Preprandial Blood Glucose Research Articles

Metformin in noninsulin-dependent diabetes mellitus.

Metformin is an oral antihyperglycemic agent that is approved by the Food and Drug Administration for the treatment of noninsulin-dependent diabetes mellitus. It differs from the sulfonylureas in that it is does not enhance insulin secretion and normally does not produce hypoglycemia. Metformin acts to decrease preprandial and postprandial blood glucose concentrations by increasing skeletal muscle uptake of glucose, decreasing gluconeogenesis, and decreasing absorption of glucose. The addition of metformin to maximum dosages of a sulfonylurea may synergistically improve glucose control. The drug may offer other potential benefits, such as weight loss or minimal weight gain, improved blood flow in patients with peripheral vascular disease, reduction of tissue plasminogen activator inhibitor, and improved lipid profiles. It is relatively safe if taken appropriately. Its most common side effects are gastrointestinal (nausea, diarrhea, anorexia), metallic taste, and vitamin B12 malabsorption. Lactic acidosis may also occur, but it is rare if metformin is avoided in patients with contraindications to its use. With careful monitoring, the agent may be considered for the initial treatment of obese patients who fail dietary measures, and those whose disease is refractory to maximum dosages of sulfonylureas or who do not tolerate them.

Effects of dietary protein restriction on glucose and insulin metabolism in normal and diabetic humans

We determined whether the amount of protein in the diet can affect insulin requirements in subjects with diabetes mellitus and glucose metabolism in normal subjects. Seven normal-weight volunteers with uncomplicated, intensively controlled, type I (insulin-dependent) diabetes and 12 similar nondiabetic subjects were studied on a metabolic ward before and after consuming a maintenance-energy but protein-free diet for 10 days. Blood glucose levels of diabetic subjects were measured seven times daily in response to insulin administration by continuous subcutaneous infusion. the plasma glucose appearance rate (R a) was measured in seven normal subjects and all diabetic subjects using a primed-continuous infusion of d-[6,6- 2H 2]glucose. After adaptation to the protein-restricted diet, diabetic subjects experienced a 30% decrease in average preprandial and average daily blood glucose concentrations ( P < .01); this occurred despite a concurrent 25% decrease in both basal and bolus insulin dosages ( P < .001). Protein restriction decreased the postabsorptive glucose R a ( P < .01) and insulin concentrations ( P < .01) of normal subjects by 20%, and increased their fasting glucagon concentrations by 24% ( P < .01). We conclude that severe protein restriction decreases insulin requirements in type I diabetes and fasting hepatic glucose output and basal insulin levels in normal subjects. This effect appears to be mediated in part by decreased hepatic gluconeogenesis, but a contributory influence of increased insulin sensitivity is not ruled out.

Effect of an orally administered sulfonylurea, glipizide, for treatment of diabetes mellitus in cats

Summary An orally administered sulfonylurea drug, glipizide, was evaluated for treatment of diabetes mellitus. Confirmation of diabetes was based on evidence of appropriate clinical signs, persistent hyperglycemia, and glucosuria. Glipizide (5 mg, PO, q 12 h) was administered to each cat. Sixteen cats were fed a commercial high-fiber diet and 4 cats were fed a commercial low-fiber diet. Insulin was not administered to any cat during the study. Each cat was evaluated 2, 4, 8, and 12 weeks after initiation of treatment. Three clinical responses to glipizide treatment were identified. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period decreased to &lt; 200 mg/dl in 5 of 20 (25%) cats. In these 5 cats, glucosuria was no longer detected and clinical signs resolved by the 4-week reevaluation. Euglycemia was maintained after discontinuing glipizide treatment in 2 of these 5 cats. Glycemic control has been maintained in 2 of 5 of the responding cats for 5 and 7 months of glipizide treatment. One of 5 of the responding cats developed insulin-requiring diabetes mellitus after 6 months of glipizide treatment. Seven of 20 (35%) cats failed to respond to treatment. Mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period did not change from pretreatment values after 2 ± 1 months; glucosuria persisted and clinical signs progressively worsened. Insulin treatment was required to establish glycemic control in these 7 cats. Eight of 20 (40%) cats partially responded to glipizide treatment. Clinical signs and abnormalities identified on physical examination improved, and mean preprandial blood glucose concentration and mean blood glucose concentration during an 8-hour postprandial period decreased by 146 ± 105 and 110 ± 50 mg/dl, respectively, at the 12 week reevaluation, compared with pretreatment values, but blood glucose concentrations remained &gt; 200 mg/dl and glucosuria persisted. These cats were treated with glipizide for a mean of 12 months (range, 7 to 21 months). Adverse reactions to treatment included vomiting shortly after administration of glipizide (3 cats), hypoglycemia (3 cats), and increased serum hepatic enzyme activities (3 cats). Retrospective analysis of information obtained from the 20 cats at the time of entry into the study failed to identify any consistent factor that could be used to predict the cats’ response to glipizide treatment. Results of the study indicated that glipizide may be a viable alternative to insulin for treatment of diabetes mellitus in some cats.

