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Biomedical subjects

L V Campbell

Publications and source records attributed to L V Campbell.

At least 19 recordsLinked to original sources
PubMed2003

The postprandial response of adiponectin to a high-fat meal in normal and insulin-resistant subjects.

OBJECTIVE: Adiponectin is an adipose-specific protein with short-term effects in vivo on glucose and fatty acid levels. We studied the plasma concentration and the proteolytic activation status of adiponectin following the consumption of a high-fat, low-carbohydrate meal. DESIGN: Analysis of adiponectin concentration and polypeptide structure after consumption of a fat meal. SUBJECTS: Normal subjects (n=24) and first-degree relatives of patients with type II diabetes (n=20). MEASUREMENTS: All subjects had a normal fasting plasma glucose and glucose tolerance. Blood was collected for the determination of plasma insulin, adiponectin, triglyceride, and free fatty acids. Body composition was assessed with dual-energy X-ray absorptiometry and whole-body insulin sensitivity with a euglycaemic, hyperinsulinaemic clamp. Postprandial response over 6 h was determined for plasma adiponectin, glucose, insulin, triglyceride, and free fatty acids. Adiponectin was measured by commercial RIA and its polypeptide structure examined by Western blotting. RESULTS: The relatives were more insulin resistant and had increased adiposity compared with control subjects. There was no significant difference in postprandial response in fatty acids, triglyceride, or insulin between the groups. Postprandial levels of adiponectin measured by radioimmunoassay were not significantly different from fasting levels, and no breakdown products of adiponectin were detectable in postprandial samples by Western blotting. CONCLUSIONS: Levels of circulating adiponectin do not alter in response to a fat meal, despite evidence in mice that acute changes in adiponectin significantly affect postprandial fatty acid flux. Moreover, a fat meal challenge did not lead to significant activation of adiponectin by proteolytic conversion.

Adiponectin↗
PubMed2003

Postprandial triglycerides in response to high fat: role of dietary carbohydrate.

BACKGROUND: The postprandial triglyceride response following a meal high in fat (HFM) has been related to atherogenesis and insulin resistance. We examined the influence of dietary carbohydrate and the accompanying insulin secretory response on the postprandial triglyceride response following a HFM. MATERIALS AND DESIGN: High-fat meals of equal fat content (fat 80 g) containing either 20 g (low) or 100 g (high) of carbohydrate (HFM-LC and HFM-HC, respectively), and therefore not isocaloric (4250 kJ of HFM-LC and 5450 kJ of HFM-HC), were consumed by seven (four male, three female) normolipidaemic subjects (aged 32.9 +/- 3.7 years, BMI 24.7 +/- 1.8 kg m-2). Blood and indirect calorimetry data were collected at 0-4 h. RESULTS: HFM-HC produced a significant rise in plasma glucose (Delta0.54 +/- 0.23 mmol L-1, P = 0.05) at 2 h, while a HFM-LC elicited no mean change from baseline. Following a HFM-LC, the plasma insulin incremental area under the curve (AUC) was significantly lower (31.3 +/- 6.7 vs. 83.2 +/- 11.9 mU l-1 h-1, P < 0.0003) and the postprandial triglyceride response AUC was significantly greater (1.66 +/- 0.36 vs. 1.24 +/- 0.31 mmol L-1 h-1, P < 0.006) compared with a HFM-HC. Plasma free fatty acids were suppressed by 44% (P = 0.04) and 66% (P < 0.0001) at 1 h following HFM-LC and HFM-HC, respectively, compared with baseline. There were no significant differences between the meals in energy expenditure, substrate oxidation rates, or respiratory quotient responses. CONCLUSIONS: By design, the HFMs were not isocaloric but the presence of carbohydrate in a HFM invoked an insulin response that significantly reduced the 4 h postprandial triglyceride response even in healthy, normolipidaemic subjects. This phenomenon may have clinical implications, particularly in relation to insulin sensitivity.

Blood Glucose↗
PubMed2003

Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.

Adult↗
PubMed2001

Independent influences of central fat and skeletal muscle lipids on insulin sensitivity.

