Weight-matched Healthy Controls Research Articles

Study of early atherosclerotic markers in women with polycystic ovary syndrome

Objective:Women with polycystic ovary syndrome (PCOS) may represent a large underappreciated segment of female population who is at increased cardiovascular risk because of the presence of cluster of metabolic abnormalities. The aim of our study was to assess atherosclerotic risk factors in women with PCOS.Materials and Methods:In a cross-sectional study, 50 women with PCOS and 50 age and weight-matched healthy controls were enrolled. Endothelial dysfunction by flow-mediated dilatation (FMD) of brachial artery, highly sensitive C-reactive protein (hs CRP), and carotid intima media thickness (CIMT) were measured in both cases and control groups.Results:The mean age of women with PCOS was 26.82 ± 3.26 years and Body-mass index (BMI) of 26.2 ± 4.8 kg/ m2. Thirty-six (72%) patients were overweight or obese,54% had central obesity and 12% had impaired glucose tolerance. Among the markers of atherosclerosis, hsCRP levels were nonsignificantly higher in patients with PCOS than in controls. The FMD was 12.18 ± 2.3% vs 8.3 ± 2.23% in patients with PCOS and controls respectively (P=0.01). CIMT was significantly different in two study groups (0.68 ± 0.11 in PCOS vs 0.52 ± 0.02 in normal subjects, (P=0.01). FMD had significant negative correlation with homeostasis model assessment (HOMA) index (r = −0.32, P=0.02) and hs CRP (r = −0.37, P=0.04) while hs CRP was correlated with BMI (r = 0.54, P=0.005), HOMA (r = 0.38, P=0.02) and FMD (r = -0.33, P=0.01). CIMT was significantly different in women with PCOS and control subjects, and it had significant correlation with age (r = 0.42, P=0.03), BMI (r = 0.36, P=0.01), waist circumference (r = 0.52, P=0.001) and HOMA (r = 0.31, P=0.04).Conclusion:Women with PCOS definitely have increased risk for future cardiovascular events. Clinicians should consider early cardiovascular screening and interventions to control all modifiable cardiovascular risk factors.

Adipocytokines and CD34+ Progenitor Cells in Alzheimer's Disease

BackgroundAlzheimer's disease (AD) and atherosclerosis share common vascular risk factors such as arterial hypertension and hypercholesterolemia. Adipocytokines and CD34+ progenitor cells are associated with the progression and prognosis of atherosclerotic diseases. Their role in AD is not adequately elucidated.Methods and FindingsIn the present study, we measured in 41 patients with early AD and 37 age- and weight-matched healthy controls blood concentrations of adiponectin and leptin by enzyme linked immunoabsorbent assay and of CD34+ progenitor cells using flow cytometry. We found significantly lower plasma levels of leptin in AD patients compared with the controls, whereas plasma levels of adiponectin did not show any significant differences (AD vs. control (mean±SD): leptin:8.9±5.6 ng/mL vs.16.3±15.5 ng/mL;P = 0.038; adiponectin:18.5±18.1 µg/mL vs.16.7±8.9 µg/mL;P = 0.641). In contrast, circulating CD34+ cells were significantly upregulated in AD patients (mean absolute cell count±SD:253±51 vs. 203±37; P = 0.02) and showed an inverse correlation with plasma levels of leptin (r = −0.248; P = 0.037).In logistic regression analysis, decreased leptin concentration (P = 0.021) and increased number of CD34+ cells (P = 0.036) were both significantly associated with the presence of AD. According to multifactorial analysis of covariance, leptin serum levels were a significant independent predictor for the number of CD34+ cells (P = 0.002).ConclusionsOur findings suggest that low plasma levels of leptin and increased numbers of CD34+ progenitor cells are both associated with AD. In addition, the results of our study provide first evidence that increased leptin plasma levels are associated with a reduced number of CD34+ progenitor cells in AD patients. These findings point towards a combined involvement of leptin and CD34+ progenitor cells in the pathogenesis of AD. Thus, plasma levels of leptin and circulating CD34+ progenitor cells could represent an important molecular link between atherosclerotic diseases and AD. Further studies should clarify the pathophysiological role of both adipocytokines and progenitor cells in AD and possible diagnostic and therapeutic applications.

