Showing papers in "Diabetes Care in 1982"

Affinity sensor: A new technique for developing implantable sensors for glucose and other metabolites

Abstract: We describe affinity sensors for monitoring various metabolites in blood plasma by optical means. The principle of detection is similar to that used in radioimmunoassays and is based on the competitive binding of a particular metabolite and a fluorescein-labeled analogue with receptor sites specific for the metabolite and the labeled ligand. This concept has been directed toward the development of an affinity sensor for glucose. Concanavalin A, a protein with specific binding character for glucose, was immobilized on the inside surface of a hollow dialysis fiber. Fluorescein-labeled dextran was selected as the competitive labeled ligand. The molecular weight cutoff of the dialysis fiber is low enough to completely retain the 70,000 MW dextran within the fiber lumen while glucose can freely pass through the dialysis membrane. The sensor is completed by inserting a single optical fiber in the lumen of the dialysis fiber, thus allowing measurement of the unbound FITC-dextran. Preliminary tests of the sensor indicated the feasibility of the approach. Sensitivity to glucose in the physiologic range was obtained, but further work will be required to optimize the sensitivity and response time of the sensor.

Absorption Kinetics and Biologic Effects of Subcutaneously Injected Insulin Preparations

Abstract: This paper describes systematic studies on the absorption kinetics of exogenous insulin from its subcutaneous tissue depot in 52 male nonobese volunteers (age 20-30 yr). Five experimental protocols were used: effect of changing injection site, effect of temperature change and local massage, effect of aprotinin and human serum, effect of mixing regular insulin with long-acting insulin preparations, and effect of temperature change, muscular exercise, and local massage on the absorption of long-acting insulin preparations. The fastest absorption of insulin occurred at the abdominal injection. Absorption after arm injection was faster than after thigh injection. A hot bath and local massage dramatically increased serum insulin levels in the first 90 min after injection; in contrast, a cold bath delayed absorption substantially. Both aprotinin and the subjects' own blood serum mixed with insulin caused a marked acceleration of the insulin absorption process. Absorption kinetics of two neutral regular insulins (Actrapid and Leo Regular) were virtually identical. Mixing Actrapid with Monotard caused higher serum insulin levels than the mixture of Leo Regular with NPH. A time lag of 5 min between the mixing of Actrapid and Monotard and the injection caused a delayed rise of serum insulin levels; in contrast, this delay could not be observed when Leo Regular and NPH were mixed. Volunteers performed bicycle exercise, applied a hot water bottle to the injection site, or rubbed the injection site 2 1/2 h after injection of long-acting insulin. Accelerated absorption of insulin was only observed after local massage of the injection site of Monotard, Leo NPH, and Mixtard. Local heat had no effect. Exercise caused only an increased absorption of insulin after the Mixtard injection but not after Monotard or NPH injection. These findings have clinical significance and should not be without potential benefit in the attempt to improve metabolic control in insulin-treated diabetic patients.

Insulin treatment reverses the insulin resistance of type II diabetes mellitus.

Abstract: Type II diabetic subjects are both insulin-deficient and insulin-resistant. Recent studies suggest that the insulin resistance is due to a combined receptor and postreceptor defect with the postreceptor defect being the predominant lesion. In the present study, we examined the effects of exogenous insulin therapy upon these defects in insulin action in six untreated type II diabetic subjects. Glycemic control and adipocyte insulin binding were measured and in vivo insulin dose-response curves for overall glucose disposal and suppression of hepatic glucose output were constructed before treatment. Following these initial studies, the diabetic subjects were treated with twice-daily injections of regular and NPH purified pork insulin for 14 days and the pretreatment studies repeated. Glycemic control was significantly improved by this treatment regimen. The mean fasting serum glucose level (±SE) fell from 287 ± 20 to 125 ± 13 mg/dl, the mean glycosylated hemoglobin level (± SE) decreased from 14.2 ± 1.1% to 8.3 ± 0.5%, and the mean 24-h urinary glucose excretion (±SE) declined from 65.6 ± 40.3 to 0.6 ± 0. 1 g/24 h. Adipocyte insulin binding did not change significantly during the treatment period. In contrast, the 14-day period of insulin treatment produced a 72% increase (P 2 /min compared with 187 ± 32 mg/M 2 /min before treatment, indicating that the postreceptor defect in insulin action was significantly ameliorated by insulin treatment. The dose-response curve for insulin-mediated suppression of hepatic glucose output was rightshifted, consistent with the decrease in insulin binding, with no decrease in the maximal effect before treatment and not significantly changed following insulin treatment. In conclusion, the postreceptor defect in insulin-stimulated glucose disposal is largely ameliorated by exogenous insulin treatment, suggesting that this defect in insulin action is an acquired abnormality which is secondary to some aspect of the insulin-deficient state.

