Glucose-controlled Insulin Infusion System Research Articles

Metabolic and Hormonal Responses during a Glucose Contrlled Insulin Infusion (Biostator®) in Subjects with Imparied Glucose Tolerance1)

The short-term effect of the glucose-controlled insulin infusion system (GCIIS) Biostator on metabolic and hormonal responses was studied in 10 non-obese subjects with glucose intolerance and insulin low response to glucose. Glucose tolerance characterized by means of a 2 h glucose infusion test (12 mg/kg/min) primed by i.v. injection of 0.33 g glucose/kg body weight was completely normalized by GCIIS. Results provide further support that normalization of glucose tolerance by means of GCIIS is accompanied by peripheral hyperinsulinaemia if compared with 33 non-obese healthy controls. Glucose-induced endogenous insulin secretion (C-peptide) was significantly reduced during the GCIIS study possibly due to inhibition of insulin secretion by exogenous insulin and/or by lower blood glucose concentration after normalization of glucose tolerance. Acute normalization of glucose tolerance in these patients failed to alter pancreatic glucagon, NEFA and glycerol responses but normalized paradoxical growth hormone response to glucose.

A stimulatory effect of tolbutamide on the insulin-mediated glucose uptake in subjects with impaired glucose tolerance (IGT).

Several studies have indicated that the long-term effectiveness of sulfonylurea therapy in the treatment of type-II diabetics is due to a potentiation of insulin action. The present investigation was undertaken in order to elucidate whether or not there is also an acute effect of sulfonylureas on insulin-mediated glucose uptake. Nine non-obese subjects classified as having impaired glucose tolerance formed the study group. In vivo insulin sensitivity was assessed by using the glucose controlled insulin infusion system (Biostator) without or with a contemporary 3-hour tolbutamide infusion. Studies were performed on subsequent days, and each subject served as its own control. Glucose was given at a fixed rate of 0.011 mmol/kg b.w./min. The computer program was set to maintain plasma glucose concentration at 3.89 mmol/l. The amount of exogenous insulin necessary to keep glycemia at this steady-state level has been accepted as an estimate of insulin sensitivity. Mean plasma glucose and insulin concentrations were constant and comparable in control and sulfonylurea treated groups. Under our experimental conditions tolbutamide did not provoke any increase of C-peptide secretion. There was no significant alteration of insulin counterregulatory hormones (glucagon and growth hormone) either. On the other hand, for the disposal of identical quantities of glucose the necessary amount of insulin has been found to be reduced by one third due to tolbutamide treatment indicating a higher insulin sensitivity. The mechanism by which tolbutamide intensifies the insulin effect is unknown. It seems to be that a successful short-term sulfonylurea therapy on glucose utilization is associated with some alterations on the receptor and/or post-receptor level.

Diurnal rhythm of insulin sensitivity in subjects with normal and impaired glucose tolerance.

We studied the insulin sensitivity in 5 normal subjects and 5 subjects with impaired carbohydrate tolerance using the glucose controlled insulin infusion system (BIOSTATOR). During a fixed glucose infusion rate of 2 mg/kg b.w./min, the computer program was set to maintain the plasma glucose concentration at 4.44 mmol/l. The ratio of infused exogenous insulin to infused glucose served as a measure of insulin sensitivity. Calculating the average insulin glucose ratio for 24 hours, the mean values amounted to 3531 and 9319 ng/gm (p less than 0.01) in subjects with normal and impaired carbohydrate tolerance, respectively, indicating that insulin resistance is the main cause of decreased glucose utilization in the latter group. Circadian rhythms of insulin sensitivity occur in both groups in a similar fashion. The insulin sensitivity was higher in the afternoon (1200-1800) as compared to the night. Thus, diurnal variations in insulin sensitivity are independent of disturbances of glucose metabolism.