Comparison of aerobic exercise capacity and muscle strength in overweight women with and without polycystic ovary syndrome

To assess maximal aerobic capacity (VO2max) and muscle strength in overweight and obese women with polycystic ovary syndrome (PCOS) and determine their relationship with metabolic and hormonal factors. Cross-sectional study. Clinical Research Unit. Overweight and obese women with PCOS (n = 10) and age-and weight-matched healthy controls (n = 16). VO2max was measured during an incremental treadmill test and maximal isometric (ImS) and isokinetic knee extensor strength (IkS) (120 degrees/second) were assessed by isokinetic dynamometry. VO2max, ImS, IkS, waist circumference, blood lipids, glucose, insulin, insulin resistance (homeostatic model assessment [HOMA2]), C-reactive protein (CRP), hormonal profile. PCOS women had higher levels of testosterone and free testosterone (P < or = 0.05), but there were no significant differences in any cardiovascular disease (CVD) risk markers between the groups. VO2max was similar in women with PCOS and healthy controls (PCOS 26.0 +/- 4.1 ml/kg/minute, controls 25.7 +/- 3.8 ml/kg/minute; P = 0.90), as was ImS (PCOS 1.50 +/- 0.54 Nm/kg, controls 1.50 +/- 0.47 Nm/kg; P = 0.96) and IkS (PCOS 1.04 +/- 0.32 Nm/kg, controls 1.16 +/- 0.23 Nm/kg; P = 0.32). VO2max was inversely related to waist circumference, insulin, HOMA2 and CRP. Waist circumference was inversely associated with ImS and IkS. No significant associations between exercise parameters and hormonal variables were identified. Compared to age- and weight-matched healthy overweight and obese women with similar insulin resistance and CVD risk profiles, women with PCOS had similar aerobic capacity and muscle strength. This suggests PCOS, at least in the absence of an adverse metabolic profile is unlikely to limit physical function. Larger studies examining the effects of PCOS on exercise tolerance in a diverse range of PCOS phenotypes is required.

Isokinetic evaluation of knee extensor/flexor muscle strength in patients with hypermobility syndrome

Benign joint hypermobility syndrome (BJHS) is a syndrome with musculoskeletal pain originating from the increased laxity of the joints and the ligaments. The study was to compare the isokinetic strength of knee extensor/flexor muscles of BJHS patients with healthy controls. Forty patients diagnosed as having BJHS with Brighton criteria and 45 years of age, height and weight-matched healthy controls were recruited for the study. Isokinetic testing was performed with isokinetic dynamometry of Biodex System 3Pro and measurements were recorded at knee extension/flexion pattern concentrically at 60, 180, and 240 degrees/s angular velocities. The study group was also evaluated for functional impairment and pain by HAQ and VAS respectively. Knee extensor muscle strength was significantly lower in the patient group compared with the controls. It was hypothesized that the muscle weakness in the study group was related to lengthening of the quadriceps muscle and pain-related inactivity as well as joint instability and proprioception defect.

Association between Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance. Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured. TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05). The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.

ENERGY AND SUBSTRATE METABOLISM IN PATIENTS WITH CHRONIC EXTENSIVE GRAFT-VERSUS-HOST DISEASE

Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). Weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Energy expenditure in chronic alcohol abuse.

In healthy subjects, alcohol decreases lipid oxidation favouring fat deposition. However, individuals who chronically abuse alcohol are not obese. To investigate this paradox, we measured energy expenditure (EE) and fuel utilization in chronic alcohol abusers in relation to their drinking behaviour. Resting and postprandial EE and nonprotein respiratory quotient (NPRQ) were measured using indirect calorimetry, in 36 alcohol abusers [mean (+/- SE) age 42 +/- 2 years; weight 67 +/- 2 kg; 21 with steatosis, eight with hepatitis; seven with cirrhosis] and in 36 gender-, age- and weight-matched healthy controls. Alcoholic patients were re-evaluated either after 14 days (n = 14) or on days 2, 4, 6, 8, 14 and 42 (n = 6) after abstinence. When alcoholics were compared to healthy controls, mean energy intake was greater, 15 +/- 1 MJ day-1 (38 +/- 2% from alcohol) cf. 9 +/- 1 MJ day-1 (P < 0.001), resting EE increased, 82 +/- 2 cf. 65 +/- 2 W (P < 0.001) and NPRQ decreased, 0.75 +/- 0.02 cf. 0.82 +/- 0.01 (P < 0.001). The postprandial increases in EE and NPRQ were of similar magnitude in both groups. Abstinence from alcohol for 14 days was accompanied by reduced energy intake, 16 +/- 1 cf. 11 +/- 1 MJ day-1 (P < 0.005) and decreased resting EE, 84 +/- 5 cf. 73 +/- 4 W (P < 0.05). The decrease in resting EE consistently occurred 4 days after abstinence from alcohol. Chronic alcohol abuse is associated with energy wasting and inhibition of adipose tissue accumulation. This may explain why alcoholics are not obese despite high total energy intakes.