Noninvasive Glucose Monitoring of the Aqueous Humor of the Eye: Part I. Measurement of Very Small Optical Rotations

Abstract: We have described the concept of using the aqueous humor glucose as a measure of the blood glucose concentration, with a view to developing a noninvasive glucose monitor for diabetic individuals. We have conceived of a scleral lens that houses a light source, polarizers, other electro-optic units, and a light detector, and which measures the optical rotation of the aqueous humor continuously. We have built an optical bench mock-up of the glucose sensor and assessed the limits of its capabilities. We have described a physical method, employing the Faraday effect, that modulates the incident light and uses a compensator to introduce a feedback mechanism giving a null-point technique capable of measuring extremely small rotations with an accuracy of 0.4 s of arc. We have used this and have measured the optical rotations of glucose solutions from 0.02 to 0.1%, and have demonstrated linearity in both cases. Miniaturization of the technique is discussed.

Continuous Subcutaneous Insulin Infusion in the Management of Painful Diabetic Neuropathy

Abstract: Nine patients with diabetic neuropathy were treated as outpatients with continuous subcutaneous insulin infusion (CSII). Painful symptoms were scored on a 10-cm horizontal graphic rating scale; motor conduction velocity (MCV) was measured in the median and peroneal nerves; and vibration perception threshold (VPT) was recorded in the great toes. All investigations were repeated after 6 wk and at the completion of 4 mo of CSII. Improved diabetic control was confirmed by significantly lower mean blood glucose levels, M-values, and glycosylated hemoglobin. Symptomatic relief was noted by all patients and was accompanied by a significant improvement in pain scores. There was also significant improvement in VPT and MCV after 6 wk of CSII, which was maintained throughout the 4-mo period. However, sensory studies in the median nerve showed no significant changes during the study. It is concluded that strict glucoregulation is indicated in all cases of symptomatic diabetic neuropathy. It remains to be seen whether strict diabetic control from diagnosis will lead to a reduction in the incidence of this complication.

Multiple daily self-glucose monitoring: its essential role in long-term glucose control in insulin-dependent diabetic patients treated with pump and multiple subcutaneous injections.

Abstract: Twenty-one insulin-dependent diabetic patients, previously treated with continuous subcutaneous insulin infusion (CSII), multiple subcutaneous insulin injections (MSI), and a combination of CSII and MSI (combined CSII-MSI) all supported by frequent capillary self-blood glucose (CBG) determinations (5-7 times daily) participated in a program to assess the importance of frequent CBG monitoring. We used a crossover design where diabetic control as measured by mean blood glucose and glycosylated hemoglobin were compared during periods of frequent and infrequent capillary blood glucose monitoring. Diabetic control was significantly better during periods of frequent self-glucose monitoring. We conclude that in compliant, motivated young adults with insulin-dependent diabetes, frequent self-glucose monitoring is critical for the long-term maintenance of glycemic control.

Noninvasive Glucose Monitoring of the Aqueous Humor of the Eye: Part II. Animal Studies and the Scleral Lens

Abstract: We have discussed the nature of a scleral lens that will allow us to follow changes in aqueous humor glucose levels in animals by a method based on optical rotation and a technique described in an earlier paper We have shown how this lens can be micro-miniaturized and can be used in humans as a non-in-vasive glucose monitor We have described preliminary experiments designed to show the correlation between the blood glucose assay (BGA) and the aqueous humor glucose concentration as determined by chemical assay (AGA) and by optical rotation determination (ARD) The last mentioned has been obtained by paracentesis directly into a microcell used in conjunction with instrumentation capable of measuring optical rotations as low as 00013° (45″) corresponding to 20 mg/dl glucose with a sensitivity of 00001° (036″) The variability among normal rabbits as a function of individuality and diurnal changes is described, and the correlation beteen AGA and ARD shown to be essentially 10 Such rabbits are examined when undergoing very rapid decreases in BGA (insulin treatment) or very rapid increases in BGA (bolus of glucose) The AGA and ARD are shown to lag behind the BGA, and this is discussed in terms of the rate of change of BGA with respect to time and its concomitant change in AGA/ARD as well as a simple procedure that would materially reduce this lag