Protein and fat effects on glucose responses and insulin requirements in subjects with insulin-dependent diabetes mellitus

The glucose responses (GR) and insulin requirements (IRs) were measured by a glucose-controlled insulin infusion system for 5 h after 12 patients with insulin-dependent diabetes mellitus consumed each of three meals: a 1890-kJ standard meal, the standard meal with 840 kJ added protein, and the standard meal with 840 kJ added fat. The GR to the protein-added meal was greater (P = 0.005) than to either the standard or fat-added meals, because of an increase in the late (last 150 min) GR. The late IR was greater for the protein-added meal (P < 0.005). The IR was not changed after the fat-added meal. Therefore, the addition of protein (but not fat) energy to a meal increases both the postprandial GR and late IR. This finding suggests that diabetic patients who inject premeal insulin may need to increase their insulin dose when protein is added to a meal.

The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system (“Artificial endocrine pancreas”)

The aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol (Betapressin TM; Hoechst Ltd., Frankfurt/Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system. The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake. After a submaximal exercise load on the bicycle ergometer (1 watt per kg body weight) following an evening meal, no difference could be observed between penbutolol and placebo in the above-mentioned parameters. The same was also true for hormonal parameters as STH, ACTH, cortisol, and catecholamines. These findings demonstrated that medication of penbutolol over a three-day period has no influence on the baseline blood sugar profile and insulin consumption or on insulin consumption after food intake during rest and physical exercise.

Cognitive and Psychomotor Function during Hypoglycemia: A Comparison between Porcine and Human Insulin

After an overnight euglycemic clamp, blood glucose levels were precisely lowered on two nonconsecutive mornings via a glucose-controlled insulin infusion system (GCIIS, Biostator) using either purified porcine insulin (PPI) or human insulin (HI). Two cognitive and psychomotor tests were significantly different in 8 type-I diabetic subjects and 8 healthy volunteers at four timepoints, when mean blood glucose concentrations (BGCs) were 100, 65, 50, and 40 mg/dl. Also, a significant difference (p = 0.005) could be found between the mean of all reaction time testing (RTT) values under HI as compared with the mean of all RTT values under PPI. Lowering the BGC resulted in a significant increase in the reaction time (p = 0.012). These effects were not dependent on the type of insulin being used nor were they typical of a particular study group.

Comparison of glycemic response and insulin requirements after mixed meals of equal carbohydrate content in healthy, type-1, and type-2 diabetic man

The postprandial insulin requirements after three mixed meals of equal carbohydrate and energy content were assessed in 10 type-1 and 12 type-2 diabetics by a glucose-controlled insulin infusion system. These were compared with the glycemic response to the same meals of 10 healthy individuals (glycemic index). In type-1 diabetics, we found the highest insulin requirements after consumption of a continental breakfast (low fibre, low protein, high fat). Ten percent less insulin was infused after milk (low fat, high protein) and 30% less after an English breakfast (high fibre, high protein). Type-2 diabetics showed no significant differences in insulin requirements between the three test meals. The glycemic response in healthy individuals had no relation to these insulin requirements. Continental and English breakfast had a similar glycemic effect, whereas milk produced only 30% of the blood glucose response observed after the continental breakfast. These results indicate that neither the carbohydrate content (exchange lists) nor the glycemic index enable prediction of postprandial insulin requirements in insulin-deficient diabetes. For this purpose, we propose the insulin-need index, elaborated by testing whole meals in closed-loop experiments with type-1 diabetics.

Fasting and feeding variations of insulin requirements and insulin binding to erythrocytes at different times of the day in insulin dependent diabetics--assessed under the condition of glucose-controlled insulin infusion.

