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Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 55 records · Page 3Linked to original sources
PubMed1997

Blood flow, lipid oxidation, and muscle glycogen synthesis after glycogen depletion by strenuous exercise.

UNLABELLED: We studied the interrelationship between blood flow, glycogen synthesis, and glucose and lipid utilization in 14 healthy men. A 4-h euglycemic insulin clamp with indirect calorimetry and muscle biopsies were done after a glycogen depletion (exercise) and after a resting day (control). In spite of the exercise induced decrease in leg muscle glycogen content (28% in the basal state, 22% after hyperinsulinemia, P < 0.05 in both as compared with the control study), basal or insulin stimulated glycogen synthase activity remained unchanged. In the basal state, glucose oxidation was 54% lower (P < 0.001) and lipid oxidation 108% higher (P < 0.001) after the glycogen depletion as compared with that in the control study. During the post-depletion insulin clamp, the glucose oxidation rate was 17% lower (P < 0.02) and lipid oxidation 169% higher (P < 0.01), while the whole body total glucose disposal was similar in both studies. Baseline forearm blood flow was similar and increased equally by over 40% during both insulin clamp studies (P < 0.05). Basal glucose extraction after glycogen depletion study was one third of that in the control study (P < 0.05). Both basal and insulin stimulated leg muscle glycogen content correlated inversely with basal forearm blood flow (r = -0.69, P < 0.01 and r = -0.82, P < 0.001, respectively) and basal lipid oxidation (r = -0.54, P < 0.05 and r = -0.64, P < 0.01, respectively) after glycogen depletion. Basal glycogen synthase fractional activity correlated positively with forearm blood flow (r = 0.78, P < 0.001) and forearm glucose uptake (r = 0.71, P < 0.05) during the insulin infusion. IN CONCLUSION: 1) the unchanged insulin sensitivity in the face of glycogen depletion is probably a result of increased lipid oxidation, and 2) blood flow is related inversely to muscle glycogen content and directly to glycogen synthase activity.

Adult↗
PubMed1997

Leptin concentration in cord blood correlates with intrauterine growth.

Leptin is an adipocyte-derived peptide hormone regulating energy balance in experimental animals. Although the physiological function of leptin in humans is still unclear, its secretion is closely related to fat mass in adult humans. To examine how fetal growth correlates with leptin levels at birth, an umbilical cord venous blood sample was obtained at the delivery from 50 term newborn infants. Twenty-eight of the newborn infants had birth weights appropriate for gestational age (AGA; mean +/- SEM, 3362 +/- 90 g; relative birth weight, -0.08 +/- 0.2 SD), 9 were large for gestational age (birth weight, 4655 +/- 165 g; relative birth weight, 3.2 +/- 0.3 SD; P < 0.001 vs. AGA newborn infants), and 13 were small for gestational age (SGA; birth weight, 2385 +/- 69 g; relative birth weight, -2.2 +/- 0.08 SD; P < 0.001 vs. AGA newborn infants). Leptin concentrations were higher in large for gestational age (35.7 +/- 8.0 micrograms/L; P < 0.005), but lower in SGA (3.3 +/- 0.5 micrograms/L; P < 0.001) than in AGA infants (14.5 +/- 2.8 micrograms/L). When adjusted for differences in body weight, mean leptin levels were similar in the three newborn groups. Leptin concentration correlated closely with both absolute and relative birth weights (r = 0.71; P < 0.001 in both), with cord blood insulin concentration (r = 0.67; P < 0.001), and with placental weight (r = 0.60; P < 0.001). These data suggest that leptin is synthesized in utero, and that the circulating leptin concentration relates to the intrauterine growth pattern.

Amniotic Fluid↗
PubMed1997

Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients.

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, insulin, and testosterone in 15 men with insulin-dependent diabetes mellitus (IDDM; age, 29 +/- 2 yr; body mass index, 22.7 +/- 0.5 kg/m2; body fat, 9.5 +/- 1.0%; insulin dose, 44 +/- 4 U/day; hemoglobin A1c, 8.1 +/- 0.3%; diabetes duration, 12.7 +/- 2.0 yr) and 15 healthy control subjects (age, 27 +/- 1 yr; body mass index, 22.6 +/- 0.4 kg/m2; body fat, 9.6 +/- 0.5%) in the fasting state. In addition, the effect of a 4-h euglycemic hyperinsulinemia (approximately 600 pmol/L) on the plasma leptin concentration was determined. The fasting leptin concentration was negatively correlated to plasma testosterone (r = -0.55; P < 0.05) in IDDM patients. The fasting plasma leptin level rose 25% in healthy subjects (from 1.0 +/- 0.2 to 1.3 +/- 0.3 ng/mL; P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained unchanged (2.7 +/- 0.2 vs. 2.7 +/- 0.2 ng/mL) during hyperinsulinemia. We reached the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is resistant to the acute effect of insulin. 2) Serum testosterone may contribute to the regulation of leptin synthesis in IDDM patients.

