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

Although the scientific literature contains numerous reports of the statistical accuracy of systems for self-monitoring of blood glucose (SMBG), most of these studies determine accuracy in ways that may not be clinically useful. We have developed an error grid analysis (EGA), which describes the clinical accuracy of SMBG systems over the entire range of blood glucose values, taking into account 1) the absolute value of the system-generated glucose value, 2) the absolute value of the reference blood glucose value, 3) the relative difference between these two values, and 4) the clinical significance of this difference. The EGA of accuracy of five different reflectance meters (Eyetone, Dextrometer, Glucometer I, Glucometer II, Memory Glucometer II), a visually interpretable glucose reagent strip (Glucostix), and filter-paper spot glucose determinations is presented. In addition, reanalyses of a laboratory comparison of three reflectance meters (Accucheck II, Glucometer II, Glucoscan 9000) and of two previously published studies comparing the accuracy of five different reflectance meters with EGA is described. EGA provides the practitioner and the researcher with a clinically meaningful method for evaluating the accuracy of blood glucose values generated with various monitoring systems and for analyzing the clinical implications of previously published data.

Evaluating Clinical Accuracy of Systems for Self-Monitoring of Blood Glucose

Glucose monitoring technology has been used in the management of diabetes for three decades. Traditional devices use enzymatic methods to measure glucose concentration and provide point sample information. More recently continuous glucose monitoring devices have become available providing more detailed data on glucose excursions. In future applications the continuous glucose sensor may become a critical component of the closed loop insulin delivery system and, as such, must be selective, rapid, predictable and acceptable for continuous patient use. Many potential sensing modalities are being pursued including optical and transdermal techniques. This review aims to summarize existing technology, the methods for assessing glucose sensing devices and provide an overview of emergent sensing modalities.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1464-5491.2008.02642.x

Glucose sensors: a review of current and emerging technology

We studied the relation in Pima Indians between obesity in children and diabetes during pregnancy in their mothers. Sixty-eight children of 49 women who had had diabetes during pregnancy had a higher prevalence of obesity than 541 children of 134 women who subsequently had diabetes (prediabetics) or than 1326 children of 446 women who remained nondiabetic. At 15 to 19 years of age, 58 per cent of the offspring of diabetics weighed 140 per cent or more of their desirable weight, as compared with 17 per cent of the offspring of nondiabetics and 25 per cent of those of prediabetics (P<0.001). Obesity in the offspring was directly related to maternal diabetes, since the association was not substantially confounded by maternal obesity. The findings strongly suggest that the prenatal environment of the offspring of diabetic women results in the development of obesity in childhood and early adulthood. (N Engl J Med. 1983; 308: 242–5.)

Excessive Obesity in Offspring of Pima Indian Women with Diabetes during Pregnancy

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.

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

Home blood glucose monitoring, using Dextrostix and an Eyetone meter, has been utilized in several subcategories of patients with insulin-dependent diabetes mellitus. These include pregnant patients, anephric patients, patients undergoing weight reduction, patients with altered renal threshold for glucose reabsorption, and patients in whom diabetic regulation is difficult. Patients monitored home blood glucose continually (on a daily basis), intermittently, or only for particular problems or symptoms. Such monitoring can be practically accomplished in a manner acceptable to patients. Motivation, compliance with protocol, and an understanding of the objectives of the program are essential on the part of the patient. Home blood glucose monitoring, however, can provide an insight diabetes regulation that cannot be attained in any other way and can greatly facilitate regulation of diabetes. Such home blood glucose monitoring may increase the likelihood of achievement of a degree of control approximating euglycemia.

Home Blood Glucose Monitoring As an Aid in Diabetes Management

Pregnant diabetic women represent a unique category of patient in whom diabetic control is most desirable, since even minor degrees of hyperglycemia have adverse effects on the conceptus. In 18 insulin-dependent pregnant diabetic women (White Class B, N = 4; C, N = 5; D, N = 7; and R, N =2), we have utilized a therapeutic program consisting of intensive patient education, a multiple-component insulin regimen (two to four injections daily), careful dietary control, and meticulous balancing of food, activity, and insulin dosage, monitoring such balance with patient-determined blood glucose measurements four to seven times daily using the Dextrostix/Eyetone system. Our goals for blood glucose management have been to attain fasting levels of 60-90 mg/dl, preprandial levels less than 105 mg/dl, and postprandial levels less than 120 mg/dl, in the absence of significant hypoglycemia. We have been able to attain these goals for most of the period of monitoring in the majority of these patients, while in the others we have achieved marked improvement in diabetic control, although we did not consistently attain our goals. Despite this, there was not infrequent neonatal morbidity, including a 33% frequency of macrosomia, an 11% frequency of significant hypoglycemia, and a 22% frequency of congenital malformation. Nevertheless, all infants survived and are generally healthy, whereas only 38% of 21 previous pregnancies in these same women have eventuated in living offspring. Thus, although further refinement is clearly indicated, it appears that our approach has resulted in improved pregnancy outcome. Patient self-monitoring of blood glucose is a procedure that is relatively simple, practical, acceptable to patients, and facilitates the attainment of glycemic control.

Blood Glucose Control During Pregnancy

Our objectives of management of diabetes are enumerated in Table 1. Success in achieving these objectives requires active patient involvement on a daily basis. The management scheme entails balancing of food intake, serving as an energy source, with energy expenditure in daily activity and with an insulin dose designed to achieve efficient energy utilization while avoiding the extremes of either hyperglycemia or hypoglycemia (Figure 1). Treatment, then, involves the balancing of these three components—food intake, activity, and insulin dosage — in order to attain euglycemia or as close to euglycemia as is possible in any given patient. The patient monitors this balance by preprandial urine glucose measurements augmented by urine ketone measurements and recognition of clinical cues,\" particularly those of hypoglycemia. It is recognized that these methods of monitoring treatment are, at best, approximations. Nevertheless, they do generally reflect treatment balance and can be successfully used by well-educated patients. In order to maintain balance between food, activity, and insulin, it is necessary to respond to alterations in one component by a modification of at least one other component. Since this involves all food intake and all daily activity, the patient must be able to make alterations in his/her treatment regimen whenever appropriate. This article outlines our approach in instructing patients in making modifications in their diabetes management, particularly in their insulin regimens.

Instructing patients in making alterations in insulin dosage.

https://care.diabetesjournals.org/content/diacare/1/1/68.2.full.pdf

Denise L Skyler

Papers

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

Home Blood Glucose Monitoring As an Aid in Diabetes Management

Blood Glucose Control During Pregnancy

Instructing patients in making alterations in insulin dosage.

Urine testing, 1978.