Biomedical subjects

E E Blaak

Publications and source records attributed to E E Blaak.

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↗

PubMed2006

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation.

BACKGROUND AND AIMS: Obesity is associated with a blunted beta-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the beta (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein beta (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation. DESIGN AND METHODS: Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m(2)) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective beta-agonist isoprenaline (ISO). RESULTS: In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation. CONCLUSION: These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo beta-adrenoceptor-mediated lipolysis and fat oxidation during beta-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.

Adipose Tissue↗

PubMed2006

Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in obese insulin-resistant subjects.

AIMS/HYPOTHESIS: This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects. METHODS: A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 +/- 2 years; BMI, 32.6 +/- 0.8 kg/m(2); homeostasis model assessment of insulin resistance, 5.6 +/- 0.5; systolic blood pressure [SBP], 140.8 +/- 3.2; diastolic blood pressure [DBP], 88.8 +/- 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content. RESULTS: Ramipril treatment decreased ACE activity compared with placebo (-22.0 +/- 1.7 vs 0.2 +/- 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, -10.8 +/- 2.1 vs -2.7 +/- 2.0 mmHg, respectively, p = 0.01; DBP, -10.1 +/- 1.3 vs -4.2 +/- 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 +/- 2.0, after: 19.1 +/- 2.4 micromol kg body weight(-1) min(-1), p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 +/- 0.39, after: 1.92 +/- 0.29 micromol 100 ml forearm tissue(-1) min(-1), p = 0.81) and IMTG content (before: 45.4 +/- 18.8, after: 48.8 +/- 27.5 micromol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments. CONCLUSIONS/INTERPRETATION: Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.

Angiotensin II↗

PubMed2006

Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes. MATERIALS AND METHODS: In the Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM), 97 men and women with IGT were randomised to a combined diet and exercise programme (47 intervention) or a control group (50 control subjects). At baseline and after 1 year the following assessments were made: an OGTT, an exercise test to determine maximal aerobic capacity, anthropometry, and analysis of the serum fatty acid profile of cholesteryl esters. RESULTS: The lifestyle programme was effective in reducing the intake of total and saturated fat, increasing physical activity, reducing obesity and improving insulin sensitivity and glucose tolerance. Regression analysis of the total population showed that an increase in the C20:4 n-6/C20:3 n-6 ratio (estimated Delta5-desaturase activity) and reductions in the C18:3 n-6/C18:2 n-6 ratio (estimated Delta6-desaturase activity) and the C16:1 n-7/C16:0 ratio (estimated Delta9-desaturase activity or stearoyl-CoA desaturase-1) were significantly associated with a decrease in homeostasis model assessment for insulin resistance. After adjustment for lifestyle changes (change in percentage body fat, aerobic capacity and saturated fat intake), these associations were partly reduced, but remained statistically significant. CONCLUSIONS/INTERPRETATION: Lifestyle-induced changes in fatty acid profile of cholesteryl esters and desaturase activities were independently related to changes in insulin sensitivity in subjects at risk of type 2 diabetes.

Blood Glucose↗

PubMed2006

Angiotensin II: a hormone that affects lipid metabolism in adipose tissue.

BACKGROUND: Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans. METHODS AND RESULTS: First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10(-14)-10(-6) M). Glycerol concentration in the medium, used as an indicator of adipocyte lipolysis, was significantly reduced (approximately 20%) after Ang II stimulation in adipocytes from normal weight (P=0.04) and obese subjects (P<0.001). Based on these observations, adipocytes of seven additional obese subjects were stimulated with lower doses of Ang II (10(-17)-10(-6) M) in the presence and absence of Ang II type 1 (AT(1)) receptor blockade. Lipolysis was dose dependently inhibited by approximately 20 to 25% after Ang II stimulation (P=0.001). AT(1) receptor blockade completely abolished the Ang II-induced effects (P=0.35). CONCLUSION: Ang II directly inhibits abdominal subcutaneous adipocyte lipolysis in normal weight and obese subjects via the AT(1) receptor.

