Effect of metabolic control on urinary excretion and plasma levels of catecholamines in diabetics.

Urinary excretion and plasma levels of catecholamines were determined in 20 normal and 39 diabetic subjects to evaluate the sympathetic activity. Diabetic patients were divided into 4 groups according to the metabolic control. Sympathetic activity showed no differences between normal and subjects with chemical diabetes (group I, n = 5). In insulin-treated diabetics in good metabolic control (group II, n = 11) only urinary excretion of free norepinephrine was significantly higher than normals (p less than .05). In insulin-treated diabetics in poor metabolic control (group III, n = 16) urinary excretion and plasma levels of norepinephrine showed a marked increase over groups I and II (p less than .001). In insulin-treated diabetics with ketosis (group IV, n = 7) urinary excretion and plasma levels of both norepinephrine and epinephrine showed the highest values (p less than .001 and less than .1). Finally, in groups III and IV, after achieving improved metabolic control, a significant decrease of urinary excretion and plasma levels of catecholamines was observed. The results confirm that there is an increased rate of catecholamine release in poorly controlled diabeties and suggest a close correlation between sympathetic activity and metabolic derangement in diabetes.     

Abnormal Glomerular Filtration Rate,Renal Plasma Flow,and Renal Protein Excretion in Recent and Short-term Diabetics

Glomerular filtration rate and renal plasma flow were simultaneously determined in comparable groups of 43 diabetics less than 40 years of age and with a duration of diabetes less than 10 years and 32 control subjects. The average glomerular filtration rate in the diabetic group was significantly higher than that in the control group (P <0·01). The average renal plasma flow in the diabetic group was found to be significantly lower than that in the control group (P <0·05). The filtration fraction in both male and female diabetics was significantly higher than in the male and female control groups (P <0·001). These changes were found to be present even in recent juvenile diabetics with disease of a duration of less than one year. No correlation was apparent between the average levels of serum growth hormone and glomerular filtration rate.The urinary protein excretion was determined in 36 diabetic and 38 healthy subjects comparable with regard to glomerular filtration rate. In the diabetic group there was a greater frequency of cases with higher protein excretion rates (P <0·02). The average protein excretion rate was increased even in diabetics with less than one year''s duration of the disease.The results of the changes in renal haemodynamics in subjects with recent and short-term diabetes are compatible with the presence of a constrictive state of the vas efferens leading to an increase in the filtration pressure. The increase in protein excretion rate may similarly be a consequence of this process or of an increase in the glomerular permeability with augmented molecular sieving of proteins or both.     

Red cell peroxide metabolism in diabetes mellitus

In a group of normal controls and in a group of diabetics subdivided for type we evaluated the following red blood cell parameters: superoxide dismutase (SOD), glutathione peroxidase (GSH.Px), catalase (C-ase), glutathione content (GSH) and membrane-protein-sulphydryl groups (P-SH). There was no difference in the enzymatic activities of superoxide dismutase, glutathione peroxidase and catalase in normals and in the diabetics. However, the erythrocyte GSH content as well as membrane P-SH groups discriminate the normals from diabetics and also the diabetics subdivided for type. None of these parameters was related to the erythrocyte filterability considered as a reflection of the red blood cell deformability. These findings reveal that the diabetic red blood cell is less protected from oxidant agents.     

The effect of exogenous growth hormone on insulin requirements during closed loop insulin delivery in insulin-dependent diabetes mellitus

The amount of insulin required to maintain similar blood glucose concentrations during an eight hour infusion of either saline or growth hormone (2 micrograms/kg/hr) was determined in five fed, insulin-dependent diabetic subjects during closed-loop insulin delivery. Elevations of serum growth hormone concentrations to levels previously observed in poorly controlled diabetic subjects were not accompanied by differences in the amount of insulin required to maintain blood glucose concentrations at levels comparable to those observed during the saline infusion. Specifically, no early insulin-like nor late anti-insulin effects of physiologic increases in serum growth hormone concentrations (10.27 +/- 0.23 mg/ml vs 5.69 +/- 1.5 mg/ml, P less than 0.05) on mean hourly blood glucose levels or mean hourly insulin requirements were observed. These studies suggest that serum growth hormone concentrations similar to those observed in poorly controlled diabetics do not affect the insulin requirements of well-insulinized diabetic subjects.     