How Fibroblasts and Giant Cells Encapsulate Implants: Considerations in Design of Glucose Sensors

Abstract: Implanted sensors ideally should measure glucose in an extracellular fluid that closely reflects changing concentrations of glucose in plasma; yet fibroblasts, fibrocytes, collagen, and giant cells provide adherent, impermeable, avascular barriers when they encapsulate irregularly-surfaced implants. Thus, sensor design should seek to provide a surface configuration that is without anchoring points for encapsulating cells, a consideration not unlike those posed in developing a nonthrombogenic surface. Examples of well-characterized host responses to various surface configurations are provided to illustrate how surface design features can avoid evoking a barrier of collagen as the host response to the sensor.

Long-term improvement of metabolic control with the insulin pump does not reverse diabetic microangiopathy.

Abstract: Restoration of near-normal glucose metabolism with the insulin pump reduces retinal fluorescein leakage and microalbuminuria in diabetes. However, it is not known whether these functional changes reflect a true reversal of diabetic retinopathy or nephropathy. To evaluate this question, we studied the effect of 1-2 yr of insulin pump treatment on clinical endpoints in 17 type I diabetic patients. In each patient, plasma glucose and total glycosylated hemoglobin levels fell to normal or near-normal levels. The total daily dose of insulin given during the first month of pump treatment (52 +/- 5 U/day) was comparable to that given during conventional treatment (44 +/- 3 U/day) and varied little over the 1-2 yr period of observation. Ten eyes without retinopathy at the start of the study remained without retinopathy after 15-23 mo of pump treatment. One of eleven eyes with background retinopathy developed proliferative retinopathy and 3 of 13 eyes with proliferative retinopathy progressed during pump treatment. Similarly, no improvement in renal function was observed in the six patients with diabetic nephropathy on entry to the study. In the first month of pump treatment, proteinuria consistently fell to values 30% below prepump levels (P less than 0.005). However, the diminution in proteinuria was not sustained and all remain proteinuric after 13-18 mo of pump therapy. Serum creatinine rose slightly and creatinine clearance did not significantly change. These data suggest that insulin pump treatment does not reverse established diabetic microvascular complications, despite a sustained improvement in metabolic control for up to 2 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Salicylates as Hypoglycemic Agents

Abstract: Salicylates lower blood sugar and enhance glucose-stimulated insulin secretion in normal and diabetic man. Although the hypoglycemic effect appears to be mediated by enhanced insulin secretion, extrapancreatic mechanisms cannot be excluded. The mechanism of the enhanced insulin secretion appears to be mediated by prostaglandin synthesis inhibition. The effect of salicylates on insulin secretion mediated by other secretagogues is imprecisely known. In addition to their glucose lowering action, salicylates have been reported to lower free fatty acids, triglycerides, and cholesterol. Salicylates have been imprecisely evaluated as hypoglycemic and hypolipidemic agents. Knowledge of their mechanism of action may provide further insight into the pathogenesis of diabetes mellitus and hyperlipidemic states.

Implanting the Glucose Enzyme Electrode: Problems, Progress, and Alternative Solutions

Abstract: An implantable glucose sensor is needed before a reliable artificial pancreas can be realized. The principles and current status of one such device, the glucose enzyme electrode, is presented and discussed. While monitoring glucose this enzyme sensor consumes enough oxygen to become oxygen-limited. This problem has been solved by developing hydrophobic membranes that are more permeable to oxygen than to glucose. Two types of membranes with this property made from (1) cross-linked albumin and (2) sebacyl chloride (nylon) are described. Placing these membranes over the glucose enzyme electrode solves the problem of oxygen limitation. Furthermore, the addition of this type of membrane increases the linear response range of the electrode to glucose to include the entire clinical range of interest (0-400 mg/dl). Other problems in developing an implantable glucose sensor are discussed. Competing strategies to achieve an implantable artificial pancreas without using electronic or mechanical components are presented and evaluated.