Adipocytes↗

PubMed2006

Angiotensin II: a major regulator of subcutaneous adipose tissue blood flow in humans.

We investigated the functional roles of circulating and locally produced angiotensin II (Ang II) in fasting and postprandial adipose tissue blood flow (ATBF) regulation and examined the interaction between Ang II and nitric oxide (NO) in ATBF regulation. Local effects of the pharmacological agents (or contralateral saline) on ATBF, measured with 133Xe wash-out, were assessed using the recently developed microinfusion technique. Fasting and postprandial (75 g glucose challenge) ATBF regulation was investigated in nine lean healthy subjects (age, 29 +/- 3 years; BMI, 23.4 +/- 0.7 kg m(-2)) using local Ang II stimulation, Ang II type 1 (AT1) receptor blockade, and angiotensin-converting enzyme (ACE) inhibition. Furthermore, NO synthase (NOS) blockade alone and in combination with AT1 receptor blockade was used to examine the interaction between Ang II and NO. Ang II induced a dose-dependent decrease in ATBF (10(-9)m: -16%, P = 0.04; 10(-7)m: -33%, P < 0.01; 10(-5)m: -53%P < 0.01). Fasting ATBF was not affected by ACE inhibition, but was increased by approximately 55% (P < 0.01) by AT(1) receptor blockade. NOS blockade induced a approximately 30% (P = 0.001) decrease in fasting ATBF. Combined AT1 receptor and NOS blockade increased ATBF by approximately 40% (P = 0.003). ACE inhibition and AT1 receptor blockade did not affect the postprandial increase in ATBF. We therefore conclude that circulating Ang II is a major regulator of fasting ATBF, and a major proportion of the Ang II-induced decrease in ATBF is NO independent. Locally produced Ang II does not appear to regulate ATBF. Ang II appears to have no major effect on the postprandial enhancement of ATBF.

Adipose Tissue↗

PubMed2006

Direct association of a promoter polymorphism in the CD36/FAT fatty acid transporter gene with Type 2 diabetes mellitus and insulin resistance.

AIMS: The membrane-bound fatty acid transporter CD36/FAT may play a role in disturbed fatty acid handling as observed in the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Genetic variation in the CD36 gene may contribute to the aetiology of diabetes. METHODS: A population-based cohort in the Netherlands [age > 40 years and body mass index (BMI) > 25 kg/m2] of 675 subjects was phenotyped with respect to glucose metabolism with an oral glucose tolerance test and was genotyped for a known 478C-->T substitution and a C/T snp in the upstream promoter region (rs1527479) in the CD36 gene. RESULTS: T2DM was more prevalent in the TT genotype than in the CC genotype. This was most pronounced in women and in subjects with a high BMI (BMI > 27 kg/m2). In addition, within the group of diabetic patients, the TT genotype was commoner in subjects with increased homeostasis model assessment (HOMA) index for insulin resistance. The 478C-->T substitution, previously found in the Japanese population, was not found in our caucasian population. CONCLUSIONS: This is the first study to show a direct association of a CD36 snp with T2DM. Moreover, within the diabetic subjects, this CD36 snp was associated with insulin resistance (HOMA index).

