Conventional Insulin Treatment Research Articles

Intensified conventional insulin treatment and neuropsychological impairment.

To assess whether intensified insulin treatment, with an increased frequency of hypoglycaemic episodes, leads to cognitive deterioration. Prospective randomised trial of intensified conventional treatment and standard treatment. Outpatient clinic for patients with insulin dependent diabetes. 96 patients with insulin dependent diabetes, high blood glucose concentrations, and non-proliferative retinopathy were randomised to intensified conventional treatment (n = 44) or standard treatment (n = 52). Glycated haemoglobin concentration (metabolic control); the number of hypoglycaemic episodes reported by patients at each visit; results of computerised neuropsychological tests performed at entry and after five years. Mean glycated haemoglobin concentration during the study was 7.2% (SE 0.1%) with intensified conventional treatment and 8.7 (0.1%) with standard treatment (p less than 0.001). During five years 34 (77%, 95% confidence interval 53% to 100%) of the patients given intensified treatment and 29 (56%, 36% to 75%) of the others had at least one episode of serious hypoglycaemia (p less than 0.05). The intensified conventional treatment group had a mean of 1.1 episodes of serious hypoglycaemia per patient per year compared with 0.4 episodes in the standard treatment group. Results of the neuropsychological tests were similar in the two groups after five years. Intensified conventional insulin treatment led to lower blood glucose concentrations and a higher frequency of hypoglycaemic episodes, but patients showed no signs of cognitive deterioration.

Intensified conventional insulin treatment retards the microvascular complications of insulin‐dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 years

Ninety-six patients with insulin-dependent diabetes mellitus (IDDM) and non-proliferative retinopathy were randomized to intensified conventional treatment (ICT) (n = 44) or regular treatment (RT) (n = 52), and followed up for 5 years. HbA1c decreased from 9.5 +/- 0.2% (mean value +/- SEM) to 7.2 +/- 0.1% in the ICT group, and from 9.4 +/- 0.2% to 8.7 +/- 0.1% in the RT group (difference between the groups, P less than 0.001). Retinopathy increased in both groups (P less than 0.001), but after 5 years it was worse in the RT group (P less than 0.05). The urinary albumin excretion rate was higher in the RT group than in the ICT group after 5 years (239.9 +/- 129.7 micrograms min-1 vs. 46.0 +/- 26.1 micrograms min-1, P less than 0.05). Eight RT patients developed manifest nephropathy, compared with none in the ICT group (P less than 0.01). After 5 years the conduction velocities of the sural (P less than 0.05), peroneal (P less than 0.01) and tibial (P less than 0.001) nerves were lower in the RT group. The respiratory sinus arrhythmia was 12.1 +/- 1.2 beats min-1 in the RT group and 16.7 +/- 1.4 beats min-1 in the ICT group at the end of the study (P less than 0.01). The increases in retinopathy (P less than 0.01), nephropathy (P less than 0.01) and neuropathy (P less than 0.001) were all related to the mean HbA1c value during the study. Smoking habits only influenced the progression of retinopathy (P less than 0.05). Serious hypoglycaemia occurred in 34 ICT patients and 29 RT patients (242 and 98 episodes, respectively) (P less than 0.05). Whereas weight was stable in the RT group, the body mass index increased by 5.8% in the ICT group (P less than 0.01). In conclusion, microvascular complications of diabetes were retarded by intensified conventional insulin treatment. However, such treatment increased the frequency of serious hypoglycaemia, and led to an increase in body weight.

