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Background: There are no published guidelines for use of real-time continuous glucose monitoring data by a patient; we therefore developed the DirecNet Applied Treatment Algorithm (DATA). The DATA provides algorithms for making diabetes management decisions using glucose values: (i) in real time which include the direction and rate of change of glucose levels, and (ii) retrospectively based on downloaded sensor data., Objective: To evaluate the use and effectiveness of the DATA in children with diabetes using a real-time continuous glucose sensor (the FreeStyle Navigator)., Subjects: Thirty children and adolescents (mean +/- standard deviation age = 11.2 +/- 4.1 yr) receiving insulin pump therapy., Methods: Subjects were instructed on use of the DATA and were asked to download their Navigator weekly to review glucose patterns. An Algorithm Satisfaction Questionnaire was completed at 3, 7, and 13 wk., Results: At 13 wk, all of the subjects and all but one parent thought that the DATA gave good, clear directions for insulin dosing, and thought the guidelines improved their postprandial glucose levels. In responding to alarms, 86% of patients used the DATA at least 50% of the time at 3 wk, and 59% reported doing so at 13 wk. Similar results were seen in using the DATA to adjust premeal bolus doses of insulin., Conclusions: These results show the feasibility of implementing the DATA when real-time continuous glucose monitoring is initiated and support its use in future clinical trials of real-time continuous glucose monitoring.

The Diabetes Control and Complications Trial (DCCT) is a multicenter, randomized clinical trial studying the effects of two different diabetes regimens on the development and progression of early vascular complications in persons with insulin-dependent diabetes mellitus (IDDM). All of the centers have a Trial Coordinator. We administered a self-report questionnaire to each center to document the different activities for which the Trial Coordinator assumed responsibility in successfully orchestrating the trial. All Trial Coordinators were responsible primarily for recruitment, screening, medical management, education and training, and adherence and administration. Although documentation indicated that the Trial Coordinator was responsible for all of the above activities, the original applications reflected that very few of the Principal Investigators anticipated such a wide variety of duties. A Trial Coordinator was named in only 13 of the 21 applications and of these, only 6 actually assumed the position. This study points out the need to develop a means to define characteristics, background, and training appropriate for candidates for a Trial Coordinator position in future studies.

To examine the effects of prolonged infusions of somatostatin in maturity-onset diabetes, we administered five-hour infusions to eight patients. This infusion resulted in a 45 to 55 per cent decline in plasma insulin and glucagon. Plasma glucose initially fell by 20 to 25 mg per 100 ml, but later rose despite continuing hypoglucagonemia. After five hours, plasma glucose concentration was 40 to 50 mg per 100 ml higher than that observed with saline infusion (P less than 0.001). The degree of hyperglycemia and plasma insulin levels correlated inversely at completion of the infusion (P less than 0.01). In addition, somatostatin resulted in a fivefold increase in beta-hydroxybutyrate and a 40 to 45 per cent rise in branched-chain amino acids (P less than 0.005). Our findings suggest that glucagon is not essential for the development and maintenance of fasting hyperglycemia. Furthermore, accentuation by somatostatin of hyperglycemia, hyperketonemia and hyperaminoacidemia in maturity-onset diabetes argues against its use in patients with residual insulin secretion.

We examined whether changes in somatomedin accompany those seen in glucose and growth hormone during treatment with the insulin-infusion pump. somatomedin levels in eight insulin-dependent diabetics (13 to 29 years of age) were measured before and after 16 weeks of outpatient insulin-pump treatment, which lowered mean glucose from 245 +/- 21 to 100 +/- 5 mg per deciliter and total glycosylated hemoglobin from 16.2 +/- 1.2 to 9.7 +/- 0.3 per cent (mean +/- S.E.M.). During conventional insulin therapy, both total somatomedin and somatomedin C were within the normal range, despite elevations in growth hormone. Pump treatment resulted in a 70 to 75 per cent increase in both total somatomedin and somatomedin C (P less than 0.05) and a fall in growth-hormone concentrations. In the two growing adolescents, growth velocity doubled during 13 to 15 months of pump treatment. Our data suggest that the improved insulin delivery or metabolic control increases somatomedin levels despite a decrease in growth hormone. Thus, insulin-pump treatment may be useful in optimizing growth in diabetic children.

