Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance. The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM:

Subcutaneous administration of insulin aspart causes a more rapid and intense maximal effect compared with regular insulin during euglycemic clamp studies in nondiabetic subjects. Abdominal administration of insulin aspart has a shorter duration of glucose-lowering effect compared with administration in the deltoid or thigh.

We have developed a noninvasive method to estimate splanchnic glucose uptake (SGU) in humans (oral glucose clamp technique [OG-CLAMP]), which combines a hyperinsulinemic clamp with an oral glucose load (oral glucose tolerance test). We validated this method in 12 nondiabetic subjects using hepatic vein catheterization (HVC) during an oral glucose tolerance test. During HVC, splanchnic blood flow increased from 1,395±64 to 1,935±109 ml/min, returning to basal after 180 min and accounted for 45±7% of SGU in lean and 19±5% in obese subjects (P < 0.05). SGU estimated during the OG-CLAMP was 22±2% of the glucose load, and this was significantly correlated (r = 0.90, P < 0.0001) with SGU (35±4%) and with first pass SGU (24±3%; r = 0.83, P < 0.001) measured during HVC. SGU was higher in obese than in lean subjects during OG-CLAMP (27±1% vs 18±3%, P < 0.01) and HVC (44±4% vs 26±5%, P < 0.05). In conclusion, SGU during the OG-CLAMP is well correlated to SGU measured during HVC. An increase in splanchnic blood flow is a major contributor to SGU in lean subjects. SGU is increased in obese subjects as measured by both methods.

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1 Ϯ 5.1 g for HVC, 76.5 Ϯ 5.5 for OG-CLAMP) compared with nondiabetic patients (46.7 Ϯ 4.4 g for HVC, 57.5 Ϯ 1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4 Ϯ 2.1 vs. 37.8 Ϯ 5.9% in nondiabetic patients, P Ͻ 0.001) and first-pass SGU (4.7 Ϯ 1.7 vs. 26.5 Ϯ 5.1% in nondiabetic patients, P Ͻ 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9 Ϯ 1.7 vs. 23.4 Ϯ 2.5% in nondiabetic patients, P Ͻ 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU ( r ϭ 0.87, P Ͻ 0.05 for NIDDM patients; r ϭ 0.94, P Ͻ 0.01 for nondiabetic patients) and first-pass SGU ( r ϭ 0.87, P Ͻ 0.05 for NIDDM patients; r ϭ 0.84, P Ͻ 0.05 for nondiabetic patients) during HVC. In conclusion, ( a ) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (

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