Glucose disposal and intermediary metabolism during one year of continuous subcutaneous insulin infusion (CSII)

To study the effects of CSII on insulin action and intermediary metabolism, seven type 1 diabetic patients (duration 17 ± 4 (SEM) years), underwent sequential euglycemic clamps 1 4 , 6 and 12 months after changing from conventional insulin treatment to continuous subcutaneous insulin infusion (CSII); seven healthy subjects served as controls. For at least 14 h before the study, blood glucose was maintained between 4–10 mmol/l in the patients by intravenous insulin infusion, to avoid negatively biased clamp measures. A metabolite profile was taken in the basal state and during euglycemic hyperinsulinemia. At 1 4 month insulin sensitivity was decreased in the patients ( ED 50 82 ± 14 vs 52 ± 4 mU/l in controls, P < 0.02), whereas insulin responsiveness was normal. During the course of one year, no change towards control values was found for insulin-stimulated glucose disposal. Concomitantly, HbA 1 did not change either, and remained elevated ( 1 4 month 11.1 ± 0.7%, 12 months 10.0 ± 0.9% vs 6.5 ± 0.3% in controls, P < 0.01). Regarding basal intermediary metabolism, triglycerides became significantly improved ( 1 4 month 1.32 ± 0.13 mmol/l, 12 months 0.70 ± 0.05 mmol/l, P < 0.05, vs 0.70 ± 0.08 mmol/l in controls). The acetoacetate/3-OH-butyric acid ratio increased from 0.10 at 3 to 0.26 at 12 months, which was similar to controls. The absolute levels of acetoacetate and 3-OH-butyric acid remained elevated 2–3 fold. For other basal metabolite levels no systematic trend for improvement was found for 1 4 to 12 months. During euglycemic hyperinsulinemia no differences were found with controls at 1 4 month and during the first year of CSII, except for alanine remaining slightly decreased. In summary, in type 1 diabetics initially presented with decreased insulin sensitivity with unchanged responsiveness did not improve during CSII in the course of one year. Triglycerides and the ketogenic index became normalized, whereas metabolite levels in the basal state and during euglycemic hyperinsulinemia did not change. At the same time, glycemic control did not improve either. Thus, even with CSII normoglycemia will not be attainable in all patients, however motivated and educated. Indirectly, these findings support the glucose toxicity hypothesis for persistence of insulin resistance by hyperglycemia.

Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion: effect of long-term improved metabolic control

Forty-seven patients with type 1 (insulin-dependent) diabetes mellitus and 14 normal subjects had renal volume determined by an ultrasonic technique. Renal volume of 299 +/- 49 ml/1.73 m2 (mean +/- SD) in type 1 diabetic patients with normal urinary albumin excretion exceeded that in the normal subjects (245 +/- 53 ml/1.73 m2, p less than 0.05). Compared with diabetic patients with normal urinary albumin excretion, renal volume was significantly higher in patients with microalbuminuria (372 +/- 24 ml/1.73 m2, p less than 0.05) and patients with clinical nephropathy (352 +/- 48 ml/1.73 m2, p less than 0.05). In a multiple linear regression with HbA1c, urinary albumin excretion, age, diabetes duration and mean blood pressure as independent variables, variations in HbA1c could account for 33% of the variations in kidney volume (n = 47, r = 0.57, p less than 0.01). The other variables played no role. When only patients without clinical nephropathy were included, HbA1c and kidney volume remained significantly correlated (n = 34, r = 0.60, p less than 0.01). In those patients a strong correlation between kidney volume and function, i.e. the glomerular filtration rate was found (n = 34, r = 0.70, p less than 0.01); metabolic control and function were also correlated (n = 34, r = 0.62, p less than 0.01). The urinary albumin excretion accounted for only 6% of the variation of the kidney volume (NS). In nine patients with microalbuminuria the kidney volume could be reduced during 2 years of improved metabolic control by means of insulin infusion pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Insulinotropic Effects of Glucagonlike Peptide I-(7–36)-Amide and Gastric Inhibitory Polypeptide in Isolated Perfused Diabetic Rat Pancreas