Nine insulin-dependent diabetic patients were examined for insulin requirement, counterregulatory hormones, and receptor binding during their connection to glucose-controlled insulin infusion system. They were of 103% ideal body weight. A diet of 45% carbohydrate, 20% protein and 35% fat was divided into three meals and three snacks averaging the daily calorie intake of 1859 kcal. Following an equilibrating phase of 14 hours after the connection to the glucose-controlled insulin infusion system the blood samples were taken at 0800, 1200 and 1800. The insulin infusion rate increased at 0300 in the early morning from 0.128 mU/kg/min to 0.221 mU/kg/min (P less than 0.02). The postprandial insulin infusion rate jumped from 0.7 U/h (0700-0800) to 7.5 U/h (0800-0900). The calorie related and carbohydrate related insulin demands after breakfast were also highest and declined after lunch respectively (1.16 uU/kg/min kj vs. 0.61 uU/kg/min kj, P less than 0.05 and 236 mU/g CHO vs. 129 mU/g CHO and 143 mU/g CHO). Of the counterregulatory hormones the cortisol showed a significant diurnal rhythm to insulin demands. The insulin tracer binding was higher at 0800 before breakfast than that at 1200 before lunch (P less than 0.05). The increased binding could be better attributed to receptor concentration change than to affinity change. The cause of insulin relative insensitivity in the morning could be due to altered liver response to the cortisol peak in type 1 diabetics. The preserved variation of insulin binding in our patients might be referred to feeding.

Reversal of D- and A-cell insensitivity to glucose in alloxan-diabetic dogs by treatment with the artificial beta cell (Biostator).

Insulin-deficient diabetes in man as well as in experimental diabetes is associated with islet cell insensitivity to glucose. The present study was designed to determine whether this abnormality could be counteracted either by increasing the intraislet insulin level or by normalizing the diabetic state by a glucose-controlled insulin infusion system (GCIIS: Biostator, Life Science Instruments, Elkhart, Indiana). Using the isolated, perfused pancreas of dogs with moderate, untreated alloxan diabetes of 4 days duration, we found that 5 mM arginine (N = 4) and 5 mM calcium (N = 4) stimulated D- and A-cell secretion, whereas an increment in glucose from 1.3 to 11 mM (N = 4) had no effect on islet hormone secretion. In the pancreas from untreated alloxan-diabetic dogs, acute infusion of large amounts of insulin (25 mU/ml) in vitro simultaneously with an elevation of perfusate glucose from 1.3 to 11 mM failed to restore the glucose from 1.3 to 11 mM failed to restore the glucose sensitivity. In contrast, treatment of alloxan-diabetic dogs (N = 3) by a GCIIS for 24 h revived some responsiveness of the glucagon, insulin, and somatostatin to glucose (1.3-11 mM) of the subsequently perfused pancreas. It is concluded that the insensitivity to glucose of islet cells in insulin-deficient diabetes is not ascribed to an intra-islet insulin deficiency per se but rather to an abnormal metabolic state secondary to insulin deficiency. The results also indicate that the glucose receptor dysfunction is not due to a direct lesion by the diabetogenic drug.

A double-blind study of the efficacy of neutral human and porcine insulin in type I diabetes using a glucose-controlled insulin infusion system

The comparative potency of equimolar amounts of soluble porcine and semisynthetic human insulin were studied in ten patients with type 1 diabetes in acute experimental situations. In both situations residual subcutaneous insulin depots were eliminated by intramuscular treatment exclusively with soluble insulin four days before the experiments. Then, practically identical metabolic states were achieved by connecting the patients to a glucose-controlled insulin infusion system (Biostator) 12 hours before the study. In one study, 0.5 g/kg body weight of glucose was administered intravenously as a bolus, and thereafter insulin was infused at a rate of 1.0 mU/kg/min. The decline in blood glucose was rectilinear and identical for the two insulins: y = −1.18 x + 206 and y = −1.17 x + 205. The insulin effect is well below maximum, and a 10% increase in the infusion rate of insulin was easily detected. Although changes in blood glucose and pancreatic glucagon were identical, a significantly lower plasma growth hormone level was noted after human insulin infusion. In the second study, 24 hours of near-normoglycemia was attained by the glucose-controlled insulin infusion system, the patients being supine and having identical meals at identical intervals. The diurnal blood glucose, plasma growth hormone, and pancreatic glucagon patterns were identical and the total 24 hour insulin consumption was 47.7 ± 3.5 units and 47.7 ± 3.7 units for the two insulins.

Developmental and application of insulin infusion profiles for therapy of type-I diabetics with portable insulin infusion systems.

