Biomedical subjects

Ian A Macdonald

Publications and source records attributed to Ian A Macdonald.

At least 19 recordsLinked to original sources

PubMed2006

Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC "diet trials".

OBJECTIVE: To compare the effectiveness of four commercial weight loss diets available to adults in the United Kingdom. DESIGN: Six month multicentre randomised unblinded controlled trial. SETTING: Community based sample of otherwise healthy overweight and obese adults. INTERVENTIONS: Dr Atkins' new diet revolution, Slim-Fast plan, Weight Watchers pure points programme, and Rosemary Conley's eat yourself slim diet and fitness plan. MAIN OUTCOME MEASURES: Weight and body fat changes over six months. RESULTS: All diets resulted in significant loss of body fat and weight over six months. Groups did not differ significantly but loss of body fat and weight was greater in all groups compared with the control group. In an intention to treat analysis, average weight loss was 5.9 kg and average fat loss was 4.4 kg over six months. The Atkins diet resulted in significantly higher weight loss during the first four weeks, but by the end was no more or less effective than the other diets. CONCLUSIONS: Clinically useful weight loss and fat loss can be achieved in adults who are motivated to follow commercial diets for a substantial period. Given the limited resources for weight management in the NHS, healthcare practitioners should discuss with their patients programmes known to be effective. TRIAL REGISTRATION: Clinical trials NCT00327821.

Adipose Tissue↗

PubMed2006

Fat oxidation before and after a high fat load in the obese insulin-resistant state.

BACKGROUND: Obesity may be associated with a lowered use of fat as a fuel, which may contribute to the enlarged adipose tissue stores. AIM: The aim of the present study was to study fatty acid use in the fasting state and in response to a high fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). METHODS: Subjects from eight European centers underwent a test meal challenge containing 95 en% fat [energy content 50% of estimated resting energy expenditure (EE)]. Fasting and postprandial fat oxidation and circulating metabolites and hormones were determined over a 3-h period. RESULTS: Postprandial fat oxidation (as percent of postprandial EE, adjusted for fat mass, age, gender, center, and energy content of the meal) decreased with increasing body mass index (BMI) category (P < 0.01), an effect present only in those obese subjects with a relatively low fasting fat oxidation (below median, interaction BMI category x fasting fat oxidation, P < 0.001). Fasting fat oxidation increased with increasing BMI category (P < 0.001), which was normalized after adjustment for fat-free mass and fat mass. Furthermore, insulin resistance was positively associated with postprandial fat oxidation (P < 0.05) and negatively associated with fasting fat oxidation (expressed as percent of EE), independent of body composition. CONCLUSIONS: The present data indicate an impaired capacity to regulate fat oxidation in the obese insulin-resistant state, which is hypothesized to play a role in the etiology of both obesity and insulin resistance.

Adult↗

PubMed2006

Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation.

A large metabolomics study was performed on 600 plasma samples taken at four time points before and after a single intake of a high fat test meal by obese and lean subjects. All samples were analyzed by a liquid chromatography-mass spectrometry (LC-MS) lipidomic method for metabolic profiling. A pragmatic approach combining several well-established statistical methods was developed for processing this large data set in order to detect small differences in metabolic profiles in combination with a large biological variation. Such metabolomics studies require a careful analytical and statistical protocol. The strategy included data preprocessing, data analysis, and validation of statistical models. After several data preprocessing steps, partial least-squares discriminant analysis (PLS-DA) was used for finding biomarkers. To validate the found biomarkers statistically, the PLS-DA models were validated by means of a permutation test, biomarker models, and noninformative models. Univariate plots of potential biomarkers were used to obtain insight in up- or downregulation. The strategy proposed proved to be applicable for dealing with large-scale human metabolomics studies.

Chromatography, Liquid↗

PubMed2006

Prevalence of self-reported symptoms attributed to hypoglycaemia within a general female population of the UK.

