Somatogenic (i.e. GH) receptors have been studied on liver microsomal membranes from male and female rats. Tracer bovine GH was displaced from its binding sites by GHs of various species, but was displaced only weakly by PRLs. Specific bovine GH binding was 3.5-fold higher to female rat liver membranes than to membranes from males. Streptozotocin-induced diabetes significantly reduced binding, by 80% in females and 50% in males, while insulin therapy to normalize weight gain reversed the decrease in binding. Competitive binding curves were consistent with two independent classes of binding site: low affinity sites with K equal to 0.5 nm-1 in both sexes, and high affinity sites with K equal to 12.1 nm-1 in males and 21.4 nm-1 in females (P less than 0.001). The addition of excess ovine PRL caused a substantial loss of high affinity binding with little loss in the low affinity region, suggesting a weak somatogenic role for ovine PRL. In diabetic animals, low affinity sites were unchanged from normal, while high affinity sites were decreased in number, with no change in affinity, and restored on insulin therapy. Serum immunoreactive rat GH levels were the same in normal and diabetic, male and female animals. These studies suggest that the apparent hepatic resistance to GH seen in diabetes when liver somatomedin release is low despite normal serum GH might be explained by the loss of GH receptors in this condition.

2002;10:401-407. Objective: Obesity is a major risk factor for the development of type 2 diabetes. Tumor necrosis factor (TNF)-␣ is a candidate gene for the development of both obesity and insulin resistance. We investigated whether a common polymorphism in the promoter region (Ϫ308 G/A) of the TNF-␣ gene was associated with increased risk for the development of insulin resistance and cardiovascular disease in an obese Australian population. Research Methods and Procedures: Obese, non-diabetic subjects (146 women and 34 men) were genotyped with polymerase chain reaction-restriction fragment length polymorphism techniques, and anthropometric and biochemical measurements were analyzed. A homeostasis model assessment (HOMA) score was used to gauge the level of insulin resistance. Results: The frequencies of the G allele and the A allele were 0.759 and 0.241, respectively. Subjects homozygous for the A allele had higher fasting insulin levels (226 vs. 131 pM; p Ͻ 0.001), higher HOMA scores (10.2 vs. 5.3; p Ͻ 0.001), higher systolic blood pressure (143 vs. 129 mm Hg; p ϭ 0.02), and lower high-density lipoprotein (HDL) cholesterol (1.13 vs. 1.25 mM; p ϭ 0.04) than did subjects homozygous for the G allele. Whereas an association between insulin resistance and body mass index or waist circumference was seen in all subjects, a highly significant negative correlation of HDL cholesterol to HOMA scores (r ϭ Ϫ0.710; p Ͻ 0.001) occurred in subjects with the A allele only. Discussion: The Ϫ308 G/A TNF-␣ gene variant conveys an increased risk for the development of insulin resistance in obese subjects. The presence of low HDL cholesterol levels further increases the risks associated with insulin resistance in carriers of the A allele.

The Diabetes Knowledge Assessment (DKN) scales were developed to meet a specific need for rapid and reliable knowledge assessment in diabetic patients. Item format and item selection from an initial pool of 89 items were determined by pilot-testing over 300 diabetic subjects. Reliability analysis of the resulting 40 multiple-choice items, with a further sample of 56 subjects, gave a Cronbach's alpha coefficient of 0.92. Parallel forms DKNA, DKNB, and DKNC, each of 15 items selected from the parent set, had alpha coefficients above 0.82 and correlated 0.90 with each other. A full clinical trial, using DKNA, DKNB, and DKNC in randomized order of presentation, was conducted with 219 subjects attending a 2-day diabetes education program. Overall DKN scores improved from 7.6 (51%) to 11.3 (75%). Analysis of variance confirmed that DKNA, DKNB, and DKNC were equivalent forms at pretest. Mean posttest scores on DKNB were lower than the other scales (P less than 0.001), but variances were equivalent for all three. A specific local change in the education program format was found to account for this discrepancy in the DKNB posttest mean. In situations where comprehensive assessment of diabetes knowledge would be time-consuming and unnecessary, these results indicate that rapid and reliable assessment is possible with a scale of only 15 validated items. The development of parallel forms of the scale extends the range of retesting possibilities for diagnosis and research.