We studied the insulin requirements of seven insulin-dependent diabetics applying a glucose controlled insulin infusion system. The data were transformed into individually programmed and rectangular profiles. The MAGE, a measure of blood sugar fluctuations, was significantly lower when individually programmed step profiles were used (P less than 0.005) than it was when rectangular profiles were applied: 57.7 +/- 24.8 mg/dl vs 89.0 +/- 42.9 mg/dl. The average of measured blood glucose levels was significantly lower in individually programmed infusion profiles (P less than 0.025). The combination of individually programmed profiles and preprandial insulin bolus significantly reduced the postprandial blood glucose level and increase (P less than 0.001). Our investigations suggest that individually programmed insulin infusion profiles are able to smooth blood glucose fluctuations. When combined with an initial insulin bolus they may lead to a reduced insulin consumption after meals.

A comparison of the artificial pancreas (glucose controlled insulin infusion system) and a manual technique for assessing insulin sensitivity during euglycaemic clamping

Two main methods are available for assessing insulin sensitivity with the hyperinsulinaemic euglycaemic clamp technique: one employs a glucose-controlled insulin infusion system (the Biostator) with automatic feedback control; the second depends on frequent glucose measurement and the use of an algorithm and a pocket calculator ('manual') to determine the glucose infusion rate. The amount of glucose infused is a measure of insulin sensitivity. The efficiency of the two methods was compared in nine normal subjects (seven lean, two obese). After an overnight fast subjects were infused with insulin at 50 mU X kg-1 X h-1 for 2 h; this rate was doubled during the first 10 min for the manual technique. Blood glucose averaged 4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l from 0 to 120 min for Biostator and manual techniques and did not deviate significantly from the desired level. Variability of the clamp was also similar over the same period (coefficient of variation 5.1 +/- 0.6% and 6.4 +/- 0.7%, Biostator and manual). Glucose infused to maintain steady state from 60 to 120 min was higher, however, with the manual than the Biostator method (5.7 +/- 0.6 versus 4.4 +/- 0.6 mg X kg-1 X min-1, p less than 0.01) even when the loading dose was omitted, although the two methods correlated closely (p less than 0.05). Glucose infusion rate varied more from minute to minute with the Biostator (coefficient of variation 28.8 +/- 3% versus 12.2 +/- 2.1%). Steady-state serum insulin levels (30-120 min) were the same during both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in uraemic insulin-dependent diabetics. Effect of dialysis therapy as assessed by the artificial endocrine pancreas.

Twenty-four hour insulin requirements were measured in 5 uraemic insulin-dependent diabetics using a glucose controlled insulin infusion system (artificial endocrine pancreas). All patients were studied twice: initially 14 (1-27) days before institution of dialysis treatment and again after a mean of 46 (21-98) days on chronic dialysis therapy. At near normal blood glucose level the daily insulin requirements decreased from 44.8 +/- 2.9 U pre-dialysis to 35.0 +/- 2.3 U post-dialysis (P less than 0.001). The reduction included the prandial as well as the basal requirements. Consistent with this, the mean plasma free insulin level was higher pre-dialysis than post-dialysis (42 +/- 12 microU/ml vs 31 +/- 7 microU/ml) especially during daytime (49 +/- 11 microU/ml vs 37 +/- 9 microU/ml, P less than 0.03), suggesting that a decreased insulin degradation was not a major factor in the difference in insulin requirements. The effect of an acute change in azotaemia on insulin requirements was also evaluated in 4 uraemic diabetics on chronic haemodialysis the day prior to and the day after a routine dialysis (serum creatinine 922 +/- 59 mumol/l vs 555 +/- 109 mumol/l). No difference in insulin administration on the two days was observed (42.5 +/- 6.1 U vs 43.2 +/- 5.6 U). It is concluded that insulin resistance is present in uraemic insulin-dependent diabetics analogous to the insulin resistance widely prevalent in non-diabetic uraemic patients. The abnormality is at least partly reversible after several weeks on chronic dialysis, but not acutely. The pathophysiologic mechanisms underlying the insulin resistance in uraemia in the diabetic remain to be clarified.

