial loss of this residue in 2.5s NGF preparations results in a ternary complex(es) with a reduced sedimentation coefficient(s). The two binary complexes formed (a2+ and P-yz) show markedly different pH stability profiles. The a and y subunits do not form a demonstrable complex, but apparently can interact in the ternary complex to render it more stable than the sum of the a-P and P-y interactions.

Partial amino acid sequence analysis of epidermal growth factor binding protein (EGF-BP), an arginine esteropeptidase that specifically associates with EGF to form a high molecular weight complex in male mouse submandibular glands, has revealed a single, distinct protein that is different from three previously reported forms of EGF-BP. This protein shows substantial sequence homology with these other putative forms of EGF-BP as well as with a large family of kallikreins expressed in the mouse submandibular gland. Purified EGF-BP contains three polypeptide chains as a result of two internal cleavages at residues 87-88 and 140-141. These modifications may represent processing events that are critical for determining the binding specificity of EGF-BP, since they occur within regions surrounding the substrate binding site.