Glycemic response to sucrose-containing mixed meals in diets of children with insulin-dependent diabetes mellitus

Our pilot study compared the short-term glycemic effects of a traditional "sucrose free" diet (Suc-Free, 2% total calories from sucrose) to a sucrose-containing diet (Suc-Con, 10% total calories from sucrose) in a clinical research center. Both weighed diets were isocaloric and included 50% carbohydrate, 30% fat, and 20% protein in three meals and three snacks; glucose, fructose, and dietary fiber were identical. Sucrose isocalorically replaced complex carbohydrate at each meal and for the afternoon snack. Ten children (7 to 12 years of age; mean total hemoglobin A1 level 8.9 +/- 0.3%) were randomly assigned, in a crossover design, to one of the two orders (Suc-Free followed by Suc-Con or Suc-Con followed by Suc-Free) for consecutive 2-day diet periods; insulin doses remained constant. Preprandial and postprandial blood glucose levels were measured for each meal and snack (18 measurements per day). To account for baseline differences, we calculated the change in blood glucose levels from baseline to 30 minutes and 1 hour for each meal and snack (mean +/- SEM). No differences were detected between diets. Total area under the glucose response curve (levels measured hourly from 8 AM to 9:30 PM in milligrams per deciliter) was not significantly different for the two diets (Suc-Free 3672 +/- 240; Suc-Con 3574 +/- 285; p = 0.74). No difference in 24-hour urinary glucose levels (measured in grams per day) was detected between the two diets (Suc-Free 35.6 +/- 7.5; Suc-Con 34.5 +/- 7.5; p = 0.84). Incidences of hyperglycemia that required supplemental short-acting insulin and of mild hypoglycemia were similar for both diet periods. Thus, in a controlled setting and during a short study period, children with insulin-dependent diabetes mellitus had a similar glycemic response to diets with and without a moderate amount of sucrose.

Preprandial blood glucose values and glycemic responses in insulin-dependent diabetes mellitus at constant insulinemia

The influence of preprandial blood glucose (PPBG) concentration on glycemic responses was studied in seven subjects with insulin-dependent diabetes who, by means of the artificial pancreas, had achieved PPBG concentrations of 6, 9, and 17 mmol/L. A test meal of 50 g parboiled rice was given at the three different occasions and a constant insulin infusion was provided during the observation periods. The mean postprandial-blood-glucose-response area (above basal) differed significantly at the three blood glucose concentrations of 6, 9, and 17 mmol/L, reaching 1371, 621, and 179 mmol/L x 240 min, respectively (P less than 0.01). A negative correlation between the PPBG concentrations and the glycemic responses to the test meal was found (r = 0.94; P less than 0.001). The fasting insulin concentration at a PPBG concentration of 17 mmol/L was lower than at a PPBG concentration of 6 and 9 mmol/L. In conclusion, the glycemic responses to a carbohydrate meal are inversely correlated to the PPBG concentration in insulin-dependent diabetic subjects.