Kinetics and metabolic activity of biosynthetic NPH insulin evaluated by the glucose clamp technique.

The glucose clamp technique has been used to evaluate the metabolic activity of NPH biosynthetic insulin in diabetic subjects free from anti-insulin antibodies. After overnight blood glucose normalization with a glucose-controlled insulin infusion system (Biostator), an s.c. injection of NPH insulin was given in the abdominal region. The insulin dose (0.236 +/- 0.05 U/kg body wt) was related to the usual intermediate-acting insulin requirement in the morning. Glucose was clamped at 100 mg/dl by a feedback i.v. glucose infusion. The end of the action of s.c. injected insulin considered conventionally to be the time of the spontaneous rise of blood glucose to 110 mg/dl. Free insulin levels were higher and the length of action was longer after NPH porcine than after NPH biosynthetic human insulin (BHI) (area under the free insulin curve: porcine 1423 +/- 556 mU/L/h; BHI 1045 +/- 338 mU/L/h, P less than 0.05; length of action: porcine 16.0 +/- 3.2 h; BHI 13.7 +/- 0.9 h, P less than 0.05); the glucose requirement was higher after porcine (76.8 +/- 13.5 g) than after BHI (58.5 +/- 14.6 g) without reaching statistical significance. However, the metabolic activity of the bioavailable insulin (index of plasma free insulin activity) was similar for the two insulins (porcine 381 +/- 77.4, BHI 342.8 +/- 54.2 mU/L/g of glucose/h). We conclude that a difference in pharmacokinetics exists between NPH BHI and porcine NPH insulin, which makes the latter metabolically more active. The different behavior does not seem to be related to the insulin molecule itself but could be a consequence of the unequal content of protamine in the two pharmacologic preparations.

INSULIN HYPOGLYCAEMIA TEST (IHT) GUIDED BY A GLUCOSE CONTROLLED INSULIN INFUSION SYSTEM (GCIIS).

Journal Article Insulin Hypoglycaemia Test (IHT) Guided by a Glucose Controlled Insulin Infusion System (GCIIS) Get access G Müller-Esch, G Müller-Esch Dept of Endocrinology, Int. Cl. A, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar P Ball, P Ball Dept of Endocrinology, Int. Cl. A, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar K Heidbüchel, K Heidbüchel Dept of Endocrinology, Int. Cl. A, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar W G Wood, W G Wood Dept of Endocrinology, Int. Cl. A, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar P C Scriba P C Scriba Dept of Endocrinology, Int. Cl. A, Belgrade, Yugoslavia Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 104, Issue 2_Supplement_b, Aug 1983, Pages S187–S194, https://doi.org/10.1530/acta.0.103S187 Published: 01 August 1983

Impact of euglycaemia and hyperglycaemia on the release of growth hormone and prolactin in type II-diabetics.

The influence of different blood glucose concentrations on the arginine (30 g/30 min i.v.) and TRH (400 micrograms i.v.) induced release of growth hormone and prolactin was studied in six male type II-diabetic patients. Blood glucose concentrations were clamped at euglycaemic (4-5 mmol/l) or hyperglycaemic (12-18 mmol/l) levels by means of an automated glucose-controlled insulin infusion system. The response of growth hormone to arginine, and irregular spikes in growth hormone concentrations following TRH seen in the euglycaemic state were suppressed during hyperglycaemia. The suppression of the arginine-induced release of growth hormone by hyperglycaemia was observed both with and without concomitant administration of exogenous insulin. The rise in serum prolactin concentrations in response to arginine was unaffected by hyperglycaemia, whereas the TRH-induced release of prolactin was suppressed. Since arginine induces the release of growth hormone and prolactin via the hypothalamus, while TRH acts at the pituitary level, the glycaemic state appears to exert a modulatory effect on the secretion of growth hormone and prolactin in type II-diabetics at both locations.