Lente Carbohydrate: A Newer Approach to the Dietary Management of Diabetes

Abstract: The dietary fiber hypothesis has stimulated interest in the possibility that the glycemic response to carbohydrate foods may be reduced by modifying gastrointestinal events to produce sustained-release or “lente” carbohydrate. Associated with this interest, a new branch of pharmacology has been developed involving the use of purified fiber preparations and enzyme inhibitors. These measures, together with the selection of diets containing foods that naturally release their carbohydrate products of digestion slowly, may contribute a useful facet to diabetic management in the future.

A Miniature Glucose Sensor, Implantable in the Blood Stream

Abstract: We have developed a miniature glucose sensor using an oxygen electrode with a glucose oxidase membrane. The special character of this sensor is that the electrodes can be placed in a blood vessel and can measure the glucose level directly from the arterial blood stream if placed into an external A-V shunt. Its second notable characteristic is that the enzyme membrane is covered with a semipermeable membrane, which partially allows passage of glucose but only sufficient oxygen. This sensor is able to respond to glucose concentrations of up to 700 mg/dl in blood. This sensor loses 10% of its activity at about 200 h of continuous use, and 30% after 400 h of use. While the sensor cannot be sterilized by conventional mechanical or gas methods, certain antibiotics can be used for sterilization. To shorten the response delay of the sensor during the decreasing phase of glucose concentration, a thinner membrane is under development.

The Role of Behavior in Diabetes Care

Abstract: The treatment of people with diabetes mellitus almost always involves an effort on the part of the health-care team to impose new patterns of behavior on their patients. Too often this behavior modification is undertaken without any specific attention to factors in the treatment regimen that may enhance or detract from patient compliance. If, however, the treatment of disease is viewed in terms of changes in both physiology and behavior, the importance of intervention aimed at either direct behavioral manipulation of physiology, or alterations of secondary behavior related to the disease and its therapy, becomes apparent. We have reviewed in this paper the current “state of the art” of both direct behavioral treatment of diabetes and techniques to enhance compliance with treatment program.

A crossover comparison of continuous subcutaneous insulin infusion (CSII) against multiple insulin injections in insulin-dependent diabetic subjects: improved control with CSII.

Abstract: Ten insulin-dependent C-peptide-negative diabetic subjects, whose control had been optimized on twice-daily injection therapy, were treated for periods of 10 wk in a crossover study, with either a thrice-daily subcutaneous insulin injection regimen (Actrapid + Ultratard) or by continuous subcutaneous insulin infusion (CSII). On CSII insulin dose stabilized at 51 +/- 5 U/day, compared with 80 +/- 9 U/day (P = 0.004) on the thrice-daily injection regimen, having been 60 +/- 6 U/day on twice-daily therapy. After 10 wk glycosylated hemoglobin was 11.7 +/- 0.6% on injection therapy and 10.0 +/- 0.7% (P = 0.026) on CSII. Mean blood glucose concentration and urinary glucose excretion were lower at most points during the study on CSII than on injection therapy. Patients on pumps gained weight compared with the thrice-daily injection regimen (P = 0.023 at 10 wk) and the previous twice-daily regimen, despite the reduction in insulin dose. Considering individual patients, four markedly improved on CSII compared with the previous twice-daily regimen and five compared with Actrapid + Ultratard. No patient showed impaired control on CSII compared with either injection regimen. The benefits of portable insulin infusion pumps over injection therapy are thus clearly demonstrable under outpatient conditions even with equal and intensive medical attention.

Implanted electroenzymatic glucose sensors.