The pathophysiological role of incretin in diabetes mellitus has not been established. We therefore examined the effects of glucagonlike peptide I-(7-36)-amide (truncated GLP-I) and gastric inhibitory polypeptide (GIP) on insulin and glucagon release from isolated perfused pancreases of diabetic rats (12-14 wk of age, mean +/- SE fasting plasma glucose 8.9 +/- 0.6 mM, n = 25) after an injection of 90 mg/kg streptozocin on the 2nd day after birth and compared the results with those of nondiabetic control rats. In diabetic rats, the infusion of 1 nM GLP-I or GIP in perfusates with varying glucose concentrations (2.8, 5.6, 8.3, 11.1, or 22.2 mM) caused a nearly equal degree of insulin stimulation from a similar basal insulin level. Meanwhile, basal and GLP-I- or GIP-stimulated insulin release increased in correlation with the ambient glucose concentration in nondiabetic rats. The degree of stimulation of insulin release at glucose concentrations of 5.6 mM in diabetic rats was approximately 33% that of nondiabetic rats. The stimulation potency was the same between GLP-I and GIP. The insulin treatment for diabetic rats (5 U/kg NPH insulin at 0900 and 2100 for 6 days) brought only a slight improvement in the glucose dependency of GLP-I-stimulated insulin release. The effects of GLP-I and GIP on glucagon release were completely opposite. GLP-I suppressed release; GIP stimulated it. In diabetic rats, the degree of suppression by GLP-I and stimulation by GIP were almost the same with similar basal glucagon levels in the perfusate with varying glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved metabolic control, clinical periodontal status and subgingival microbiology in insulin‐dependent diabetes mellitus

The effect of improved metabolic control on the clinical periodontal condition and the subgingival microflora of diseased and healthy periodontal pockets in 6 ambulatory insulin-dependent diabetes mellitus (IDDM) patients was prospectively studied. Duplicate measurements with a time-interval of 3 days were made every 4 moths for assessment of the metabolic status, the clinical periodontal condition and the subgingival microflora. During the study, patients maintained personal oral hygiene measures as they usually did before the study. Neither supplementary dental prophylaxis nor oral hygiene measures were applied during the investigation. Long-term metabolic control (HbAlc) improved significantly with intensive conventional insulin treatment. Gingival redness decreased significantly whereas gingival swelling showed a not significant trend to decrease. It is suggested that microvascular changes associated with improved metabolic control in diabetes mellitus may mediate the observed change in gingival redness. No effect could be demonstrated for probing pocket depth, probing attachment level, bleeding on probing and the plaque index. Statistical analysis of the effect of improved metabolic control on the subgingival microflora revealed that only the % of streptococci increased significantly in diseased periodontal pockets. In general, no significant changes were found in either healthy or diseased pockets with regard to the bacterial flora associated with periodontal disease. The results of the present study indicate that improved metabolic control in IDDM patients may have no potential impetus for an improved clinical periodontal condition nor on the subgingival bacterial flora. It is concluded that the periodontal condition in IDDM patients may only ameliorate when local oral hygiene measures are applied.

Diabetic ketoacidosis in Denmark: epidemiology, incidence rates, precipitating factors and mortality rates

The epidemiology of uncontrolled diabetes mellitus was studied in an 11.2% sample of the Danish population (574,696 inhabitants) during a 24-month period. Some 175 admissions in ketoacidosis (heavy ketonuria and plasma bicarbonate below 21 mmol/l) were recorded. Based on prevalence rates from a socio-economically and ethnically comparable Danish county, the annual incidence rate was calculated to be 0.045 per diabetic. The incidence rate of moderate and severe episodes (bicarbonate less than 16 mmol/l) was 0.032 and of severe episodes only (bicarbonate less than 10 mmol/l) 0.017 per diabetic. The major risk group was female teenagers. The total annual frequency of recurrence was 8.7%: 48% of the male episodes were ketoacidosis (DKA) associated with onset of diabetes, against 30% of the female episodes (P = 0.02). All Danish diabetics were at the time of the survey (1978-79) treated with conventional insulin treatment. Annual incidence rate in these established diabetics was 0.028, i.e. three to five times less than reported during treatment with continuous subcutaneous insulin infusion. Mortality of DKA was low, 3.4%, and dependent upon age and precipitating factor but not upon the degree of acidosis. The overall annual mortality rate was 1.5 per 100 diabetics.