Aged↗

PubMed2004

Impaired beta-adrenergically mediated lipolysis in skeletal muscle of obese subjects.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether the beta2-adrenergically mediated increase in interstitial glycerol concentrations (used as an indicator of local lipolysis) was impaired in the skeletal muscle (the gastrocnemius muscle) of obese subjects compared with in that of lean subjects, and whether any differences in muscle lipolysis were related to differences in intramyocellular muscle triglyceride content. METHODS: A microdialysis experiment was performed in the gastrocnemius muscle of eight lean and eight obese men (body fat 22.1+/-1.6% vs 32.7+/-1.6% respectively). After determining baseline extracellular glycerol concentrations, the probe was perfused with increasing concentrations of the beta2-agonist, salbutamol (doses of 1, 10 and 100 micromol/l for 45-min periods). Local blood flow was determined using the ethanol dilution technique. Intramyocellular lipid content was determined using 1H-magnetic resonance spectroscopy. RESULTS: Compared with that in lean subjects, the beta2-adrenergically mediated increase in glycerol concentrations (absolute and percentage change) was blunted in obese subjects (at 100 micromol/l of salbutamol, percentage change 12.0+/-12% vs 48+/-12%, p<0.05). The decrease in ethanol out:in ratio was less pronounced in the obese individuals ( p<0.05), indicating a diminished increase in local muscle blood flow. Intramyocellular lipid content was comparable in both groups. CONCLUSIONS/INTERPRETATION: The capacity to increase skeletal interstitial glycerol concentrations during direct beta2-adrenergic stimulation is impaired in obese subjects with normal intramyocellular concentrations, suggesting that this may be an early event in the process of triglyceride accumulation.

Adrenergic beta-Agonists↗

PubMed2004

Basic disturbances in skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus.

The present article addresses the hypothesis that disturbances in skeletal muscle fatty acid handling in abdominal obesity and type 2 diabetes mellitus may play a role in the aetiology of increased adipose tissue stores, increased triacylglycerol storage in skeletal muscle and skeletal muscle insulin resistance. The uptake and/or oxidation of fatty acids have been shown to be impaired during post-absorptive conditions in abdominally-obese subjects and/or subjects with type 2 diabetes. Also, human studies have shown that muscle of subjects that are (abdominally) obese and/or have type 2 diabetes is characterized by an inability to increase fatty acid uptake and/or fatty acid oxidation during beta-adrenergic stimulation and exercise. This disturbance in fat oxidation may promote, on one hand, the development of increased adipose tissue stores and obesity. On the other hand, fatty acids that are taken up by muscle and not oxidized may increase triacylglycerol storage in muscle, which has been associated with skeletal-muscle insulin resistance. Disturbances in the capacity to increase fat oxidation during post-absorptive conditions, beta-adrenergic stimulation and exercise in subjects who are obese and/or have type 2 diabetes persist after weight reduction, indicating that the diminished fat oxidation may be a primary factor leading to the obese and/or insulin-resistant state rather than an adaptational response. Clearly, the precise sequence of events leading to an increased adiposity and insulin resistance in obesity and type 2 diabetes mellitus is not yet fully understood.

Diabetes Mellitus, Type 2↗

PubMed2004

The insulin receptor substrate-1 Gly972Arg polymorphism is not associated with Type 2 diabetes mellitus in two population-based studies.

AIMS: The insulin receptor substrate-1 (IRS-1) gene is among the most frequently studied candidate genes for Type 2 diabetes, but findings have been inconsistent. This may have been due to generally small study sizes, or to interaction with body fatness as suggested by studies of insulin sensitivity. The aim of this study was to test the hypothesis that the IRS-1 Gly972Arg variant increases risk of Type 2 diabetes. METHODS: We conducted two large population-based studies including a total of 725 cases and 742 control subjects, who were Caucasian Dutch men and women aged 40-70 years. We calculated odds ratios adjusted for body mass index, study centre, sex and age. RESULTS: Carriers of the Arg allele did not have a higher prevalence of newly detected (OR 0.49, 95% CI 0.24-1.01) or treated (OR 0.71, 0.37-1.35) Type 2 diabetes in the first study, or a higher prevalence of glucose intolerance (OR 1.07, 0.71-1.59) in the second study. The summary odds ratio was 0.86 (0.62-1.17) for carrying the Arg allele as compared with the Gly/Gly genotype. Associations did not differ appreciably by degree of obesity. Also, the Arg variant was not associated with detrimental values for body mass index, waist circumference, plasma HDL-and total cholesterol or hypertension. CONCLUSIONS: Our findings indicate that the IRS-1 Gly972Arg variant does not substantially increase risk of common Type 2 diabetes, or Type 2 diabetes in obese persons.

