O ptimal treatment of type 1 diabetes should achieve normoglycemia at all times, without risk of hypoglycemia. Such a treatment should dramatically reduce or prevent diabetes complications and significantly improve patients' quality of life. This goal may be accomplished through pancreatic or islet cell transplantation, but availability of these tissues is limited, survival and function are unpredictable, and longterm immunosuppressive therapy is required (1). The potential for an automated closed-loop system, or artificial ␤-cell, to achieve round-the-clock glycemic control, has not been fully explored.An artificial ␤-cell requires a glucose sensor, an insulindelivery pump, and an algorithm for calculating insulin delivery. Technological and scientific advances have made sensors and pumps available, but linking the two as a "closed loop" has been challenging (2). Lingering questions remain regarding the suitability of different glucosesensing sites (subcutaneous versus intravascular), insulindelivery sites (subcutaneous versus intravascular versus intraperitoneal), and sensor reliability. In addition, no one algorithm has been universally accepted as optimal for insulin delivery (3).Herein, we describe the feasibility of achieving glycemic control in patients with type 1 diabetes using a system comprised of a subcutaneous glucose sensor, an external insulin pump, and an algorithm emulating the ␤-cell's multiphasic glucose-induced insulin release (4 -6). ). Subjects had been treated with continuous subcutaneous insulin infusion (CSII) using Lispro insulin (Lilly, Indianapolis, IN) for at least 6 months before study enrollment and were required to have an HbA 1c Ͻ9%. Data from a previously published study (7) characterizing insulin secretion over a 24-h period in nondiabetic subjects are included for comparison of the glucose profiles (n ϭ 17) obtained with a similar diet. The study was approved by the University of California, Los Angeles Institutional Review Board, and all patients gave written informed consent. RESEARCH DESIGN AND METHODSGlycemic control under CSII therapy was characterized over a 3-day outpatient period using a continuous glucose monitoring system (CGMS) (Medtronic MiniMed, Northridge, CA). The CGMS records sensor current every 5 min and glucose profiles are obtained retrospectively (8). Patients were instructed to keep their daily routine but to take a minimum of seven fingerstick blood glucose readings per day (preprandial and 2-h postprandial and at bedtime) with their home glucose meters. Patients were also instructed to record meal carbohydrate content, physical activity, and any hypoglycemic episodes or supplemental carbohydrate in a logbook.To evaluate the closed-loop insulin delivery system, patients were admitted to the general clinical research center at ϳ5:00 P.M., and their insulin pump was replaced with a Medtronic 511 Paradigm Pump capable of communicating telemetrically with a laptop computer. Two subcutaneous glucose sensors were inserted in the abdominal area and connected to...

Aims/hypothesis: Glucose sensors often measure s.c. interstitial fluid (ISF) glucose rather than blood or plasma glucose. Putative differences between plasma and ISF glucose include a protracted delay during the recovery from hypoglycaemia and an increased gradient during hyperinsulinaemia. These have often been investigated using sensor systems that have delays due to signal smoothing, or require long equilibration times. The aim of the present study was to define these relationships during hypoglycaemia in a well-equilibrated system with no smoothing. Methods: Hypoglycaemia was induced by i.v. insulin infusion (360 pmol·m −2 ·min −1 ) in ten non-diabetic subjects. Glucose was sequentially clamped at ∼5, 4.2 and 3

Modeling analysis of glucose, insulin, and C-peptide following a meal has been proposed as a means to estimate insulin sensitivity (S i ) and ␤-cell function from a single test. We compared the model-derived meal indexes with analogous indexes obtained from an intravenous glucose tolerance test (IVGTT) and hyperglycemic clamp (HGC) in 17 nondiabetic subjects (14 men, 3 women, aged 50 ؎ 2 years [mean ؎ SE], BMI 25.0 ؎ 0.7 kg/m 2 ). S i estimated from the meal was correlated with S i estimated from the IVGTT and the HGC (r ‫؍‬ 0.59 and 0.76, respectively; P < 0.01 for both) but was ϳ2.3 and 1.4 times higher (P < 0.05 for both). The meal-derived estimate of the ␤-cell's response to a steady-state change in glucose (static secretion index) was correlated with the HGC second-phase insulin response (r ‫؍‬ 0.69; P ‫؍‬ 0.002), but the estimated rate-of-change component (dynamic secretion index) was not correlated with first-phase insulin release from either the HGC or IVGTT. Indexes of ␤-cell function obtained from the meal were significantly higher than those obtained from the HGC. In conclusion, insulin sensitivity and ␤-cell indexes derived from a meal are not analogous to those from the clamp or IVGTT. Further work is needed before these indexes can be routinely used in clinical and epidemiological studies. Diabetes 53:1201-1207, 2004 E stablishing a single test that assesses insulin secretion and insulin sensitivity under normal physiologic conditions is potentially of great value for both epidemiological and clinical studies. To this end, a minimal model estimate of insulin sensitivity based on a meal tolerance test has recently been developed by Caumo et al. (1), and several groups (2-10) have proposed model-based methods for assessing ␤-cell function from arbitrary glucose excursions. The meal-derived estimate of insulin sensitivity [S i(MEAL) ] has been shown to correlate with that obtained from an intravenous glucose tolerance test (IVGTT) [S i(IVGTT) ] (1), but none of the model-based indexes of ␤-cell function have been rigorously compared with estimates of first-and second-phase insulin release obtained from standard tests such as the IVGTT (11-13) or hyperglycemic clamp (HGC) (14 -16).To more fully assess whether indexes of insulin sensitivity and ␤-cell function can both be obtained from a meal test, we measured plasma glucose, insulin, and C-peptide concentrations over a 24-h period. On separate days, an IVGTT and HGC were performed. The IVGTT was used to assess insulin sensitivity [S i(IVGTT) ] and first-phase insulin release [⌽ 1(IVGTT) ]. The HGC was used to assess first-[⌽ 1(HGC) ] and second-phase insulin release [⌽ 2(HGC) ] and to obtain an additional estimate of insulin sensitivity [S i(HGC) ]. These estimates were then compared with analogous estimates of S i and ␤-cell function obtained from the breakfast meal. The role of potentiation in enhancing ␤-cell secretion throughout the day was evaluated by comparing the secretion indexes obtained from breakfast with those obtained from lunch and di...

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Conclusions: Measurements of urinary albumin, total protein, and albumin-to-creatinine ratio are minimally affected by storage at ؊70°C for approximately 2.5 yr. Prolonged storage results in small decreases of urinary albumin and protein that do not substantially affect phenotype classification of overt renal disease.

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