Early Neonatal Predictors of Neonatal Hypocalcemia in Infants of Diabetic Mothers: An Epidemiologic Study

Prematurity, neonatal asphyxia, hypomagnesemia, and advanced maternal diabetes are traditional risk factors for hypocalcemia in infants of diabetic mothers (IDMs). The aim of this study was to determine the relative contribution of these factors separately and combined in a cohort of diabetic pregnancies managed prospectively in the recent 9 years and to find accurate predictors of neonatal hypocalcemia in infants of diabetic mothers. We hypothesized that these factors plus low cord blood calcium (Ca) concentration allow prediction of IDMs who develop neonatal hypocalcemia. We studied 186 IDMs (White class B-RT); gestational age (GA, weeks) was by last menstrual period, confirmed +/- 2 weeks by Ballard score. The goals of glycemic control were: preprandial blood glucose less than 100 mg/dl and 90-minute postprandial blood glucose less than 140 mg/dl. Apgar scores, and cord, 24-, 48- and 72-hour serum calcium (Ca) (mg/dl) and magnesium (Mg; mg/dl) were determined. In univariate analysis, lowest serum Ca correlated with cord blood Ca (r = 0.48, p less than 0.001), GA (r = 0.37, p less than 0.001), and 1-minute Apgar score (r = 0.18, p = 0.09), but did not correlate with cord Mg or with advanced White class. In multiple regression, cord Ca and GA were dominant effects and other variables became insignificant. Lowest Ca (mg/dl) was predicted as follows: lowest Ca = 34.05 - 3.22 (Ca cord) - 0.84 (GA) + 0.10 (GA) (Ca cord). This equation predicts neonatal hypocalcemia (lowest Ca less than 8 mg/dl) with a sensitivity of 72% and a specificity of 75%. Thus, GA and cord Ca allow determination of IDMs at risk for neonatal hypocalcemia.

An Evaluation of the Therapeutic Effects and Dosage Equivalence of Glyburide and Glipizide

Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.

Preprandial blood glucose values: influence on glycemic response studies

Through regressional analyses on data from two glycemic response studies, the influence of various preprandial blood glucose (PPBG) values upon glycemic response is highlighted. Repeated calculations on different subsamples of meals where the PPBG was below a given value showed that the influence of PPBG upon net glycemic response not was linear in the whole PPBG range. It was found that a PPBG less than 13 mmol/L had no influence upon net glycemic response whereas PPBGs greater than 13 mmol/L were significantly negatively correlated to the net glycemic response. To obtain more valid glycemic index figures we recommend that participants with PPBG greater than 13 mmol/L are excluded from glycemic response studies and that the number of participants are increased substantially.

Composition of very-low-density lipoproteins in non-insulin-dependent diabetes mellitus.

We studied the characteristics of very-low-density lipoproteins (VLDLs) composition in patients with non-insulin-dependent diabetes mellitus. VLDLs were isolated from 28 diabetics and 33 nondiabetics with a wide range of plasma lipid concentrations, so we could compare VLDL composition between the two groups at similar lipid concentrations. The mean cholesterol and triglyceride concentrations in plasma of diabetic subjects were 2170 (SD 570) and 2510 (SD 2230) mg/L, respectively, and 2230 (SD 560) and 2210 (SD 1830) mg/L in nondiabetics. Diabetic subjects showed positive correlations between plasma triglyceride concentrations and either preprandial blood glucose or glycated hemoglobin values (P less than 0.02 and less than 0.01, respectively). Concentrations of triglycerides, cholesterol, and apolipoproteins (apo) B, CII, CIII, and E in VLDL were not significantly different between diabetics and nondiabetics. At comparable triglyceride concentrations, the chemical compositions of the VLDL in the two groups were still very similar. Dividing the concentration of each component by the VLDL-apo B concentrations yielded similar contents of each component per unit of VLDL for the two groups. We conclude that the composition of VLDLs in diabetics is much the same as that in nondiabetics at comparable concentrations of triglycerides in plasma.

Effect of fat-free diet on insulin requirements in type I diabetes controlled with artificial beta-cell.