Abstract: The advent of electrochemical sensors for intermittent sampling of blood gases and hydrogen ions in the clinic, intensive care, and surgical units has revolutionized diagnostic and critical care medical technics. The use of electrochemical sensors for continuous transcutaneous monitoring of blood gases is further enhancing the medical surveillance of patients. The more recent introduction of glucose and other electroenzymatic sensors has stimulated broad research in the development of metabolic monitoring. For the present research, the glucose sensor widely used for the rapid specific micro-analysis of whole blood and plasma is explored for possible use as an in vivo intravascular or tissue-implanted sensor. This sensor is based on the polarographic measurement of hydrogen peroxide generated by glucose oxidase (EC 1.1.3.4) held between two membranes. The first membrane allows the diffusion of glucose, ions, and many other small molecules, while the second membrane allows the diffusion of the glucose-generated hydrogen peroxide to the platinum surface, but excludes ascorbic acid, bilirubin, and uric acid. Such sensors respond rapidly and specifically when acutely implanted subcutaneously in cats and dogs. They function well as glucose-sensor-tipped venous catheters. One sensor was repeatedly used for in vitro polarograms, subcutaneous and blood glucose monitoring, over a period of ten months, with storage in the cold between uses, with the complete retention of its response characteristics.

Crisis intervention program in newly diagnosed diabetic children.

Abstract: A group of 223 insulin-dependent diabetic patients, aged 7–24 yr, who had been under the regular care of our clinic up to 15 yr, were rated by two independent judges on a two-level scale of adjustment and maladjustment. The patients were divided into two groups. Group A (N = 107) comprised those who had been under care from diagnosis of the disease and had been subjected to the special crisis intervention program offered to every family upon referral of a newly diagnosed patient. Group B (N = 116) comprised patients who were diagnosed and treated initially in a clinic that had no crisis intervention program. Significant differences between the two groups were found in respect to three of the four aspects studied, i.e., compliance, familial relationships, and sociability, with group A showing a better adjustment than group B. There was no significant difference in the fourth aspect studied, i.e., school achievement and work performance. It was found that it took three times the effort, i.e., the time invested in counseling and psychotherapeutic measures, to bring group B to a good level of adjustment than it did to achieve similar results with group A. It is suggested that the initial period after diagnosis of diabetes in a child should be considered a period of crisis, requiring special muitidisciplinary services to reduce future psychosocial maladjustments and improve compliance.

Adult Respiratory Distress Syndrome Complicating Severely Uncontrolled Diabetes Mellitus: Report of Nine Cases and a Review of the Literature

Abstract: We report the occurrence of the adult respiratory distress syndrome (ARDS) in association with uncontrolled diabetes in nine patients. In reviewing the literature we found nine similar cases reported in little over a decade. In most cases no condition known to precipitate ARDS was discovered. The evidence suggests that the severely uncontrolled diabetic state in some way may initiate pathologic events leading to the capillary leak of ARDS. This description of the association of these two entities not commonly recognized as occurring simultaneously has important clinical implications: the entity should be anticipated in uncontrolled diabetic patients who present with acidosis, hypotension, hypothermia, and/or coma. The clinical or radiologic diagnosis of pneumonia or fluid overload should not be made in the uncontrolled diabetic patient in the absence of unequivocal evidence of infection or congestive heart failure. The development of dyspnea, hypoxemia, rales, or infiltrates in the otherwise routine resuscitation of these patients should lead the clinician to suspect the development of ARDS. Prompt invasive monitoring in these cases is indicated to aid in their management and may help to improve survival. We found calculation of the A-a gradient to be useful in patients with uncontrolled diabetes. Although not necessarily predictive, widened gradients were the earliest detectable abnormality found in all patients who developed ARDS.

Improvement of the plasma lipoprotein pattern after institution of insulin treatment in diabetes mellitus

Abstract: Plasma lipids and lipoproteins were studied in 26 nonobese diabetic patients, either newly diagnosed or unsatisfactorily controlled by oral antidiabetic treatment Measurements were performed before and 3-4 mo after the institution of insulin treatment In a subgroup of seven patients, the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma and the elimination rate of exogenous triglyceride were also monitored After beginning insulin treatment, diabetic control was improved as demonstrated by decreasing levels of HbA1 Mean plasma cholesterol and triglyceride levels decreased by about 10% (P less than 001) and 40% (P less than 005), respectively The decrease in plasma cholesterol was largely accounted for by a fall in LDL cholesterol levels (-8%, P less than 005), while plasma HDL cholesterol concentrations increased by about 12% (P less than 001) The elimination rate of exogenous triglycerides increased significantly There was a suggestive, but not significant, increase in LPL activity while the HL activity remained unchanged It is concluded that the improved diabetic control after institution of insulin treatment results in a significant improvement of the plasma lipoprotein profile Since the improvement of the lipoprotein pattern is not strictly correlated to the amelioration of indices reflecting glucose transport, we suggest that the plasma lipoprotein pattern may provide an additional tool for monitoring the degree of control in diabetes mellitus

Progress toward a potentially implantable, enzyme-based glucose sensor.

Abstract: Our efforts toward the development of a potentially implantable, enzyme-based glucose sensor have concentrated on understanding in sufficient detail the most important component, the enzyme-containing membrane. We describe here some features that this membrane must have to operate as a constituent of a chronically implanted sensor. A model of reaction and diffusion within the membrane is outlined and methods of membrane characterization are reviewed.

Risk factors associated with severe proliferative retinopathy in insulin-dependent diabetes mellitus.

Abstract: The natural history of disease and suspected risk factors for bad prognosis were investigated in 40 subjects with insulin-dependent diabetes mellitus who had severe retinopathy and in 22 patients with a similar duration of diabetes without evidence of complications. The retinopathy group showed a marked excess of men (ratio 2:1). Examination of the data in the literature also showed a striking excess of men, 61% (P

Development of IgE antibodies to human (recombinant DNA), porcine, and bovine insulins in diabetic subjects.

Abstract: Thirty-one previously untreated diabetic individuals received only human insulin (recombinant DNA) for 1 yr with no adverse reactions. The development of serum IgE antibodies to human, porcine, and bovine insulins was assessed by a sepharose radioallergoabsorbent test (RAST). Immunoglobulin (total Ig antibody) binding was assessed by a nonabsorbed species-specific radioimmunoassay. During therapy 2 patients developed IgE antibodies to human insulin as well as increased total Ig binding. The IgE antibodies to human insulin cross-reacted with porcine and bovine insulins, were transient, and were not accompanied by insulin allergy. Ig binding to insulin developed and persisted in 11 of the human insulin-treated diabetics. In comparison, 62 previously untreated diabetic persons received only purified porcine insulin (PPI, less than 5 ppm proinsulin, N = 40) or a mixed bovine-porcine insulin (proinsulin less than 50 ppm, N = 21). Increased Ig antibody developed in 16 of 21 patients receiving mixed bovine-porcine insulin and 25 of 41 PPI-treated patients (P less than 0.05). Seven of 41 PPI-treated patients and 4 of 21 mixed bovine-porcine-treated patients developed anti-insulin IgE antibodies, which were transient in 4 and persisted in 6 diabetic patients. IgE antibody levels did not correlate with total Ig antibody. These data suggest that IgE and total Ig antibodies develop less often after human insulin treatment. Also, the immunoregulation mechanisms responsible for anti-insulin IgE antibody synthesis differ from those regulating other Ig that bind to insulins. Since none of the patients in this study have developed clinical manifestations of insulin allergy or resistance, the clinical relevance of the antibody data must remain speculative.

Response of Non-insulin-dependent Diabetic Patients to an Intensive Program of Diet and Exercise

Abstract: To assess the effectiveness of the Pritikin program of diet and exercise for treating patients with non-insulin-dependent diabetes mellitus (NIDDM), data were obtained from 60 patients who completed the 26-day residential program. Of the 23 patients who were taking oral hypoglycemic agents upon entry, all but 2 were off medication by the end of the program. Of the 17 patients who were taking insulin, all but 4 were off medication at discharge. Two of the four had their insulin reduced by 50% while the remaining two had no major change in their insulin dosage. Fasting blood glucose was reduced from 194.9 +/- 10.1 to 144.6 +/- 7.1 mg/dl. Serum cholesterol was reduced from 225.4 +/- 5.7 to 181.7 +/- 4.9 mg/dl while triglycerides were reduced from 283.7 +/- 28.8 to 186.2 +/- 11.6 mg/dl. The group as a whole lost an average of 4.3 kg/body wt and achieved 40.5% of their desired weight loss. Maximum work capacity increased from 5.6 +/- 0.3 to 7.9 +/- 0.4 METs, while daily walking increased from 11.7 +/- 2.4 to 102.8 +/- 4.8 min/day. The decrease in fasting glucose was not correlated with weight loss (r = 0.24), increase in walking time (r = 0.00), or increase in MET capacity (r = 0.05). We conclude that the total program is an effective means for treating NIDDM patients. We also feel that the high-complex-carbohydrate, high-fiber, low-fat diet is of primary importance.

Quantitative evaluation of sympathetic and parasympathetic control of iris function.

Abstract: The use of quantitative measurements of pupil size as an index of autonomic nervous system (ANS) activity in normal and diabetic subjects is described. The dual innervation of the iris by the parasympathetic (PNS) and sympathetic (SNS) nervous system was demonstrated by measurement of steady-state pupil size before and after changes in ANS activity by pharmacologic agents. In the presence of total PNS blockade, dark-adapted pupil size was a reliable index of SNS activity to the iris. Latency time (time from light stimulation to initial pupil response) appeared to be a good index of PNS activity. However, increased SNS activity may also prolong the latency time. Thus, consideration of SNS activity is necessary when evaluating the latency time. In 25 diabetic subjects, there was evidence of impaired SNS activity (smaller dark-adapted pupil size during total PNS blockade) and PNS activity (prolonged latency time). In a subgroup of diabetic subjects without clinical manifestations of autonomic neuropathy and normal subjects, both dark-adapted pupil size during PNS blockade (SNS index) and latency time (PNS index) were abnormal. The coefficient of variation for these two indices was less than 5% in glycemic stable diabetic subjects. Thus, these two indices are reliable and sensitive measures of the SNS and PNS activity to the iris in normal and diabetic subjects.

Optimal insulin delivery for the pregnant diabetic patient.

Abstract: It is now possible to virtually normalize ambient blood glucose levels in insulin-dependent diabetic women during pregnancy. Successful programs have been developed that utilize home blood glucose monitoring, physiologic delivery of insulin, and quantitation of caloric intake carefully matched to insulin dosage. The results of establishing normoglycemia throughout gestation appear to be a normalization of mortality and morbidity for both infant and mother. Pregnancy provides a need for continuous upward adjustment of insulin dose concomitant with the ongoing fetal and hormonal changes associated with gestation.

Parental Perceptions of the Psychological Adjustment of Children with Diabetes and Their Siblings

Abstract: This study examined the psychological adjustment of children with diabetes and their siblings. Data were collected for 41 diabetic children and their siblings between ages 6 and 11 yr who were followed in a large pediatric practice. The diabetic group was matched with 35 control children who were followed for routine pediatric care and their siblings. Diabetic families and the controls did not differ on divorce rate or level of marital adjustment. Behavior problems were measured through the use of the Achenbach Behavior Checklist for both sexes separately at the 6–11 and 12–16-yr-old age levels. Diabetic boys, aged 6–11 yr, were higher than nondiabetic boys on internalizing and externalizing symptom scales, particularly on measures of schizoid tendencies, obsessive compulsive symptoms, hyperactivity, and aggression. Neither female patients, male siblings, nor female siblings in the 6–11-yr-old age group differed from controls on emotional adjustment. Among the 12–16-yr-old males, diabetic patients were higher on internalizing symptoms than male siblings and their controls. Male siblings tended to be lower than diabetic patients and controls on school performance. Social class differences may have contributed to the differences at the 12–16-yr age levels. Female subjects in the 12–16-yr-old age group did not differ on measures of adjustment. Level of control was unrelated to patients9 or siblings9 adjustment, but behavioral symptoms tended to increase for male diabetic patients with length of illness, and tended to decrease for male siblings. Results are interpreted according to social class effects and sex differences.

Insulin delivery during surgery in the diabetic patient.

Abstract: The usual treatment of diabetic patients during surgery with general anesthesia owes little to logic, common sense, or knowledge of requirements, and mortality and morbidity remain high in many centers. In the nondiabetic patient, surgery is accompanied by a rise in secretion of catabolic hormones, insulin-resistance and loss of protein. Therapy of the diabetic patient should be designed to account for these changes and to avoid hypoglycemia, hyperglycemia, and hyperketonemia. It is suggested that for major operations for well-controlled non-insulin-dependent diabetic (NIDDM) persons and for all minor and major operations for insulin-dependent diabetic (IDDM) persons and poorly controlled NIDDM, a combined insulin (3.2 U/h), glucose (10 g 10% dextrose/h), and potassium infusion should be used until oral feeding recommences. The insulin dose should be modified periodically according to bedside glucose monitoring. Fluids should be used as in nondiabetic patients, except that lactate-containing solutions should be avoided. Insulin requirements will be increased (1) by infection, (2) in patients with hepatic disease, (3) in obese patients, (4) in steroid-treated patients, and (5) during cardiovascular surgery. A diabetes-care team should preferably be responsible for the care of the diabetic pre-, per-, and postoperatively.

