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Biomedical subjects

M C Foss

Publications and source records attributed to M C Foss.

At least 37 records · Page 2Linked to original sources

Role of bradykinin in postprandial hypotension in humans.

A transient significant decrease in mean arterial blood pressure (MAP) from 107 +/- 3 to 98 +/- 3 mmHg (P < 0.05) was observed in elderly (59-69 years of age), healthy volunteers 25-30 min following ingestion of a test meal. In young volunteers (22-34 years of age), a postprandial decrease of MAP from 88 +/- 3 to 83 +/- 4 mmHg was also noted but it was not statistically significant. A 40% decrease in bradykinin (BK) content of circulatory high molecular weight kininogen had previously been observed in human subjects given the same test meal. We presently demonstrate by specific ELISA that the stable pentapeptide metabolite (1-5 BK) of BK increases from 2.5 +/- 1.0 to 11.0 +/- 2.5 pg/ml plasma (P < 0.05) in elderly volunteers and from 2.0 +/- 1.0 to 10.3 +/- 3.2 pg/ml plasma (P < 0.05) in young volunteers 3 h following food intake. This result suggests that ingestion of food stimulates BK release from kininogen in normal man. Postprandial splanchnic vasodilatation, demonstrated by a decrease of plasma half-life of intravenously administered indocyanine green (ICG), a marker of mesenteric blood flow to the liver, from 4.4 +/- 0.4 to 3.0 +/- 0.1 min (P < 0.05) in young volunteers and from 5.2 +/- 1.0 to 4.0 +/- 0.5 min (P < 0.05) in elderly volunteers, accompanied BK release. The participation of BK in this response was investigated in subjects given the BK-potentiating drug captopril prior to food intake. Postprandial decreases of ICG half-lives were not changed by this treatment in either young or elderly subjects, a result which may indicate that BK released following food intake plays no role in postprandial splanchnic vasodilatation in normal man.

Adult↗

Abnormal intragastric distribution of a liquid nutrient meal in patients with diabetes mellitus.

Disordered gastric motility and emptying are well known complications of diabetes mellitus (DM), but the pattern of intragastric distribution of food has not been extensively studied in diabetics. We examined the partition of a liquid nutrient meal between the proximal and distal stomach and the relationships between intragastric distribution of food and gastric emptying (GE) and the symptoms in DM patients with and without autonomic neuropathy (AN). Fourteen healthy volunteers and 20 DM patients (13 with AN; 9 with dyspepsia symptoms) ingested a liquid nutrient meal (250 ml; 437 kcal) labeled with [99mTc]phytate. Anterior and posterior serial images of the stomach were taken for 90 min with a gamma camera. Regions of interest for the proximal and the distal halves of the stomach and for the total gastric area were defined. Counts from each region along time allowed estimation of GE and the proportion of activity retained in the proximal stomach after meal ingestion (initial) and throughout GE (mean). GE half-times in controls (median; range: 66 min; 29-90 min) were not significantly different from diabetics (76 min; 5->150 min, P > 0.10), but abnormal GE was found in 11 DM patients (seven delayed and four rapid). In DM patients, initial retention in the proximal stomach (42%; 16-79%) was significantly lower (P < 0.02) than in controls (55%; 44-71%). Mean retention in the proximal stomach throughout emptying also was significantly lower (P < 0.05) in DM patients (43%; 18-58%) than in controls (51%; 32-69%). There were no differences between subgroups of patients with normal, delayed, or rapid gastric emptying regarding mean meal retention in the proximal stomach. Patients with evidence of AN or with dyspepsia symptoms had significantly decreased retention of food in the proximal stomach throughout gastric emptying. We concluded that patients with diabetes mellitus have abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal, which seems to be related to the occurrence of autonomic neuropathy and dyspepsia symptoms, but not to disordered gastric emptying.

Adult↗

Effects of hypophosphatemia on glucose tolerance and insulin secretion.

Phosphate is an active participant in energy metabolism, and its deficiency has been associated with changes in insulin sensitivity and glucose tolerance. In the present study, we have investigated insulin secretion and glucose tolerance in individuals with moderate and acute phosphate deprivation and in patients with chronic hypophosphatemia. The individuals with dietary phosphate deprivation, evidenced by a significant reduction in phosphaturia from 232.3 +/- 37.1 to 56.8 +/- 23.9 mmol/24 hours, but with normal serum levels of inorganic phosphorus, presented circulating glucose and insulin levels similar to those of the pre-dietary period during the oral and intravenous glucose tolerance tests. In contrast, patients with chronic hypophosphatemia (inorganic phosphorus < 0.65 mmol/l) presented in hyperinsulinemia during the postabsorptive state and during the early and late phases of insulin secretion after the oral and intravenous glucose stimulus. The physiological response of a fall in serum phosphate after glucose administration observed in individuals with chronic hypophosphatemia was similar to that of normal individuals. The presence of hyperinsulinemia both basally and after glucose stimulation, with normal glycemia, in phosphate-depleted individuals suggests that this condition is associated with reduced insulin sensitivity. However, severe phosphate deprivation is necessary for the manifestation of this undesirable association. The deviation of phosphate to the intracellular medium occurring after glucose administration in hypophosphatemic individuals is similar to that of normal individuals and explains the occurrence of severe hypophosphatemia in malnourished hypophosphatemic individuals when submitted to parenteral refeeding.

Administration, Oral↗

Rapid distal small bowel transit associated with sympathetic denervation in type I diabetes mellitus.

BACKGROUND: The pattern of progression of a meal from the stomach to the caecum in diabetes mellitus is controversial and the differential roles of transit through the jejunum and the ileum have not been investigated in diabetes. AIMS: To determine gastric emptying and transit rates through proximal and distal regions of the small bowel in type I diabetic patients. SUBJECTS: The study included six diabetic patients with evidence of autonomic neuropathy (DM-AN group), 11 diabetics without autonomic dysfunction (DM group), and 15 control volunteers. METHODS: Gastric emptying and small bowel transit of a liquid meal were evaluated scintigraphically in these subjects. Transit through regions of interest corresponding to the proximal and distal small intestine up to the caecum was determined and correlated with gastric emptying rates, cardiovascular measurements of autonomic function, and the occurrence of diarrhoea. RESULTS: Gastric emptying and transit through the proximal small bowel were similar in the three groups. The meal arrived to the caecum significantly earlier in DM-AN patients (median; range: 55 min; 22-->180 min) than in the DM group (100 min; 44-->180 min, p < 0.05) or in controls (120 min; 80-->180 min, p < 0.02). Accumulation of chyme in the distal small bowel was decreased in DM-AN patients, who showed values for peak activity (30%; 10-55%) significantly lower than in the DM group (49%; 25-77%, p = 0.02) and controls (50%; 30-81%, p = 0.02). In DM patients (n = 17), the time of meal arrival to the caecum was significantly correlated with both orthostatic hypotension (coefficient of contingency, C = 0.53, p < 0.01) and diarrhoea (C = 0.47, p < 0.05), but not with gastric emptying rates. CONCLUSIONS: Patients with type I diabetes mellitus and sympathetic denervation have abnormally rapid transit of a liquid meal through the distal small bowel, which may play a part in diarrhoea production.

Adolescent↗

Effect of hemodialysis on peripheral glucose metabolism of patients with chronic renal failure.

Glucose intolerance has been shown in patients with chronic renal failure (CRF), probably associated with insulin resistance in peripheral tissues. The present study was thus designed to investigate the effect of hemodialysis on peripheral muscle glucose metabolism of patients with CRF. Nine normal subjects and 6 patients with CRF were studied after an overnight fast (12-14 h) and during 3 h after ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate the muscle exchange of substrates combined with indirect calorimetry. The CRF patients were studied before and after at least 1 month of hemodialysis treatment. Plasma glucose levels (arterial and venous) were higher in uremic patients before dialysis than in normal controls. After the dialysis therapy there was improvement in the glycemic profile of the CRF patients. Decreased forearm muscle glucose uptake was observed in the uremic patients before dialysis compared to the normal subjects (234 +/- 71 vs. 858 +/- 52 mumol/100 ml forearm . 3 h, p < 0.05) with diminished nonoxidative glucose metabolism (128 +/- 78 vs. 686 +/- 58 mumol/100 ml forearm . 3 h, p < 0.05). After the hemodialysis treatment of the CRF patients, the forearm glucose uptake and the nonoxidative glucose metabolism increased significantly to values of 527 +/- 64 and 384 +/- 87 mumol/100 ml forearm . 3 h, respectively. Muscle glucose oxidation did not differ significantly between normals and CRF patients before and after dialysis, as well as the serum insulin levels. These data demonstrate that insulin resistance in the presence of chronic uremia is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism, which are significantly improved by the hemodialysis treatment.

Adult↗

Treatment of diabetic gastroparesis with oral clonidine.

BACKGROUND/AIMS: Clonidine, a specific alpha-2-adrenergic receptor agonist, has been suggested to improve symptoms of gastroparesis in diabetics with diarrhoea. The aim of this study was to investigate the effects of clonidine on gastric emptying and symptoms suggestive of gastroparesis in patients with longstanding diabetes mellitus and evidence of autonomic neuropathy. METHODS: Six diabetics with chronic, refractory symptoms of bloating, nausea and vomiting were studied. Gastric emptying of a liquid nutrient meal (250 mL; 430 kcal) was evaluated by scintigraphy and symptoms were scored. Patients were treated with clonidine (median dose: 0.3 mg/day) for 2-12 weeks (median: 4 weeks), after which symptoms and gastric emptying were re-evaluated. Treatment was then sustained for a median follow-up period of 7 weeks (range: 2-56 weeks). RESULTS: Gastric emptying half-time values in diabetic patients ranged from 16 to 180 min (median: 100 min) and four patients had abnormally delayed emptying before treatment. In all patients, half-time values decreased during treatment (median: 35 min; range: 14-106 min, P < 0.025 vs. pre-treatment values) and in three of the four patients with abnormal gastric retention, half-time values returned to the normal range. During clonidine treatment, a substantial decrease in the score for symptoms was observed (median and range: 7.5; 2-9 vs. 0; 0-9). In four patients, symptoms virtually disappeared, an effect that was maintained throughout follow-up (6-56 weeks). CONCLUSIONS: These findings suggest that impairment of adrenergic influences on gastrointestinal motility control may play a role in the pathophysiology of diabetic gastroparesis and that clonidine may be a useful alternative for treating patients with this condition.

Administration, Oral↗

Peripheral glucose metabolism in human hyperprolactinaemia.

OBJECTIVE: Prolactin has important biological actions in several species which include metabolic control and water/electrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism. DESIGN: The study was designed to determine forearm muscle glucose uptake and utilization (oxidative and non-oxidative metabolism) in normal and hyperprolactinaemic subjects in the post-absorptive state and for 3 hours after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrates combined with local indirect calorimetry. PATIENTS: Eight hyperprolactinaemic patients (HP group, 6 females and 2 males) and ten normal subjects (N group, 7 females and 3 males) were studied. The hyperprolactinaemic patients showed no clinical or laboratory evidence of acromegaly or hypothyroidism and were not using any PRL releasing drugs. MEASUREMENTS: Forearm blood flow was measured by capacitance plethysmography and arterial and venous blood samples were drawn simultaneously to determine plasma glucose, serum FFA, total blood CO2 and O2 and serum insulin in the post-absorptive state (0 time) and at 30, 60, 120 and 180 minutes after glucose ingestion. RESULTS: No significant difference in glucose uptake by the forearm muscle tissue was observed between the N and HP groups (823 +/- 103 vs 828 +/- 110 mumol/100 ml forearm 3 h, respectively), nor were any significant differences observed in the intracellular utilization of glucose (oxidative and non-oxidative metabolism). However, the serum insulin levels after glucose ingestion were significantly higher in hyperprolactinaemic patients than in normal subjects, especially at 30 (N 283 +/- 46 vs HP 581 +/- 133 pmol/l) and 60 minutes (N 291 +/- 37 vs HP 544 +/- 61 pmol/l). Furthermore, after glucose ingestion the suppression of serum FFA levels was smaller in the hyperprolactinaemic patients than in normal subjects. CONCLUSIONS: This study demonstrated that insulin resistance is associated with the presence of spontaneous human hyperprolactinaemia. The hyperinsulinaemia detected in the hyperprolactinaemic patients after the oral glucose stimulus did not determine a proportional increase in forearm glucose uptake and utilization, which were similar to the normal levels. The suppression of serum free fatty acid concentrations was also smaller in hyperprolactinaemic patients during the oral glucose challenge, suggesting an impaired antilipolytic effect of insulin.

Adult↗

Insulin secretion in obese and non-obese women with polycystic ovary syndrome and its relationship with hyperandrogenism.

Insulin resistance has been reported to be associated with hyperandrogenism and polycystic ovaries. To study the prevalence of insulin resistance in patients with polycystic ovary syndrome (PCO) and the correlation between hyperinsulinemia and hyperandrogenism, 48 patients were divided into four groups: group 1, non-obese ovulatory women (n = 10); group 2, obese ovulatory women (n = 9); group 3, non-obese women with PCO (n = 14); group 4, obese women with PCO (n = 15). Each patient was submitted to an oral glucose tolerance test (OGTT). Glucose, insulin, androstenedione and testosterone levels were determined and the blood glucose and insulin response of women with PCO and normal women were compared. Glucose intolerance was observed in group 3 (28.6%) and group 4 (40%) but not in groups 1 or 2, and hyperinsulinemia was observed in group 2 (66.7%), group 3 (64.3%) and group 4 (86.6%). There was a correlation between androstenedione and testosterone levels and insulinemia in group 4. There was also a high prevalence of insulin resistance in patients with PCO regardless of obesity, and hyperandrogenism-aggravated insulin resistance.

Adolescent↗

Peripheral glucose metabolism in patients with chronic renal failure.

The present study was designed to determine the effect of chronic renal failure on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Twelve normal subjects and sixteen patients with chronic renal failure were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in uremic patients compared to normal subjects (91.5 +/- 11.4 vs 154.8 +/- 7.8 mg 100 ml forearm-1 3 h-1) with diminished nonoxidative glucose metabolism (69.4 +/- 12.1 vs 117.2 +/- 12.8 mg 100 ml forearm-1 3 h-1). Muscle glucose oxidation did not differ significantly between groups. Both serum free fatty acid levels and lipid oxidation rates were similar in the normal subjects and the uremic patients, and declined in a similar fashion after glucose ingestion. Basal serum insulin levels did not differ significantly between normal and uremic patients, whereas the insulinemic response to glucose load was greater among the patients with chronic renal failure. These data show that insulin resistance occurring in patients with chronic renal failure is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism.

Adult↗

Androgen-related effects on peripheral glucose metabolism in women with congenital adrenal hyperplasia.

The study was designed to investigate the influence of androgens on peripheral glucose metabolism in women with congenital adrenal hyperplasia (CAH). Nine normal women and seven women with CAH were studied (4 with the classical form of 21-hydroxylase deficiency [C 21-OH] and 3 with nonclassical 21-hydroxylase deficiency [NC 21-OH]). The study was performed using the forearm model combined with local indirect calorimetry. The insulin level reached 30 minutes after glucose ingestion was significantly greater (p < .05) in patients with CAH. The patients with C 21-OH had elevated androstenedione (A) and testosterone (T) and low DHEA-S and presented a 35% greater insulin response to a glucose stimulus than the control group, area under the curve (AUC) of 9457 +/- 887 vs 6989 +/- 833 microU/ml.3 hours. Patients with NC 21-OH had slightly elevated T, A and DHEA-S and presented an insulin response that was similar to the control group, AUC = 7208 +/- 1935 microU/ml.3 hours. Despite the greater muscle mass of the patients with CAH the forearm glucose uptake during the three hours of the study was lower in these patients than in normal women (CAH = 100.9 +/- 10.0 vs control group = 132.5 +/- 21.2 mg/100 ml forearm). The ratio of insulin response to the increment of forearm glucose uptake over a period of 3 h was significantly higher in patients with CAH (control group = 59.6 +/- 6.5 vs CAH = 98.6 +/- 19.4 microU.ml-1/mg.100 ml forearm-1, p < 0.05). These results suggest that insulin sensitivity is decreased in patients with CAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Hyperplasia, Congenital↗

Effect of local diets with added sucrose on glycemic profiles of healthy and diabetic Brazilian subjects.

OBJECTIVE: We set out to determine the daily glycemic profile of healthy and non-insulin-dependent diabetes mellitus (NIDDM) persons and to test the hypothesis that small amounts of sucrose added to NIDDM meals would not change their responses. METHODS: Thirteen NIDDM and six healthy volunteers participated in the study. They initially consumed a diet similar to their home diet and later a diabetic hospital dietary regimen, with and without 30 g/day sugar replacing equivalent food energy. The hospital diet included their usual foods: bread, milk, rice, beans, meat, vegetables and fruits at breakfast, lunch and dinner. To follow their glycemic profile we drew several blood samples during a 22-hour period. RESULTS: The day-long plasma glucose profile of the NIDDM and healthy subjects showed similar patterns, increasing after the meals and returning later to baseline levels. The extra amount of sucrose consumed did not change the daily glycemic profile or the calculated glycemic area under the 22-hour glycemic curves. These results call attention to the importance of the 22-hour glycemic profile compared to other shorter glycemic indexes. CONCLUSION: The 22-hour profile has obvious advantage for planning day-long diabetic diets, taking in consideration local daily foods and usual eating habits. Maintenance of a small and traditional amount of food, e.g., sucrose, without harmful effects to the subjects, is another advantage of this proposition. It improves patient compliance as well as social daily life.

Adult↗

Hyperandrogenism due to 3 beta-hydroxysteroid dehydrogenase deficiency with accessory adrenocortical tissue: a hormonal and metabolic evaluation.

1. Adrenal ectopic tissue has been detected in the paragonadal region of normal women. In patients with congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency, the manifestation of hyperplasia of paragonadal accessory adrenal tissue has been usually reported to occur in males. Probably, this is the first report of a female with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency with ectopic adrenal tissue in ovaries. However, the occurrence of hyperplasia of adrenal rests among women with classical congenital adrenal hyperplasia may not be rare, especially among patients with a late diagnosis. 2. We report a woman with 3 beta-HSD deficiency whose definitive diagnosis was made late at 41 years of age immediately before surgery for the removal of a uterine myoma. During surgery, exploration of the abdominal cavity revealed the presence of bilateral accessory adrenal tissue in the ovaries and in the para-aortic region. The patient had extremely high levels of ACTH (137 pmol/l), DHEA (901.0 nmol/l), DHEA-S (55.9 mumol/l), androstenedione (70.2 nmol/l), testosterone (23.0 nmol/l) and 17 alpha-hydroxypregnenolone (234.4 nmol/l) suggesting 3 beta-HSD deficiency. 3. In view of these elevated androgen levels, with an absolute predominance of DHEA and DHEA-S, we evaluated the effect of this hormonal profile on carbohydrate tolerance and insulin response to glucose ingestion. 4. The patient presented normal glucose tolerance but her insulin response was lower than that of 14 normal women (area under the curve, 3 beta-HSD = 17,680 vs 50,034 pmol/l for the control group over a period of 3 h after glucose ingestion).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Peripheral glucose metabolism in healthy subjects and in endocrine diseases.

1. Seventeen healthy male subjects were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose to investigate peripheral glucose metabolism (uptake, oxidative and nonoxidative metabolism) using the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. In normal subjects, during the 3-h study period, 30.3 +/- 2.1 g (40.4% of the ingested load) of glucose were processed by skeletal muscle in the body as a whole and 8.1 +/- 0.6 g were completely oxidized while 22.2 +/- 2.3 g were utilized through the nonoxidative pathway in muscle tissue. 2. After ingesting 75 g of glucose, normal women showed greater glucose uptake per unit of muscle mass and a predominant tendency toward utilizing glucose by a nonoxidative pathway than did normal men. The higher glucose uptake of the female group and an insulin response not significantly different from that of the male group suggest that muscle insulin sensitivity is greater in normal women. 3. The study of the effects of 50 and 100 g glucose loads on the peripheral glucose metabolism of normal men revealed a dose-dependent metabolic response in muscle tissue to these oral glucose challenges with respect to forearm muscle glucose uptake and nonoxidative glucose metabolism. The oxidative responses of the muscle tissue were not directly proportional to the oral glucose loads. 4. The administration of carbohydrate, usually glucose, leads to a decrease in the serum level of inorganic phosphorus (Pi), attributed to Pi flow from the extracellular to the intracellular compartment as part of the increased glucose metabolism induced by insulin. However, our data indicate that muscle tissue is not the site responsible for the fall in serum Pi after glucose ingestion. 5. Spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with increased fluxes of glucose through the oxidative and nonoxidative pathways. 6. The insulin resistance occurring in the presence of chronic growth hormone (GH) excess is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism. These probably are early derangements because they are also observed in acromegalic patients with normal glucose tolerance. 7. A clear-cut dissociation between peripheral glucose and potassium transport was observed in the forearm muscle of acromegalic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗

Restoration of fuel homeostasis in IDDM patients during pregnancy by an open-loop insulin infusion system.

OBJECTIVE: To characterize the effects of subcutaneous insulin pump therapy on the metabolic response (CHO and lipid oxidation, and nonoxidative glucose metabolism) to a glucose challenge of diabetic women at early pregnancy. RESEARCH DESIGN AND METHODS: Seven nondiabetic and seven IDDM pregnant patients on insulin pump therapy were studied at the first trimester. Fuel oxidation rates were determined by indirect calorimetry, and blood levels of substrates and hormones were measured before and for 2 h after ingestion of a 50 g oral glucose load. RESULTS: The increments in npRQ and CHO oxidation rates after the glucose meals in the diabetic women on insulin pump therapy were similar to those in the normal subjects. The glucose disposal data during the 2 h of the studies revealed that the amounts of oxidative and nonoxidative glucose utilization in the control subjects and in the IDDM patients on insulin pump therapy did not show significant differences. CONCLUSIONS: This investigation demonstrated that the treatment of IDDM patients during early pregnancy by an open-loop insulin infusion system is sufficient to normalize their glucose-processing capability with respect to cellular oxidative and nonoxidative glucose metabolism in response to an oral glucose challenge, but some abnormalities in their blood profiles of glucose, lactate, and pyruvate persisted.

Adult↗

Peripheral glucose metabolism in patients with insulin resistance and acanthosis nigricans.

The present study was designed to determine forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge in patients with type A insulin resistance and acanthosis nigricans. Nine normal subjects and six acanthotic patients were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry in forearm. Two patients (1 and 6) with insulin resistance and acanthosis nigricans had impaired glucose tolerance. All other patients and normals revealed normal glucose tolerance during the tests. Decreased forearm muscle glucose uptake was observed in patients 1 and 6 compared to normal subjects (6.3 and 51.1 vs 127.7 +/- 10.1 mg/100 ml forearm.3 h, respectively). Decreased forearm muscle glucose oxidation was also observed in patient 1 as well as in patient 3 who showed normal glucose tolerance. Serum FFA levels were elevated in patient 1 but not in patient 3 and in the other acanthotic patients compared to the normal subjects. Serum insulin levels were significantly higher in acanthotic patients than in normals before and after glucose loading. The results of the present study revealed that two of six patients with type A insulin resistance and acanthosis nigricans who exhibited glucose intolerance also showed a decrease in peripheral muscle glucose uptake and nonoxidative glucose metabolism. Another patient (3) with normal glucose tolerance showed impaired muscle glucose oxidation but unaltered muscle glucose uptake and nonoxidative metabolism during the 3 hours of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗

Cholinergic bronchomotor tone and airway caliber in insulin-dependent diabetes mellitus.

