This study demonstrates that CGMS can be successfully employed in large clinical trial settings in patients with T2DM. This easy-to-implement method may provide additional insights into glucose levels and valuable information regarding the time patients spend within the preferred glucose range.

The effect of elevated serum thyroid hormone concentrations on insulin-induced glucose metabolism was studied in healthy subjects before and after T4 administration (250 micrograms T4/day for 10-14 days). This treatment induced moderate hyperthyroidism (T4, 15.2 micrograms/dl; T3, 200 ng/dl). The following results were obtained. Insulin receptor binding to a 90% enriched monocyte fraction or to mitogen-stimulated cultured T lymphocytes was decreased by T4 administration, whereas insulin binding to erythrocytes was unaffected. Despite down-regulation of cellular insulin receptors, T4 administration did not alter oral glucose tolerance, but increased the disappearance of glucose after an iv load and the amount of glucose metabolized during euglycemic clamp studies infusing 1.0 or 1.5 mU insulin/kg BW X min; no effect was found at insulin infusion rates of 0.5, 2.0, and 4.0 mU/kg X min. At increasing steady state plasma glucose levels (up to 175 mg/dl) and an insulin infusion rate of 1.0 mU/kg BW X min, T4 administration reduced insulin-induced glucose metabolism. We conclude that experimental hyperthyroidism decreases insulin receptor binding but increases insulin-induced glucose metabolism during euglycemia. This may be due to the direct effect of thyroid hormones on glucose metabolism; however, during hyperglycemia, thyroid hormone induced insulin resistance is unequivocal.

Aims/hypothesis: The aim of the study was to assess a new steel ball-bearing test as a means of evaluating protective sensation in the diabetic foot. Methods: Subjects were enrolled for this study as follows: (1) 39 patients (mean age 61.3±9.7 years) with neuropathy and prior neuropathic ulcer (Group A); (2) 36 patients (mean age 63.7±10.1 years) with neuropathy without neuropathic ulcer (Group B); (3) 34 patients (mean age 52.1±10.4 years) without neuropathy (Group C); and (4) 21 healthy volunteers (mean age 46.7±8.7 years) (Group D). Neuropathy was diagnosed by means of neuropathy disability score (NDS). The plantar area over the second metatarsal head of each foot was examined with steel ball-bearings of varying diameters. The smallest diameter that the patient could feel was used to define the ball-bearing score (range 1-6). Results: A high ball-bearing score was significantly more frequent in patients with neuropathic ulceration than in neuropathic patients without ulceration and in diabetic patients without neuropathy (p<0.001). A high score was also more frequent in neuropathic patients without ulceration, than in patients without neuropathy (p<0.001). The ball-bearing score was significantly (p=0.01) correlated with the NDS, the monofilament test, the vibration perception threshold and the thermal perception threshold. The ball-bearing test had a sensitivity of 84% and a specificity of 100% for impaired protective sensation due to neuropathy, and a sensitivity of 84.6% and a specificity of 86.1% for detection of patients with prior neuropathic ulceration. Conclusions/interpretation: The steel ball-bearing test has a high sensitivity and specificity both for the evaluation of protective sensation and for detection of patients with prior neuropathic ulceration.

1. Renal handling of pig- and rat-insulin was studied in the isolated perfused rat kidney. 2. Metabolic clearance rates of both pig- and rat-insulin exceeded GFR. 3. Peritubular uptake of pig-insulin accounted for 13% of rat-insulin for 31% of the total metabolic clearance. 4. The nonfiltering kidney does not remove insulin from the peritubular circulation. 5. Metabolic clearance rates of pig- and rat-insulin are directly related to GFR. 6. The filtration process seems to be necessary for the uptake of insulin at the peritubular site.