An infusion system for infusing a liquid into a body includes an external infusion device and a remote commander. The external infusion device includes a housing, a receiver, a processor and an indication device. The receiver is coupled to the housing and for receiving remotely generated commands. The processor is coupled to the housing and the receiver to receive remotely generated commands and to control the external infusion device in accordance with the commands. The indication device indicates when a command has been received and indicates when the command is being utilized to control the external infusion device so that the external infusion device is capable of being concealed from view when being remotely commanded. The remote commander includes a commander housing, a keypad for transmitting commands, and a transmitter for transmitting commands to the receiver of the external infusion device.

External infusion device with remote programming, bolus estimator and/or vibration alarm capabilities

OBJECTIVE —To conduct a meta-analysis of the metabolic and psychosocial impact of continuous subcutaneous insulin infusion (CSII) therapy on adults, adolescents, and children. RESEARCH DESIGN AND METHODS —Studies were identified and data regarding study design, year of publication, sample size, patient’s age, diabetes duration, and duration of CSII therapy were collected. Means and SDs for glycohemoglobin, blood glucose, insulin dosages, and body weight for CSII and comparison conditions were subjected to meta - analytic procedures. Data regarding pump complications and psychosocial functioning were reviewed descriptively. RESULTS —A total of 52 studies, consisting of 1,547 patients, were included in the meta-analysis. Results indicate that CSII therapy is associated with significant improvements in glycemic control (decreased glycohemoglobin and mean blood glucose). A descriptive review of potential complications of CSII use (e.g., hypoglycemia, diabetic ketoacidosis [DKA], pump malfunction, and site infections) suggests a decreased frequency of hypoglycemic episodes but an increased frequency of DKA in studies published before 1993. CONCLUSIONS —CSII therapy is associated with improved glycemic control compared with traditional insulin therapies (conventional therapy and multiple daily injections) and does not appear to be associated with significant adverse outcomes. Additional studies are needed to further examine the relative risks of CSII therapy, including the potential psychosocial impact of this technologically advanced therapy.

https://care.diabetesjournals.org/content/diacare/26/4/1079.full.pdf

Insulin Pump Therapy: A meta-analysis

ContextNewer insulin therapies, including the concept of physiologic basal-prandial
insulin and the availability of insulin analogues, are changing clinical diabetes
care. The key to effective insulin therapy is an understanding of principles
that, when implemented, can result in improved diabetes control.ObjectiveTo systematically review the literature regarding insulin use in patients
with type 1 and type 2 diabetes mellitus (DM).Data SourcesA MEDLINE search was performed to identify all English-language articles
of randomized controlled trials involving insulin use in adults with type
1 or type 2 DM from January 1, 1980, to January 8, 2003. Bibliographies and
experts were used to identify additional studies.Study Selection and Data ExtractionStudies were included (199 for type 1 DM and 144 for type 2 DM, and
38 from other sources) if they involved human insulins or insulin analogues,
were at least 4 weeks long with at least 10 patients in each group, and glycemic
control and hypoglycemia were reported. Studies of insulin-oral combination
were similarly selected.Data SynthesisTwenty-eight studies for type 1 DM, 18 for type 2 DM, and 48 for insulin-oral
combination met the selection criteria. In patients with type 1 DM, physiologic
replacement, with bedtime basal insulin and a mealtime rapid-acting insulin
analogue, results in fewer episodes of hypoglycemia than conventional regimens.
Rapid-acting insulin analogues are preferred over regular insulin in patients
with type 1 DM since they improve HbA1C and reduce episodes of
hypoglycemia. In patients with type 2 DM, adding bedtime neutral protamine
Hagedorn (isophane) insulin to oral therapy significantly improves glycemic
control, especially when started early in the course of disease. Bedtime use
of insulin glargine results in fewer episodes of nighttime hypoglycemia than
neutral protamine Hagedorn regimens. For patients with more severe insulin
deficiency, a physiologic insulin regimen should allow lower glycemic targets
in the majority of patients. Adverse events associated with insulin therapy
include hypoglycemia, weight gain, and worsening diabetic retinopathy if hemoglobin
A1C levels decrease rapidly.ConclusionsMany options for insulin therapy are now available. Physiologic insulin
therapy with insulin analogues is now relatively simple to use and is associated
with fewer episodes of hypoglycemia.

https://jamanetwork.com/journals/jama/articlepdf/196498/JSR20024.pdf

Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review.