Blood rheology during an intensified conventional insulin treatment (ICIT) in insulin-dependent diabetes

Fifteen insulin-dependent diabetes mellitus (IDDM) patients with minor diabetic complications underwent an intensified conventional insulin treatment (ICIT) program consisting of multiple daily insulin injections with an insulin pen. Blood viscosity parameters were measured before the start, after 6 weeks, 1 and 2 years with a Contraves LS30 viscosimeter. At the start several rheological parameters were disturbed in the diabetic subjects. Mean total hemoglobin A 1 (HbA 1) significantly (at least P < 0.05) decreased while the plasma free insulin level significantly increased (at least P < 0.05) under ICIT. During the first 6 weeks hematocrit ( P < 0.01), plasma ( P < 0.05), whole blood ( P < 0.05) and erythrocyte ( P < 0.01) viscosities significantly decreased but they increased again at 1 year of ICIT. Only plasma viscosity ( P < 0.05) remained below the starting value after 1 and 2 years. Normalization of the blood sugar level improved plasma and whole blood viscosity by an insulin-induced dilution phenomenon after 6 weeks. The persisting decrease in plasma viscosity was accompanied by a significant alteration of the plasma protein profile. These findings suggest that metabolic status influences blood rheology in IDDM patients but by different mechanisms on a short- or long-term basis.

Oscillatory Potentials, Macular Recovery Time, and Diabetic Retinopathy Through 3 Years of Intensified Insulin Treatment

Forty-five diabetic patients, 18 to 45 years of age, with mild or no retinopathy, were randomly assigned to continuous subcutaneous insulin infusion (CSII), multiple injections (MIs), and conventional insulin treatment (CIT). The effects of near-normoglycemia (CSII and MI) on oscillatory potentials (electroretinography [ERG]) and macular recovery time (nyctometry) were studied prospectively for 41 months. Before randomization, the amplitudes of oscillatory potentials were negatively correlated to age (P = 0.002) and positively correlated to the diameter of retinal veins (P < 0.05). Men had shorter macular recovery time than women (P = 0.03). Nyctometry and oscillatory potentials were not related to mean blood glucose values, glycosylated hemoglobin (HbA1), retinopathy, blood pressure levels, or duration of diabetes. Changes in metabolic control (MI and CSII; P < 0.01) and in microaneurysms and hemorrhages (CSII and CIT) during the study did not affect oscillatory potentials or nyctometry. Soft exudates (15 patients) and proliferative retinopathy (1 patient) transiently developed with MI and CSII regimens. No changes in oscillatory potentials or nyctometry were observed and no pretreatment characteristics of these parameters predicted the occurrence of these ischemic lesions. At the stage of proliferation, however, lowered amplitudes of oscillatory potentials and lengthened macular recovery time were observed.

Glucagon responses to intravenous arginine and oral glucose in insulin-dependent diabetic patients during six months conventional or continuous subcutaneous insulin infusion

To elucidate the impact of subcutaneous insulin infusion (CSII) treatment on the glucagon response to intravenous (IV) arginine and to oral glucose a 6-month prospective randomized study in insulin-dependent diabetics was carried out. The effects were investigated of CSII (7 patients) and conventional insulin treatment (UCT) (9 patients) on the changes in glucagon, growth hormone, glucose, lactate, glycerol, 3-hydroxybutyrate, and alanine to IV arginine and to oral glucose in insulin-dependent diabetics who were made euglycemic and isoinsulinemic using the artifical pancreas (Biostator, Miles, Elkhart, IN). HbA 1c was significantly lower in the group treated by CSII. Despite the improved glycemic control no significant change in the responses of A-cell secretion to arginine or glucose challenges was found. In addition, there were no significant differences in hormone or metabolite values between the two groups at entry to the study or after 6 months of either therapy. Thus, normalization of the A-cell sensitivity to glucose in insulin-dependent diabetic subjects requires further amelioration of the intermediary metabolism than can be achieved with insulin pump treatment.