Impaired Glucose Tolerance and Diabetes Mellitus in Elderly Subjects

Abstract: In a 10-yr prospective population study 406 subjects who were 70 yr old received an oral glucose tolerance test. Of these subjects 169 were retested at 80. Three sets of diagnostic criteria were evaluated, of which the WHO criteria are recommended for screening studies in this age group. The prevalences of diabetes mellitus (DM) and impaired glucose tolerance (IGT) according to the latter criteria were 10% and 26% at 70 and 12% and 35% at 80 in men and women. Excess 10-yr mortality was seen in both sexes when DM existed at 70, and in men also when IGT existed at this age. The excess mortality in men could solely--and in women partly--be explained by cardiovascular diseases. The 10-yr incidence of DM was 20% if IGT existed at 70, but only 4% when normal glucose tolerance was present at 70.

Use of a physiologic pharmacokinetic model of glucose homeostasis for assessment of performance requirements for improved insulin therapies.

Abstract: Methods are presented for assessing insulin therapies using a physiologic pharmacokinetic model of glucose homeostasis in man. The model is composed of simultaneous differential equations that represent physiologic compartments and spaces in which glucose and insulin are distributed and undergo metabolic reactions. The model is used to simulate clinical experiments in which blood glucose concentration is controlled by artificial device therapies. Predictions of the theoretical model for responses of normal and diabetic individuals to standard intravenous and oral glucose tolerance tests are compared to clinical data. Reasonable agreement is obtained between predictions of the computer simulations and clinical data for normal individuals. The responses of a diabetic person to oral glucose tolerance tests are simulated by removal of the pancreas from the glucose homeostasis model and introduction of insulin into the model by a prescribed therapy. Model simulations reaffirm expectations concerning the poor blood glucose control attainable by intramuscular insulin injection. Simulations of blood glucose regulation by an artificial pancreas using closed-loop feedback control for controlling insulin delivery rate reveal hyperinsulinemia that results in a net shift in the deposition of a glucose load from liver to peripheral tissues. Simulations of this system in which the time delay for glucose measurement is varied from 1.5 to 30 min show that increases in sensor delay result in progressive loss in glucose regulation, exacerbation of hyperinsulinemia, and increased insulin requirements.

Lipid Disorders in Diabetes

Abstract: available to deal with problematic situations, and (4) incentives (or lack of such) for engaging in particular behaviors. Note that none of these variables imply a \"pathological\" view of diabetes; all are important for the day-to-day functioning of nondiabetic persons also. The theory also emphasizes the interaction between these variables and implies a need for the development of specific measures relevant to the specific behaviors of interest rather than global personality measures. For example, rather than employing general measures of problem-solving skills, we have developed measures that are specific to situations commonly faced by persons with diabetes (e.g., how can you overcome the inconvenience of urine testing at work; what do you do when urged to have a rich dessert?). As another example, one important type of \"incentive\" is the degree of social support available from family members. Instead of using global measures of social support or family interaction, we have developed a \"diabetes family behavior checklist\" to assess supportive and nonsupportive actions of family members. Dr. Skyler commented on the need for research on behavioral interventions designed to facilitate coping with the diabetes self-care regimen. A better theoretical understanding and empirical detailing of the factors affecting adherence should decrease the number of premature behavior change attempts that are, in Skyler's words, \"poorly conceived or irrelevant studies by investigators unfamiliar with clinical diabetes\" (ref. 1, p. 656). Most of the social learning variables suggest specific intervention strategies rather than focusing on relatively unchangeable demographic or personality measures. It may eventually be possible to address relevant psychosocial variables in a preventive fashion. Health professionals, in collaboration with the person who has diabetes, could construct strategies during initial patient education that would assist coping with the requirements of the regimen. The ultimate usefulness of a social learning approach to psychological issues in diabetes is, of course, an empirical question. We feel, however, that such an approach avoids many of the problems noted by Skyler.