Objective: To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. Design: A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. Subjects: 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. Outcome measures: Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. Results: Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A 1c , systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A 1c , and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41(1.06 to 1.88). Conclusion: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.

Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were also seen in a 16-residue segment. On extraction, the islet amyloid is particulate and insoluble like the core particles of Alzheimer disease. Their monomers have similar molecular masses, each having a hydropathic region that can probably form 13-pleated sheets.

A radioimmunoassay method for the measurement of plasma insulin is described relying on activated charcoal for the separation of free and bound fractions. The technique illustrates the application of theoretical precepts designed to maximise assay precision in all radioimmunoassay and other saturation assay techniques. In addition, because particular emphasis has been placed on ensuring that, as far as is possible, all incubation mixtures are similar as possible other than in hormone concentration, non-specific effects appear to have been essentially eliminated. The technique yields a mean normal fasting value of 5.3μU/ml (range 2–14 μU/ml). Its sensitivity is such that 10 μl samples of serum (or plasma) may be assayed.

Impaired glucose tolerance (IGT) and Type II (noninsulin-dependent) diabetes mellitus result from different contributions of deficient insulin secretion and impaired insulin sensitivity [1±8]. Routine quantification of these abnormalities is rarely done as simple, user friendly methods have not been validated or received general approval [9,10]. The choice of therapy might depend on the causative pathophysiology in a patient and, with the prospect of insulin-sensitising drugs as well as life-style changes to improve insulin sensitivity, routine assessment of insulin sensitivity might become more appropriate than at present [11, Diabetologia (1999) AbstractAims/hypothesis. Adequate comparison of the relative performance of insulin sensitivity tests is not yet available. We compared the discrimination of four insulin sensitivity tests, commonly used in vivo, across a range of glucose tolerance. Methods. Normal (n = 7), impaired glucose tolerant (n = 8) and Type II (non-insulin-dependent) diabetic subjects (n = 9) had in random order two tests from the following: frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT-MinMod); homeostasis model assessment (HOMA) and 2-h continuous infusion of glucose with model assessment (CIGMA) with immunoreactive or specific insulin; short insulin tolerance tests (ITT). The discriminatory power of tests was assessed by the ratio of the within-subject standard deviation to the underlying between-subject standard deviation (discriminant ratio ± DR). The degree to which tests measured the same variable was assessed by comparing rank correlation with the maximum expected correlation given the imprecision of the tests. The unbiased lines of equivalence taking into account the precision of tests were constructed.Results. Reciprocal fasting plasma insulin (FPI ±1 ), HOMA %S and 2-h CIGMA %S, had similar DRs with ITT being less informative. The FSIVGTT-MinMod analysis was able to assess 13 out of 24 subjects and had a performance similar to ITT. Using specific rather than immunoreactive insulin for HOMA-CIG-MA did not improve the DR. Reciprocal fasting plasma insulin FPI ±1 , HOMA %S, 2-h CIGMA %S and S I FSIVGTT intercorrelated more than 90 % of the expected rank correlation given the imprecision of the tests, but ITT gave only limited correlation. Conclusion/interpretation. The HOMA-CIGMA test with immunoreactive insulin provides similar information in distinguishing insulin sensitivity between subjects with normal glucose tolerance, those with impaired glucose tolerance and those with Type II diabetes as does FSIVGTT, whereas ITT is less informative. [Diabetologia (1999) 42: 678±687]