OBJECTIVE: To investigate the prevalence of symptoms attributed to hypoglycaemia that are reported by a general female population of the UK. METHOD: A health and well-being questionnaire, including questions relating to symptoms of low blood 'sugar', medical history and anthropometry, was administered by post to 2000 randomly selected women (17-50 years) in Nottinghamshire. To avoid biasing responses, participants were not made aware of the specific focus of the study. RESULTS: One thousand one hundred and thirty-six women returned the questionnaire (56.8% response rate). After exclusions, 37.9% of respondents reported symptoms that they attributed to hypoglycaemia, with a median of four episodes reported per month. A significant variation in the reporting of symptoms was found across body mass index (BMI) categories, with the highest prevalence of symptomatic subjects being found at the lowest BMI range (P<.05). CONCLUSION: More than a third of women in the UK report experiencing symptoms that they attribute to hypoglycaemia. Body mass index appears to be related to the experiencing of symptoms.

Adolescent↗

PubMed2006

Ambulatory blood glucose measurement, dietary composition and physical activity levels in otherwise healthy women reporting symptoms that they attribute to hypoglycaemia.

Reactive hypoglycaemia (RH) is a condition that has been popularised in the media and lay literature, particularly that targeting women, over the past 30 years. The objective of the present study was to investigate whether a non-patient group reporting symptoms that they attributed to a low blood glucose level would demonstrate biochemical hypoglycaemia when symptomatic and whether their habitual diet and activity level differed from those of controls. Thirty non-obese, healthy women (aged 19-45 years) reporting symptoms more than once a week that they attributed to hypoglycaemia (RH group), and eighteen controls, measured their finger-prick blood glucose level 3 h after breakfast and lunch, and recorded their diet and activity daily for 7 d. The RH group also measured their blood glucose when symptoms were being experienced. Symptoms less than 4 h after eating were classed as postprandial. The mean postprandial blood glucose level in the RH group when asymptomatic (4.66 (SEM 0.08) mmol/l) was significantly lower than that of controls (5.05 (SEM 0.11) mmol/l; P<0.01). Symptoms occurred 2.6 (SEM 0.13) h after eating, at a lower blood glucose level (4.18 (SEM 0.10) mmol/l; P<0.001) than when the women were asymptomatic. On symptomatic days, the RH group were more physically active than the controls (1.64 (SEM 0.04) v. 1.50 (SEM 0.03) multiples of resting energy expenditure; P<0.05), with a lower energy intake (7901 (SEM 311) v. 9332 (SEM 227) kJ; P<0.001). In conclusion, subjects reporting symptoms they associated with hypoglycaemia generally did not demonstrate biochemical hypoglycaemia but did have significantly lower blood glucose levels than controls. Higher physical activity and a failure to match energy intake to estimated energy requirement may be important in the aetiology of symptoms.

Adolescent↗

PubMed2006

Asthma as a barrier to children's physical activity: implications for body mass index and mental health.

OBJECTIVES: The purpose of this work was to identify barriers to physical activity in children with asthma and to compare their customary activity levels, BMI and emotional well-being with that of children with other medical conditions. It was hypothesized that children with asthma would have higher BMI and lower levels of customary activity. PATIENTS AND METHODS: We studied children aged 7 to 14 years attending hospital outpatient clinics for either asthma (asthma group: n = 56) or for otorhinolaryngology or dermatological conditions (nonasthma group: n = 61). In this cross-sectional survey, children's weight and height were recorded and their BMI classified according to International Obesity Task Force classification of obesity. Child mental health was assessed by the parent-rated Strengths and Difficulties Questionnaire. The child-rated Physical Activity Questionnaire assessed total sedentary and physical activities during the previous 24 hours. RESULTS: The asthma group had a higher mean BMI (20.78 vs 18.82) and higher rates of obesity (21.4% vs 6.6%). Children with asthma reported fewer physical activities than the nonasthma group (median 4 per day vs 6 per day) but comparable levels of sedentary activities. Asthma was the strongest predictor of lower activity scores, followed by younger age. The asthma group had higher levels of emotional difficulties and, within this group, more active children had better mental health. More parents in the asthma group identified the child's health as a barrier to exercise (60.7% vs 11%). The same was true of children (66.1% vs 11.5%). CONCLUSIONS: We found that children attending a hospital clinic for asthma were more likely to be obese and were significantly less active than a comparison group with other medical conditions. Asthma was identified as a barrier to exercise by parents and children. Strategies to promote exercise within pediatric asthma care are needed to protect both mental and physical health.