We investigated the effect of eliminating calories derived from fat sources on postprandial and basal insulin requirements in five patients with type I (insulin-dependent) diabetes mellitus. The patients were studied on a metabolic ward on two solid-food diets with similar quantities of carbohydrate and protein with or without the addition of fat. Diet A was isocaloric (weight maintenance) with calories distributed as 45% carbohydrate, 15% protein, and 40% fat. Diet B contained the same carbohydrate and protein content as diet A but was virtually fat free and therefore hypocaloric (1233 +/- 106 vs. 1830 +/- 99 cal, mean +/- SE). The diets were given as five equal meals each day on consecutive days. Insulin requirements and blood glucose measurements were determined by use of the artificial beta-cell. During the study, mean (+/- SE) preprandial blood glucose levels were maintained at 85 +/- 11 mg/dl, and peak postprandial blood glucose levels were less than 180 mg/dl. The elimination of fat calories had no effect on total (68.9 +/- 10.3 vs. 69.3 +/- 4.9 U/day), postprandial (9.8 +/- 3.8 vs. 10.3 +/- 3.7 U/meal), or basal (1.9 +/- 0.2 vs. 1.8 +/- 0.2 U/h) insulin requirements. Thus, despite a hypocaloric diet, no change in insulin requirements was noted when fat-derived calories were deleted from the diet. We conclude that fat-derived calories do not alter short-term basal or postprandial insulin requirements in type I diabetes.

Management of diabetics with the use of a microprocessor: comparison of insulin treatments based on blood and urine glucose levels.

The insulin treatment of 8 insulin-dependent diabetics was controlled with a microprocessor (Better Control Medical Computer, BCMC, Inc., Toronto, Canada) with information derived from blood or first voided urine glucose concentrations assessed by reagent strips four times a day, before the three main meals and bedtime snack. The microprocessor recommends modification of the insulin doses so as to reach a pre-prandial blood glucose value of 110 mg/dl or a urine glucose concentration of 0.1 g/dl. During the first two weeks self-management was uniformly applied by the patients, based on their blood glucose concentration. Subsequently, it was continued by the patients who were divided into two groups, one using the blood, the other the urine glucose concentrations, each for three weeks, alternately. During microprocessor treatment the patients' mean blood glucose profiles decreased from 152 +/- 37 mg/dl to 126 +/- 28 mg/dl. No difference was found between treatments based on blood or urine glucose concentrations concerning either the mean blood glucose profiles or the number of hypoglycemic episodes in the presence of an average glucose threshold and good renal function. The first voided urine glucose concentration and mean and maximal blood glucose values obtained at the time of urine filtration were closely correlated (r = 0.82 and 0.86, p less than 0.001).

Type A behavior pattern and blood glucose control in diabetic children.

We studied the relationship between presence of Type A behavior pattern and glycemic response to stress in children with insulin dependent diabetes mellitus (IDDM). Twelve male (six Type A and six Type B) and nine female (four Type A and five Type B) insulin-dependent diabetic patients between the ages of 8 and 16 years received a standard meal and blood glucose values were assessed two hours later. All subjects then played a competitive videogame for 10 minutes following which blood glucose was assessed again. Preprandial and postprandial blood glucose values did not differ between the groups. However, only Type A subjects showed a hyperglycemic response to the videogame stress. Type A subjects also demonstrated significantly higher glycohemoglobin values. In order to assure that this effect was due to a differential response to stress and not simply a difference in metabolic response to a meal, a second study was conducted in which blood glucose values were assessed at one, two and three hours following a standard meal. No significant differences in postprandial blood glucose values were observed between Type A and Type B subjects. These data support previous research which has suggested that some but not all patients with IDDM show a hyperglycemic response to stress.

Improved diabetic control in adolescents using the Penject syringe for multiple insulin injections.

Eleven adolescent diabetics, aged 15.1 +/- 1.3 years (mean +/- 1SD) in poor glycaemic control (HbA1 12.0 +/- 1.5% at entry) were commenced on a four times daily insulin injection regimen using the Penject fountain-pen syringe with Initard (50:50 mixture of porcine soluble and isophane) insulin on a sliding scale. Diabetic control improved over a 3-month period, assessed by a reduction in both the mean preprandial blood glucose concentrations (10.9 +/- 3.3 mmol/l to 7.7 +/- 2.3 mmol/l) and mean glycosylated haemoglobin concentrations (12.0 +/- 1.5% to 9.5 +/- 0.9%). Further improvement was again seen in 5 patients who remained on four daily injections for an additional 3 months (mean HbA1: 9.6 +/- 0.9% to 8.4 +/- 1.0%), whereas diabetic control in 6 patients who returned to twice daily injections deteriorated (mean HbA1 rose from 9.5 +/- 1.0% to 10.6 +/- 1.6%). Multiple insulin injections using an injection pen are acceptable to adolescent diabetics and improve their control.