An early-life femoral shaft fracture and bone mineral density at adulthood.

High peak bone mass and density in early adulthood is an important protective factor against osteoporotic fractures in later life, but it is not known whether injuries to growing bones adversely affect the attainment of peak bone mass and density. The purpose of this study was therefore to examine with dual-energy X-ray absorptiometry the areal bone mineral density (BMD) of the injured and uninjured extremity (the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia and distal tibia), lumbar spine and distal radius of young adults with a history of an early-life femoral shaft fracture and to find out whether the fracture had affected the attainment of peak bone density of these patients. Thus, the BMD and clinical status of 41 patients (28 men, 13 women) who had sustained a femoral shaft fracture in childhood or adolescence (between 7 and 15 years of age, average 13 years before the study) were examined. The fracture had led to a statistically significant difference in BMD between the injured and uninjured side distal to the fracture site (men/women: distal femur, -3.7%/-3.9%; patella, -3.1%/-5.9%; proximal tibia, -2.0%/-4.6%; distal tibia, -3.4%/-5.2%), whereas the proximal femur did not show such differences. The male patients' spinal BMD was significantly lower (-7.9%) than that in their age-, height- and weight-matched healthy controls. The female patients' spinal BMD tended to be fairly comparable (-1.6%) to that of the controls (NS). In summary, this study indicates that early-life femoral shaft fracture results in a moderate (-2% to -6%) long-term side-to-side BMD difference distal to the fracture site. Patients' spinal BMD values also tend to be lower than that of controls. Thus, a femoral shaft fracture sustained in childhood or adolescence seems to disturb somewhat the attainment of peak bone density, the important predictor of osteoporotic fractures in later life.

A tibial shaft fracture sustained in childhood or adolescence does not seem to interfere with attainment of peak bone density.

High peak bone mass or density in early adulthood is an important protective factor against osteoporotic fractures in later life, but it is not known whether injuries on growing bones affect the attainment of peak bone mass and density. The purpose of this study was therefore to examine with dual-energy X-ray absorptiometry the areal bone mineral density (BMD) of the injured and uninjured extremity (the femoral neck, trochanter area of the femur, distal femur, patella, proximal tibia, and distal tibia), lumbar spine, and distal radius of young adults with a history of early life tibial shaft fracture and to find out whether the fracture had affected the attainment of peak bone density of these patients. The second objective was to clarify whether any background or clinical follow-up variable would predict the BMD difference between the affected and unaffected extremity. Thus, the BMD and clinical status of 45 patients (34 men and 11 women), who had sustained a tibial shaft fracture in childhood or in adolescence (between 7 and 15 years of age) an average 11 years before the study, were examined. The results showed that the fracture had created a small but statistically significant injured-to-uninjured side BMD difference (proximal tibia -1.7%; p = 0.011, and distal tibia 2.6%; p = 0.014), while the other sites showed no significant side-to-side differences. There were neither significant differences in the spinal or radial BMDs between the patients and their age-, height-, and weight-matched healthy controls. A further analysis of the data showed that the better the muscle strength in the injured lower limb, the lower the side-to-side BMD deficit in the proximal tibia of the same limb (r = 0.51; p < 0.001). Smoking had a significant association with the relative BMD in the injured distal tibia (mean injured-to-uninjured side BMD difference: smokers 6.1% vs. nonsmokers -0.6%, p = 0.016). Also patient's age at the time of the injury showed an association: the younger the patient at the time of the injury, the lower the side-to-side BMD deficit in the injured distal tibia (r = -0.35; p = 0.048). In conclusion, this study indicates that early life tibial fracture leads to a small long-term BMD deficit in the fractured bone while the other sites of the skeleton seem not to be affected. Thus, a tibial shaft fracture sustained in childhood or adolescence seems to only marginally interfere the attainment of peak bone density, the important predictor of the osteoporotic fractures in later life.