Amino Acid Substitution↗

PubMed2004

Angiotensin II-induced effects on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects.

The present study was designed to investigate the effects of angiotensin II (Ang II) on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects using the microdialysis technique. Microdialysis probes were placed in the abdominal sc adipose tissue left and right from the umbilicus and in the gastrocnemius muscle of both legs in eight normal-weight and eight obese men. Probes were consecutively perfused with 1.0 nM Ang II, 1.0 microM Ang II, and 1.0 microM Ang II + 48 microM hydralazine or with Ringer solution (control). Ethanol and glycerol concentrations in the dialysate were measured as an indicator of local blood flow and lipolysis, respectively. Ang II caused an increase in ethanol outflow/inflow ratio, compared with baseline values both in adipose tissue (average of both groups, Ang 1.0 nM: 0.03 +/- 0.01, P = 0.02; Ang 1.0 microM: 0.05 +/- 0.01, P < 0.01) and muscle (average of both groups, Ang 1.0 nM: 0.02 +/- 0.01, P = 0.09; Ang 1.0 microM: 0.04 +/- 0.01, P = 0.01), indicating a decrease in local blood flow. These effects were not significantly different in obese and normal-weight subjects. The decrease in local blood flow was accompanied by unchanged interstitial glycerol concentrations in adipose tissue (except during the supraphysiological dose) and skeletal muscle, suggesting that Ang II inhibits lipolysis in both tissues. Thus, the present data suggest that Ang II decreases local blood flow in a dose-dependent manner and inhibits lipolysis both in adipose and skeletal muscle tissue. These effects were not significantly different in obese and normal-weight subjects in both tissues.

Adipose Tissue↗

PubMed2003

Lifestyle changes and lipid metabolism gene expression and protein content in skeletal muscle of subjects with impaired glucose tolerance.

AIMS/HYPOTHESIS: Skeletal muscle of pre-diabetic patients is characterised by a diminished capacity to handle fatty acids. A diminished content of several enzymes involved in fatty-acid transport and oxidation have been suggested to underlie these defects. The aim of this study was to investigate whether the combination of dietary advice, increased physical activity and weight loss improves lipid metabolic gene and protein expression in skeletal muscle of subjects with impaired glucose tolerance. METHODS: Before and after 1 year of a lifestyle-intervention programme, expression of several genes and proteins involved in lipid metabolism were measured in vastus lateralis muscle biopsies from subjects in the intervention ( n=7) and control group ( n=6). RESULTS: After 1 year the intervention group had an improved glycaemic control and reduced body fat compared to the control group. Significant differences were observed for acetyl CoA-carboxylase 2 and uncoupling protein 2 expression (ACC2: -16.8+/-12.4% vs +51.5+/-32.3% for the intervention and control group respectively; p<0.05) (UCP2: -26.9+/-10.3% vs +10.5+/-6.2% for the intervention and control group respectively; p<0.05). Change in 3-hydroxyacyl-CoA dehydrogenase protein content tended to be different between groups (+3.2+/-1.1 vs -0.9+/-1.9 U/mg.ww for the intervention and control group, p=0.07). CONCLUSIONS/INTERPRETATION: Lifestyle changes leading to an improved glycaemic control and reduced adiposity, resulted in a down-regulation of ACC-2 and UCP2 expression and in an increase in HAD protein content, reflecting a better capacity to utilise fatty acids.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2003

Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year.