Evaluation of 24-hour growth hormone spontaneous secretion: comparison with a nocturnal and diurnal 12-hour study

Spontaneous growth hormone (GH) secretion in 116 short children was studied by sampling blood for GH measurement every 20 min over 24 h. We calculated 24-h mean GH concentration (MGHC), diurnal 12-h MGHC (dMGHC) and nocturnal 12-h MGHC (nMGHC). The children were subdivided into four groups: prepubertal children with 'classical' GH deficiency (group 1, n = 12, low responses to two provocative stimuli tests and MGHC less than 3 ng/ml), prepubertal children with 'nonclassical' GH deficiency (group 2, n = 36, normal GH responses to two provocative tests and MGHC less than 3 ng/ml), short normal children (normal GH responses to two provocative tests and MGHC greater than 3 ng/ml) at stage P1 of puberty (group 3, n = 41) and at stage P2 of puberty (group 4, n = 27). The values of MGHC, dMGHC and nMGHC were significantly higher in groups 3 and 4 than in groups 1 and 2, and in group 4 than in group 3. The values of MGHC and nMGHC were significantly higher in group 2 than in group 1. MGHC correlated highly with nMGHC and dMGHC (r = 0.97 and 0.94, respectively; p less than 0.001). On the basis of regression equations between MGHC and nMGHC or dMGHC, the study of the diagnostic accuracy showed values higher for nMGHC than for dMGHC: 94.1 vs. 89.6% for sensitivity, and 93.7 vs. 89.7% for specificity, respectively.     

Lower 24-hour growth hormone levels in type I diabetics responding to thyrotropin-releasing hormone (TRH).

The aim of the study was the evaluation of growth hormone secretion under physiologic conditions in two groups of type I diabetics: responding and nonresponding to TRH stimulation. Both groups matched for age and metabolic control of diabetes were studied during 24-hours and after GHRH stimulation. The whole diabetic group (n = 18) showed circadian rhythm of GH secretion with mesor value of 4.03 micrograms/l. TRH-responders had lower mesor GH value than TRH-nonresponders: 3.53 vs. 5.32, p < 0.05. GH response to GHRH was almost identical in both groups. C-peptide level was lower in TRH-responders: 0.16 vs. 0.56 microgram/l, p < 0.05. No correlation was found between growth hormone response and HbA1 and C-peptide levels. It is concluded that type I diabetics responding to TRH stimulation are characterized by lower mean 24-hour GH levels and lower C-peptide values.     

Substrate and hormonal responses to exercise in women using oral contraceptives

Hormone and substrate responses to mild and heavy treadmill exercise were compared in women who used oral contraceptives (OC group; n = 7) and in normally menstruating women (control group; n = 8). Venous blood samples were obtained before exercise (-5 min), during exercise (15, 30, 45, and 60 min), and 30 min after exercise. All samples were analyzed for glucose, lactate, free fatty acids (FFA), glycerol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (hGH), cortisol, insulin, estradiol (E2), and progesterone (P). Substrate patterns during exercise were not altered by the phase of the menstrual cycle or OC usage. However, in the OC group the FFA concentrations were consistently higher during mild exercise and the glucose concentrations were lower at rest and during exercise than in the control group (P less than 0.05). No differences in lactate or glycerol responses were observed between the groups (P greater than 0.05). The responses of insulin and hGH to exercise were not related to the OC use per se but rather to the steroid status, either endogenous or exogenous. Specifically, during the steroid phases (OC use phase and luteal phase) 1) insulin concentrations were not quite as markedly reduced (i.e., 12% higher when luteal phase and OC usage phase data were combined; P less than 0.05), and 2) hGH concentrations at rest and during light exercise were higher in the OC group during the OC use phase (P less than 0.05). LH patterns were not affected by exercise (P greater than 0.05), but a slight decrease was found in FSH (P less than 0.05). Increments in P and E2 were observed in the control group in both the follicular and luteal phase (P less than 0.05), but much greater increments in P occurred in the luteal phase than in the follicular phase (P less than 0.05). In contrast to the control group, no increments in P, E2, or cortisol occurred in the OC users during exercise (P greater than 0.05). Therefore the new observations in this study are that 1) insulin and growth hormone respond in a complex manner during exercise with either the phase of the menstrual cycle or the phases of OC use and disuse and 2) the steroid concentrations (P, E2, cortisol) are increased in the controls but not in the OC users during exercise. The latter point suggests that normal steroid increments are due to an increased rate of secretion rather than a decrease in the hepatic clearance of these steroids.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pupillary signs in diabetic autonomic neuropathy.

