Effect of somatostatin on insulin-induced hypoglycemia in man

In order to study the interaction of insulin and somatostatin on glucose regulation in the posthypoglycemic phase of a somatostatin infusion we have applied a bolus of i.v. insulin to healthy subjects receiving a continuous infusion of somatostatin. Glucose, insulin and counterregulatory hormones were determined. Somatostatin suppressed the growth hormone and glucagon responses to hypoglycemia but did not augment the hypoglycemic action of insulin. In contrast, the K-value for the decrease in blood glucose was significantly lower in the presence of somatostatin. Thus, the interaction of insulin and somatostatin on glucose metabolism is complex and time-dependent. While the peptide potentiates the action of insulin during the first hour of somatostatin infusion, it counteracts if after two hours. As somatostatin has currently been introduced in the therapy of upper gastrointestinal bleedings, these effects of the peptide must be taken into consideration.     

Hypoglycemia in diabetics on dialysis with poor glycemic control: hemodialysis versus continuous ambulatory peritoneal dialysis.

Eight diabetic men with poor glycemic control, probably worsened by severe congestive heart failure and gastroparesis, were sequentially dialyzed by CAPD and hemodialysis. Mean blood glucose concentration, blood glycosylated hemoglobin, and insulin dose were higher during CAPD than during hemodialysis. Among blood glucose determinations, however, the frequency of hypoglycemia (glucose less than 3.3 mmol/L) was higher during hemodialysis (13.2 +/- 8.9%) than during CAPD (2.8 +/- 2.1% p = 0.012), whereas the frequencies of hyperglycemia (glucose greater than 11.1 mmol/L) and euglycemia (glucose between 3.5 and 11.1 mmol/l) did not differ between the two dialysis modalities. Furthermore, hypoglycemia was severe during hemodialysis and was associated with two deaths. There were no deaths linked to abnormalities in blood glucose concentration during CAPD. When hypoglycemia is frequent in diabetics with poor glycemic control, CAPD is preferable to hemodialysis.     

Effect of anti-insulin antibodies on glycemic control in insulin treated diabetic patients

In order to examine the effect of anti-insulin antibodies on serum insulin concentration and glycemic control, sera from 49 insulin-treated diabetic patients (20 males and 29 females) were examined for their titer of anti-insulin antibodies, and concentrations of total insulin (TIRI), free insulin (FIRI) and hemoglobin A1c. Titer of anti-insulin antibodies correlated only with TIRI (r = 0.72, p less than 0.001) and did not correlate with duration of insulin treatment, FIRI concentration, daily dose of insulin, or HbA1c concentration. These results indicate that elevated titer of anti-insulin antibodies in patients under insulin therapy, (1) increases total serum insulin concentration but does not affect serum free insulin level, and (2) has little effect, if any, on glycemic control and the required daily dose of insulin.     

Effect of anti-insulin antibodies on glycemic control in insulin treated diabetic patients

In order to examine the effect of anti-insulin antibodies on serum insulin concentration and glycemic control, sera from 49 insulin-treated diabetic patients (20 males and 29 females) were examined for their titer of anti-insulin antibodies, and concentrations of total insulin (TIRI), free insulin (FIRI) and hemoglobin A1c. Titer of anti-insulin antibodies correlated only with TIRI (r = 0.72, p less than 0.001) and did not correlate with duration of insulin treatment, FIRI concentration, daily dose of insulin, or HbA1c concentration. These results indicate that elevated titer of anti-insulin antibodies in patients under insulin therapy, increases total serum insulin concentration but does not affect serum free insulin level, and has little effect, if any, on glycemic control and the required daily dose of insulin.     

The effect of training on responses of Β-endorphin and other pituitary hormones to insulin-induced hypoglycemia