It has been suggested that the autonomic bronchomotor tone may be altered in diabetes. In the present study, we assessed the cholinergic bronchomotor tone in 34 insulin-dependent diabetic patients and in a control group of 32 healthy subjects (group C). As an index of the intensity of cholinergic tone to the airways, we measured the increase in specific airway conductance (Gaw/VL) induced by aerosol administration of atropine sulfate. In all of the patients and normal individuals the autonomic cardiovascular activity was also evaluated by the tilting test and by the magnitude of the respiratory sinus arrhythmia (RSA). In 19 patients without symptoms of autonomic neuropathy (AN) (group D-1), the autonomic cardiovascular activity was comparable to that of group C. The other 15 patients presented with at least one symptom of AN and a depressed heart rate (HR) control when submitted to the tests of autonomic activity (group D-2). Before atropine administration, Gaw/VL was significantly higher (p less than 0.05) in group D-2 (2.48 +/- 0.12 s-1.kPa-1 [mean +/- SE]) than in group D-1 (2.11 +/- 0.10 s-1.kPa-1). Aerosol atropine caused a significant increase (p less than 0.001) in airway caliber in all three groups; however, the increase in Gaw/VL was significantly lower in group D-2 (0.26 +/- 0.05 s-1.kPa-1) when compared with group D-1 (0.63 +/- 0.09 s-1.kPa-1; p less than 0.01) and group C (0.67 +/- 0.06 s-1.kPa-1; p less than 0.001). A weak but significant (p less than 0.02) correlation was observed between the increases in Gaw/VL provoked by atropine and the magnitude of RSA. Our findings suggest that the reduction in parasympathetic bronchomotor tone may cause an increase in basal airway caliber in diabetic patients with AN, compared to patients without AN.

Adolescent↗

Fuel oxidation by insulin-dependent diabetics during late pregnancy in response to an oral glucose load.

1. To determine the oxidative response to a 50-g oral glucose challenge by diabetic women during late pregnancy under a more intensive therapeutic regimen than is conventionally employed, six normal pregnant women and ten insulin-dependent pregnant diabetic women were studied during the third trimester. Fuel (carbohydrate and lipid) oxidation rates were determined by indirect calorimetry, blood levels of substrates and C-peptide were measured directly, and glucose metabolism data (oxidation and nonoxidative metabolism) were estimated for both groups at the postabsorptive state and for the 2-h period following glucose ingestion. 2. The increases in the non-protein respiratory quotient (npRQ) and carbohydrate oxidation rates in response to glucose ingestion in the diabetic pregnant group were significantly smaller than in the normal pregnant individuals. The total amount of glucose oxidized by the diabetic pregnant group during the 2-h tests (6.1 +/- 0.6 g/m2) was significantly smaller than the oxidized by the normal pregnant group (8.3 +/- 0.4 g/m2), whereas there was more but not statistically significant lipid oxidation in the diabetic group (3.0 +/- 0.3 vs 2.6 +/- 0.1 g/m2). 3. The diabetic pregnant group not only oxidized less glucose (10.9 +/- 1.1 vs 14.1 +/- 0.8 g, P < 0.05) but more of this hexose remained in their glucose space (9.1 +/- 1.6 vs 3.2 +/- 1.1, P < 0.05) and they excreted 2.8 +/- 1.0 g into the urine. 4. The diabetic pregnant subjects had significantly lower blood levels of lactate, pyruvate and C-peptide than the normal pregnant subjects, but significantly higher blood levels of glucose, beta-hydroxybutyrate and acetoacetate. 5. The present data show that an intensive conventional therapeutic regimen during late pregnancy was not sufficient to completely normalize the glucose-processing capability of insulin-dependent diabetic patients.

Administration, Oral↗