Pupillary function was investigated in 36 insulin-dependent diabetics and 36 controls matched for age and sex. About half of the diabetics had evidence of peripheral somatic or autonomic neuropathy, or both. The diabetic patients had abnormally small pupil diameters in the dark and less fluctuation in pupil size (hippus) during continuous illumination than the controls. They also had reduced reflex responses to light flashes of an intensity adjusted for individual retinal sensitivities. The pupillary findings were compared with results of five tests of cardiovascular function and five tests of peripheral sensory and motor nerve function. Almost all the patients with autonomic neuropathy had pupillary signs, which we therefore conclude are a common manifestation of diabetic autonomic neuropathy.     

Human plasma C-peptide immunoreactivity: its correlation with immunoreactive insulin in diabetes, and chronic liver and renal diseases.

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.     

Serum angiotensin-converting enzyme in diabetes mellitus: a negative report

Serum angiotensin-converting enzyme (ACE) was measured by a direct photometric method in 78 normotensive diabetic patients and in 34 controls. For comparison, ACE was also assayed in 24 subjects by a radiometric procedure. We found no ACE elevations in diabetics and no significant difference in mean ACE levels between diabetics and normals. Within the diabetic group, enzyme levels were not affected by duration of disease, degree of metabolic control, or presence or not of microangiopathy. Only type I subjects had mean ACE significantly (p less than 0.05) higher than type II, very likely due to their younger age. Serum ACE data from photometric and radiometric methods significantly correlated. ACE measurement seems to be of scarce significance in diabetes mellitus.     

Serum glucose and free fatty acids modulate growth hormone and luteinizing hormone secretion in the pig

Two experiments were conducted to determine the effect of free fatty acids (FFA) and glucose treatment on growth hormone (GH) and luteinizing hormone secretion in the pig. In Experiment (Exp) 1, 15 prepuberal gilts received an intravenous infusion of FFA (n = 5; 3 ml of 10% Liposyn II/kg), glucose (n = 5; 1 g/kg), or saline (n = 5; 3 ml of 0.9%/kg). Jugular blood samples were collected every 15 min for 2 hr before and 3 hr after intravenous infusion of saline, FFA, and glucose. Synthetic [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (1 microgram/kg) and gonadotropin-releasing hormone (0.2 micrograms/kg) were administered 30 min after infusion (Time 0 = infusion). In Exp 2, eight prepuberal gilts received either FFA (n = 4) or saline (n = 4) as described in Exp 1, except that treatments were given every hour ove a 10-hr period. Blood samples were collected every 15 min from 1 hr before to 10 hr after the start of FFA or saline infusion. In Exp 1, the peak GH response to growth hormone-releasing factor was delayed by 45 min (P less than 0.01) by glucose treatment and suppressed (P less than 0.01) by FFA treatment. The luteinizing hormone response to gonadotroph-releasing hormone was suppressed (P less than 0.03) by glucose and enhanced (P less than 0.03) by FFA. In Exp 2, the number of GH pulses was increased (P less than 0.05) by FFA infusion and GH concentrations were positively correlated (r = 0.58, P less than 0.0003) with FFA concentrations, while luteinizing hormone pulse amplitude was greater (P less than 0.01) in FFA gilts than in saline gilts. These results indicate that FFA are more effective modulators of GH secretion than acute hyperglycemia, while metabolic status can alter pituitary responsiveness to gonadotropin-releasing hormone.     