Adolescent↗

PubMed2005

Effects of elevated plasma adrenaline levels on substrate metabolism, effort perception and muscle activation during low-to-moderate intensity exercise.

The aim of this study was to differentiate the role of raised plasma adrenaline (Adr) concentrations from sympathoadrenal activation associated with moderate-intensity exercise, on muscle activation, cardiopulmonary responses, fuel metabolism, and ratings of perceived exertion (RPE) during low-intensity exercise. Two groups of subjects (MOD, n=6; LOW, n=7) cycled on two occasions for 90 min. MOD cycled at 68% VO(2max) with saline infusion, and at 34% VO(2max) with Adr infusion. LOW cycled twice at 34% VO(2max), with either Adr or saline infusion. Infusions (0.015 g Adr/kg/min) started at 15 min and increased plasma [Adr] somewhat higher than during exercise at 68% VO(2max) (approximately 1.9 vs. 1.4 nM, at 75 min). Mean plasma glucose and lactate concentrations during LOW were significantly higher with Adr than saline infusion (5.1+/-0.6 vs. 4.4+/-0.3 mmol/l, P<0.01 and 2.1+/-0.8 vs. 1.3+/-0.5 mmol/l, P<0.01, respectively). Elevated [Adr], without increased exercise intensity, did not alter glycogenolysis. There were also no effects of Adr infusion at 34% VO(2max) on heart rate, oxygen consumption, [FFA], respiratory exchange ratio, intramuscular triglyceride utilization, muscle activation or RPE. In conclusion, elevated [Adr] similar to those found during moderate-intensity exercise increased plasma glucose and lactate availability, but did not alter intramuscular fuel utilization, effort perception or muscle activation.

Adolescent↗

PubMed2005

Effects of acute starvation on insulin resistance in obese patients with and without type 2 diabetes mellitus.

BACKGROUND & AIMS: Starvation decreases insulin sensitivity and glucose tolerance in both lean and obese (OB) non-diabetic subjects. Influence of drastic calorie reduction on insulin resistance in patient with type 2 diabetes (T2DM) is not known. METHODS: We enrolled 10 T2DM (diabetes duration 11.1+/-7.9 years) and 10 OB age and weight-matched subjects and performed isoglycaemic hyperinsulinaemic clamp (two 120 min phases of 60 and 120 mIU min-1 m-2 i.v. insulin) with indirect calorimetry at baseline and after 60 h of fasting. RESULTS: After starvation insulin-mediated glucose disposal decreased significantly in both hyperinsulinaemic phases in T2DM (phase 1: from 46+/-28 to 33+/-17, P<0.04; phase 2 from 122+/-47 to 80+/-30 microg kg-1 min-1, P<0.01) as well as in OB (phase 1: from 94+/-52 to 52+/-24, P<0.04; phase 2: from 131+/-46 to 106+/-43 microg kg-1 min, P<0.01). Both oxidative and non-oxidative components of glucose disposal tended to be reduced after fasting. A change of insulin sensitivity was found to be highly dependent upon pre-starvation conditions: more insulin resistant subjects tended to maintain (or modestly improve) insulin resistance whilst subjects with better insulin sensitivity tended to worse it. CONCLUSION: Insulin sensitivity worsens similarly in both T2DM and OB subjects during 60-h fast. The change is probably predictable according to pre-starvation insulin sensitivity.

Area Under Curve↗

PubMed2005

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women.

BACKGROUND: Breakfast consumption is recommended, despite inconclusive evidence of health benefits. OBJECTIVE: The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. DESIGN: In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. RESULTS: Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). CONCLUSION: OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.