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS)

Monomeric insulins and their experimental and clinical implications.

Type 1 diabetes is a metabolic disorder resulting from a defect in insulin secretion. Onset of type 1 diabetes mellitus may occur at any age and it is one of the most common chronic diseases of childhood and adolescence. Since there are no interventions known to prevent onset, it is vital that effective treatment regimes are available. Glycaemic control is maintained by replacement of insulin and may be in the form of 'conventional' insulin therapy (multiple injections per day) or continuous subcutaneous insulin infusion (CSII).
 
The objective of this review is to assess the effects of CSII compared to multiple insulin injections (MI) in people with type 1 diabetes mellitus.

Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus

Patient self-monitoring of blood glucose is a useful adjuvant to diabetes therapy that facilitates improved glycemic control when used as part of an intensive diabetes management program that includes careful balancing of food intake, energy expenditure, and insulin dosage. This paper describes an approach by which patient-determined blood glucose measurements may be used to attain and maintain glycemic control. The patient is provided with a set of algorithms by which minor adjustments in a therapeutic routine may be made to achieve the desired control.

Algorithms for Adjustment of Insulin Dosage by Patients Who Monitor Blood Glucose

Glycemic control in insulin-dependent diabetes mellitus. Comparison of outpatient intensified conventional therapy with continuous subcutaneous insulin infusion.

The use of portable devices for the subcutaneous infusion of insulin may facilitate the attainment of improved glycemic control in selected patients with insulin-dependent diabetes mellitus. Successful use of a program of continuous subcutaneous insulin infusion requires patient cooperation and motivation, routine monitoring of glycemia, and attention to food intake and activity. This article describes an approach by which patients may optimize glycemic control utilizing a set of algorithms based on patientdetermined blood glucose measurements. The algorithms permit programing the insulin infusion device
to achieve the desired control.

Optimizing Pumped Insulin Delivery

We studied the psychological effects of a program of intensification of glycemic control, using three different insulin regimens: (1) twice-daily regular and lente insulin; (2) multiple preprandial doses of regular insulin coupled with long-acting ultralente insulin; and (3) continuous subcutaneous insulin infusion (CSII). Ten patients used each of the regimens for periods of 2 mo. Patients monitored blood glucose 4-7 times daily. Using the Hopkins Symptom Checklist, there were significant reductions in depression, interpersonal sensitivity, and anxiety during all three treatment programs. Self-concept scores were more positive following CSII therapy. Positive self-concept ratings were correlated with positive attitudes about diabetes, medical care, persons with diabetes, and current diabetes regimens. After all subjects had experienced CSII, self-concept was positively related to attitudes regarding the insulin pump. Patients reporting more positive attitudes toward their current diabetes regimens had lower glycosylated hemoglobin levels. Thus, there were no adverse psychological effects of blood glucose monitoring, intensification of therapy, or use of infusion pumps by the parameters measured.

D. E. Seigler

Papers

Algorithms for Adjustment of Insulin Dosage by Patients Who Monitor Blood Glucose

Glycemic control in insulin-dependent diabetes mellitus. Comparison of outpatient intensified conventional therapy with continuous subcutaneous insulin infusion.

Optimizing Pumped Insulin Delivery

Psychological effects of intensification of diabetic control.

Medial plantar sensory response: Sensitive indicator of peripheral nerve dysfunction in patients with diabetes mellitus