8 Macrovascular disease and hyperinsulinaemia

The evidence that hyperinsulinaemia represents an independent risk factor for cardiovascular disease is tantalizing but the hypothesis cannot be said to be proven. The inconsistencies arising from the major prospective studies require that further work be done. Hyperinsulinaemia may not carry the same implications in all subjects and its interactions with other risk factors and with blood glucose are not well described. Possible further research has been discussed and outlined at a recent meeting (Colwell, 1985). The suggestions include delineating the action of growth factors and insulin in defined serum-free tissue culture, and the use of more sophisticated culture models, such as smooth muscle covered by vascular endothelium. The choice of human or primate tissue is desirable because of the species specificity of the atherosclerotic lesions. Prospective trials of modifying peripheral insulin levels in treated diabetic patients are probably still impracticable. The case for attempting to achieve normoglycaemia in diabetes to avoid microvascular complications is strong, and current insulin treatment regimens accept peripheral hyperinsulinaemia as a consequence of achieving portal insulin concentrations sufficient to suppress hepatic glucose output. It is hard to envisage a trial to examine reduced peripheral insulin concentrations which would not give unacceptably poor blood glucose control. Current studies of different methods and degrees of control of blood glucose might be used to provide some indication of whether such a trial could ever be justified. The Diabetes Control and Complication Trial (DCCT) is a prospective multicentre study of intensive versus conventional insulin treatment in insulin-dependent diabetic patients in the USA, and the UK Prospective Study of therapies of maturity onset diabetes (UKPS) is following patients not satisfactorily controlled on diet, randomized to different treatment modalities. These may produce some evidence within the next few years, on insulin concentrations and complications (Tattersall and Scott, 1987). Should any of this change current management of non-insulin-dependent diabetes? Despite claims of enthusiasts, special treatment regimens with intensive exercise, a particular oral agent or the addition of sulphonylureas to insulin therapy are either not generally applicable or have little theoretical basis (Martin, 1986). Current 'good practice' in Europe as put forth in a consensus document (Alberti and Gries, 1988), recognizes the need to address risk factors other than diabetes in the management of the non-insulin-dependent diabetic patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Does strict metabolic control prevent long‐term diabetic complications?

AbstractAlthough insulin has been in use for 65 years, it is still not kn„n whether strict metabolic control can prevent long‐term diabetic complications. There are two major reasons for this: conventional insulin treatment is unable to normalise or near‐normalise blood glucose levels; and until recently there were no methods for long‐term monitoring of blood glucose. During the last decade infusion pumps and pens have been marketed which enable us to simulate the endogenous insulin secretion and thereby normalise or near‐normalise blood glucose levels and home blood glucose monitoring methods are widely available. Therefore, it should n„ be possible to test the hypothesis that strict metabolic control prevents long‐term diabetic complications. This paper reviews the results of six prospective, controlled, randomised, clinical trials which have been published. The consensus is that near‐normalisation of blood glucose levels is able to retard or arrest the progression of long‐term diabetic complications.

Sustained Normoglycemia and Remission Phase in Newly Diagnosed Type I Diabetic Subjects.Comparison Between Continuous Subcutaneous Insulin Infusion and Conventional Therapy During a One Year Follow-Up

After onset of type I diabetes 7 diabetics were randomized to subcutaneous insulin pump treatment (CSII) (age 12 to 29 years, mean: 21 years) and 7 diabetics to conventional insulin treatment (CI) (age 14 to 28 years, mean: 21 years). HbA1, glycosylated serum proteins and mean blood glucose (MBG) as parameters of metabolic control were determined monthly. After 2 months both groups showed HbA1 values in the normal range. Mean MBG values were (mean +/- SD) 116 +/- 7 mg/dl for CSII and 118 +/- 14 mg/dl for CI. Residual insulin secretion was determined monthly by fasting C-peptide. After 14 days, 5, 7, 8 months fasting C-peptide values were significantly (P less than 0.05) higher in CI. After one year fasting C-peptide was comparable in both groups (CSII and CI mean: 0.06 nmol/l). The administered insulin dose was comparable in both groups with a 55% reduction of insulin dose after 5 months in CSII (0.35 +/- 0.15 U/kg/24 h) and in CI after 7 months (0.31 +/- 0.28 U/kg/24 h). After 12 months of insulin therapy about 60% of the initial insulin dose was injected in both groups. 1 patient on CSII (12 years) and 2 patients on CI (15, 28 years) showed a complete remission (for 3-9 months) with no exogenous insulin and normal HbA1 values. 50% of the patients had episodes where they did need less than 0.2 U/kg/24 h insulin to maintain optimal diabetic control (3 CSII, 4 CI). During the first year of insulin treatment in type I diabetes with CSII as well as with CI a comparable near normalisation of diabetic control could be achieved.