Adult↗

PubMed2005

Beneficial metabolic effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in healthy obese women.

BACKGROUND: Although a regular meal pattern is recommended for obese people, its effects on energy metabolism have not been examined. OBJECTIVE: We investigated whether a regular meal frequency affects energy intake (EI), energy expenditure, or circulating insulin, glucose, and lipid concentrations in healthy obese women. DESIGN: Ten women [x +/- SD body mass index (in kg/m(2)): 37.1 +/- 4.8] participated in a randomized crossover trial. In phase 1 (14 d), the subjects consumed their normal diet on 6 occasions/d (regular meal pattern) or followed a variable meal frequency (3-9 meals/d, irregular meal pattern). In phase 2 (14 d), the subjects followed the alternative pattern. At the start and end of each phase, a test meal was fed, and blood glucose, lipid, and insulin concentrations were determined before and for 3 h after (glucose and insulin only) the test meal. Subjects recorded their food intake on 3 d during each phase. The thermogenic response to the test meal was ascertained by indirect calorimetry. RESULTS: Regular eating was associated with lower EI (P < 0.01), greater postprandial thermogenesis (P < 0.01), and lower fasting total (4.16 compared with 4.30 mmol/L; P < 0.01) and LDL (2.46 compared with 2.60 mmol/L; P < 0.02) cholesterol. Fasting glucose and insulin values were not affected by meal pattern, but peak insulin concentrations and area under the curve of insulin responses to the test meal were lower after the regular than after the irregular meal pattern (P < 0.01 and 0.02, respectively). CONCLUSION: Regular eating has beneficial effects on fasting lipid and postprandial insulin profiles and thermogenesis.

Adult↗

PubMed2005

Metabolic responses to exercise after carbohydrate loads in healthy men and women.

PURPOSE: This study aimed to investigate gender differences in i) pancreatic insulin secretory (beta-cell sensitivity) and whole body insulin sensitivity responses to an intravenous carbohydrate (CHO) load, and (ii) metabolic responses to exercise after both intravenous and oral CHO loads. METHODS: Seven untrained healthy men and seven age-, body mass-, and VO2max-matched women performed two trials. In one trial they cycled for 60 min at 50% VO2max, starting 60 min after ingestion of a carbohydrate-rich meal (ME trial). In the other trial, subjects were infused with 20% dextrose solution to maintain blood glucose concentration at approximately 8 mmol x L(-1) for 60 min (INF trial), then the infusion rate was maintained constant during the following 60 min while exercising at 50% VO2max. RESULTS: There was no gender effect on beta-cell sensitivity (serum insulin: 161 +/- 37 and 159 +/- 28 pmol x L(-1) for men and women, respectively) and whole body insulin sensitivity (155 +/- 24 and 135 +/- 29 mg x KgFFM(-1) x min(-1) per pmol x L(-1) x 100 for men and women, respectively). This may explain the similarity in glycemic, substrate oxidation and other metabolic responses to exercise after both intravenous and oral CHO loads in men and women. CONCLUSION: These results suggest that moderate exercise performed in the postprandial state presents a similar challenge to the ability of healthy, untrained men and women to perform exercise without a substantial decline in plasma glucose concentration below fasting values.

Adult↗

PubMed2005

Oscillations of fatty acid and glycerol release from human subcutaneous adipose tissue in vivo.

We sought evidence for pulsatility of lipolysis in human subcutaneous adipose tissue in vivo. Arterialized and adipose tissue venous blood samples were drawn at 2-min intervals from nine healthy subjects. This procedure was repeated during hyperinsulinemic-euglycemic clamp to remove insulin pulsatility. We found evidence for pulsatile release of both nonesterified fatty acids (NEFAs) (seven of nine subjects) and glycerol (five of six subjects) with a period of approximately 12-14 min. This pulsatility was maintained even during the hyperinsulinemic clamp. Checks were made for spurious pulse detection, including the creation of "mock" venoarterialized differences by subtracting one subject's arterialized concentrations from another's venous; the peaks detected were less consistent in character than with real data (peak width, P = 0.006; peak interval, P < 0.004). Significant cross-correlations between NEFA and glycerol release also provided evidence of a real effect. Arterialized norepinephrine concentrations were also pulsatile, but the period did not match that of NEFA and glycerol release. Insulin concentrations were pulsatile with a typical period of 12 min, but this was not significantly cross-correlated with lipolysis. We conclude that release from adipose tissue of the products of lipolysis is pulsatile in humans.

