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Biomedical subjects

H A Keizer

Publications and source records attributed to H A Keizer.

At least 19 recordsLinked to original sources
PubMed2006

Substrate source utilisation in long-term diagnosed type 2 diabetes patients at rest, and during exercise and subsequent recovery.

AIMS/HYPOTHESIS: Disturbances in substrate source metabolism and, more particularly, in fatty acid metabolism, play an important role in the aetiology and progression of type 2 diabetes. However, data on substrate source utilisation in type 2 diabetes are inconclusive. METHODS: [U-(13)C]palmitate and [6,6-(2)H(2)]glucose tracers were used to assess plasma NEFA and glucose oxidation rates and to estimate the use of muscle- and/or lipoprotein-derived triacylglycerol and muscle glycogen. Subjects were ten male patients who had a long-term (7 +/- 1 years) diagnosis of type 2 diabetes and were overweight, and ten matched healthy, male control subjects. Muscle biopsy samples were collected before and after exercise to assess muscle fibre type-specific intramyocellular lipid and glycogen content. RESULTS: At rest and during exercise, the diabetes patients had greater values than the controls for palmitate rate of appearance (Ra) (rest, 2.46 +/- 0.18 and 1.85 +/- 0.20 respectively; exercise, 3.71 +/- 0.36 and 2.84 +/- 0.20 micromol kg(-1) min(-1)) and rate of disappearance (Rd) (rest, 2.45 +/- 0.18 and 1.83 +/- 0.20; exercise, 3.64 +/- 0.35 and 2.80 +/- 0.20 micromol kg(-1) min(-1) respectively). This was accompanied by significantly higher fat oxidation rates at rest and during recovery in the diabetes patients (rest, 0.11 +/- 0.01 in diabetes patients and 0.09 +/- 0.01 in controls; recovery, 0.13 +/- 0.01 and 0.11 +/- 0.01 g/min respectively), despite significantly greater plasma glucose Ra, Rd and circulating plasma glucose concentrations. Furthermore, exercise significantly lowered plasma glucose concentrations in the diabetes patients, as a result of increased blood glucose disposal. CONCLUSION: This study demonstrates that substrate source utilisation in long-term-diagnosed type 2 diabetes patients, in whom compensatory hyperinsulinaemia is no longer present, shifts towards an increase in whole-body fat oxidation rate and is accompanied by disturbances in fat and carbohydrate handling.

Biopsy↗
PubMed2005

Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients.

AIMS/HYPOTHESIS: In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. MATERIALS AND METHODS: We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. RESULTS: Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05). CONCLUSIONS/INTERPRETATION: This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.

Adipose Tissue↗
PubMed2004

Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a).

OBJECTIVES: To investigate the effects of two different regimens of androgenic-anabolic steroid (AAS) administration on serum lipid and lipoproteins, and recovery of these variables after drug cessation, as indicators of the risk for cardiovascular disease in healthy male strength athletes. METHODS: In a non-blinded study (study 1) serum lipoproteins and lipids were assessed in 19 subjects who self administered AASs for eight or 14 weeks, and in 16 non-using volunteers. In a randomised double blind, placebo controlled design, the effects of intramuscular administration of nandrolone decanoate (200 mg/week) for eight weeks on the same variables in 16 bodybuilders were studied (study 2). Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and lipoprotein (a) (Lp(a)) were determined. RESULTS: In study 1 AAS administration led to decreases in serum concentrations of HDL-C (from 1.08 (0.30) to 0.43 (0.22) mmol/l), HDL2-C (from 0.21 (0.18) to 0.05 (0.03) mmol/l), HDL3-C (from 0.87 (0.24) to 0.40 (0.20) mmol/l, and Apo-A1 (from 1.41 (0.27) to 0.71 (0.34) g/l), whereas Apo-B increased from 0.96 (0.13) to 1.32 (0.28) g/l. Serum Lp(a) declined from 189 (315) to 32 (63) U/l. Total cholesterol and triglycerides did not change significantly. Alterations after eight and 14 weeks of AAS administration were comparable. No changes occurred in the controls. Six weeks after AAS cessation, serum HDL-C, HDL2-C, Apo-A1, Apo-B, and Lp(a) had still not returned to baseline concentrations. Administration of AAS for 14 weeks was associated with slower recovery to pretreatment concentrations than administration for eight weeks. In study 2, nandrolone decanoate did not influence serum triglycerides, total cholesterol, HDL-C, HDL2-C, HDL3-C, Apo-A1, and Apo-B concentrations after four and eight weeks of intervention, nor six weeks after withdrawal. However, Lp(a) concentrations decreased significantly from 103 (68) to 65 (44) U/l in the nandrolone decanoate group, and in the placebo group a smaller reduction from 245 (245) to 201 (194) U/l was observed. Six weeks after the intervention period, Lp(a) concentrations had returned to baseline values in both groups. CONCLUSIONS: Self administration of several AASs simultaneously for eight or 14 weeks produces comparable profound unfavourable effects on lipids and lipoproteins, leading to an increased atherogenic lipid profile, despite a beneficial effect on Lp(a) concentration. The changes persist after AAS withdrawal, and normalisation depends on the duration of the drug abuse. Eight weeks of administration of nandrolone decanoate does not affect lipid and lipoprotein concentrations, although it may selectively reduce Lp(a) concentrations. The effect of this on atherogenesis remains to be established.