Near normoglycemia for 1 year has no effect on platelet reactivity, factor VIII, and von willebrand factor in insulin-dependent diabetes mellitus: A controlled trial

The impact of prolonged near-normoglycemia on platelet reactivity (spontaneous and induced platelet aggregation), factor VIII, and von Willebrand factor in patients with insulin-dependent diabetes mellitus (IDDM) was evaluated in a prospective, randomized, controlled clinical trial. Twenty IDDM patients with no or only minor clinical signs of microvascular disease were randomly assigned to 1 year of continuous subcutaneous insulin infusion (CSII) or unchanged conventional insulin treatment (CIT). Hemoglobin A 1c declined during the 12 month observation period from 7.3±1.2% to 6.4±0.9% (2p<0.01) in the CSII group, while this measure of glycemic control was unchanged in the CIT group: 7.2±1.1% vs 8.0±1.6% (NS). Platelet reactivity, factor VIII, and von Willebrand factor concentrations were identical in the two groups at entry into the study, and no significant changes in these variables were seen in either group. Thus, the present results do not support the concept of increased platelet reactivity following CSII treatment.

Effect of continuous subcutaneous insulin infusion on kidney function and size in IDDM patients: A 2 year controlled study

Glomerular filtration rate (GFR), renal plasma flow (RPF), kidney volume, and urinary albumin excretion rate were measured in 24 insulin-dependent diabetics, aged 29±7 years (mean ± SD) with diabetes duration of 8±4 years who were randomly allocated to either continuous subcutaneous insulin infusion (CSII) (n=12) or unchanged conventional insulin treatment (CIT) (n=12). GFR, RPF, and kidney volume were identical but signiticantly increased above normal values in the two groups at the start of the study. After 24 months of CSII treatment, significant reduction in GFR was seen compared to pre-treatment values (145±21 ml/min vs 139±21 ml/min, 2p<5.0%). However, RPF was not reduced after 24 months of CSII treatment (608±104 ml/min vs 601±106 ml/min). In the CIT group no changes in GFR or RPF was seen, and kidney volume remained unchanged in both groups; urinary albumin excretion was normal or near normal in both groups and remained unchanged. Thus, improved glycemic control in longterm IDDM patients is associated with normalization (reduction) of renal “hyperfunction,” but despite this, no reduction was seen in the associated nephromegaly.

Evaluation of insulin pump treatment under routine conditions

Sixty-six patients with insulin-dependent diabetes mellitus (IDDM) initiated insulin pump treatment under routine conditions. Four patients (6%) discontinued treatment. One patient died. 61 patients were followed for a total period of 130 patient years. A sustained decrease in HbA1c was obtained during insulin pump treatment. The frequency of the following acute side effects was: ketoacidosis 0.06 episodes per patient per year, severe hypoglycaemia 0.09 episodes per patient per year and infection at the injection site 0.06 episodes per patient per year. Insulin pump treatment was well accepted by the patients; all but one wanted to continue insulin pump treatment. The major advantages were greater quality of life, greater flexibility as to meal times and better blood glucose regulation. The major disadvantages were technical problems: blockage of the infusion system, greater treatment expenses and the large pump size. We conclude that insulin pump treatment is well accepted as long-term treatment in selected IDDM patients. The improvement in metabolic control can be sustained through several years, and the frequency of severe hypoglycaemia during pump treatment is comparable to that of conventional insulin treatment. The risk of ketoacidosis requires more attention from the physician.

Clinical use of a portable infusion pump and pen-type injector in type 1 diabetes mellitus.