Adipose Tissue↗

PubMed2004

Optimising nutrition in chronic renal insufficiency--growth.

The need to optimise nutrition to promote growth in infants with chronic renal insufficiency (CRI) is well recognised, but there is less enthusiasm for such an approach in older children and those with milder degrees of CRI. Energy intakes and growth outcomes were prospectively monitored over a 2-year period in children aged 2-16 years with differing levels of severity of CRI, as part of their ongoing joint medical/ dietetic care. Children were grouped following [(51)Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m(2)) estimations, into 'normal' kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51-75, n =25), moderate (GFR 25-50, n =21), and severe (GFR <25, n=19) CRI. Children were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI), and were excluded if they required dialysis. None received growth hormone. Regular dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly anthropometric measurements were obtained. Mean height standard deviation score (SDS) was maintained in those with mild and moderate CRI and significantly increased in children with severe CRI [0.1 SDS (0.32 SD), F =9.45, 1 df, P =0.003]. There was a non-significant reduction in energy intake from dietary records overall (median -8.5% estimated average requirement), associated with poor adherence to supplements in severe CRI and under-reporting in the mild group. An increase in height or body mass index SDS, however, was observed in all children who took the supplements as prescribed. A correlation between change in energy intake and change in height SDS was observed in severe CRI ( r(2)=0.58, P =0.011). Regular dietetic advice, with particular attention to adherence to optimise energy intake, may improve growth, irrespective of age and should form an integral part of the clinical care package.

Adolescent↗

PubMed2004

Influence of insulin on glucose metabolism and energy expenditure in septic patients.

INTRODUCTION: It is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers. METHODS: Glucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test. RESULTS: Differences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers. CONCLUSION: A hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers.

APACHE↗

PubMed2004

Optimising nutrition in chronic renal insufficiency--progression of disease.

There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2-16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [5'Cr]-labelled EDTA glomerular filtration rate(GFR, ml/min per 1.73 m 2) estimations, into 'normal'kidney function [GFR >75, mean 106 (SD 19.5), n=58],providing baseline data only, mild (GFR 51-75, n=25),moderate (GFR 25-50, n =21), and severe (GFR <25, n=19) CRI. Children with CRI were followed for 2 years,with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary di-aries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were -9.4, -5.8, and -6.0 ml/min per 1.73 m2 for mild,moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes,median sodium intakes increased (+10 mmol/day) and protein intakes decreased (-0.4 g/kg per day). Median phosphate intakes did not change significantly, where as calcium intakes fell in all groups, with an overall median of -20% reference nutrient intake (RNI) (F=33.3,P<0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F=6.0, P=0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r2=0.30,P=0.02; r-=0.31, P=0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression.

Adolescent↗

PubMed2004

Influence of autonomic neuropathy on QTc interval lengthening during hypoglycemia in type 1 diabetes.