Kidney function after improved metabolic control in newly diagnosed diabetes and in diabetic patients with nephropathy.

To evaluate the effect of improved metabolic control on kidney function, urinary excretion rate of beta-2-microglobulin, lysozyme, and gamma-glutamyltransferase were evaluated in nine poorly controlled, newly diagnosed diabetic patients before and during treatment. In six poorly controlled insulin-dependent nephropathic diabetic patients, besides the parameters cited above, urinary albumin excretion rate and IgG/transferrin clearance ratio were further investigated to estimate the permeability and the selectivity of glomerular barrier during conventional treatment and after improvement of the metabolic control by a glucose-controlled insulin infusion system (GCIIS). The improved glycemic control resulted in a significant reduction of urinary beta-2-microglobulin and lysozyme excretion in all diabetic patients. Significant decreases of urinary albumin excretion and of IgG/transferrin clearance ratio (indicating a more selective proteinuria) during strict metabolic control were also observed in nephropathic diabetic patients. The reduction of urinary beta-2-microglobulin and lysozyme excretion indicates that a tubular reabsorptive dysfunction, reversible with the amelioration of glycemic control, can be observed in poorly controlled, newly diagnosed and in insulin-dependent nephropathic diabetic patients during conventional treatment. In the latter patients, the permeability and the selectivity properties of glomerular barrier also improved during GCIIS.

The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: studies with a glucose controlled insulin infusion system (artificial endocrine pancreas).

Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3 +/- 0.7 compared with 5.6 +/- 0.3 mmol/l on feedback control and 5.5 +/- 0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94 +/- 0.04 on subcutaneous insulin, 0.91 +/- 0.04 on feedback control and 0.74 +/- 0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600-1800 h) was normal on feedback control (1.41 +/- 0.20 versus 1.55 +/- 0.18 mg X kg-1 X min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04 +/- 0.09 mg X kg-1 X min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.

Development of the Biostator Glucose clamping algorithm.

The "glucose clamping" technique has been proposed as a method for the early detection of a beginning derangement of glucose homeostasis and thus for the possible prevention of maturity-onset diabetes. This technique interrupts the physiological glucose-insulin relationship by placing a patient's blood glucose concentration under an investigator's control, for quantification of the pancreatic beta-cell response during hyperglycemic clamps and of sensitivity of body tissue to exogenous insulin during normoglycemic clamps. We report the development of a glucose clamping algorithm for use with the Biostator glucose-controlled insulin-infusion system (Horm. Metab. Res., Suppl. 8: 23-33, 1977). This algorithm adds simplicity and precision to the glucose clamping procedure and reduces operator effort to a minimum. We describe the early development of the algorithm with a model system and report evaluations made during animal studies and preliminary investigations with human subjects.

Use of a Glucose-Controlled Insulin Infusion System in Children and Adolescents with Insulin-Dependent Diabetes

Seven children and adolescents (aged 8 to 23 years, mean 16 years) with poorly controlled insulin-dependent diabetes mellitus were evaluated with a glucose-controlled insulin infusion system (GCIIS) to determine whether its use could help define appropriate long-term insulin treatment regimens and increase patient understanding and compliance with such regimens. The GCIIS-derived insulin regimen was characterized by a mean insulin requirement of 1.0 +/- 0.1 units/kg/day, with 55% of the total insulin dose given in the morning and 45% in the evening. Forty-eight percent of the total insulin was short acting. Both clinical and biochemical indices of metabolic control (HbA1c levels) improved after insulin dose readjustment based on GCIIS data. The continuous documentation of blood glucose levels provided by the GCIIS was valuable in educating patients about the interrelationship between insulin, exercise, and diet. Using GCIIS data, patients were taught to apply the new regimen flexibly to variations in activity and diet. Thus, the GCIIS can aid in the management of selected children and adolescents with insulin-dependent diabetes millitus. Insulin patterns derived from its use suggest that a flexible, twice daily regimen characterized by nearly equal proportions of short- and intermediate-acting preparations may be beneficial for other pediatric patients.