AIMS: Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity, diet and physical inactivity. The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance (IGT). METHODS: A total of 102 subjects were studied, randomised into two groups. Subjects in the intervention group received regular dietary advice, and were stimulated to lose weight and to increase their physical activity. The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity. Before and after the first year, glucose tolerance was measured and several other measurements were done. RESULTS: Body weight loss after 1 y was higher in the intervention group. The 2-h blood glucose concentration decreased 0.8+/-0.3 mmol/l in the intervention group and increased 0.2+/-0.3 mmol/l in the control group (P<0.05). Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity. CONCLUSION: A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle, which improve glucose tolerance in subjects with IGT. Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity.

Adult↗

PubMed2003

Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men.

OBJECTIVE: beta-Adrenoceptor-mediated whole-body lipolysis is impaired in obesity. This study investigated whether local adipocyte beta-adrenergic sensitivity and changes in nutritive blood flow in subcutaneous abdominal adipose tissue contribute to this impaired response. METHODS: Three microdialysis probes were placed in the subcutaneous abdominal adipose tissue of eight obese and nine lean men. Each probe was perfused with either 0.1, 1 and 10 microM isoprenaline; 1, 10 and 100 microM dobutamine or 1, 10 and 100 microM salbutamol, each dose for 45 min. RESULTS: At baseline, interstitial glycerol concentrations and ethanol out/in ratios were comparable between groups. During nonselective beta-, beta(1)- and beta(2)-adrenergic stimulation, interstitial glycerol concentrations increased and ethanol out/in ratios decreased similarly in obese and lean men. CONCLUSION: The lipolytic and nutritive blood flow response to beta(1)- beta(2)- and nonselective beta-adrenergic stimulation in situ is comparable in lean and obese male subjects. The present data suggest that a blunted beta-adrenergic sensitivity of the fat cell and an impaired local nutritive blood flow response do not contribute to the previously reported diminished whole-body beta-adrenoceptor-mediated lipolytic response in obese males.

Abdominal Wall↗

PubMed2003

Subscapular skinfold thickness distinguishes between transient and persistent impaired glucose tolerance: Study on Lifestyle-Intervention and Impaired Glucose Tolerance Maastricht (SLIM).

AIMS: To assess whether adding anthropometric measurements to an oral glucose tolerance test (OGTT) can help to distinguish between transient and persistent impaired glucose tolerance (IGT). METHODS: From the SLIM project (Study on Lifestyle-Intervention and IGT Maastricht), a study designed to evaluate whether diet and physical activity intervention can improve glucose tolerance in subjects at risk for diabetes, 108 subjects with IGT underwent a repeated OGTT 2-4 months after the initial OGTT. Following the second test, subjects were classified as transient IGT, or persistent IGT. Anthropometric measurements, including body mass index, waist and hip circumference, sagittal and transverse abdominal diameters and skinfold thickness measurements, were done during the second OGTT. RESULTS: Persistent IGT was diagnosed in 47 subjects (44%), transient IGT in 40 (37%), impaired fasting glucose in eight subjects (7%), and diabetes in 13 cases (12%). Two-hour blood glucose levels at the initial OGTT and subscapular skinfold thickness were significantly higher in subjects with persistent IGT (2-h blood glucose 9.8+/-0.1 mmol/l vs. 10.2+/-0.1 mmol/l for transient IGT and persistent IGT, respectively; subscapular skinfold thickness 25.4+/-1.4 mm vs. 29.8+/-1.2 mm for transient IGT and persistent IGT, respectively). After adjustment for age, sex and family history of diabetes mellitus, logistic regression indicated that 2-h blood glucose level during the initial OGTT represented the strongest predictor of persistent IGT (P<0.02), followed by subscapular skinfold thickness (P<0.05). After adjustment for 2-h blood glucose levels during the first OGTT, subscapular skinfold thickness remained significantly associated with persistent IGT (odds ratio 1.84; P<0.05). CONCLUSIONS: In addition to the 2-h blood glucose level, subscapular skinfold thickness was the best predictor of persistent IGT, suggesting that adding simple anthropometric measures to oral glucose tolerance testing may improve the distinction between persistent and transient glucose intolerance.