Regulators of Calcium Homeostasis and Bone Mineral Density in Patients with Crohn's Disease

Background: Several papers have reported on vitamin D, parathyroid hormone (PTH), and other regulators of calcium metabolism in patients with Crohn's disease, but results have been conflicting. Bone mineral density (BMD) has been found to be reduced in several papers. A recent study from our laboratory suggested that the expected reduction in BMD disappears when the patients are compared with sex-, age-, and weight-matched healthy controls. The relationship between BMD and regulators of calcium homeostasis is not well established in patients with Crohn's disease. Methods: BMD and biochemical regulators of calcium metabolism were measured in 115 unselected patients with Crohn's disease, most of whom were in remission. Results:

Serum lipid concentrations in patients with major depressive disorder

This study compared the serum lipid concentrations in 100 patients with major depressive disorder (MDD) with those from 100 matched healthy controls. It was found that the serum total cholesterol concentration in patients with MDD (5.27 +/- 1.18 mmol/L) was significantly lower than the value (6.63 +/- 1.32 mmol/L) in sex-, age-, and weight-matched healthy controls. This significant decrease in serum cholesterol in patients with MDD was noted in both sexes and in all age groups. Patients with MDD, however, had significantly higher HDL cholesterol than matched controls. There were no statistically significant differences in serum concentrations of triglycerides, apolipoprotein (Apo) A1, Apo B, transferrin, and albumin between patients and controls. Clinical recovery of patients with MDD was accompanied by a significant increase in serum total cholesterol from 5.27 +/- 1.18 mmol/L to 6.12 +/- 1.2 mmol/L. These results suggest an association between low serum total cholesterol and depression in both sexes and at all age groups.

Postprandial changes in high-density lipoprotein composition and subfraction distribution are not altered in patients with insulin-dependent diabetes mellitus

A detailed analysis of postprandial changes in the size, density, composition, and relative proportion of the major high-density lipoprotein (HDL) subfractions, HDL 2 and HDL 3, was performed in seven normolipidemic patients with insulin-dependent diabetes mellitus (IDDM) in moderate glycemic control and seven age-, sex-, and weight-matched healthy nondiabetic controls. IDDM subjects received an overnight insulin infusion to maintain euglycemia, with an incremental increase in the insulin infusion rate at the time of the test meal (containing 60 g fat/m 2). Samples for detailed analysis of HDL by gradient density ultracentrifugation and nondenaturing gradient gel electrophoresis (GGE) were collected at 0, 4, 8, and 12 hours after the test meal. The composition of HDL, HDL 2, and HDL 3 was significantly altered in the postprandial state in IDDM subjects and controls with an increase in triglyceride content at 4 to 8 hours and a reciprocal decrease in cholesteryl ester, reflecting exchange of lipid constituents of HDL with triglyceride (TG)-rich lipoproteins. In addition, the phospholipid content of the particles increased at 8 hours after the meal. Peak density of HDL 2 and HDL 3 decreased slightly at 4 to 8 hours, reaching significance only in controls at 8 hours ( P < .05), whereas the mean radius size of these subfractions did not change significantly. In controls and IDDM subjects, the ratio of HDL 3 to HDL 2 at 8 to 12 hours increased significantly ( P < .005). Significant differences in the composition, size, density, or subfraction distribution of HDL between subjects with IDDM and controls were not observed following ingestion of the lipid-rich meal. We conclude from these data that in patients with IDDM in moderate glycemic control, there do not appear to be any significant gross abnormalities in postprandial HDL metabolism with respect to the size, density, or compositional changes of HDL particles.

Blood pressure rhythm and endocrine functions in normotensive women on oral contraceptives.

Twenty-four hour blood pressure profiles were determined by non-invasive ambulatory blood pressure measurements in young normotensive women during the follicular and luteal phases of the menstrual cycle. Forty women participated, 20 of whom were on oral contraceptives (ethinyl-ethylestradiol 0.03 mg + levonorgestrel 0.15 mg) and 20 of whom were age- and weight-matched control individuals not on oral contraceptives. Data on systolic and diastolic blood pressure and heart rate were analyzed in each case by linear and rhythm analysis. Urine was collected day and night on each occasion on which ambulatory blood pressure measurements were recorded. Daytime, night-time, and 24 h mean systolic and diastolic blood pressure and heart rate did not depend on the cycle phase. The nocturnal fall in blood pressure was preserved in both groups and during both phases. Rhythm analysis by partial Fourier series showed that, of 240 individual 24 h blood pressure profiles, only 12 (5%) did not exhibit a significant circadian rhythm. Linear and rhythm analyses revealed that during both phases of the menstrual cycle systolic and diastolic blood pressure were significantly higher throughout the 24 h, especially during the night, in women taking oral contraceptives. During both phases of the menstrual cycle urinary aldosterone excretion was significantly higher in women taking oral contraceptives. This increase could contribute to the night-time blood pressure elevations caused by oral contraceptives. The results suggest a modulating influence of sex steroids on the circadian blood pressure profile even in normotensive healthy volunteers.