OBJECTIVE: Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action. RESEARCH METHODS AND PROCEDURES: Eighteen older (56 to 75 years of age) men were studied before elective knee surgery. Insulin sensitivity (M/Delta I) was determined by hyperinsulinemic-euglycemic clamp. Central abdominal fat (CF) was assessed by DXA. Skeletal muscle was excised at surgery and assayed for content of metabolically active long-chain acyl-CoA esters (LCAC). RESULTS: Significant inverse relationships were observed between LCAC and M/Delta I (R(2) = 0.34, p = 0.01) and between CF and M/Delta I (R(2) = 0.38, p = 0.006), but not between CF and LCAC (R(2) = 0.0005, p = 0.93). In a multiple regression model (R(2) = 0.71, p < 0.0001), both CF (p = 0.0006) and LCAC (p = 0.0009) were independent statistical predictors of M/Delta I. Leptin levels correlated inversely with M/Delta I (R(2) = 0.60, p = 0.0002) and positively with central (R(2) = 0.41, p = 0.006) and total body fat (R(2) = 0.63, p = 0.0001). DISCUSSION: The mechanisms by which altered lipid metabolism in skeletal muscle influences insulin action may not be related directly to those linking central fat and insulin sensitivity. In particular, it is unlikely that muscle accumulation of lipids directly derived from labile central fat depots is a principal contributor to peripheral insulin resistance. Instead, our results imply that circulating factors, other than nonesterified fatty acids or triglyceride, mediate between central fat depots and skeletal muscle tissue. Leptin was not exclusively associated with central fat, but other factors, secreted specifically from central fat cells, could modulate muscle insulin sensitivity.

Absorptiometry, Photon↗
PubMed2001

Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach.

OBJECTIVE: To construct a simple physiological model of leptin kinetics, based on measures of body size and composition, which is suitable for investigating the influence of genetic and other influences on circulating leptin levels in humans. METHODS: Consideration of the kinetics of the secretion and clearance of leptin led to a predicted linear relationship between ln(leptin), ln(fat mass), and a function of non-fat body compartments. Results obtained from this model were compared with those from two published empirical models based on adjustment for fat mass alone or for body mass index. Overnight fasted leptin levels, body composition data (dual-energy X-ray absorptiometry) and questionnaire responses were obtained from 527 twin pairs (127 monozygotic, 400 dizygotic; 37 male (age 18-68 y, BMI 18-32 kg/m2), 489 female (age 18-71, BMI 17-44) drawn from the St Thomas' UK Adult Twin Registry. RESULTS: In a partial correlation analysis ln(fat mass) and ln(height) (r=0.80, P<0.0001) and r=-0.22, P<0.0001 respectively) were independent predictors of ln(leptin) in females but ln(lean mass) was not (r=-0.01). A regression model incorporating ln(fat mass), ln(height) and a second order polynomial in age provided an adequate fit of the ln(leptin) data in females (r2=71%). ln(Leptin) values adjusted for body size and composition using the model were not significantly heritable (P=0.11), were significantly related to gender (r2=2.3%) and to ln(insulin) (r2=5.7%), but not to menopausal status (r2=0.7%), hormone replacement therapy (r2=0.4%), past or current smoking (r2=1.1%), or percentage trunk fat (r2=0.5%). Both empirical models found significant heritability (h2=36-42%), overestimated the effect of gender in the data (r2=14-16%), and produced significant relationships between adjusted ln(leptin) and percentage trunk fat (r2=4-12%). CONCLUSIONS: We conclude that our physiologically based model provides an adequate description of the relationship between leptin and body composition and provides a more reliable framework than current empirical approaches for the investigation of other influences on circulating leptin levels. Heritable variations in the control of leptin secretion are unlikely to contribute significantly to variations in leptin levels at the population level.

Absorptiometry, Photon↗
PubMed2000

The lower limb in people with diabetes. Position statement of the Australian Diabetes Society.

Diabetic lower-limb problems result in significant social, medical and economic consequences and are the most common cause of hospitalisation for people with diabetes. In people with diabetes, amputations are 15 times more common than in people without diabetes, and 50% of all amputations occur in people with diabetes. Peripheral neuropathy, vascular disease, infection and deformity of the feet are the major predisposing factors leading to ulceration or amputation. All people with diabetes should receive basic footcare education, and regular foot examinations. The risk for the development of ulceration can be assessed by basic clinical examination of the foot. Management strategies depend on the risk category, and range from basic education and annual review to specialist care by a multidisciplinary team.

Aged↗
PubMed2000

Effects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjects.

Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal. NA did not significantly alter 24-h mean systolic or diastolic blood pressure. Fasting glucose, insulin and non-esterified free fatty acid (NEFA) levels remained unchanged, energy expenditure and substrate oxidation were not altered by NA. These results suggest a short term reduction in insulin sensitivity with NA is not accompanied by a change in blood pressure. This may relate to the short duration of treatment, to a dissociation between insulin resistance and hypertension or to other homeostatic mechanisms which prevent blood pressure rising in subjects not predisposed to hypertension.

Adult↗
PubMed2000

Predicting the occurrence of diabetes mellitus in recipients of heart transplants.

