Efficacy, safety and feasibility of intravenous iloprost in the domiciliary treatment of patients with ischemic disease of the lower limbs.

OBJECTIVE: Intravenous iloprost is an important option in the treatment of ischemic disease of the lower limbs; however, the administration of therapy is frequently compromised because of the need for long cycles of infusion in a hospital setting. The aim of the study is to evaluate the efficacy, safety, feasibility, and the economic impact of infusion therapy in the outpatient setting. PATIENTS AND METHODS: Twenty-four consecutive patients were treated with iloprost at their homes where they were administered a slow rate of infusion for 24 hours a day, during 9.9 ± 2.3 days, with a portable syringe pump (Infonde®). RESULTS: The clinical condition of patients evaluated with the modified SVS/ISCVS scale significantly improved after treatment (+1.29 ± 1.04 points vs. baseline, p<0.001). The drug was well tolerated; neither significant adverse events associated with medication nor problems related to venous access were recorded at home. Ninety-six percent of patients successfully completed the entire treatment cycle, and the evaluation questionnaire showed a high acceptance of the therapy. From the perspective of the hospital authority, lower direct medical costs were estimated for the domiciliary infusion process compared with the inpatient infusion setting. CONCLUSIONS: Treatment with iloprost in the outpatient setting is effective, safe, feasible, and more acceptable to patients than infusion at the hospital. In addition, it has a favorable economic and organizational impact on the medical ward.

Insulin supplement in type 2 diabetic patients with secondary failure to oral agents ameliorates hepatic and peripheral insulin sensitivity but not insulin secretion.

In order to investigate the mechanism of amelioration of metabolic abnormalities with supplementary doses of insulin, islet B-cell function and insulin sensitivity were measured in 10 patients with Type 2 diabetes in secondary failure to oral agents. A small dose of ultralente insulin (0.26 +/- 0.07 U kg-ideal-body-weight-1) was added in the morning before breakfast. After 3 months insulin therapy and progressive improvement of metabolic control (HbA1 from 10.5 +/- 0.4 to 9.0 +/- 0.3% at the end of insulin treatment, p less than 0.001), basal C-peptide and incremental area during an oral glucose tolerance test were unchanged. In vivo peripheral insulin sensitivity (euglycaemic clamp with insulin infusion of 40, 160, and 600 mU m-2 min-1, respectively) was significantly improved (glucose requirement: to 4.7 +/- 1.0 from 3.0 +/- 0.6 mg kg-1 min-1, p less than 0.05 at first insulin level; to 10.8 +/- 0.5 from 9.3 +/- 0.7 mg kg-1 min-1, p less than 0.01 at second level; to 13.3 +/- 0.6 from 11.8 +/- 0.8 mg kg-1 min-1, p less than 0.025 at third level). Basal hepatic glucose production was also significantly reduced (from 4.3 +/- 0.4 to 3.3 +/- 0.3 mg kg-1 min-1, p less than 0.05), and residual glucose production further suppressed after insulin supplement (from 1.1 +/- 0.4 to 0.3 +/- 0.2 mg kg-1 min-1 after 120 min at 100 mU l-1 plasma insulin, p less than 0.05). Specific insulin binding to mononuclear leucocytes was unchanged (from 3.1 +/- 0.3 to 3.5 +/- 0.3%, NS).

Insulin secretion and insulin sensitivity defects are a common feature of mild, clinically homogeneous, recently diagnosed type II (non-insulin-dependent) diabetics.

Alteration in insulin secretion and reduced peripheral sensitivity to the hormone have been reported in type II diabetes. In this paper, a comparison is made of basal glucose production (3H-6 glucose), insulin secretion and insulin sensitivity in vivo (hyperglycemic clamp) and in vitro (binding to circulating monocytes) in 24 patients with recently diagnosed type II diabetes, matched for age and fasting glycemia and divided into non-obese (14 subjects) and moderately obese (10 subjects), and in 9 non-obese controls. The non-obese diabetics were slightly hyperinsulinemic during fasting (10.8 +/- 1.0 vs 4.8 +/- 0.8 microU/ml in controls, p less than 0.0005), with a significant reduction in early and late insulin secretion (14.0 +/- 1.5 vs 20.8 +/- 2.0 microU/ml, p less than 0.01 and 24.8 +/- 3.3 vs 34.7 +/- 2.14 microU/ml, p less than 0.025). The insulin sensitivity index MCR/I was significantly reduced (2.30 +/- 0.32 vs 4.14 +/- 0.40, p less than 0.005). Endogenous glucose production was significantly increased (107 +/- 10.2 vs 84 +/- 3.7 mg/m2 per min, p less than 0.025) and displayed a positive correlation with fasting glycemia (r = 0.51, p less than 0.05). Insulin binding to monocytes was significantly lower than in controls (2.36 +/- 0.22% vs 4.06 +/- 0.32%, p less than 0.0005). Moderately obese diabetics also were significantly hyperinsulinemic in the fasting state (18.1 +/- 2.8 microU/ml, p less than 0.0005 vs controls) but, typically, lacked the early secretory phase (20.6 +/- 3.6 microU/ml vs baseline, n.s.). A similar increase of hepatic glucose production (107 +/- 11.2 mg/m2 per min, p less than 0.025 vs controls, n.s. vs non-obese diabetics) and decrease of peripheral sensitivity to insulin (MCR/I = 1.78 +/- 0.31, p less than 0.0005 vs controls, n.s. vs non-obese diabetics) was found in moderately obese diabetics, as well as a significant reduction of insulin binding to insulated monocytes (2.62 +/- 0.4% p less than 0.01 vs controls, n.s. vs non-obese diabetics). These results confirm that common defects of both non-obese and moderately obese type II diabetics are: lack of early phase of glucose induced insulin secretion, increase in hepatic glucose production and decrease of peripheral insulin sensitivity together with reduction of insulin binding to circulating monocytes. The hypothesis of a unique defect as a cause of hyperglycemia in type II diabetes in early clinical phase is not borne out by the results of this study. Moderate obesity, even if able to reduce insulin sensitivity, seems to be less important in determining hyperglycemia.