To examine whether an increase in the glucagon concentration is essential for restoring hepatic glucose output following moderate decrements in blood glucose, we used isotope dilution techniques in trained conscious dogs (n = 5) to measure glucose production (Ra) and glucose utilization (Rd) during mild hyperinsulinemia (19 +/- 1 mU/l). In Study A, when insulin was infused to raise plasma insulin (IRI) from 13 +/- 2 to 19 +/- 1 mU/l, basal glucose (93 +/- 3 mg/dl) fell at a rate of 0.37 +/- 0.06 mg/dl/min over 30 min. Ra fell from 2.8 +/- 0.4 mg/kg/min by 0.5 +/- 0.1 mg/kg/min at 20 min (P less than 0.05), but recovered to baseline by 30 min; glucagon (IRG) fell transiently but returned to baseline by 45 min. In Study B, endogenous secretion of IRI and IRG was suppressed by infusion of somatostatin (0.2 microgram/kg/min), while peripheral concentrations were maintained constant by replacing glucagon (0.65 ng/kg/min) and insulin (0.225 mU/kg/min). Steady-state baseline plasma IRI, IRG, glucose and glucose turnover rates were similar to Study A; hyperinsulinemia was then induced as in Study A. Glucose fell by 0.78 +/- 0.19 mg/dl/min over 30 min and, as in Study A, Ra decreased transiently, but recovered to baseline by 30 min. The restoration of Ra occurred in study B despite constant IRG, and preceded later increments in cortisol and catecholamines at 60-90 min. Thus, in both studies A and B, Ra recovered to baseline without an increase in IRG and before the onset of significant hypoglycemia (glucose 83 +/- 1 and 70 +/- 1 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Orally administered liposome-entrapped insulin in diabetic animals. A critical assessment.

We investigated the effects of liposome-entrapped insulin (LEI) administered orally one-half to one-tenth of previously reported doses, on plasma glucose and insulin in the spontaneously diabetic BB Wistar rat and in alloxan-induced diabetic rabbits. Incorporation of insulin within the liposome fraction ranged from 15 to 23%. Radioimmunoassay of Triton X-100 treated LEI yielded insulin values in high agreement (82 +/- 10%) with those predicted based on estimated incorporation. Whereas insulin alone, or liposomes devoid of insulin had no effect, LEI 5 U/kg significantly reduced glucose and raised insulin in 54% of rats (13 of 24) and 67% of the rabbits (6 of 9). Among the rats that responded, blood glucose fell from a basal of 318 +/- 21 mg/dl to a nadir of 186 +/- 22 mg/dl at 2 h (p less than 0.001); values at 1, 2 and 4 h were all significantly less (58-69%) than basal. Similarly, glucose declined significantly for 3 h post LEI in the rabbits while IRI rose from 30 +/- 7 micro U/ml to a peak of 399 +/- 75 micro U/ml at 1 h (p less than 0.001); values at 2 and 3 h remained significantly elevated. Some batches of LEI failed to reduce glucose despite apparently adequate incorporation, while even with effective batches some animals failed to respond. Thus, although orally administered LEI can be effective, their stability and effectiveness are not completely predictable.

Administration, Oral↗

PubMedDate not supplied

Assessment of the effect of a comprehensive diabetes management program on hospital admission rates of children with diabetes mellitus.

Admission records at Children's Hospital Medical Center in Cincinnati were reviewed to determine the impact of a comprehensive diabetes management program on selected indicators of health status in children with diabetes mellitus. Two periods were compared: January 1973 through June 1978 (period A), prior to institution of the program, and July 1978 through December 1987 (period B). Although the number of children admitted with a diagnosis of type I diabetes not associated with DKA or other diagnoses increased by 10% during these 10 years, the number of children with diabetic ketoacidosis (DKA) not associated with other diagnoses fell from 58% in period A to 24% in period B. Similarly, average length of stay for the reported DKA admissions decreased from a mean of 5.84 days in period A to a mean of 4.62 days in period B. This reduction of 1.2 days saved an estimated $342,000 in hospitalization costs. These findings suggest that a comprehensive diabetes management program consisting of medical treatment, education, and psychological support services, has a positive influence on patient outcome and can be cost effective.

Adolescent↗

PubMedDate not supplied

Effects of exercise training on insulin sensitivity in adolescents with type I diabetes.

We investigated the influence of a program of exercise training consisting of three weekly sessions, each 45 min long, for 12 wk, on indices of physical fitness, glycemic control, and insulin sensitivity in nine adolescents with type I diabetes; six age-matched adolescents with diabetes of equivalent duration served as nonexercised controls. All subjects were instructed not to change dialy insulin dose or caloric intake. In the exercised group, maximal oxygen uptake during graded cycle ergometry to volitional exhaustion increased by 9 +/- 2.7% (P less than 0.01) and lean body mass increased by 4 +/- 1.8% (P less than 0.05). Insulin sensitivity, assessed via the euglycemic clamp technique at insulin infusion rates of 100 mU/M2/min, showed an increase of insulin-mediated glucose disposal from 274 +/- 33 to 338 +/- 28 mg/M2/min, representing an increase in insulin sensitivity of 23 +/- 5% (P less than 0.01). None of these indices changed in the control group. Despite increased insulin sensitivity, glycohemoglobin levels remained at 12 +/- 1% before and after the 12 wk of exercise training, indicating no improvement in overall glycemic control. No increase in hypoglycemic reactions was reported in either group. We conclude that exercise training may be a valuable adjunct in managing type I diabetes providing there is concomitant attention to diet and insulin. Exercise training alone, however, does not improve glycemic control, although it improves physical fitness and insulin sensitivity.

Adolescent↗