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We present an evaluation of time-resolved fluorescence measurements on human skin for screening type 2 diabetes. In vivo human skin is excited with a pulse diode at 375 nm and pulse width of 700 ps. Fluorescence decays are recorded at four different emission wavelengths: 442, 460, 478, and 496 nm. Experiments are performed at various locations, including the palms, arms, legs, and cheeks of a healthy Caucasian subject to test single-subject variability. The fluorescence decays obtained are modeled using a three-exponential decay. The variations in the lifetimes and amplitudes from one location to another are minimal, except on the cheek. We compare the fluorescent decays of 38 diabetic subjects and 37 nondiabetic subjects, with different skin complexions and of ages ranging from 6 to 85 yr. The average lifetimes for nondiabetic subjects were 0.5, 2.6, and 9.2 ns with fractional amplitudes of 0.78, 0.18, and 0.03, respectively. The effects of average hemoglobin A1c (HbA1c) from the previous 4 yr and diabetes duration are evaluated. While no significant differences between the fluorescence lifetimes of nondiabetic and diabetic subjects are observed, two of the fractional amplitudes are statistically different. Additionally, none of the six fluorescence parameters correlated with diabetes duration or HbA1c. One of the lifetimes as well as two of the fractional amplitudes differ between diabetic subjects with foot ulcers and nondiabetic subjects.

Objective: Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections., Research Design and Methods: Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study., Results: HbA1c decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA1c < 7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group., Conclusions: Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen., (Copyright 2004 American Diabetes Association)

Introduction: Insulin secretion in the pancreatic islet of Langerhans is closely related to glucose oxidation. Our previous membrane preparations from the islet of Langerhans and kidney contained Na+/K+ ATPase. Although ATP is a modulator of insulin release, we have not demonstrated that membranes contain glycolytic enzymes., Aims: To compare glucose oxidation in intact islets of Langerhans with that seen in islet membranes, and to examine renal tissue because of easy access to this tissue and because our previous work contrasted islets and kidney Na+/K+ ATPase activity., Methodology: To examine whether membrane preparations of both islets and kidney contain glycolytic activity, we designed an apparatus that determines tissue glucose oxidation rates by measuring 14CO2 production from 14C-1-D-glucose. In contrast to previous methods, O2 was supplied and pH was maintained in physiologic ranges throughout the incubations., Results: At 5.5 mM glucose, oxidation was linear over 2 hours in intact islets and kidney. Islets produced approximately twice the 14CO2 as kidney, or 1000 nmol CO2/mg protein/hour. Membranes oxidized glucose at less than 10% of the rates observed with intact tissue. Concentration dependency was linear from 0-11.0 mM glucose; however, at 16.5 mM, oxidation decreased to less than half of that seen at 11.0 mM., Conclusion: Our "membrane" preparations contain some glycolytic activity but are unlikely to contribute significant amounts of ATP in most studies of ATP hydrolysis, such as that seen in experiments that measure ATPase activity.