Continuous subcutaneous insulin infusion (CSII) in insulin-dependent diabetes.

Six patients with insulin-dependent diabetes mellitus were treated by continuous subcutaneous insulin infusion for a period of 24–64 weeks. Diabetic control improved, indicated by a fall in the mean preprandial blood glucose and haemoglobin A1 levels. Renal function was unaltered in one patient with diabetic nephropathy but background retinopathy deteriorated in another. However, all patients reported an improved sense of well-being and expressed a reluctance to revert to conventional twice daily insulin despite the inconvenience of wearing the device and need for frequent blood glucose monitoring. Continuous subcutaneous insulin infusion is an acceptable means of managing insulin-dependent diabetes. *** DIRECT SUPPORT *** A00IA373 00004

Abnormal immunoregulation in patients with insulin dependent diabetes mellitus and their healthy first degree relatives

Autoantibodies, cell-mediated autoimmunity, and impaired suppressor T cell function. suggesting abnormal immunoregulation, have been implicated in the pathogenesis of juvenile-onset insulin dependent diabetes mellitus (IDDM). To examine one of the parameters of immunoregulation, and to explore its relationship to the disease, we tested suppressor cell function in IDDM patients, their clinically healthy relatives, and in normal unrelated controls. 9/15 IDDM had impaired suppressor cell compared to 1 8 age-matched healthy sibs ( p < 0.04) and to 0 9 unrelated controls ( p < 0.005). There was no correlation between abnormal suppressor cell function and the patient's age, sex, preprandial blood glucose levels, age at the time of diagnosis, or duration of the disease. However, there was a trend for a higher proportion of HLA DR3 positive diabetics to have abnormal suppressor cell function compared to DR3 negative patients. Impaired suppressor cell function was also found in 5 23 clinically healthy first degree relatives; 4 5 were related to a diabetic who demonstrated abnormal suppressor cell function. These findings raise the possibility that underlying familial, probably genetically determined abnormalities in immunoregulation, acting in concert with other environmental or genetic factors, may contribute to disease susceptibility in IDDM.

Self-Monitoring of Blood Glucose

Self-monitoring of blood glucose (SMBG) is an essential tool in the management of diabetes. If properly used, SMBG values are employed by the patient to make immediate treatment decisions. The decisions are based on a predetermined action plan that consists of actions designed to achieve blood glucose values within a given target range. Optimal treatment of diabetes is guided by the knowledge of prevailing blood glucose levels. SMBG is an essential component of any intensive therapy program directed toward achieving meticulous glycemic control. SMBG enables therapeutic goals to be clearly defined and permits assessment of glycemic control during ordinary life, thus being complementary to glycated hemoglobin measurements. SMBG determinations are used on an ongoing basis by patients, to aid in the adjustment of the therapeutic regimen. Optimal use of SMBG requires the goals of treatment to be clearly defined and for patients to be taught proper interpretation of the data. Patients need to learn how to use the data to adjust food intake, exercise, or pharmacological therapy to achieve specific glycemic goals. SMBG is the only practical means of detecting asymptomatic hypoglycemia in the outpatient setting. SMBG may also be used to detect temporal glycemic patterns, so that therapy may be modified in an attempt to prevent hypoglycemia. A great advantage of SMBG is its use in intercurrent illness and other emergency situations, in which SMBG allows objective documentation of acute destabilization of diabetic control. Patients may be provided with a home management plan to use during illness. SMBG may be particularly important in children and adolescents who have wide day-to-day variations in activity. Instrumental to the use of SMBG is the choice of blood glucose targets. There should be defined blood glucose targets, individualized for the needs of each patient. Frequency of monitoring depends on the treatment program and varies considerably depending on the clinical situation. Knowledge of preprandial, bedtime, and nocturnal blood glucose concentrations is required to determine the appropriate basal and preprandial insulin doses. The best predictor of compliance with SMBG is the perception of improved control with such monitoring. Record keeping is essential to successful treatment, particularly if one is to consider the impact of previous responses. In response to blood glucose fluctuations, the patient must learn how to take appropriate action, predetermined with the diabetes management team. Keywords: blood glucose; insulin; meticulous control; treatment guidelines; dose adjustment; patterns; SMBG