Summary We studied whether the previously reported intensified -endorphin response to exercise after training might result from a training-induced general increase in anterior pituitary secretory capacity. Identical hypoglycemia was induced by insulin infusion in 7 untrained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 49±4 ml · (kg · min)^–1, mean and SE) and 8 physically trained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 65±4 ml · (kg · min)^–1) subjects. In response to hypoglycemia, levels of -endorphin and prolactin immunoreactivity in serum increased similarly in trained (from 41±2 pg · ml^–1 and 6±1 pg · ml^–1 before hypoglycemia to 103±11 pg · ml^–1 and 43±9 pg · ml^–1 during recovery, P<0.05) and untrained (from 35±7 pg · ml^–1 and 7±2 pg · ml^–1 to 113±18 pg · ml^–1 and 31±8 pg · ml^–1 P<0.05) subjects. Growth hormone (GH) was higher 90 min after glucose nadir in trained (61±13 mU · l^–1) than in untrained (25±6 mU · l^–1) subjects (P<0.05). Levels of thyrotropin (TSH) changed in neither of the groups. It is concluded that, in contrast to what has been formerly proposed, training does not result in a general increase in secretory capacity of the anterior pituitary gland. TSH responds to hypoglycemia neither in trained nor in untrained subjects. Finally, differences in -endorphin responses to exercise between trained and untrained subjects cannot be ascribed to differences in responsiveness to hypoglycemia.     

A controlled study of the influence of continuous subcutaneous insulin infusion treatment on diabetic retinopathy during pregnancy

Forty consecutive pregnant patients with insulin-dependent (Type I) diabetes mellitus were randomized at the end of the first trimester for treatment with conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion therapy (CSII). Nine patients randomized into the CSII group declined the pump treatment. The mean glycosylated haemoglobin (Hb AIc) decreased (p less than 0.001) both in the CIT and the CSII groups with no difference between the groups. Some deterioration in retinopathy was found in 2/18 patients in the CIT group, in 5/13 in the CSII group, and in 3/9 of those who declined the pump treatment. The proportion of patients whose retinopathy progressed did not differ significantly between the groups, and in the majority the deterioration was mild. However, two patients in the CSII group developed acute ischaemic retinopathy, which progressed to proliferative stage in spite of laser treatment. In these two cases the decrease in the Hb AIc level was among the greatest and fastest in the study. These data suggest that a rapid near normalization of glycaemic control by CSII during pregnancy can accelerate the progress of retinopathy in poorly controlled diabetic patients.     

The effect of asymptomatic nocturnal hypoglycemia on glycemic control in diabetes mellitus

To assess the effect of asymptomatic nocturnal hypoglycemia on glycemic control in insulin-dependent diabetes mellitus, we studied, on three nights, 10 patients receiving their usual regimens of continuous subcutaneous insulin infusion. During a control night, the patients' mean (+/- SE) plasma glucose level reached a nadir of 4.5 +/- 0.2 mmol per liter at 3 a.m.; the fasting glucose level was 5.9 +/- 0.3 mmol per liter at 7:30 a.m., and a peak glucose level of 8.6 +/- 0.3 mmol per liter was reached at 10 a.m., after breakfast. During nights two and three, supplemental insulin was infused intravenously from 10 p.m. to 2 a.m. to simulate a clinical overdose of insulin. On these nights, either hypoglycemia (2.4 +/- 0.2 mmol per liter) was permitted to occur or a nearly normal glucose level (5.5 mmol per liter) was maintained by infusion of glucose. The subjects were asymptomatic on all three nights. Despite comparable plasma free insulin levels from 4 to 11 a.m., both fasting (7.3 +/- 0.2 mmol per liter) and postbreakfast (12.5 +/- 0.4 mmol per liter) plasma glucose levels were significantly higher after hypoglycemia than when hypoglycemia was prevented (6.2 +/- 0.2 mmol per liter and 8.7 +/- 0.4 mmol per liter, respectively; P less than 0.001 in both cases). Fasting levels of plasma glucose correlated directly with overnight plasma levels of epinephrine (r = 0.78, P less than 0.001), growth hormone (r = 0.57, P less than 0.009), and cortisol (r = 0.52, P less than 0.02) but correlated inversely with the overnight nadir of plasma glucose (r = -0.62, P less than 0.005). We conclude that asymptomatic nocturnal hypoglycemia can cause clinically important deterioration in glycemic control (the Somogyi phenomenon) in patients receiving intensive insulin therapy, and should therefore be considered in the differential diagnosis of unexplained morning hyperglycemia.     