Plasma concentrations of thyroid hormones in dogs: influence of sampling hour, breed and age

Thyroxine (T4) and triiodothyronine (T3) plasma concentrations have been determined during 24-hr sampling periods in six mongrels (age 12-36 months), six beagles (age 35-37 months), three labradors (age 3.5 months) and three beagles (age 5 months). The mean T4 levels of the labradors were significantly lower than the values found for mongrels or older beagles (P less than 0.05), whereas T3 was higher in the 5 month old beagles compared to the mongrels (P less than 0.001), young beagles (P less than 0.05) or labradors (P less than 0.01). Circadian and ultradian rhythmicities have been evaluated by cosinor and Fourier analysis. Mongrels and older beagles did have a 12-hr rhythmicity in plasma T4 (P less than 0.05), whereas 5 month old beagles had a circadian one (P less than 0.01). A 12-hr rhythmicity was also found for T3 in the older Beagles (P less than 0.05). However, Fourier analysis indicated that the daily variation in T4 and T3 plasma levels was inadequately mathematically described by single sinusoidal rhythm and that more harmonic components are to be taken into account. The obtained data during a 24-hr period indicate that T4 and T3 concentrations in plasma may vary according to breed, age and sampling hour.     

Dietary thyrotropin-releasing hormone stimulates growth rate and increases the insulin: glucagon molar ratio of broiler chickens

The effects of thyroid manipulation on growth, feed efficiency, and plasma hormone levels were determined in rapidly growing chickens. Beginning at 3 weeks of age, eight broiler cockerels were provided with control feed (CF) or feed containing either 1 ppm of triiodothyronine (T3), 1 ppm of thyroxine (T4), 0.3% propylthiouracil (PTU), or 5 ppm of thyrotropin-releasing hormone (TRH) for 3 weeks. Blood samples were taken at 4, 5, and 6 weeks for determination of plasma levels of growth hormone, insulin-like growth factor, T3, T4, insulin, glucagon, glucose, and nonesterified fatty acids. Dietary TRH increased (P less than 0.05) the growth rate of chickens by 14% when compared with the CF group. Plasma growth hormone levels were reduced (P less than 0.05) 65% by dietary T3 and 33% by treatment with either T4 or TRH when compared with the CF group. Plasma insulin-like growth factor levels were 16% lower (P less than 0.05) in PTU-fed birds than the other treatment groups. Plasma T3 levels were elevated (P less than 0.05) 3-fold by dietary T3 and 38% by TRH whereas plasma T3 in the PTU group was 38% below the average of CF birds. Plasma T4 levels were increased (P less than 0.05) by 12-fold in T4-fed birds, decreased 48% in TRH-fed birds, and nondetectable in birds treated with either T3 or PTU. Compared with the other treatments, dietary PTU increased (P less than 0.01) plasma insulin levels 4.3-fold whereas TRH provided a 2.7-fold increase in plasma insulin. Plasma glucagon levels were 26% higher (P less than 0.05) in T3-fed birds than those fed either T4 or PTU. These observations indicate that thyroid activity plays an important role in regulating secretion of GH and the pancreatic hormones. Furthermore, our study demonstrates the potential use of TRH as an orally active growth promoter for poultry.     

Red blood cell deformability index in diabetic retinopathy

In order to investigate the relationship between haemorheological disturbances and diabetic microangiopathy we have studied the red blood cell deformability index (RBCD-index) by means of a filtration technique in 69 diabetics, aged 49-83 years, and in 40 non diabetic healthy controls (group A) of respective age and sex. The diabetics were classified into the following groups, according to the findings of a thorough clinical and laboratory investigation. Twenty patients (group B) were free of vascular complications, whereas 9 (group C) suffered from background retinopathy, 27 (group D) background retinopathy and ischaemic cardiopathy or peripheral arterial occlusive disease and 13 (group E) of proliferative retinopathy with diffuse micro- and macroangiopathy. The RBCD-index was significantly (P less than 0.001) decreased in diabetics with retinopathy compared to the diabetic and non diabetic controls. The lowest RBCD-index was observed in diabetics with proliferative retinopathy and in those with diffuse micro- and macrovascular complications (RBCD-index, means +/- SDM ml/min: A 0.68 +/- 0.15; B 0.64 +/- 0.08; C 0.60 +/- 0.08; D 0.49 +/- 0.09; E 0.48 +/- 0.09). These findings suggest that the RBCD is impaired in diabetics with retinopathy, especially in those with severe vascular complications, and that this abnormal rheological behavior of erythrocytes can be found even in the early stages of diabetic microangiopathy.     