Adult↗
PubMed1997

Reduction of postprandial hyperglycemia and frequency of hypoglycemia in IDDM patients on insulin-analog treatment. Multicenter Insulin Lispro Study Group.

Insulin lispro, an insulin analog recently developed particularly for mealtime therapy, has a fast absorption rate and a short duration of action. We compared insulin lispro and regular human insulin in the mealtime treatment of 1,008 patients with IDDM. The study was a 6-month randomized multinational (17 countries) and multicenter (102 investigators) clinical trial performed with an open-label crossover design. Insulin lispro was injected immediately before the meal, and regular human insulin was injected 30-45 min before the meal. Throughout the study, the postprandial rise in serum glucose was significantly lower during insulin lispro therapy. At the endpoint, the postprandial rise in serum glucose was reduced at 1 h by 1.3 mmol/l and at 2 h by 2.0 mmol/l in patients treated with insulin lispro (P < 0.001). The rate of hypoglycemia was 12% less with insulin lispro (6.4 +/- 0.2 vs. 7.2 +/- 0.3 episodes/30 days, P < 0.001), independent of basal insulin regimen or HbA1c level. The reduction was observed equally in episodes with and without symptoms. When the total number of episodes for each patient was analyzed according to the time of occurrence, the number of hypoglycemic episodes was less with insulin lispro than with regular human insulin therapy during three of four quarters of the day (P < 0.001). The largest relative improvement was observed at night. In conclusion, insulin lispro improves postprandial control, reduces hypoglycemic episodes, and improves patient convenience, compared with regular human insulin, in IDDM patients.

Adult↗
PubMed1997

Strategies toward improved control during insulin lispro therapy in IDDM. Importance of basal insulin.

OBJECTIVE: To examine whether overall glycemic control can be improved with insulin lispro by adjustment of the basal insulin regimen without an increased risk of hypoglycemia. RESEARCH DESIGN AND METHODS: A 5-month open study was performed in 66 IDDM patients after they had been transferred from human regular insulin to insulin lispro as a premeal therapy. The premeal and basal insulin regimens were adjusted according to self-monitoring of blood glucose during the visits at 2-week to 1-month intervals. Diurnal glucose profile, hypoglycemic events, HbA1c, and patient satisfaction were evaluated. RESULTS: The mean daily glucose level decreased from 9.2 +/- 0.2 to 8.4 +/- 0.2 mmol/l (P = 0.001) and HbA1c decreased from 8.8 +/- 0.1 to 8.0 +/- 0.1% (P < 0.001) (mean +/- SD). The number of daily NPH injections increased from 1.4 +/- 0.1 at baseline to 3.1 +/- 0.1 at the end of the study. Total daily insulin dose increased by 3 U (7%) because of an 8-U (43%) rise in basal insulin, whereas premeal insulin dose decreased by 5 U (20%). The number of hypoglycemic episodes did not change during the study. Of the patients, 86% considered insulin lispro equal or better than human regular insulin. CONCLUSIONS: Although the study was open, the date suggest that the appropriate combination of insulin lispro and basal insulin can improve postmeal hyperglycemia, HbA1c, and treatment satisfaction without increasing the risk of hypoglycemia.

Adolescent↗
PubMed1996

Influence of morbidity and health care structure on hospitalization among adult diabetic patients.

