Measurement of interstitial insulin in human adipose and muscle tissue under moderate hyperinsulinemia by means of direct interstitial access.

Insulin's action to stimulate glucose utilization is determined by the insulin concentration in interstitial fluid (ISF) of insulin-sensitive tissues. The concentration of interstitial insulin has been measured in human subcutaneous adipose tissue and skeletal muscle, however, never in parallel. The aim of this study was to compare interstitial insulin levels between both tissue beds by simultaneous measurements and to verify and quantify low peripheral ISF insulin fractions as found during moderate hyperinsulinemia. Nine healthy subjects (27.2 +/- 0.8 yr) were investigated. A euglycemic-hyperinsulinemic clamp was started with a primed-constant intravenous insulin infusion of 1 mU x kg(-1) x min(-1). For direct access to ISF, macroscopically perforated open-flow microperfusion catheters were inserted in both tissues. During steady-state conditions (9.5 h), interstitial effluents were collected in 30-min fractions using five different insulin concentrations in the inflowing perfusates ("no net flux" protocol). Regression analysis of insulin concentrations in perfusates and effluents yielded the relative recovery and the perfusate insulin concentration, which was in equilibrium with the surrounding tissue. Thus, in subcutaneous adipose tissue and skeletal muscle, the mean ISF-to-serum insulin level was calculated as 21.0% [95% confidence interval (CI) 17.5-24.5] and 26.0% (95% CI 19.1-32.8; P = 0.14), respectively. Recoveries for insulin averaged 51 and 64%, respectively. The data suggest that the concentrations of insulin arising in healthy subjects at the level of ISF per se are comparable between subcutaneous adipose and skeletal muscle tissue. The low interstitial insulin fractions seem to confirm reports of low peripheral insulin levels during moderate insulin clamps.

Evaluation of the impact of chiropodist care in the secondary prevention of foot ulcerations in diabetic subjects.

OBJECTIVE: To evaluate the influence of regular chiropodist care on the recurrence rate of diabetic foot ulcers within 1 year. RESEARCH DESIGN AND METHODS: Ninety-one diabetic outpatients with healed foot ulcers (age 65 +/- 11 years, 40 women and 51 men, diabetes type 1 (n = 6) or 2 (n = 85), BMI 28.5 +/- 4.4, diabetes duration 16 +/- 11 years, HbA(1c) 8.4 +/- 1.6%) were randomized to a group that received monthly remunerated routine chiropodist care (n = 47) or a control group (n = 44). RESULTS: Within a median follow-up of 386 days, ulceration recurred in 18 patients in the chiropodist group and 25 patients in the control group (hazard ratio [HR] 0.60; 95% CI, 0.32, 1.08; P = 0.09). Analysis of ulceration per foot demonstrated a significant reduction (20 vs. 32 ulcerations; Cox relative risk [Cox RR] 0.52; 95% CI, 0.30, 0.93; P = 0.03) in favor of chiropodist care. Per protocol, analysis of patients who actually underwent chiropodist foot care on a regular basis also indicates the beneficial influence of chiropodist care with ulceration in 13 vs. 30 patients (HR, 0.53; 95% CI, 0.30-1.01; P = 0.05) and in 15 vs. 37 feet (Cox RR, 0.46; 95% CI, 0.24-0.90; P = 0.02) for the intervention and control groups, respectively. Minor amputation was required in two patients in the intervention group and one patient in the control group. Four patients in the control group and two patients in the intervention group died during the trial. CONCLUSIONS: These data suggest that secondary preventive measures by a chiropodist may reduce recurrence of foot ulcers in diabetic patients.

A direct comparison of insulin aspart and insulin lispro in patients with type 1 diabetes.

OBJECTIVE: Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients (age 36 +/- 8 years, 16 men and 8 women, BMI 24.3 +/- 2.6 kg/m(2), diabetes duration 17 +/- 11 years, HbA(1c) 7.9 +/- 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal. RESULTS: With respect to blood glucose excursions from time 0 to 6 h (Exc(glu(0-6 h))) and from time 0 to 4 h (Exc(glu(0-4 h))), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (C(max(glu))) (estimated ratio aspart/lispro ANOVA [90% CI]: 0.95 [0.80-1.13], 0.97 [0.82-1.17], and 1.01 [0.95-1.07] for Exc(glu(0-6 h)), Exc(glu(0-4 h)), and C(max(glu)), respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed. CONCLUSIONS: These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions.