Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial.

AIM: To confirm the superiority, compared with placebo, of adding liraglutide to pre-existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)]. METHODS: In this 26-week, double-blind, parallel-group study, conducted in clinics or hospitals, 451 subjects were randomized 1 : 1 to once-daily liraglutide 1.8 mg (dose escalated from 0.6 and 1.2 mg/day, respectively, for 1 week each; n = 226) or placebo (n = 225) added to their pre-existing basal insulin analogue (≥20 U/day) ± metformin (≥1500 mg/day). After randomization, insulin adjustments above the pre-study dose were not allowed. The primary endpoint was HbA1c change. RESULTS: After 26 weeks, HbA1c decreased more with liraglutide [-1.3% (-14.2 mmol/mol)] than with placebo [-0.1% (-1.2 mmol/mol); p < 0.0001]. More subjects on liraglutide reached HbA1c targets: <7.0% (59% vs 14%; p < 0.0001) and ≤6.5% (43% vs 4%; p < 0.0001) using slightly less insulin (35.8 IU vs 40.1 IU). Greater decreases from baseline (estimated treatment differences vs placebo; p < 0.0001) occurred in fasting plasma glucose (-1.3 mmol/l), seven-point glucose profiles (-1.6 mmol/l), body weight (-3.1 kg) and systolic blood pressure (-5.0 mmHg). Transient gastrointestinal adverse events (nausea: 22.2% vs 3.1%) and minor hypoglycaemia (18.2% vs 12.4%) were more frequent with liraglutide than placebo, and pulse increased (4.5 beats/min) compared with placebo. No severe hypoglycaemia or pancreatitis occurred. CONCLUSIONS: Adding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo. Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide.

Natriuretic peptide and echocardiography after operation of atrial septal defect.

Patients benefit from surgical seclusion of atrial septal defect but have excessive cardiovascular morbidity after the operation. We evaluated haemodynamics and looked for abnormalities of cardiac structures and function late after surgical seclusion of the defect. Serum N-terminal natriuretic peptide measurement and transthoracic and transoesophageal echocardiography were performed in 61 patients aged 43+/-15 years (mean+/-standard deviation) 21+/-5 years after surgery. The findings were compared with 67 control subjects. The patients had higher serum N-terminal atrial natriuretic peptide concentration than the control subjects (0.40+/-0.32 vs. 0.24+/-0.12 nmol/l, P=0.0001). Peptide levels correlated with current age (P=0.0001) and age at operation (P=0.0014), but not with age in the control subjects. In the patients, echocardiography measurements of cardiac dimensions correlated with hormone levels (atrial natriuretic peptide concentration with left atrial end-systolic diameter (P=0.042), left ventricular end-diastolic (P=0.021) and end-systolic diameter (P=0.042). There were only 10 patients (16%) without any abnormality in echocardiography. Their peptide concentration was 0.25+/-0.18 nmol/l (P=not significant compared to the control subjects). The association between increasing N-terminal atrial peptide levels and operation age together with echocardiography findings support the clinical consensus of treating atrial septal defect patients in their childhood and adolescence.

Hepatic subcapsular steatosis in diabetic CAPD patients treated with intraperitoneal insulin. Description of a typical pattern.

PURPOSE: To describe a specific imaging pattern of hepatic fatty change typical of diabetic patients on continuous ambulatory peritoneal dialysis (CAPD) treated with intraperitoneal (i.p.) insulin. MATERIAL AND METHODS: Liver ultrasound was applied in 16 CAPD patients with insulin-dependent diabetes mellitus. Presence of hepatic subcapsular steatosis and maximum thickness of the fatty layer were recorded. Liver MR examination was made of 1 patient found to have extensive subcapsular steatosis. RESULTS: Hepatic ultrasound revealed a typical pattern of subcapsular steatosis ("coating-of-fat") in 7/8 patients treated with i.p. insulin. None (0/8) of the diabetic CAPD patients treated with subcutaneous insulin had subcapsular steatosis. CONCLUSION: Hepatic subcapsular steatosis is specific to CAPD patients on i.p. insulin treatment. To our knowledge this is the first report to describe imaging findings in this particular form of hepatic fatty change.

Serum N-terminal atrial natriuretic peptide in adult patients late after surgical repair of atrial septal defect.

BACKGROUND: The purpose of surgical closure of atrial septal defect (ASD) is to relieve the cardiovascular system from a haemodynamic burden. Excessive amounts of atrial peptides are released in congestive heart failure, valvular diseases and congenital heart diseases. AIMS: To examine whether patients after surgical repair of ASD have higher concentrations of N-terminal atrial natriuretic peptide (ANP-N) than age-, sex- and body mass index (BMI)-matched control subjects. METHODS: Medical history, physical examination, standard 12-lead electrocardiogram, and ANP-N concentrations were obtained in 65 adult patients operated for ASD at the age of 21+/-13 years (mean+/-standard deviation), 21+/-6 years after surgical closure of ASD. Sixty-seven healthy subjects matched for age, sex and BMI served as controls. RESULTS: In the patients serum ANP-N was higher than in the control subjects 0.41+/-0.32 nmol/l, median 0.31 nmol/l, interquartile range (IQR) 0.21-0.49 nmol/l vs. 0.24+/-0.12 nmol/l, median 0.23 nmol/l, IQR 0.17-0.29 nmol/l, (P=0.0003). Patients with concomitant diseases had higher ANP-N concentrations (0.51+/-0.39 nmol/l, median 0.34, IQR 0.26-0.73 nmol/l) than ASD patients without any history or signs of disease (0.28+/-0.16 nmol/l, median 0.27, IQR 0.17-0.40 nmol/l, P=0.01). The 'healthy' ASD patients had higher hormone concentrations than age-, sex- and BMI-matched control subjects (0.28+/-0.16 median 0.27 nmol/l, IQR 0. 17-0.40 nmol/l and 0.21+/-0.07 nmol/l, median 0.20 nmol/l, IQR 0. 15-0.27 nmol/l, P=0.01). Multiple stepwise linear regression analysis showed that age at operation was strongly associated with the post-operative ANP-N concentration (r(2)=0.25, P=0.0002). CONCLUSION: ASD patients have higher ANP-N concentrations late after surgical repair. Hormone levels correlate with age at operation. Our finding supports the clinical praxis of operating on these patients in their childhood and adolescence.

Intraperitoneal insulin reduces plasma leptin concentration in diabetic patients on CAPD.

OBJECTIVE: To determine the effects of subcutaneous (SC) and intraperitoneal (IP) insulin on serum leptin concentration in type I diabetic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective, open, before-after study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Twelve type I diabetic patients with stabilized CAPD, age 43.9 +/- 2.8 years, and duration of diabetes 30.4 +/- 3.5 years. INTERVENTION: After stabilized CAPD therapy, all patients were treated first with SC insulin for a median of 3 months, and thereafter with IP insulin for another 3 months. MAIN OUTCOME MEASURES: Plasma leptin, insulin sensitivity with euglycemic clamp, and glycemic and uremic status after both treatment periods. RESULTS: During SC insulin therapy, plasma leptin concentration was significantly higher than during IP insulin (19.8 +/- 5.9 ng/mL and 12.8 +/- 6.2 ng/mL, respectively; p < 0.001). Leptin concentration was higher in CAPD patients and was related to body mass index in both genders. No correlation was detected between plasma leptin and fasting insulin, glycemic control, glucose disposal rate, or serum lipids. CONCLUSION: Plasma leptin concentration is lower during IP insulin therapy compared to SC insulin. Insulin has probably a direct effect on both peritoneal leptin clearance and adipose tissue leptin production. The significance of leptin in regulating appetite and anorexia in uremia remains unclear.

High peritoneal permeability predisposes to hepatic steatosis in diabetic continuous ambulatory peritoneal dialysis patients receiving intraperitoneal insulin.

OBJECTIVE: To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. PATIENTS: We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34-70 years), duration of diabetes was 27.5 years (range: 17-39 years), and duration of CAPD was 16.5 months (range: 2-59 months). OUTCOME MEASURES: Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. RESULTS: Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR (r = -0.82, p < 0.05). The area of the lesions correlated directly with body weight (r = 0.80, p < 0.05) and inversely with weekly Kt/V urea (r = -0.90, p < 0.01). CONCLUSIONS: Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high.

The effect of insulin delivery route on lipoproteins in type I diabetic patients on CAPD.

OBJECTIVE: To evaluate the influence of subcutaneous and intraperitoneal (i.p.) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A before-after trial. SETTING: University hospital outpatient care. PARTICIPANTS: Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 +/- 2.9 (SEM) years and duration of diabetes 31.4 +/- 3.4 years. INTERVENTION: Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with i.p. insulin. The studies were performed after a median time of 3 months on each treatment. MAIN OUTCOME MEASURES: Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. RESULTS: After changing from subcutaneous insulin to i.p. insulin, plasma HDL cholesterol decreased (from 1.29 +/- 0.13 mmol/L to 0.96 +/- 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased (p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 (p < 0.01). ApoA-I (p < 0.05) decreased while the ApoB/ApoA-I ratio (p < 0.01) and the ApoA-I/HDL-cholesterol ratio (p < 0.01) increased during i.p. insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin (p < 0.01). CONCLUSIONS: In diabetic patients on CAPD therapy, i.p. insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

Late postoperative follow-up of ostium secundum defect.

AIM: To perform late postoperative assessment of patients with ostium secundum defect. METHODS: We studied 45 patients 22+/-4 years after operation using clinical examination, transthoracic and transoesophageal echocardiography and electrocardiography. RESULTS: Patients operated on at 24 years reported dyspnoea upon exercise. Mitral regurgitation occurred more frequently in patients operated on at 24 years (29% vs 69%, P<0.05). Tricuspid regurgitation was mild in 20 patients (45%). There was an inter-atrial communication in 13 patients (28%). Eighteen patients (40%) had an enlarged right ventricular diameter. A tricuspid regurgitation gradient >30 mmHg was measured in seven patients (16%). Seventeen patients (38%) had significant electrocardiographic abnormalities. CONCLUSIONS: Late after uncomplicated seclusion of ostium secundum defect patients operated at >24 years have more symptoms than those operated on at an earlier age. Residual lesions are common. Mitral regurgitation is more frequent in patients operated on at >24 years. Our findings support the clinical consensus of operating on these patients in their childhood and adolescence.

Effect of acetaldehyde and acetylsalicylic acid on HbA1c chromatography in the FPLC method with Mono S cation exchanger.

The effects of alcohol and aspirin on HbA1c chromatography in the Mono S method were studied in vitro and in vivo. A modified chromatography with enhanced resolution was used, making possible detailed examination of minor interfering peaks included in the routine HbA1c value. Incubation with acetylsalicylic acid increased a hemoglobin fraction separate from HbA1c. In vivo this fraction was elevated by 0.1% of the total hemoglobin during therapeutic aspirin ingestion for one month. In vitro acetaldehyde generated two labile hemoglobin fractions and slightly increased a minor stable fraction which was also elevated in vivo in both alcoholics and heavy drinkers. In relation to the HbA1c concentration, this stable fraction was equal in both alcoholic groups. We conclude that the in vivo effects of both aspirin and alcohol are negligible in routine HbA1c determination. Factors other than acetaldehyde might account for the unexpected HbA1c values in alcoholics.

Does uremia interfere with HbA1c results in the FPLC method with Mono S cation exchanger?

To study the effect of uremia on hemoglobin A1c determination by the Mono S FPLC method, samples from uremic patients, with and without diabetes, and controls, were analysed with a modified chromatography with enhanced resolution. Besides specific HbA1c, four minor peaks could be seen, included in routine HbA1c values. Two of these differed in concentration in the patient groups studied: a shoulder-like peak close to the specific HbA1c (S fraction) and a slightly less cationic minor peak (M fraction). Both S and M peaks were higher in uremic than in nonuremic subjects, but the M peak was associated more with diabetes. In the nondiabetic group, the mean routine HbA1c value was 0.8% units higher in uremic than nonuremic individuals. The specific HbA1c was nondependent on uremia. Thus, in uremic patients, there seems to be falsely elevated HbA1c values, mainly because of small interfering hemoglobin fractions, not specific HbA1c.

The influence of peritoneal dialysis and the use of subcutaneous and intraperitoneal insulin on glucose metabolism and serum lipids in type 1 diabetic patients.

BACKGROUND: Intraperitoneally administered insulin is regarded as the most physiological replacement therapy, leading to lower peripheral insulin concentrations and equal or better glycaemic control than subcutaneous insulin. This two-part study was undertaken to evaluate the effect of CAPD, as well as the use of subcutaneous vs. intraperitoneal insulin on insulin sensitivity, glycaemic control and serum lipids in type 1 diabetes. METHODS: Eleven patients with type 1 diabetes mellitus and chronic renal failure participated the studies. Glycated haemoglobin (HbA1c), euglycaemic hyperin-sulinaemic clamp, serum lipids, and patient well-being were measured. During CAPD all patients were first treated with subcutaneous insulin and then with intraperitoneal insulin. The metabolic studies were repeated after both treatment periods for at least 3 months. Metabolic studies were performed on six of the patients also before initiation of CAPD. RESULTS: HbA1c rose after the initiation of CAPD from 8.85 +/- 0.54% to 9.58 +/- 0.66%, NS) and improved after changing from subcutaneous to intraperitoneally administered insulin (from 9.49 +/- 0.43% to 8.13 +/- 0.39%, P < 0.01). Insulin dose increased by 15% after initiation of CAPD and 128% after switching from subcutaneous to intraperitoneal insulin. Glucose disposal rate enhanced by 39% (P = 0.05) and 14% respectively (P < 0.01). Initiation of CAPD had no significant effects on serum lipids but intraperitoneally administered insulin reduced HDL cholesterol and increased LDL/HDL ratio significantly. CONCLUSIONS: Intraperitoneal insulin therapy offers better glycaemic control and insulin sensitivity than subcutaneous insulin. Deterioration of HbA1c after initiation of CAPD while patients remained on subcutaneous insulin may be partly due to absorbed energy from the dialysate. Intraperitoneal insulin therapy seems to have detrimental effects on serum lipids. The clinical significance in modifying the risk of atherosclerosis remains unclear.

Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. A case report.

OBJECTIVE: To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro B29) in severe insulin resistance caused by human insulin antibodies. CASE: A 27-year-old man with a history of diabetes treated with human insulin for 3 years developed severe immunological insulin resistance caused by human insulin antibodies. Throughout follow-up (12 months) the insulin analog lispro was administered with an infusion pump as the only insulin therapy. The insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. CONCLUSIONS: The insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased insulin antibody levels Apparently, the structural difference between the lispro and human insulin molecules prevented lispro from binding to the human insulin antibodies in this patient and consequently was nonimmunogenic.

Subcutaneous and intraperitoneal insulin therapy in diabetic patients on CAPD.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A1c 10.00 +/- 0.38% after subcutaneous and 8.40 +/- 0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28 +/- 0.18 mmol/L vs 0.88 +/- 0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect of serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.

Comparison of intraperitoneal and subcutaneous insulin administration on insulin sensitivity and serum lipids in type I diabetic patients on continuous ambulatory peritoneal dialysis treatment.

1. The metabolic effects of intraperitoneal and subcutaneous insulin delivery were compared in a cross-over manner in six C-peptide-negative diabetic patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. Each treatment period lasted at least 3 months. Hyperinsulinaemic euglycaemic clamp was performed and glucose turnover assessed using [3-(3)H]glucose as a tracer. 2. During intraperitoneal delivery the daily insulin dose was 2.4 times higher than during subcutaneous administration and glycaemic control was significantly better (HbA1c 7.63% +/- 0.46% and 9.52% +/- 0.51% during intraperitoneal and subcutaneous insulin respectively, P < 0.01). The number of hypoglycaemic episodes was lower during intraperitoneal insulin than during subcutaneous therapy. 3. Intraperitoneal insulin resulted in an enhanced glucose disposal rate (P < 0.01) and reduced fasting hepatic glucose production (P < 0.01). High-density lipoprotein-cholesterol decreased and the ratio of low-density lipoprotein/high-density lipoprotein-cholesterol increased significantly (P < 0.05) during intraperitoneal insulin delivery. 4. The results suggest that intraperitoneal insulin, while resulting in better glycaemic control and improved insulin sensitivity than subcutaneous insulin, increases serum triacylglycerol and total cholesterol and reduces high-density lipoprotein-cholesterol, possibly via a direct effect on the liver.

Effects of celiprolol on insulin sensitivity and glucose tolerance in dyslipidemic hypertension.

The effects of celiprolol on insulin sensitivity, glucose tolerance and serum lipids were compared to those of other antihypertensive drugs (beta- or Ca-blocker or ACE-inhibitor) in 23 dyslipidemic non-diabetic patients with controlled hypertension. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed before and 6 months after the study treatment. Six patients out of 23 were randomized to the control group where antihypertensive monotherapy was kept unchanged. Mean glucose disposal rate (M, mean +/- SEM) determined in the clamp test increased in the celiprolol group from 24.4 +/- 2.3 to 34.9 +/- 2.4 mumol/kg/min (p < 0.001). Insulin sensitivity improved during celiprolol treatment independent of the previous treatment. In the control group, M remained practically unchanged (21.6 +/- 3.7 mumol/kg/min). During 2 h OGTT, incremental glucose and insulin AUC decreased in the celiprolol group from 4.5 +/- 0.7 to 2.0 +/- 0.6 mM*h (p < 0.002) and from 113 +/- 16 to 72 +/- 10 mU/l*h (p < 0.005), respectively. There was also a small beneficial change in serum lipids in the celiprolol group: a reduction in serum total cholesterol (-4%), triglycerides (-11%) and LDL-cholesterol (-9%), and an increase in HDL-cholesterol (+6%) and HDL/LDL ratio (+15%). No significant change occurred in the control group. Fasting serum glucose and insulin did not change significantly in either group. In this study with a limited control group, celiprolol improved insulin sensitivity, glucose tolerance and serum lipid profiles of dyslipidemic hypertensive patients.

Fetal hemoglobin in diabetic patients.

OBJECTIVE: To determine the occurrence of elevated fetal hemoglobin (HbF) among the diabetic population and determine the clinical situation of importance. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted. HbA1c and HbF were measured with high-performance liquid chromatography in 1,104 consecutive diabetic patients attending our clinic for HbA1c determination. The expression of clinical correlations between the high and low HbF group was performed for adults (> or = 15 years). A nondiabetic control group (n = 258) with the same age and sex distribution was included. RESULTS: HbF was elevated (> 1.0% of total hemoglobin) in 7.5% of the total diabetic group. In the adult diabetic group, HbF was elevated in 6.5% of the patients, and in the control group, HbF was elevated in 1.9% (P < 0.01). In the insulin-treated adult group, HbF was elevated in 10.2% of the patients, and in the non-insulin-treated group, HbF was elevated in 3.8%. The mean HbA1c was 8.90 +/- 2.00% among the patients and 5.52 +/- 0.53% in the control subjects (P < 0.001). Patients with elevated HbF were younger (P < 0.02) and more often on insulin therapy (P < 0.001) or type I diabetic patients (P < 0.001). Sex, glycemic control, or duration of diabetes were not significantly different in the patients with high or low HbF. Correlation was not detected between the amount of HbF and HbA1c or age in the group of patients with elevated HbF. Hemoglobinopathies, anemias, or malignancies were not diagnosed from the patients with high HbF. CONCLUSIONS: Level of HbF is increased (> 1.0%) among 7.5% of unselected diabetic patients. In adult (> or = 15 years) diabetic patients, it is increased among 6.5%, which is 3.4 times more often than in the control population. Acute hematological conditions or malignancies do not explain the difference. Elevated HbF seems to be associated with type I diabetes and insulin treatment.

Glucose metabolism and recycling by hepatocytes of OB/OB and ob/ob mice.

Hepatocytes were prepared from livers of ob/ob (obese diabetic) mice and their lean (OB/OB) siblings that had been fasted for 24 h. The hepatocytes were incubated with [U-14C, 2-3H]-, [U-14C, 3-3H]-, and [U-14C, 6-3H]glucose at concentrations from 20 to 120 mM. 14C was recovered mainly in CO2, glycogen, and lactate. Tritium was recovered in water and glycogen. The yield in labeled products from [2-3H]glucose ranged from two to three times that from [U-14C]glucose. The yields from [3-3H]- and [6-3H]glucose were similar, and 1.3-1.7 times that from [U-14C]glucose. At 40 mM, total utilization of glucose by obese mice was about twice that for lean mice, but there was little difference at 120 mM. The rate of recycling between glucose and glucose 6-phosphate was calculated. An equation to calculate the rate of recycling of glucose from the 2-3H/U-14C ratio in glycogen is derived in the APPENDIX. Our results show that 1) the utilization of glucose by hepatocytes from obese diabetic mice exceeds that of their lean controls, 2) the rate of glucose phosphorylation in both groups greatly exceeds glucose uptake and the rate of glycogen synthesis, 3) glucose phosphorylation represents a difference between a high glucokinase rate and hydrolysis of glucose 6-phosphate, and 4) recycling of glucose carbon between glucose 6-phosphate and pyruvate occurs within mouse hepatocytes.

Effect of short-acting nitroglycerin on heart rate: evaluation by a self-monitoring device.

The efficacy of two sublingual nitroglycerin formulations was compared in 10 healthy subjects and 10 patients with ischaemic heart disease. A new microcomputerized device was used to record and analyze heart rate. The rise in heart rate began 1-1.5 min after administration of nitroglycerin tablets and was maximal within 3 min. The effect was more rapid with a quickly dissolving compound. The recording equipment was reliable, simple to use and inexpensive.