Hypoglycemia produces electrocardiographic QTc lengthening, a predictor of arrhythmia risk and sudden death. This results from both sympatho-adrenal activation and a lowered serum potassium. It has been suggested that cardiac autonomic neuropathy (CAN) might indicate those who are at particular risk. We tested this hypothesis in 28 adults with type 1 diabetes and 8 nondiabetic control subjects. After standard tests of autonomic function and baroreflex sensitivity (BRS) measurement, diabetic participants were divided into three groups: 1) CAN- with normal BRS (BRS+; n = 10), 2) CAN- with impaired BRS (BRS-; n = 9), and 3) CAN+ (n = 9). QTc was then measured during controlled hypoglycemia (2.5 mmol/l) using a hyperinsulinemic clamp. Mean (+/-SE) QTc lengthened from 377 +/- 9 ms (baseline) to a maximum during hypoglycemia of 439 +/- 13 ms in BRS+ subjects and from 378 +/- 5 to 439 +/- 10 ms in control subjects. Peak QTc tended to be lower in CAN+ (baseline, 383 +/- 6; maximum, 408 +/- 10) and BRS- groups (baseline, 380 +/- 8; maximum, 421 +/- 11; F = 1.7, P = 0.18). Peak epinephrine concentrations (nmol/l) were 3.1 +/- 0.8 (BRS+), 2.6 +/- 0.5 (BRS-), 1.4 +/- 0.3 (CAN+), and 5.7 +/- 0.8 (control subjects). These data do not indicate that those with CAN are at particular risk for abnormal cardiac repolarization during hypoglycemia. Indeed, they suggest that such patients may be relatively protected, perhaps as a result of attenuated sympatho-adrenal responses.

Adult↗

PubMed2002

Effects of insulin on adipose tissue blood flow in man.

Adipose tissue blood flow (ATBF) rises after nutrient ingestion. It is not clear whether this is due to insulin. The aim of this study was to investigate the role of insulin in the regulation of subcutaneous ATBF. We have investigated the role of insulin in the regulation of ATBF in normal, healthy subjects in a three-step procedure to determine the functional level at which insulin may potentially exert its effect. Fifteen subjects were studied on two occasions. On the first visit, 75 g oral glucose was given. In the second, similar plasma concentrations of insulin and glucose were achieved by dynamic intravenous infusions of insulin and glucose. The increase in ATBF after oral glucose (4.2 +/- 1.4 ml min(-1) (100 g tissue)(-1), P = 0.01) was significantly greater (P < 0.05) than that after intravenous infusions (1.5 +/- 0.6 ml min(-1) (100 g tissue)(-1) P < 0.05). For the local delivery of potentially vasoactive substances and simultaneous measurement of ATBF, we describe a novel combination of methods, which we have called 'microinfusion'. We have used this technique to show that locally infused insulin, even at pharmacological concentrations, had no demonstrable effect on ATBF in nine subjects. We conclude that whilst insulin does not have a direct effect on ATBF, it is likely to be an important mediator, possibly acting via sympathetic activation. In the postprandial state, other candidate peptides and hormones are also likely to play important roles.

Adipose Tissue↗

PubMed2002

Impaired postprandial adipose tissue blood flow response is related to aspects of insulin sensitivity.

Obesity has been associated with dysfunctional postprandial adipose tissue blood flow (ATBF), but it has also been recognized that the interindividual response is highly variable. The present work aimed at characterizing this variability. Fifteen subjects were given 75 g oral glucose, and abdominal subcutaneous ATBF was monitored by the (133)Xe washout method. Determinants of insulin sensitivity based on nonesterified fatty acid (NEFA) suppression after oral glucose administration [ISI(NEFA)] were higher in the top tertile ATBF response group (1.29 +/- 0.09 vs. 0.90 +/- 0.08 in the lower tertiles, P = 0.01). ISI(NEFA) was related to ATBF response (r(s) = 0.73, P < 0.002) as well as insulin sensitivity based on postprandial glycemia [ISI(gly), r(s) = 0.58, P < 0.05], whereas the homeostasis model assessment (HOMA) index (r(s) = -0.39, P = 0.16) was not. The relationship between increase in ATBF and ISI(NEFA) was independent of BMI (P = 0.015) in multivariate analysis. Subjects with a high ATBF response had significantly higher increase of plasma norepinephrine (P < 0.05), indicating a link between postprandial insulinemia, sympathetic activation, and ATBF response. There is a close relationship between insulin sensitivity and the regulation of postprandial ATBF, independent of adiposity. Impaired regulation of ATBF seems to be another facet of the insulin resistance syndrome.

Adipose Tissue↗