AIMS: To establish the incidence of post-transplant diabetes mellitus (PTDM) and factors predictive of its development. METHODS: This was a retrospective review (using hospital records and transplant database) of 97 consecutive adult patients who underwent cardiac transplantation at St Vincent's Hospital, Sydney, Australia. RESULTS: Mean follow-up was 27 months. Excluding five patients who had pre-existing diabetes, the cumulative incidence of PTDM was 15.7%. Pre-transplant random blood glucose (5.6 +/- 0.8 vs. 5.2 +/- 0.6 mmol/l, P<0.05), family history (46% vs. 15%, P<0.05) and a continuing requirement for insulin on the second post-transplant day (54% vs. 15%, P< 0.01) differed in those who developed PTDM as opposed to those who remained free of diabetes. Patients who developed PTDM had received slightly higher mean doses of prednisolone at three months (0.21 +/- 0.03 vs. 0.19 +/- 0.03 mg. kg(-1)/day(-1), P<0.01). Of the factors identifiable prior to initial hospital discharge, only family history of diabetes mellitus and second post-transplant day insulin requirement independently predicted the occurrence of PTDM. CONCLUSIONS: A family history of diabetes and the need for insulin beyond the first 24 h after transplantation are factors identifiable prior to hospital discharge, which predict patients at risk of developing PTDM. In such patients, consideration to minimizing the dose of glucocorticoids should be given where possible.

Adult↗
PubMed2000

Improved indices of insulin resistance and insulin secretion for use in genetic and population studies of type 2 diabetes mellitus.

Homeostasis model assessment (HOMA) provides indices of insulin secretion (beta) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P<0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA') indices were obtained from beta' = (Ln(FPI) - c)/FPG and R' = (Ln(FPI) - c)*FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R'), 0.45 (beta), 0.39 (beta'), all P< 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA-beta and R were strongly related (r = 0.78, P<0.0001 vs. 0.13) demonstrating substantial misclassification. The relationship between beta' and R' (r = 0.13) was not different from that between the two direct measures and significant heritability of beta' (h2 = 0.68, P<0.01) and R' (h2 = 0.59, P<0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG.

Adult↗
PubMed1999

Genetic and environmental influences on total-body and central abdominal fat: the effect of physical activity in female twins.

BACKGROUND: The increasing prevalence of obesity has focused attention on the contribution of physical activity and its interaction with predisposing genetic factors. OBJECTIVE: To examine 1) the relation between physical activity and total-body and central abdominal fat, independent of genetic and other environmental factors, and 2) the influence of physical activity in persons who are genetically susceptible to generalized or central adiposity. DESIGN: Cross-sectional study. SETTING: A London academic teaching hospital. PATIENTS: 970 healthy female twins (mean age, 55.5 years [range, 39 to 70 years]; body mass index, 24.4 kg/m2 [range, 16.4 to 44.0 kg/mg2]). There were 241 monozygotic pairs, 228 dizygotic pairs, and 32 women whose co-twin lacked complete data. Fifty-six percent of participants were of normal weight, 30% were overweight, 7% were obese, and 7% were underweight. MEASUREMENTS: Total-body and central abdominal fat were measured by dual-energy x-ray absorptiometry. Physical activity was assessed by quantitative and semiquantitative questionnaires. Data on dietary intake, socioeconomic status, smoking status, and use of hormone replacement therapy (HRT) were also gathered. RESULTS: Total-body and abdominal central adiposity were lower with higher levels of home, sporting, and sweating-associated activity. Total-body and central abdominal fat were 5.6 kg and 0.44 kg lower, respectively, in participants who reported vigorous weight-bearing activity. Physical activity was the strongest independent predictor of total-body fat (beta = -0.6 [CI, -1.06 to -0.15]; P = 0.009) and central abdominal fat (beta = -0.07 [CI, -0.1 to -0.03]; P < 0.001) in a regression model that included age, diet, smoking, HRT use, and socioeconomic status. Monozygotic twin pairs who were concordant for smoking and HRT status but were discordant for moderate-intensity sport showed greater within-pair differences in total-body fat than those who were concordant for activity level. In this model, 1 and 2 hours of moderate-intensity sport accounted for within-pair differences of 1.0 kg (P = 0.050) and 1.4 kg (P = 0.040), respectively, of total-body fat. In participants who had an overweight twin, higher levels of physical activity were still associated with 3.96-kg lower total-body fat and 0.53-kg lower central abdominal fat. CONCLUSIONS: Current physical activity predicts lower total-body and central abdominal adiposity in healthy middle-aged women. After controlling for genetic and environmental factors, the influence of physical activity was greater than that of other measured environmental factors. Participants with a genetic predisposition to adiposity did not show a lesser effect of physical activity on body fat mass.

Abdomen↗
PubMed1999

Dietary underreporting is prevalent in middle-aged British women and is not related to adiposity (percentage body fat).

OBJECTIVE: To determine the phenotypic and dietary characteristics of energy underreporters in a healthy population of middle-aged women using accurate body composition measures. DESIGN: Cross-sectional study of 436 healthy middle-aged female volunteers, unaware of any hypotheses regarding diet and body fat: mean age 58 y (39-70 y), body mass index (BMI) 24.3 kg/m2 (17.0-41.9 kg/m2). The prevalence of overweight (25.0 > BMI > 29.9 kg/m2) and obesity (BMI > 30 kg/m2) were 30% and 5% respectively. MEASUREMENTS: Dietary intake by food frequency questionnaire (FFQ) (n = 436), 197 subjects also completed seven-day food records; body composition by dual energy X-ray absorptiometry (DXA); physical activity by standardised questionnaire. Underreporters were subjects whose estimated energy expenditure (EE) exceeded reported energy intake (EI). Three cut-off levels of underreporting were determined from estimates of EE utilising DXA body composition measures: basal, and two including EE from physical activity (using the ratio 1.35 or ratios from reported physical activity level). RESULTS: Underreporters had significantly greater weight (P < 0.01), BMI (P < 0.01), total fat P < 0.05), fat free mass (P < 0.0001), but not adiposity (% body fat) than adequate-reporters, at each of the three cut-off levels. Underreporters reported significantly lower intakes of energy and all macronutrients (P < 0.0001). Expressed as a percentage of EI, the reported diet of underreporters was significantly lower in fat, similar in carbohydrate and higher in protein. Similar results were found with seven-day food record data, although reported intakes from these were significantly lower than those from FFQ. The prevalence of underreporting was highest in obese subjects (defined by BMI only), with up to 65% of these subjects underreporting EI and in the highest BMI tertile (prevalence of 57%). In those with BMI < 24.9 kg/m2, the maximal prevalence rate of underreporting was 43%. Importantly, however, the rates of underreporting were similar between tertiles of adiposity. Most (68%), but not all, underreporters were found in the lowest tertile for reported EI. CONCLUSIONS: A low reported EI and greater BMI may help identify energy underreporters. However, whilst underreporters may more frequently be 'bigger' (by BMI), they are not necessarily fatter (using direct measures of body fat). As underreporting was present among all tertiles of BMI and adiposity, these results emphasise the importance of following past recommendations to identify and exclude energy underreporters in nutritional studies. Where underreporters have not been excluded, reported nutrition-disease relationships must remain in doubt.

Adult↗
PubMed1999

Clustering of insulin resistance, total and central abdominal fat: same genes or same environment?

Obesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in 'normal' populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged (+/- SD) 52 +/- 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P < 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on beta-cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type 2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.

Abdomen↗
PubMed1999

Effects of postmenopausal hormone replacement therapy on central abdominal fat, glycemic control, lipid metabolism, and vascular factors in type 2 diabetes: a prospective study.

OBJECTIVE: To examine the effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure (BP), and arterial pulse wave velocity (APWV) in overweight postmenopausal females with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 12-month prospective study of 14 subjects (mean +/- SD age 57.5+/-5.6 years, BMI 29.5+/-4.8 kg/m2) randomized to 6 months of observation or HRT before crossover. HRT consisted of 2 months of conjugated equine estrogen (CEE) 0.625 mg daily, followed by 4 months CEE and medroxyprogesterone 5 mg daily. Measures included anthropometry, fasting glucose, insulin, HbA1c, total and HDL cholesterol, triglycerides, apolipoprotein B, LDL particle size, nonesterified fatty acids (NEFA), sex hormone-binding globulin, resting energy expenditure (REE), total and central abdominal fat (by dual-energy X-ray absorptiometry), resting BP, APWV (by applanation tonometry), physical activity, well-being, and sexual function. RESULTS: Six months of HRT resulted in significant reductions in waist-to-hip ratio (-0.03+/-0.01 vs. 0.01+/-0.009, P = 0.007), HbA1c (-0.34+/-0.24 vs. 0.6+/-0.4%, P = 0.04), total cholesterol (-0.6+/-0.1 vs. 0.2+/-0.2 mmol/l, P = 0.001), central abdominal fat (-175+/-51 vs. -24+/-56 g, P = 0.05), and improved physical functioning (P = 0.05), compared with observation. There was a minor increase in REE with HRT (33+/-23 vs. -38+/-23 kJ/day, P = 0.04). Total fat mass, fasting glucose, insulin, triglyceride, apolipoprotein B, NEFA, resting BP, APWV, and physical activity were unchanged. CONCLUSIONS: Postmenopausal HRT in these overweight women with type 2 diabetes was associated with a reduction in central adiposity and improvement in lipid metabolism and glycemic control without deterioration in weight status or cardiovascular parameters measured. Whether HRT-induced improvements in these cardiovascular risk factors result in lower long-term cardiovascular morbidity and mortality, as observed in nondiabetic women, awaits further study.

Abdomen↗