Investigation of subclinical signs of autonomic neuropathy in the early stage of childhood diabetes

It has been suggested that subclinical signs of neuropathy appear earlier than microvascular complications of diabetes. To evaluate the occurrence of autonomic nervous system dysfunction in the early stage of childhood diabetes, subclinical signs of autonomic neuropathy (resting heart rate, hyperventilatory arrhythmia, standing/lying heart rate ratio, orthostatic decrease in blood pressure, and increase in blood pressure during sustained handgrip) were investigated in 54 children with type 1 diabetes divided into three groups: 14 recent-onset diabetics (3 weeks after the diagnosis), 20 diabetics in the remission phase, and 20 patients after the remission phase. 30 healthy age-matched children were used as control group. The mean resting heart rates of the diabetic groups in the remission phase and after the remission phase were significantly higher than those in the healthy control group (81.7 +/- 5/min and 88.5 +/- 6/min vs. 72.2 +/- 8/min; p less than 0.01). The hyperventilatory arrhythmia in the group of diabetic children after the remission phase in comparison with the control group was significantly decreased (29.1 +/- 4/min vs. 22.7 +/- 3/min; p less than 0.01). In a few cases of the recent-onset diabetic group, the increase in resting heart rate, the decrease in hyperventilatory arrhythmia, and the standing/lying heart rate ratio proved to be significant. In the remission phase, the same parameters showed abnormal values in one third to one fifth of the children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive increase in kidney insulin-like growth factor I and initial renal enlargement in uninephrectomized-diabetic rats

The initial renal hypertrophy in experimental diabetes and in response to uninephrectomy is associated with renal accumulation of insulin-like growth factor I (IGF-I). Since the combination of diabetes and nephrectomy almost doubles the initial renal growth rate the aim of the present study was to investigate the kidney IGF-I levels in the combined situation in uninephrectomized diabetic rats. Three experimental groups were exposed to either unilateral nephrectomy, streptozotocin-diabetes or both conditions and for four days animals from each group were taken out for investigation. After 4 days the wet kidney weight increased from baseline by 31% (from 661 +/- 16 mg (SEM) to 866 +/- 27 mg) (P less than 0.01) in the uninephrectomized group, 32% (to 872 +/- 18 mg) (P less than 0.01) in the diabetic group and 46% (to 962 +/- 27 mg) (P less than 0.01) in the uninephrectomized-diabetic group. Kidney IGF-I concentrations were analyzed by radioimmunoassay and the increase from baseline on day 2 was 74% (from 262 +/- 12 ng/g (SEM) to 456 +/- 21 ng/g) (P less than 0.01) in the uninephrectomized group, 58% (to 414 +/- 18 ng/g) (P less than 0.01) in the diabetic group and 176 +/- % (to 722 +/- 56 ng/g) (P less than 0.01) in the combined group. Thereafter a decline in kidney IGF-I occurred in all groups, being normal at day 4 for the diabetic group, but still significantly higher in the uninephrectomized and uninephrectomized-diabetic groups compared to controls (P less than 0.05%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of nifedipine in the treatment of arterial hypertension in various types of diabetes mellitus