The aim of the study was to investigate the influence of outpatient care, overall hospital bed provision and the prevalence of diabetes on the hospital use by adult diabetic patients. Population based data were collected in Finland from a 3-year period. Hospital admissions, inpatient days, and mean length of stay due to diabetes were derived from the Hospital Discharge Register. Estimates of diabetes prevalence were derived from the Central Drug Register. Primary outpatient site, annual number of physician visits, and age at onset among diabetic patients were assessed by questionnaire. The unit of analysis was hospital district (n = 21) and all analyses refer to the 15-64 years age group. Linear regression models were used to explain discharge rates and inpatient days in the district. Large variations between hospital districts were observed in diabetes prevalence, discharge rates due to diabetes, and mean length of stay among diabetic patients. Prevalence of diabetes and overall supply of hospital beds in the district were not related to hospital use. Univariate analyses showed that the larger the proportion of diabetic patients primarily using a private practitioner, the lower the hospital use. In districts where early onset of diabetes was more common, the average number of inpatient days was significantly lower than in other districts. In stepwise regression analyses, early onset of diabetes was the only variable that entered the models. In the full model, 24.6% of the variance in inpatient days and 16.1% of the variance in discharge rates were explained. In conclusion, factors related to health care structure, provision of hospital beds or morbidity explain little of the regional variation in hospital use. The observed variations in hospital use probably depend mainly on local treatment policies and differences in clinical decision-making.

Adolescent↗
PubMed1996

Acute administration of metoprolol and enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow.

OBJECTIVE: To examine the acute effects of intravenous metoprolol and enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity. DESIGN: Randomized, single-blind, placebo-controlled trial. SETTING: Helsinki University Central Hospital, Finland SUBJECTS: Seven moderately insulin-resistant nondiabetic subjects. INTERVENTIONS: Each subjects was studied three times at 2-3 week intervals: metoprolol (5 mg), enalaprilat (2 mg) or saline infusions were used. METHODS: A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed. MAIN OUTCOME MEASURES: Glucose uptake, forearm and skin blood flow, and energy expenditure. RESULTS: Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to enalaprilat (2.1 +/- 0.2 vs. 2.8 +/- 0.4 mL per 100 mL min-1; P < 0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditures were reduced both by metoprolol (71 and 5.2%; P < 0.05 in both) and enalaprilat (59%, P = 0.06; and 7.6%, P < 0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P < 0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearms and whole-body glucose uptake was not influenced by metoprolol or enalaprilat administration. CONCLUSIONS: (i) Both metoprolol and enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.

Adrenergic beta-Antagonists↗
PubMed1996

Athletic heart: a metabolic, anatomical, and functional study.

Previous studies have suggested a reduced glucose uptake by the athlete's heart at rest. To examine whether there is a compensatory increase in the myocardial fatty acid utilization, we studied nine male endurance-trained athletes (age 26 +/- 2 yr, VO2max 60 +/- 1 ml.kg-1.min-1, mean +/- SEM) and eight sedentary subjects (age 26 +/- 1 yr, VO2max 38 +/- 2 ml.kg-1.min-1) by single photon emission tomography using 123I-heptadecanoic acid (HDA) and mathematical modeling. Magnetic resonance imaging (MRI) and echocardiography were performed for the measurements of cardiac dimensions and left ventricular (LV) mass. No significant differences were found in the myocardial HDA beta-oxidation index (5.2 +/- 2.0 vs 7.4 +/- 1.6 mumol.min-1.100 g-1, P = NS) between endurance-trained and sedentary subjects. Fractional amounts of HDA beta-oxidation, backdiffusion, and esterification were also similar. In MRI study, LV mass was greater in the trained subjects (213 +/- 9 vs 179 +/- 10 g, P < 0.01) and in particular, LV long-axis diameter measured from the mitral valve level to the apex was increased (102 +/- 2 vs 88 +/- 2 mm, P < 0.001, trained vs sedentary subjects). VO2max correlated with LV long-axis diameter (r = 0.77, P < 0.001). In contrast to our hypothesis, myocardial HDA utilization was not enhanced in endurance-trained athletes at rest. Increases in LV mass and especially in LV long-axis diameter were observed in the athletes, indicating LV longitudinal remodeling.

Adult↗
PubMed1996

Postmarathon paradox: insulin resistance in the face of glycogen depletion.

Acute physical exercise enhances insulin sensitivity in healthy subjects. We examined the effect of a 42-km marathon run on insulin sensitivity and lipid oxidation in 19 male runners. In the morning after the marathon run, basal serum free fatty acid concentration was 2.2-fold higher, muscle glycogen content 37% lower (P < 0.01), glycogen synthase fractional activity 56% greater (P < 0.01), and glucose oxidation reduced by 43% (P < 0.01), whereas lipid oxidation was increased by 55% (P < 0.02) compared with the control study. During euglycemic-hyperinsulinemic clamp, whole body glucose disposal was decreased by 12% (P < 0.01) because of a 36% lower glucose oxidation rate (P < 0.05), whereas the rate of lipid oxidation was 10-fold greater (P < 0.02) than in the control study. After the marathon, muscle glycogen content correlated positively with lipid oxidation (r = 0.60, P < 0.05) and maximal aerobic power (Vo2peak; r = 0.61, P < 0.05). Vo2peak correlated positively with basal lipid oxidation (r = 0.57, P < 0.05). In conclusion, 1) after the marathon run, probably because of increased lipid oxidation, the insulin-stimulated glucose disposal is decreased despite muscle glycogen depletion and the activation of glycogen synthase; 2) the contribution of lipid oxidation in energy expenditure is increased in proportion to physical fitness; 3) these adaptations of fuel homeostasis may contribute to the maintenance of physical performance after prolonged exercise.

Adult↗
PubMed1996

Structure and costs of health care of diabetic patients in Finland.

OBJECTIVE: The aim of the present study was to examine both the structure, including modes of drug treatment, ambulatory care, and hospital inpatient care, and the costs of health care for drug-treated diabetic patients in Finland. RESEARCH DESIGN AND METHODS: The modes of drug treatment and ambulatory care were studied with the help of a questionnaire given to all diabetic patients obtaining their medication through pharmacies in Finland during a 7-week period in 1989. The questionnaire sought information on drug treatment, site of health care, and frequency of visits to physicians. Hospital inpatient care was evaluated by linking the patient data from the Hospital Discharge Register and the Central Drug Register. The direct costs of health care were calculated by using relevant average costs. RESULTS: A total of 30,266 questionnaires were returned, representing > 70% of all drug-treated diabetic patients receiving medication in the period studied. Of the diabetic patients, 63% were treated by oral medication only, 31% by insulin only, and 6% by a combination of insulin and oral agents. Of the patients in whom diabetes was diagnosed at > or = 30 years of age, 75% were treated at health centers, whereas > 60% of those in whom diabetes was diagnosed at < 30 years of age were treated at outpatient clinics. The mean annual frequency of visits was 4.0 for patients receiving insulin treatment and 3.3 for patients receiving treatment with oral medications. The diabetic patients used 1.5 million hospital inpatient days per year, which was 13% of the total inpatient days in Finland. Of the inpatient days, 20% were for diabetes as the principal cause, 52% for diabetes-related diseases, and 28% for causes unrelated to diabetes. The direct costs of the health care of drug-treated diabetic patients in 1989 were 5.8% of the total costs of health care in Finland and were three times higher than the average costs of care for nondiabetic individuals. The direct costs were divided into inpatient care (81%), medication (9%), ambulatory care (8%), and self-care equipment (2%). CONCLUSIONS: Hospital inpatient care is the major contributor to the excess of health care expenditures for diabetic patients.

Ambulatory Care↗
PubMed1996

Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group.

OBJECTIVE: To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS: The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean +/- SD duration of diabetes was 14.7 +/- 9.3 years. RESULTS: The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15-29 years old to 25% in patients 45-59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS: The overall prevalence of CVD in these IDDM patients was approximately 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Adolescent↗
PubMed1995

Exercise-induced hypoglycaemia in IDDM patients treated with a short-acting insulin analogue.

In order to examine the effect of short-acting insulin analogue on the exercise-induced hypoglycaemia in insulin-dependent diabetes mellitus (IDDM) patients we compared the glycaemic response of 40 min cycle ergometer exercise performed either shortly (40 min) or later (180 min) after a breakfast meal and subcutaneous injection of either short-acting insulin analogue [Lys(B28) Pro(B29)] or soluble human insulin (Humulin Regular) in ten IDDM patients with long duration of the disease. Both preparations had been used 1 month before respective studies. Changes in blood glucose, insulin and counterregulatory hormones were assayed. As compared to human insulin, after the analogue injection the peak insulin concentration came earlier, was 56% higher (p < 0.05) and disappeared faster, and the postprandial blood glucose response was lower (p < 0.05). In the analogue-treated patients the exercise-induced hypoglycaemia was 2.2-fold greater (p < 0.01) during the early exercise, but 46% less (p < 0.05) during late exercise as compared to the treatment with human insulin. Serum insulin or analogue concentration at the beginning of the exercise correlated closely with the fall in blood glucose during exercise (r = 0.74, p < 0.01; r = 0.73, p < 0.02, respectively). In the analogue-treated patients, fasting serum glucagon and adrenalin concentrations were higher than during human insulin therapy (p < 0.05) and remained so throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Androgens and insulin resistance in type 1 diabetic men.