Adult↗
PubMed2003

Androgenic anabolic steroid use and severe hypothalamic-pituitary dysfunction: a case study.

The data of the present case demonstrate that the abuse of androgenic anabolic steroids (AAS) may lead to serious health effects. Although most clinical attention is usually directed towards peripheral side effects, the most serious central side effect, hypothalamic-pituitary-dysfunction, is often overlooked in severe cases. Although this latter central side-effect usually recovers spontaneously when AAS intake is discontinued, the present case shows that spontaneous recovery does not always take place. We suggest that hypothalamic-pituitary dysfunction should always be considered in the differential diagnosis in athletes seen with typical presentation of anabolic steroid use. In order to regain normal hypothalamic-pituitary function, supraphysiological doses of 200 microg LH-RH should be considered when the physiological challenge test with LH-RH (50 microg) fails to show an acceptable response.

Adult↗
PubMed2003

Diminished performance on response-selection tasks in Type 2 diabetes.

Comparisons of visual perception, response-selection, and response-execution performance were made between Type 2 diabetes mellitus patients and a matched nondiabetic control group. 10 well-controlled male patients with Type 2 diabetes without diabetic complications (M age 58 yr.) and an age and IQ-matched non-diabetic control group consisting of 13 male healthy volunteers (M age 57 yr.) were included. Significant differences were found only between the two groups on response-selection performance, which concerns the selection and preparation of an appropriate motor action.

Aged↗
PubMed2002

Misuse of androgenic-anabolic steroids and human deltoid muscle fibers: differences between polydrug regimens and single drug administration.

The objective of this investigation was to study the effects of androgenic-anabolic steroid (AAS) misuse on deltoid muscle fiber characteristics in experienced, male strength-trained athletes. In a double-blind study, 15 volunteers were administered nandrolone decanoate (ND) for 8 weeks (200 mg/week, intramuscularly). In an additional study, 12 subjects self-administered various AASs at supratherapeutic dosages (AAS group), while 7 non-users served as controls. In all subjects, a percutaneous needle biopsy sample of the deltoid muscle was obtained at baseline and after 8 weeks. Muscle sections were pre-incubated at pH 4.4, stained with adenosine triphosphatase and analyzed morphometrically. In each biopsy sample, at least 150 fibers were classified for "gray level" and "lesser fiber diameter" to determine the mean fiber size, the sizes of type I and type II fibers, and the fiber type distribution. ND administration did not seem to affect any of those parameters. In the AAS group, mean muscle fiber size (+ 12.6%), and the size of type I (+ 10.8%) and type II (+ 14.6%) muscle fibers increased. The fiber type distribution remained unaltered. We conclude that polydrug regimens of AAS misuse at supratherapeutic dosages increased the size of deltoid muscle fibers (especially type II fibers) in experienced strength-trained athletes, while ND at a therapeutic intramuscular dose of 200 mg did not exert any effect.

Adult↗
PubMed2002

Substrate utilization in non-obese Type II diabetic patients at rest and during exercise.

Recently, we observed that impairments exist in skeletal muscle free fatty acid (FFA) utilization during exercise in obese subjects with Type II diabetes. The main objective of the present study was to investigate whether plasma FFA oxidation is impaired during exercise in non-obese Type II diabetic patients. Stable isotope tracers of palmitate and glucose were infused for 2 h at rest and 1h of bicycle exercise at 40% peak oxygen consumption ( V*O(2)max) in volunteers with Type II diabetes and a healthy control group. At rest, plasma FFA oxidation was not significantly different between subjects with Type II diabetes and control subjects (2.13+/-0.51 versus 1.93+/-0.54 micromol.kg(-1).min(-1) respectively). During exercise, Type II diabetic patients and control subjects had similar rates of total fat [Type II diabetes, 9.62+/-1.84 micromol.kg(-1).min(-1); control, 12.08+/-4.59 micromol.kg(-1).min(-1); not significant (NS)] and glucose oxidation (Type II diabetes, 44.24+/-10.36 micromol.kg(-1).min(-1); control, 57.37+/-14.54 micromol.kg(-1).min(-1); NS). No aberrations were present in plasma FFA uptake [rate of disappearance ( Rd ); Type II diabetes, 11.78+/-4.82; control, 10.84+/-3.39; NS] and oxidation rates (Type II diabetes 8.10+/-1.44; control 8.00+/-3.12, NS) in Type II diabetic patients; triacylglycerol-derived fatty acid oxidation was 2.6-fold lower in Type II diabetic patients than in control subjects, but this difference was not statistically significant. Muscle glycogen oxidation was lower in diabetes patients than in control subjects (Type II diabetes, 25.16+/-13.82 micromol.kg(-1).min(-1); control, 42.04+/-10.58 micromol.kg(-1).min(-1); P <0.05) and plasma glucose contributed more to energy expenditure in Type II diabetes (26+/-3% in diabetic versus 15+/-2% in control, P <0.05). We conclude that plasma FFA oxidation is not impaired during exercise in non-obese Type II diabetic patients. The data confirm that Type II diabetes is a heterogeneous disease, and that the adaptation at the substrate level differs between obese and non-obese patients and may contribute to differences in the final appearance of the various phenotypes.

Adult↗
PubMed2002

Red blood cell profile of elite olympic distance triathletes. A three-year follow-up.

The purpose of this study was to monitor general and individual changes in hematological variables during long-term endurance training, detraining and altitude training in elite Olympic distance triathletes. Over a period of three years, a total of 102 blood samples were collected in eleven (7-male and 4 female) elite Olympic distance triathletes (mean +/- SD; age = 26.4 +/- 5.1 yr; VO(2) max = 67.9 +/- 6.6 ml/min/kg) for determination of hemoglobin (Hb), hematocrit (Hct), red blood cell count (RBC), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin content (MCHC), Mean corpuscular volume (MCV) and plasma ferritin. The data were pooled and divided into three periods; off-season, training season and race season. Blood samples obtained before and after altitude training were analyzed separately. Of all measured variables only RBC showed a significant decrease (p < 0.05) during the race season compared to the training season. Hematological values below the lower limit of the normal range were found in 46 % of the athletes during the off-season. This percentage increased from 55 % during the training season to 72 % of the athletes during the race season. Hemoglobin and ferritin values were most frequently below the normal range. There was a weak correlation between Hb levels and VO(2) max obtained during maximal cycling (r = 0.084) and running (r = 0.137) tests. Unlike training at 1500 m and 1850 m, training at an altitude of 2600 m for three weeks showed significant increases in Hb (+ 10 %; p < 0.05), Hct (+ 11 %; p < 0.05) and MCV (+ 5 %; p < 0.05). Long-term endurance training does not largely alter hematological status. However, regular screening of hematological variables is desirable as many athletes have values near or below the lower limit of the normal range. The data obtained from altitude training suggest that a minimum altitude (>2000 m) is necessary to alter hematological status.

Adaptation, Physiological↗
PubMed2001

[Long-term intensive athletic training; few adverse effects on later physical health].

In general, physical activity benefits health. However, long-term intensive physical training may have detrimental effects on the health of some individuals. In cyclists, changes in the femoral arteries may occur leading to stenoses that are manifested in claudication type symptoms. Some endurance athletes may experience atrial fibrillations that are possibly related to long-term physical training. Older athletes only have an increased risk of osteoarthritis in joints that have suffered injuries. Menstrual disturbances and premature osteoporosis may occur in women as a consequence of intensive physical training. However, the risk for these adverse consequences of long-term physical training is small.

Amenorrhea↗
PubMed2001

Validation of a computerized metabolic measurement system (Oxycon-Pro) during low and high intensity exercise.

The aim of the study was to validate a new, fast metabolic measurement system (the Oxycon-Pro) during low and high exercise intensities against the Douglas bag method. For this purpose twelve highly trained subjects performed an incremental cycle ergometer test. In the third minute of each exercise step simultaneous measurements of the Douglas bag and the Oxycon-Pro were performed. No significant differences between the Oxycon-Pro and the Douglas bag measurements for minute ventilation (VE), oxygen uptake (VO2) and carbon dioxide expiration (VCO2) were found. Bland and Altman analysis of validity demonstrated minimal bias and low standard deviations. In conclusion, the results show that the Oxycon-Pro is a valid apparatus for determination of minute ventilation (VE), oxygen uptake (VO2) and carbon dioxide expiration (VCO2) during low as well as during maximal exercise intensities. Unlike with the Douglas bag method, this fast metabolic measurement system can be used for accurate and quick determination of ventilatory variables during exercise.

Adult↗
PubMed2001

A reduction in training volume and intensity for 21 days does not impair performance in cyclists.

OBJECTIVES: (a) To investigate the effects of reduced training on physical condition and performance in well trained cyclists; (b) to study whether an intermittent exercise programme would maintain physiological training adaptations more effectively than a continuous exercise programme during a period of reduced training. METHODS: Twelve male cyclists participated in a 21 day training programme and were divided into two training groups. One group (age 25.3 (7) years; weight 73.3 (5.7) kg; VO(2)MAX 58.6 (4.5) ml/kg/min; means (SD)) underwent a continuous endurance exercise training programme (CT) whereas the second group (age 22.8 (3.5) years; weight 74.1 (7.0) kg; VO(2)MAX 59.7 (6.7) ml/kg/min) followed an intermittent endurance exercise training programme (IT). During this reduced training period, both groups trained for two hours a day, three days a week. RESULTS: Neither group showed changes in maximal workload (WMAX) (4.6 (0.5) v 4.8 (0.5) W/kg and 4.6 (0.5) v 4.7 (0.6) W/kg for the CT and IT group respectively) and VO(2)MAX (58.6 (4.5) v 60.1 (5.8) ml/kg/min and 59.7 (6.7) v 58.8 (7.5) ml/kg/min for the CT and IT group respectively). During the submaximal steady state exercise test, substrate use and heart rate remained unchanged after reduced training. CONCLUSIONS: These results indicate that well trained cyclists who reduce training intensity and volume for 21 days can maintain physiological adaptations, as measured during submaximal and maximal exercise. An intermittent training regimen has no advantage over a continuous training regimen during a detraining period.

Adaptation, Physiological↗
PubMed2001

Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.

Blood Glucose↗
PubMed2000

GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study.

In whole muscle homogenates, the glucose transporter-4 (GLUT-4) content is reported to be higher in muscles consisting predominantly of oxidative (type-1) muscle fibres than in muscles consisting predominantly of glycolytic (type-2) fibres. From these findings, it has been deduced that in rat muscle, oxidative fibres have an intrinsically higher level of GLUT-4 protein than glycolytic fibres. No data is available concerning human muscle. Moreover, the fibre-type-specific expression of GLUT-4 has not yet been examined directly. In this study, the relative abundance of GLUT-4 protein expression in individual fibres of different types within a muscle was compared directly in immunohistochemical assays. The human vastus lateralis muscle and a selection of rat muscles were studied using a novel GLUT-4 antiserum. It is concluded that the pattern of fibre-type-specific GLUT-4 expression differs between human and rats and varies between the different muscles studied, indicating that non-fibre-type-specific factor(s) affect expression of GLUT-4. The observation that within a muscle a fibre-type-specific expression of GLUT-4 was observed indicates that fibre-type-specific factors contribute to GLUT-4 expression as well. Thus, it can be postulated that both fibre-type-dependent and fibre-type-independent factors affect GLUT-4 expression.

Animals↗
PubMed2000

Exercise and insulin sensitivity: a review.

Physical activity has a beneficial effect on insulin sensitivity in normal as well as insulin resistant populations. A distinction should be made between the acute effects of exercise and genuine training effects. Up to two hours after exercise, glucose uptake is in part elevated due to insulin independent mechanisms, probably involving a contraction-induced increase in the amount of GLUT4 associated with the plasma membrane and T-tubules. However, a single bout of exercise can increase insulin sensitivity for at least 16 h post exercise in healthy as well as NIDDM subjects. Recent studies have accordingly shown that acute exercise also enhances insulin stimulated GLUT4 translocation. Increases in muscle GLUT4 protein content contribute to this effect, and in addition it has been hypothesized that the depletion of muscle glycogen stores with exercise plays a role herein. Physical training potentiates the effect of exercise on insulin sensitivity through multiple adaptations in glucose transport and metabolism. In addition, training may elicit favourable changes in lipid metabolism and can bring about improvements in the regulation of hepatic glucose output, which is especially relevant to NIDDM. It is concluded that physical training can be considered to play an important, if not essential role in the treatment and prevention of insulin insensitivity.

Diabetes Mellitus, Type 2↗
PubMed1999

Different metabolic adaptation of heart and skeletal muscles to moderate-intensity treadmill training in the rat.

The effect was investigated of treadmill training of moderate intensity on the fatty acid-binding protein (FABP) content in relation to parameters of oxidative and glycolytic metabolism. To this end, the cytoplasmic FABP content and the activity of beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), citrate synthase (CS), and 6-phosphofructokinase (PFK) were measured in heart, fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles (SOL) of male Wistar rats. To investigate the influence of the amount of training (defined as the product of exercise duration, intensity and frequency), two training groups were created that differed in training frequency (HF, high frequency 5 days x week(-1), n = 9; LF, low frequency 2 days x week(-1), n = 9; the exercise being 20 m x min(-1) for 2 h with no gradient, over 6 weeks) and compared with SC, sedentary controls (n = 7). In heart muscle, the cytoplasmic FABP content was 34% higher in HF than in SC but was the same as in LF. The CS and HAD activities were no different in the three groups, suggesting that the capacity to oxidize fatty acids (FA) was not affected by training. The PFK activity was higher (43%) in HF, suggesting a shift towards carbohydrate utilization. The FABP content and HAD activity did not change in SOL and EDL after training whereas the CS activity increased (27%) in SOL and decreased (21%) in EDL in both training groups. In addition, PFK activity in EDL was much higher (113%) in the HF than in SC group. The HF training was associated with a fine-tuning of FA availability and use in heart muscle, and with a more efficient energy production. It is suggested therefore that cytoplasmic FABP could be an early marker of muscle adaptation to training in heart but not in skeletal muscle. The training reinforced the metabolic profile of the skeletal muscles, in particular that of the fast-twitch glycolytic muscle. We concluded that a large amount of training is needed when the effect on both oxidative and glycolytic parameters is to be studied.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

Effect of training intensity on insulin sensitivity as evaluated by insulin tolerance test.

The purpose of this study was to evaluate the role of exercise intensity in the effect of physical training on insulin sensitivity. The insulin tolerance test (ITT) was applied to quantify insulin sensitivity. Eighteen healthy, young, untrained men and women participated in a 4-week, five times per week, 1-h per session bicycle-ergometer training program. Training consisted of 3-min bouts of cycling interspersed with 2 min at a lower exercise intensity. Intensities were 80 and 40% of pretraining maximal power output (W(max)) in the high-intensity (HI) and 40 and 20% W(max) in the low-intensity (LI) group. The insulin sensitivity index (IS(index)) was similar in the HI and LI group before the training intervention [mean (SD) -0.1898 (0.058) and -0.1892 (0.045), respectively]. After training, the IS(index) was -0.2358 (0.051) (P = 0.005 vs pretraining) in the HI group and -0.2050 (0.035) (P = 0. 099 against pretraining) in the LI group. We conclude that improvements in insulin sensitivity are more pronounced with high-intensity training, when exercise frequency and duration are kept similar. We further conclude that the ITT is suitable for use in intervention studies.

Adult↗