Abbreviations: ANCOVA, analysis of covariance; ANOVA, analysis of variance; IRI, immunoreactive insulin; NEFA, nonesterified fatty acid; T 75% , time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Pharmacokinetics of 125 I-Labeled Insulin Glargine (HOE 901) in Healthy MenComparison with NPH insulin and the influence of different subcutaneous injection sitesOBJECTIVE -To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine (HOE 901) differing only in zinc content (15, 30, and 80 µg/ml). RESULTS -In study 1, the time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection (T 75% ) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively, P Ͻ 0.0001). Mean residual radioactivity with NPH insulin was also significantly lower at 24 h (21.9 vs. 43.8 and 52.2%, P Ͻ 0.0001). The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibit a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P Ͻ 0.001). In study 2, there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites (T 75% = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in residual radioactivity at 24 h. RESEARCH DESIGN AND METHODSCONCLUSIONS -Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin. There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites. r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s Diabetes Care

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Beta-cell secretion and insulin sensitivity was studied in healthy subjects and newly diagnosed Caucasian (Welsh) NIDDM patients. A standardized meal tolerance test (MTT) and frequent sampled intravenous glucose tolerance tests (FSIVGTT) were employed and the patients stratified according to fasting plasma glucose (FPG). A deficient early (first hour) post-prandial (MTT) insulin secretion was demonstrated in all NIDDM patients, deteriorating with increasing fasting hyperglycaemia. For the patient group fasting and post-prandial hyperproinsulinaemia was evident with diminishing post-prandial excursions as fasting hyperglycaemia increased. The early phase (0-10 min) insulin secretion to intravenous glucose (300 mg kg-1 ) was severely impaired in NIDDM patients. A shortlived paradoxical fall in plasma insulin concentrations was observed in those with FPG >9 mmoll-1 • Insulin sensitivity utilizing the insulin modified FSIVGTT demonstrated that all NIDDM patients had marked insulin insensitivity. Characteristic of the newly diagnosed previously untreated Caucasian NIDDM is a dysfunctional beta cell, resulting in a deficit in insulin secretion with relative hyperproinsulinaemia. The quantitative and qualitative secretory status of the beta cell decreases with increasing fasting hyperglycaemia. Insulin sensitivity is markedly reduced when FPG exceeds 7.0 mmol J-1 with little or no further discernible fall with deteriorating glycaemic control.

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