OBJECTIVE: In healthy men, both high and low serum testosterone concentrations are associated with insulin resistance, whereas low concentration of sex hormone binding globulin (SHBG) is related to reduced insulin sensitivity. The aim of our study was to examine the association of sex hormones, SHBG, dehydroepiandrosterone (DHEAS) and insulin-like growth factor binding protein-1 (IGFBP-1) on insulin sensitivity in type 1 diabetic patients. PATIENTS: We examined 23 male patients with the mean age of 29 +/- 1 years, body mass index 22.9 +/- 0.4 kg/m2, insulin dose 47 +/- 3 units/day, glycosylated haemoglobin (HbA1c) 7.8 +/- 0.3% and duration of diabetes 13 +/- 1 years. DESIGN: Each patient was studied with a 4-hour euglycaemic (5.5 +/- 0.1 mmol/l), hyperinsulinaemic (612 +/- 26 pmol/l) clamp with indirect calorimetry. Muscle biopsies (quadriceps femoris) for the determination of glycogen synthase were performed in 15 patients before and at the end of the clamp. RESULTS: Insulin infusion reduced the concentrations of IGFBP-1 by 90% (P < 0.001), DHEAS by 11% (P < 0.001), and SHBG by 4% (P < 0.01), whereas free or bound testosterone levels remained unchanged. The fall in IGFBP-1 level was closely related to the basal concentration (r = 0.99, P < 0.001). Basal SHBG concentration correlated directly with total (r = 0.51, P < 0.05) and non-oxidative glucose disposal (r = 0.41, P < 0.05), and with the decrease in lipid oxidation (r = 0.47, P < 0.05) during insulin infusion. The fall in SHBG was inversely related to the mean (30-240 min) FFA concentration during hyperinsulinaemia (r = -0.64, P < 0.001). The fractional activity of glycogen synthase at the end of insulin infusion correlated directly with fasting SHBG (r = 0.71, P < 0.01) and DHEAS concentrations (r = 0.67, P < 0.01). CONCLUSIONS: In male type 1 diabetic patients: (1) acute hyperinsulinaemia decreases IGFBP-1, DHEAS and SHBG concentrations with the greatest decline in IGFBP-1, (2) SHBG concentration is positively associated with factors indicating good insulin sensitivity, (3) association between fuel homeostasis and SHBG, DHEAS and insulin antagonists suggests a network of these factors in the regulation of insulin action in type 1 diabetic patients.

Adult↗
PubMed1995

Insulin action on heart and skeletal muscle glucose uptake in essential hypertension.

Essential hypertension is characterized by skeletal muscle insulin resistance but it is unknown whether insulin resistance also affects heart glucose uptake. We quantitated whole body (euglycemic insulin clamp) and heart and skeletal muscle (positron emission tomography and 18F-fluoro-2-deoxy-D-glucose) glucose uptake rates in 10 mild essential hypertensive (age 33 +/- 1 yr, body mass index 23.7 +/- 0.8 kg/m2, blood pressure 146 +/- 3/97 +/- 3 mmHg, VO2max 37 +/- 3 ml/kg per min) and 14 normal subjects (29 +/- 2 yr, 22.5 +/- 0.5 kg/m2, 118 +/- 4/69 +/- 3 mmHg, 43 +/- 2 ml/kg per min). Left ventricular mass was similar in the hypertensive (155 +/- 15 g) and the normotensive (164 +/- 13 g) subjects. In the hypertensives, both whole body (28 +/- 3 vs 44 +/- 3 mumol/kg per min, P < 0.01) and femoral (64 +/- 11 vs 94 +/- 8 mumol/kg muscle per min, P < 0.05) glucose uptake rates were decreased compared to the controls. In contrast, heart glucose uptake was 33% increased in the hypertensives (939 +/- 51 vs 707 +/- 46 mumol/kg muscle per min, P < 0.005), and correlated with systolic blood pressure (r = 0.66, P < 0.001) and the minute work index (r = 0.48, P < 0.05). We conclude that insulin-stimulated glucose uptake is decreased in skeletal muscle but increased in proportion to cardiac work in essential hypertension. The increase in heart glucose uptake in mild essential hypertensives with a normal left ventricular mass may reflect increased oxygen consumption and represent an early signal which precedes the development of left ventricular hypertrophy.

Adult↗
PubMed1995

Acute hyperinsulinemia, androgen homeostasis and insulin sensitivity in healthy man.

The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 +/- 1 yrs, body mass index 24 +/- 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose and lipid oxidation were determined by indirect calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG) concentration decreased by 5% (P < 0.01), insulin-like growth factor binding protein (IGFBP-1) by 88% (P < 0.001) and dehydroepiandrosterone sulphate (DHEAS) by 12% (P < 0.001), with no change in total or free testosterone concentrations. In the basal state, IGFBP-1 and C-peptide were inversely related (r = -0.54, P < 0.05). Fasting concentrations of serum free testosterone (r = 0.59, P < 0.01) and DHEAS (r = 0.47, P < 0.05) correlated positively with serum free fatty acid (FFA) concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid oxidation rate in the basal state correlated positively to the decline in SHBG (r = 0.61, P < 0.01) and DHEAS concentrations (r = 0.62, P < 0.01) during hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol level correlated positively with the insulin-induced decline in DHEAS level (r = 0.58, P < 0.01), no associations were found between serum androgens and total cholesterol, low density lipoprotein cholesterol or triglyceride concentrations. Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

Athletes with IDDM exhibit impaired metabolic control and increased lipid utilization with no increase in insulin sensitivity.

Physical exercise is traditionally recommended to diabetic patients as part of their treatment. Although healthy athletes exhibit enhanced skeletal muscle insulin sensitivity, the metabolic effects of vigorous training in patients with insulin-dependent diabetes mellitus (IDDM) are not known. This study was designed to examine the effects of competitive sports on fuel homeostasis and insulin sensitivity in athletes with IDDM. We studied 11 athletes and 12 matched sedentary men with IDDM. In each subject, we measured glycemic control, insulin-stimulated glucose uptake in the whole body and forearm, rates of glucose and lipid oxidation, and muscle glycogen, glycogen synthase, and glucose transport protein (GLUT4) concentrations. The athletes had higher VO2max (52 +/- 1 vs. 42 +/- 1 ml.kg-1.min-1, P < 0.001) and HbA1c levels (8.4 +/- 0.4 vs. 7.2 +/- 0.2%, P < 0.05) than sedentary patients, but took smaller insulin doses (41 +/- 3 vs. 53 +/- 3 U/day, P < 0.05). The insulin-stimulated rates of whole-body and forearm glucose uptake and glucose oxidation were similar in the two groups, whereas both energy expenditure and lipid oxidation were increased in the athletes. Lipid oxidation correlated inversely with glycogen synthase activity. The mean glucose arterialized venous blood-deep venous blood (A-V) difference during the insulin infusion (60-240 min) correlated with the whole-body glucose disposal throughout the insulin infusion (after 60 min, r > 0.73, P < 0.001 for all 30-min periods). This association is accounted for by the relationship between glucose A-V difference and nonoxidative glucose disposal. Muscle glycogen and GLUT4 protein contents were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Physiological importance of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA), with its sulphate conjugate (DHEAS), is the most abundant steroid hormone in the circulation but its physiological importance is unclear. We propose that DHEA has either oestrogen-like or androgen-like effects depending on the hormonal milieu. In premenopausal women DHEA is either an oestrogen antagonist, perhaps through the competitive binding of its metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) and oestradiol to the oestrogen receptor, or an androgen through its metabolism to androstenedione and testosterone. In women DHEA contributes to abdominal obesity and insulin resistance: in the premenopausal high oestrogen concentrations may counterbalance the androgenic effects of DHEA but in the postmenopausal metabolism to testosterone may increase the risk of cardiovascular disease, though this effect may be counterbalanced by the age-dependent decline in DHEA and also by the oestradiol-like effects of ADIOL. In some breast cancer cell lines in a low oestrogen milieu DHEA has an oestradiol-like effect, stimulating tumour growth, whereas in oestradiol abundance DHEA antagonises the growth-stimulating effect of oestradiol. In men, with an androgenic milieu, DHEA acts like an oestrogen and protects against cardiovascular disease.

Breast Neoplasms↗