AbstractIntensive insulin therapy was studied in six children with type 1 diabetes mellitus which was refractory to conventional insulin treatment. The methods used were continuous subcutaneous insulin infusion with a portable pump, and pre‐meal pulse infusion of short‐acting insulin with a pen‐type syringe supplemented with a bolus of long‐acting insulin. The former method was used in three patients for two weeks and in one patient for four months, in hospital, and the latter was used in two patients, starting in hospital and continuing for one year at home. Both these methods achieved better metabolic control than conventional therapy. In addition, insulin requirements decreased with continuous subcutaneous infusion but it had to be discontinued after discharge because of costs and the complexity of the equipment. With pre‐meal pulse infusion, insulin requirements increased compared with conventional therapy.

Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion

In addition to hyperglycaemia, derangement of metabolic and hormonal control may play an important role in the development of microvascular complications in diabetes. Little, however, is known about the impact of insulin pump treatment on metabolic and hormonal parameters. In a 6-month prospective randomized study in insulin-dependent diabetics we therefore investigated the effects of continuous subcutaneous insulin infusion by pump (10 patients) and conventional insulin treatment (10 patients) on the 24-h profiles of blood glucose, glycerol, lactate, 3-hydroxybutyrate, insulin, glucagon and growth hormone by measuring the respective concentrations every 2 h. We found that average blood glucose levels and HbA1c were significantly lower in the group treated by continuous subcutaneous insulin infusion as compared with the group on conventional insulin treatment. Furthermore, we observed an improvement in diurnal levels of lactate and 3-hydroxybutyrate in the pump-treated group which was not seen in the conventionally treated group. A slight increment in alanine was seen in the group treated with insulin pump. Serum growth hormone, glycerol, plasma free insulin as well as the daily insulin supply were unchanged and identical in the two groups. It is noteworthy that in the pump group, the decrease in blood glucose and 3-hydroxybutyrate takes place concomitantly with a significant suppression of glucagon.

Prediction of starting dose for conventional insulin treatment (using the practical closed-loop system).

AbstractThis study was undertaken in 10 newly diagnosed diabetic children to assess the usefulness of the practical closed‐loop system in determining insulin doses in conventional treatment. During application of this system of continuous intravenous insulin infusion, the infusion dose was changed according to the hourly monitored blood glucose values. Conventional insulin treatment was started, based on the daily insulin profile obtained by the practical close‐loop system. This consisted of two daily injections of a mixture of short‐ and intermediate‐acting insulins. There was no significant difference in mean blood glucose, M‐value or mean amplitude of glycemic excursions between the two treatments.Compared with the previous insulin regimen in which conventional insulin treatment was performed following the initial treatment for diabetic ketoacidosis without this practical closed‐loop system, good glycemic control was obtained in a shorter period by using this system.Thus, the practical closed‐loop system could be helpful in predicting the starting insulin dose for conventional insulin treatment.

EFFECT OF TWO YEARS OF STRICT METABOLIC CONTROL ON PROGRESSION OF INCIPIENT NEPHROPATHY IN INSULIN-DEPENDENT DIABETES

36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years. The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventional-treatment group (median 8.6%, range 7.2-13.4) (p<0.001). Clinical diabetic nephropathy (a urinary albumin excretion rate above 300 mg/24 h in at least two of three 24 h urine collections) developed in 5 patients in the conventional-treatment group, but not in the insulin-infusion group (p<0.05, two-tailed). Fractional albumin clearance (mean and range × 10 7) increased in the conventional-treatment group from 160 (35-468) to 360 (29-1580) and was unchanged in the insulin-infusion group (170 [31-608] before to 160 [26-460] after) (p<0.05). Insulin infusion had an overall beneficial effect on the annual increase in urinaryb albumin excretion (p<0.05), and the mean glycosylated haemoglobin values correlated positively with annual change in albumin excretion (r=0.57, p<0.0001). The diastolic, blood pressure rose significantly in the conventional-treatment group (p<0.001), and annual change in mean blood pressure correlated with change in urinary albumin excretion (r=0.49, p<0.001).