Selection of indications and the general tactics of nifedipine monotherapy of hypertension in diabetic subjects is not clearly established, as yet. It refers specifically to different forms and phases of diabetes mellitus. This was the reason to carry out a respective study. In 4 groups of hypertension: 1) in diabetics without vascular complications, 2) in diabetic nephropathy, 3) in diabetics type II without nephropathy, and 4) in comparative group of subjects without diabetes mellitus, a 6-week controlled, open trial was performed. Before, during and after nifedipine (3 X 10-20 mg p.d.), the following parameters were monitored: 1) systolic, diastolic and mean blood pressures, 2) glycaemic indices of diabetes control, 3) serum cholesterol: total, HDL, LDL, triglycerides, 4) daily albuminuria and GFR, 5) adverse reactions to nifedipine. It could be concluded that nifedipine therapy was relatively most effective and safe in hypertensive diabetics type II without nephropathy. It was less effective in diabetics type I without nephropathy and failed in diabetics type I with nephropathy.     

Vascular alterations and GH secretion in latent chemical diabetes]

The AA. have investigated the relationship between the secretion of GH and diabetic angiopathy a group of 17 subjects with chemical diabetes during a standard dexamethasone os i.v. glucose test. The results show that functional subclinical microangiopathy was present in the majority of the diabetics studied, who also showed an exaggerated growth hormone response to glucose. Thus, these results suggest that a positive correlation exists between alterations in the secretion of growth hormone and the development of diabetic microangiopathy.     

Decreased response of epinephrine and norepinephrine to insulin-induced hypoglycemia in diabetic autonomic neuropathy

The responses of epinephrine, norepinephrine and other counter-regulatory hormones to insulin-induced hypoglycemia were investigated in 5 diabetics who showed signs of autonomic neuropathy, in 7 age-matched diabetics without autonomic neuropathy and in 7 healthy subjects. The presence of autonomic neuropathy was evaluated by decreased beat-to-beat variation in heat rates during hyperventilation or orthostatic hypotension. Catecholamines were determined by a totally automated plasma catecholamine analyzing system using a two-column system of high performance liquid chromatography. Plasma epinephrine and norepinephrine responses to hypoglycemia in diabetics with autonomic neuropathy were significantly lower than those in diabetics without autonomic neuropathy. Plasma glucagon response in diabetics was apparently attenuated compared to normal controls and there was no significant difference in glucagon response between the two patient groups. Other counter-regulatory hormone responses did not differ among the three groups. The data demonstrate that the responses of plasma epinephrine and norepinephrine to insulin-induced hypoglycemia are impaired in diabetics with autonomic neuropathy.     

Oxygen transport and peripheral microcirculation in long-term diabetes

The purpose of this investigation was to evaluate the impact of long-term diabetes on muscle blood flow (MBF) and oxygen transport (vO2) during exercise. Twelve male patients (58 +/- 8 years, mean +/- SD), with at least a 10-year history of diabetes controlled by insulin, and seven age-matched controls (56 +/- 5 years, mean +/- SD) participated in this study. No patient had been clinically diagnosed as having peripheral vascular disease, and on the average resting ankle/arm systolic blood pressure ratios were normal. Following a baseline period, 5 min of cycle ergometer exercises at 75 W were performed in the upright position and, after 1-hr recovery, in the supine position. Continuous vO2 was determined via breath-by-breath analysis. MBF was measured in the vastus lateralis (VL) and tibialis anterior (TA) by 133Xe clearance. In the erect position, the diabetic group (compared with the control group, respectively) exhibited significantly (P less than 0.05) lower exercise MBF [ml. (100 g.min)-1] in both VL (19 +/- 2.5 vs 30.9 +/- 2) and TA (13.7 +/- 2 vs 22.0 +/- 4), a lower steady-state VO2 (1.3 +/- 0.3 vs 1.7 +/- 0.2 liters.min-1) during exercise including the values in the last 15 sec of exercise, and greater accumulation of blood lactate (35 +/- 2 vs 22.0 +/- 2 mg/100 ml). The same trends in the data were observed during supine exercise; however, the blood pressure of the diabetics was significantly elevated during exercise when compared with that of controls. The reduced exercise MBF in the TA and VL demonstrated that impaired microvascular flow, without clinically overt peripheral vascular disease, in long-term diabetics leads to reduced oxygen delivery and exercise tolerance.