A structured outpatient DTTP as used in this study is able to improve overall metabolic control and decrease the frequency of severe hypoglycemia in patients with IDDM.

The absolute concentration of albumin was measured in the interstitial fluid of subcutaneous adipose tissue and skeletal muscle in six healthy volunteers by combining the method of open-flow microperfusion and the no-net-flux calibration technique. By use of open-flow microperfusion, four macroscopically perforated double lumen catheters were inserted into the tissue regions of interest and constantly perfused. Across the macroscopic perforations of the catheters interstitial fluid was partially recovered in the perfusion fluid. Catheters were perfused with five solutions, each containing different concentrations of albumin. Absolute interstitial albumin concentrations were calculated by applying linear regression analysis to perfusate vs. sampled albumin concentration (no-net-flux calibration technique). Interstitial albumin concentrations were significantly lower (P < 0.0001) in adipose tissue (7.36 g/l; r = 0.99, P < 0.0003; range: 4.3-10.7 g/l) and in skeletal muscle (13.25 g/l; r = 0.99, P < 0.0012; range: 9.7 to 15.7 g/l) compared with the serum concentration (48.9 +/- 0.7 g/l, mean +/- SE, n = 6; range: 46.4-50.4 g/l). Furthermore, interstitial albumin concentrations were significantly higher in skeletal muscle compared with adipose tissue (P < 0.01). The study indicates that open-flow microperfusion allows stable sampling of macromolecules from the interstitial space of peripheral tissue compartments. Moreover, the present data report for the first time in healthy humans in vivo the true albumin concentrations of interstitial fluid of adipose tissue and skeletal muscle.

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 Ϯ 8 years, 16 men and 8 women, BMI 24.3 Ϯ 2.6 kg/m 2 , diabetes duration 17 Ϯ 11 years, HbA 1c 7.9 Ϯ 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) 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. Diabetes Care 25:2053-2057, 2002I n accordance with the results of the Diabetes Control and Complication Trial, near-normoglycemic blood glucose levels prevent the onset or delay the progression of long-term complications in type 1 diabetes (1). To mimic the physiological insulin secretion profile, intensified insulin therapy with unmodified human soluble insulin is performed as standard treatment regimen by a majority of patients (2,3). However, postprandial blood glucose peaks and excursions are not comparable with nondiabetic subjects. Absorption of unmodified insulin from the injection site is a complex process affected by only partially changeable factors, such as anatomic area, blood flow, injection volume, concentration of insulin, and possible local degradation process (4 -6). Therefore, considerable attention has been devoted to the development of insulin molecules with accelerated absorption kinetics (7-9). This more physiological profile of these shortacting insulin analogs leads to reduced prandial glucose excursions (10 -13). In well-controlled type 1 diabetic patients, postprandial administration of insulin aspart and insulin lispro has shown to be at least as effective as mealtime application o...

To gain direct access to the interstitial fluid (ISF), a new technique called open-flow microperfusion has been evaluated. This method is based on a double-lumen catheter with macroscopic (0.3–0.5 mm diameter) perforations that is inserted into the subcutaneous adipose tissue and constantly perfused. Thus partial equilibration between the ISF and the perfusion fluid occurs. The glucose concentration of the ISF was determined by established (zero flow rate, no net flux, and recirculation procedures) and new (ionic reference and suction technique) calibration methods by use of open-flow microperfusion. The data show that 1) the glucose concentration in the ISF is significantly lower than the corresponding arterialized venous plasma values during basal steady-state conditions (adipose tissue 3.2 ± 0.10 mM, plasma 5.27 ± 0.12 mM) as well as during hyperglycemic clamp experiments (adipose tissue 7.3 ± 0.13 mM, plasma 9.91 ± 0.16 mM), and 2) it is possible to determine the recovery continuously by using the ion concentration of the ISF as an internal standard (ionic reference).