Skeletal muscle sodium and potassium changes after successful surgery in acromegaly: relation to body composition, blood glucose, plasma insulin and blood pressure

The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p < 0.01) but the sodium content and the Na/K ratio were lower (p < 0.05 and p < 0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [medium (range)] 9.8 (9.2-11.5) to 7.7 (5.7-9.5) mmol/100 g wet wt (p < 0.001). The skeletal muscle sodium content increased from 2.8 (2.5-3.9) to 5.1 (4.3-6.7) mmol/100 g wet wt (p < 0.001) and the Na/K ratio increased from 0.28 (0.26-0.38) to 0.56 (0.51-1.18) (p < 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39-0.84) (p < 0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.

Plasma C-peptide response to oral glucose load in hyperthyroidism

Aim of the present study was to evaluate the pancreatic beta cell response to oral glucose load in a group of patients with hyperthyroidism. For this purpose plasma C-peptide at fasting and after a 100 g oral glucose load was measured in 8 newly-diagnosed untreated hyperthyroid patients with fasting normoglycemia, and 8 sex-, age-, and weight-matched healthy controls. As compared to healthy subjects, patients with hyperthyroidism showed higher plasma glucose levels (incremental area 5405 +/- 742 vs 2729 +/- 539 mg/dl x 180 min, p less than 0.05), and slightly reduced plasma C-peptide concentrations (incremental area 166 +/- 12 vs 182 +/- 36 pmol/ml x 180 min, p = NS) following oral glucose load. The ratios between plasma C-peptide and plasma glucose incremental areas were lower in hyperthyroid patients than in controls (3.66 +/- 0.85 vs 10.41 +/- 3.08, p less than 0.05). These data suggest that hyperthyroidism is characterized by a decreased pancreatic beta cell response to oral glucose load.

Thyroid gland volume and serum concentrations of thyroid hormones in chronic renal failure.

Thyroid gland volume, ultrasonically determined, and thyroid function were investigated in 40 patients with chronic renal failure (33 of these on hemodialysis) and 40 sex-, age- and weight-matched healthy controls. None had thyroid autoantibodies or a clinically detectable goiter. The median thyroid gland volume was significantly elevated in the uremic patients: 24 ml (range 8-43 ml) compared with the healthy controls 17 ml (range 10-22 ml) (p less than 0.005). The serum concentrations of thyroxine (T4), triiodothyronine (T3), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were significantly decreased in uremic subjects compared with the controls. The serum concentration of thyrotropin did not differ significantly between patients and controls. None of the thyroid function variables correlated with thyroid gland volume. In conclusion, thyroid gland volume was increased in patients with chronic renal failure. The alterations in thyroid hormone concentrations could, however, not explain this finding.

Optimal glycaemic control in unrestrained diabetic dogs using programmed compound squarewave insulin infusions.

A glycaemic control identical with the normal has been achieved in unrestrained totally depancreatised dogs using a portable open-loop insulin delivery system. The device consisted of a battery power pack with a flow-rate controller, an insulin reservoir and a peristaltic pump from which pulses of insulin were delivered every 90 seconds into the inferior vena cava through an exteriorised indwelling catheter. Insulin was infused at the basal rate of 0.45±0.03 mUkg−1 min−1 (Mean±s.e.m.) in the postabsorptive state resulting in peripheral IRI and plasma glucose levels of 12±1 μU ml−1 and 86±7 mg dl−1. In the postprandial period the infusion rate was enhanced sevenfold to the rate of 3.16±0.21 mU kg−1min−1 for 7h and then reduced to 1.05±0.07 mU kg−1 min−1 for an additional 2.25 h. A weight-maintaining constant diet was provided and the resulting glycaemic profiles were similar to age, sex and weight-matched healthy controls. Fasting peripheral insulin levels in the infused diabetic dogs were not significantly different from non-diabetic controls (10±1μUml−1). However, in the postprandial period of enhanced delivery, insulin levels in the diabetic dogs were 3.1 times higher than the controls. With the compound square waveforms of preprogrammed insulin infusion found appropriate in this study unaccountable low or high plasma glucose levels did not occur but hyperinsulinism accompanied the glycaemic normalisation following a mixed meal.