Although the benefits of metabolic intervention on the microvascular complications of diabetes mellitus remain unproven, it is generally assumed though not proven that prognosis in terms of blindness and renal failure will reflect the long-term glycemic response to therapy. Treatment goals however remain poorly defined. Costs and hazards of achieving near-normoglycemia in insulin-dependent diabetes mellitus (IDDM) are major. A multicenter trial was proposed to test the hypothesis that in IDDM two levels of mean glycemia, sufficiently separated to examine the control/complications relationship, could be maintained by the six collaborating centers, using randomized patient allocation to conventional insulin therapy (CIT) and continuous subcutaneous insulin infusion (CSII) as the alternative treatment modalities. Methods of maintaining and monitoring metabolic control and of assessing renal and retinal responses were to be applied, evaluated, and possibly improved. All clinics shared a common experimental protocol, which received ethical approval at each treatment center. Retinal assessment facilities were provided by the Fundus Photograph Reading Center at the University of Wisconsin in Madison, and at the Diabetic Retinopathy Department, Royal Postgraduate Medical School, Hammersmith, United Kingdom. The Central Biochemistry Laboratory was at the University of Newcastle, United Kingdom. Collaborators agreed on policy for recruitment, baseline assessment, and randomization of patients with IDDM, complicated by early microvascular disease. CIT took the form of the unchanged prestudy regimen; glycemic goals were set for CSII and their achievement based on inpatient and outpatient sampling of plasma glucose. Glycosylated hemoglobin was measured, retinal abnormalities recorded photographically, and urinary albumin excretion quantitated at baseline, 4, and 8 mo in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine the role of basal insulin and glucagon secretion in potassium and sodium homeostasis, somatostatin, a potent inhibitor of insulin and glucagon secretion, was infused for 5 h into healthy human subjects, maturity-onset diabetes, juvenile-onset diabetics, and normal dogs. Infusion of somatostatin resulted in an increase in serum potassium (0.5-0.6 meq/liter) in normal subjects and maturity-onset diabetics, but not in juvenile-onset diabetics despite equivalent reductions in plasma glucagon in all three groups. A similar rise in serum potassium was observed in normal conscious dogs given somatostatin and was reversed by insulin replacement. Urinary excretion of potassium was unaffected by somatostatin. In dogs given intravenous potassium chloride in doses (0.375 meq/kg per h) which do not alter basal insulin levels, the rise in serum potassium (0.6 meq/liter in controls) increased 100% when somatostatin was administered together with the KCl infusion. Addition of replacement doses of insulin to the somatostatin infusion resulted in increments in serum potassium which were comparable to infusion of KCl alone. Urinary potassium excretion rose after KCl administration and was unchanged by the addition of somatostatin. Serum sodium concentration was unaffected by somatostatin administration in both the human and dog studies. However, urinary sodium excretion displayed a biphasic response falling by 20-60% within the first 2 h of somatostatin administration and then rising to values 50-80% above basal levels at 3-4 h. Inulin and p-aminohippurate clearances were unaffected by somatostatin. It is concluded that (a) potassium homeostasis is influenced by basal insulin levels in the absence of which serum potassium concentration rises and potassium tolerance declines; (b) this effect of insulin is mediated via extrarenal mechanisms of potassium disposal; (c) somatostatin has a biphasic effect on urinary sodium secretion, the mechanism of which remains to be established.

Determination of glycemic differences between groups treated with continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) was central to the major objective of the study. Assessment of glycemia was based on 24-h inhospital profiles of plasma glucose; pre- and postprandial and bedtime (seven time points) diurnal profiles performed monthly on outpatient samples; and glycosylated hemoglobin (HbA1) measured bimonthly at each center. The correlation between plasma glucose determinations in the central laboratory and in local laboratories was 0.988. Significance of differences between treatments was by analysis of variance and least-squares regression. At baseline, mean inhospital plasma glucose and HbA1 concentrations and insulin dosages were identical in the groups randomized to CSII or CIT. A prompt decrement of indices of glycemic control during CSII was observed such that mean decrements sustained over the 8-mo treatment period in home and in hospital plasma glucose profiles and HbA1 relative to values obtained during CIT (P less than 0.0001). The likelihood of CSII-treated patients achieving glycemic indices within the normal range was increased. The standardization of the mean and the M-value calculated from inhospital glucose profiles during CSII and CIT at 4 and 8 mo indicated that there was less plasma glucose fluctuation during CSII. The method of pooling standardized local HbA1 measurements from the six centers appeared to be an adequate substitute for centrally performed HbA1 determinations. Advantages of inhospital plasma glucose measurements in terms of accuracy and ability to obtain nocturnal samples contrasted with the likelihood of increased realism and superior correlation with HbA1 in home-obtained samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral glucose tolerance was examined in five maturity-onset diabetics during the infusion of somatostatin or saline. Somatostatin inhibited glucose-stimulated insulin release and reduced plasma glucagon by 50%--65%. The rise in plasma glucose after glucose ingestion was initially (at 30--120 min) reduced by somatostatin. However, beyond 3 hr, plasma glucose levels were 50--200 mg/100 ml higher, with somatostatin reaching concentrations at 6 hr that were twofold higher than those observed with saline ( p less than 0.005). The degree of late glucose intolerance was inversely related to postglucose plasma insulin concentrations (p less than 0.01). These findings demonstrate a biphasic effect of somatostatin on oral glucose tolerance in maturity-onset diabetes. The exaggerated later hyperglycemia is related to suppression of insulin secretion. The initial blunting of postprandial hyperglycemia may reflect decreased carbohydrate absorption and/or hypoglucagonemia-mediated enhancement of glucose disposal.

To determine whether abnormalities of lipid and aminoacid metabolism observed in diabetes are corrected when plasma-glucose levels are restored to normal, eight insulin-dependent diabetics were treated for 7-14 days with a portable infusion pump which delivers insulin subcutaneously in basal (between-meal) doses with pulse-dose increments before meals. Mean plasma-glucose (206 +/- 24 mg/dl during conventional insulin treatment) fell to 89 +/- 3 mg/dl at day 7 and 84 +/- 2 mg/dl at day 14 of pump treatment; glycosuria was eliminated. Plasma cholesterol, triglycerides, and free fatty acids were elevated during conventional insulin treatment but fell to normal after 7 days of pump treatment. Plasma-levels of branched-chain aminoacids were 50-60% above control levels during conventional treatment but fell to normal after 7 days of pump therapy. Aminoacids were reduced from their high postprandial levels to normal values after insulin-pump treatment. In addition to restoring plasma-glucose to normal, treatment of diabetes with a portable insulin-infusion system results in restoration of normal lipid and aminoacid metabolism. Long-term use of this system may determine whether metabolic changes resulting from insulin lack cause the complications of diabetes.