Anthropometry↗

PubMed2003

Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders.

Angiotensin II (Ang II), acting on the AT1 and AT2 receptors in mammalian cells, is the vasoactive component of the renin-angiotensin system (RAS). Several components of the RAS have been demonstrated in different tissues, including adipose tissue. Although the effects of Ang II on metabolism have not been studied widely, it is intriguing to assume that components of the RAS produced by adipocytes may play an autocrine, a paracrine and/or an endocrine role in the pathophysiology of obesity and provide a potential pathway through which obesity leads to hypertension and type 2 diabetes mellitus. In the first part of this review, we will describe the production of Ang II, the different receptors through which Ang II exerts its effects and summarize the concomitant intracellular signalling cascades. Thereafter, potential Ang II-induced mechanisms, which may be associated with obesity and obesity-related disorders, will be considered. Finally, we will focus on the different pharmaceutical agents that interfere with the RAS and highlight the possible implications of these drugs in the treatment of obesity-related disorders.

Adipose Tissue↗

PubMed2003

Fatty acid metabolism in obesity and type 2 diabetes mellitus.

Disturbances in pathways of lipolysis and fatty acid handling are of importance in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that a lowered catecholamine-mediated lipolytic response may play a role in the development and maintenance of increased adipose tissue stores. Increased adipose tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high lipolytic rate may increase circulating NEFA concentrations, which may promote insulin resistance and cardiovascular complications. In addition, a disturbance of NEFA uptake by adipose tissue postprandially is also a critical determinant of plasma NEFA concentration. Furthermore, evidence is increasing that insulin-resistant muscle is characterised by a lowered ability to oxidise fatty acids. A dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a factor promoting accumulation of lipid intermediates and triacylglycerols within skeletal muscle, which is strongly associated with skeletal muscle insulin resistance. The present review describes the reported disturbances in pathways of lipolysis and skeletal muscle fatty acid handling, and discusses underlying mechanisms and metabolic consequences of these disturbances.

Diabetes Mellitus↗

PubMed2001

Increase in skeletal muscle fatty acid binding protein (FABPC) content is directly related to weight loss and to changes in fat oxidation following a very low calorie diet.

AIMS/HYPOTHESIS: There is increasing evidence that intracellular fatty acid binding proteins (FABPc's; 15 kD) function as vehicles of cytosolic fatty acid transport. We studied skeletal muscle cytosolic FABPc, and enzymes reflecting beta-oxidation and oxidative capacity (3-hydroxyacyl-CoA dehydrogenase, HAD, and citrate synthase, CS) in relation to weight loss and changes in substrate utilisation in a group of 35 obese women and obese men with Type II (non-insulin-dependent) diabetes mellitus (women = 27, men = 8). METHODS: Muscle biopsies (vastus lateralis), and measurements of body composition, resting energy expenditure and respiratory exchange ratio were taken before and after dietary intervention (by means of a very low calorie diet). RESULTS: Muscle FABPc tended to increase after diet (178 +/- 13 vs 204 +/- 12 mg x gww(-1), p = 0.06), whereas there were no changes in CS (10.5 +/- 0.7 vs 11.1 +/- 0.6 U x gww(-1)) and HAD (11.2 +/- 0.7 vs 11.7 +/- 0.6 U x gww(-1)). There was a positive relation between the increase in FABPc as result of diet and the amount of weight lost (p < 0.01; adjusted R2, 15.4 %), even when adjusted for mean body weight, and changes in CS and in HAD by partial regression analysis. Interestingly, the increase in FABPc was positively related to increases in resting fat oxidation (adjusted R2, 24 %), even when adjusted for mean resting fat oxidation, and changes in CS and in HAD. CONCLUSION/INTERPRETATION: In conclusion, the ability to increase muscle FABPc could be directly related to weight loss and to changes in fat oxidation following dietary intervention in obesity and Type II (non-insulin-dependent) diabetes mellitus.

Adult↗