Meal related effects of IV glucose, glucagon and insulin on blood glucose level: Role in glucoregulation exhibited by self-injecting rats

In previous works, it was demonstrated that rats self-injected with (IV) glucose, insulin and/or glucagon and that the self-administration pattern was related to the meal. It was suggested that the different preprandial or postprandial blood glucose level (B.G.L) determinated the meal and were dependent on it. Previously self-injected amounts of glucose, glucagon and insulin were here injected by an automatic device and their effect on B.G.L. were compared in the post and preprandial conditions. Results indicated that the effects of insulin, glucagon and glucose on B.G.L., which were different during the postprandial hyperglycemia compared to the preprandial normoglycemia, accounted for the different self-injection patterns. Furthermore successive injection of glucose and insulin or glucagon and insulin suggest that rats, by pressing alternatively two levers performed a regulatory correction of variations of their B.G.L. It is concluded that rats may learn to perform a behavioral regulation of their B.G.L. by IV self-injections of glucose and glucoregulatory hormones.

Audit in a diabetic clinic.

Diabetic control was assessed in 82 established insulin-dependent diabetics using a microcapillary system for home preprandial blood glucose sampling. At initial assessment control in the majority (62%) was found to be unsatisfactory (at least 1 preprandial blood glucose greater than 13.0 mmol/l or frequent and severe hypoglycaemia). Sixty-three of these patients were assessed on more than one occasion. Only 24% were satisfactorily controlled at their first assessment, but this proportion had risen to 60% after 12 months. The ability of patients to perform unsupervised blood glucose levels using Ames Glucometers or BM-Glycemie 20-800 test strips was also assessed: 86% of the meter results were within one-third of the laboratory-based results, but there was evidence of bias towards the under-reading of higher glucose values using BM-Glycemie 20-800 test strips. Random blood glucose estimations performed in the diabetic clinic were of little value.

Combined sulphonylurea-biguanide therapy for non-insulin dependent diabetics. Metabolic effects of glibenclamide and metformin or phenformin in newly diagnosed obese patients

SummaryFasting, pre-prandial and post-prandial blood glucose levels and blood lactate, blood pyruvate, serum cholesterol, serum triglycerides and body weight were measured in 30 obese, newly diagnosed, non-insulin-dependent diabetics at the end of 4 subsequent periods of different regimens, each lasting for 5 days. In the first period, patients remained on free diet; in the second period, a hypocaloric diet (20 kcal/kg IBW) was followed; in the third period, glibenclamide (2.5 mg 3-times daily) was added to hypocaloric diet. During the last period, the patients were divided into two groups: Group A (15 patients) received, in addition to diet and glibenclamide, phenformin (25 mg 3-times daily) and Group B (15 patients) received, in addition to diet and glibenclamide, metformin (500 mg 3-times daily). Five similar patients served as controls and, at the end of the free-diet period, were put on hypocaloric diet and continued this regimen throughout the study period. The results showed that biguanides allowed...

Combined continuous subcutaneous insulin infusion and multiple subcutaneous injections in type I diabetic patients.

Seven insulin-dependent diabetic patients (aged 16-34 yr) were treated for 10 mo with a combination of continuous subcutaneous insulin infusion (CSII) during the night and premeal boluses of insulin during the day. The technology and strategy of the system are discussed. Three of these patients had been on CSII for 1 yr before the start of this study. Mean fasting (126 +/- 44 mg/dl), mean preprandial blood glucose (131 +/- 54 mg/dl), and mean postprandial blood glucose (216 +/- 73 mg/dl) before starting this treatment fell to 86 +/- 12 mg/dl, 83 +/- 19 mg/dl, and 132 +/- 17 mg/dl, respectively, after 1 mo of treatment. Glycosylated hemoglobin (10.8 +/- 2.9% before the study) reached normal values (7.8 +/- 0.6%) after 2 mo of treatment. Improvement of glycemic control may be achieved with this form of insulin administration, which is of immediate practical application, until an ideal system of insulin delivery becomes available. This technique provides the conditions for testing the hypothesis that near normalization of glycemic control prevents or minimizes the degenerative complications associated with diabetes mellitus.