Transient effect of the combination of insulin and sulfonylurea (glibenclamide) on glycemic control in non-insulin dependent diabetics poorly controlled with insulin alone

In a double-blind cross-over study we compared the effects of insulin plus glibenclamide, 5 mg twice daily, with insulin plus placebo during 8-week periods on metabolic parameters in 13 non-insulin dependent diabetic (NIDDM) patients poorly controlled with insulin alone. The combination therapy improved diabetic control as assessed by fasting blood glucose (p less than 0.001), 24-hour urinary glucose (p less than 0.01) and glycohemoglobin (HbA1) concentrations (p less than 0.05 at week 12). The effect tended to cease with time. Significantly higher C-peptide values were found during combination treatment than during insulin-placebo (p less than 0.01) and the changes in fasting C-peptide concentrations correlated positively with the changes in HbA1 concentrations (r = 0.56, p less than 0.05). There was no difference in glucagon concentrations, insulin binding to erythrocytes or insulin sensitivity between the two study periods. Neither did the combination therapy influence blood lipids significantly. The present study shows that the combination of insulin and glibenclamide may be of limited value in the treatment of NIDDM patients poorly controlled with insulin alone. However, thus far the long-term results are uncertain. In the absence of significant effects on insulin binding and insulin sensitivity, the improved diabetic control seems to be explained, at least partly, by glibenclamide-induced stimulation of insulin secretion.     

Control oriented model of insulin and glucose dynamics in type 1 diabetics

The aim of the study was to realize a mathematical model of insulin–glucose relationship in type I diabetes and test its effectiveness for the design of control algorithms in external artificial pancreas. A new mathematical model, divided into glucose and insulin sub-models, was developed from the so-called “minimal model”. The key feature is the representation of insulin sensitivity so as to permit the personalisation of the parameters. Real-time applications are based on an insulin standardised model. Clinical data were used to estimate model parameters. Root mean square error between simulated and real blood glucose profiles (G_rms) was used to evaluate system efficacy. Results from parameter estimation and insulin standardisation showed a good capability of the model to identify individual characteristics. Simulation results with a G_rms 1.30 mmol/l in the worst case testified the capacity of the model to accurately represent glucose–insulin relationship in type 1 diabetes allowing self tuning in real time.     

Effects of twice-daily injections of premixed insulin analog on glycemic control in type 2 diabetic patients

Purpose

Premixed insulin is effective to improve glycemic control; however, clinicians may be less likely to know which premixed insulin is appropriate for which patients. This study aimed to evaluate the effects of twice-daily injections of premixed insulin lispro on glycemic control in type 2 diabetic patients.

Materials and Methods

Forty type 2 diabetic patients, who had been treated with twice-daily injections of human protamine mixture 30/70 insulin for at least 12 months, were divided into two groups; one group whose blood glucose 2 hours after breakfast was greater than 200 mg/dL, was switched to lispro mix50, and the other group whose blood glucose 2 hours after breakfast < 200 was switched to lispro mix25.

Results

Glycated haemoglobin (HbA1c) significantly improved in the Mix50 group from 8.3% to 7.5% (at 12 weeks; p < 0.05), and to 7.5% (at 24 weeks; p < 0.05). On the other hand, HbA1c levels in the Mix25 group were slightly decreased from 8.1% to 7.7% at 12 weeks (p < 0.05), and to 7.9% at 24 weeks (not significant). Both postprandial plasma glucose and fasting plasma glucose levels were significantly improved in the Mix50 group, but not in the Mix25 group. Overall, 95% of subjects preferred premixed lispro insulin from human insulin in the viewpoint of the timing of insulin injection by questionnaire analysis.

Conclusion

Switching from human protamine mixture 30/70 insulin to lispro mix50 twice-daily injection therapy in patients with high postprandial plasma glucose could improve their glycemic control and quality of life.     

Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. II. Glomerular basement membrane thickness

Stereological studies were performed on renal glomeruli from control rats, untreated streptozotocin-diabetic rats and diabetics treated by subcutaneous infusion of insulin for 16 weeks. Estimates of glomerular basement membrane thickness were obtained by dividing membrane volume by membrane surface area. In addition, arithmetic and harmonic mean thicknesses were calculated from orthogonal intercept lengths, and used to provide information on the variability of basement membrane thickness. In untreated diabetics, both arithmetic and harmonic mean thicknesses were significantly greater than values found in control animals. The thickening of the basement membrane appeared to be generalized rather than markedly focal. All thickness variables were normalized by insulin infusion therapy. These findings underline the importance of good glycaemic control and early intervention in experimental diabetes and one of its main complications.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.     

胰岛素强化治疗在2型糖尿病骨折患者围手术期的应用

Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation.