Lesley V. Campbell
Garvan Institute of Medical Research
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Featured researches published by Lesley V. Campbell.
The New England Journal of Medicine | 1993
Mark Borkman; Leonard H Storlien; David A. Pan; Arthur Jenkins; Donald J. Chisholm; Lesley V. Campbell
BACKGROUND Insulin resistance and hyperinsulinemia are features of obesity, non-insulin-dependent diabetes mellitus, and other disorders. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty-acid composition of the phospholipids within the muscle membranes involved in the action of insulin. METHODS We determined the relation between the fatty-acid composition of skeletal-muscle phospholipids and insulin sensitivity in two groups of subjects. In one study, we obtained samples of the rectus abdominis muscle from 27 patients undergoing coronary artery surgery; fasting serum insulin levels provided an index of insulin sensitivity. In the second study, a biopsy of the vastus lateralis muscle was performed in 13 normal men, and insulin sensitivity was assessed by euglycemic-clamp studies. RESULTS In the patients undergoing surgery, the fasting serum insulin concentration (a measure of insulin resistance) was negatively correlated with the percentage of individual long-chain polyunsaturated fatty acids in the phospholipid fraction of muscle, particularly arachidonic acid (r = -0.63, P < 0.001); the total percentage of C20-22 polyunsaturated fatty acids (r = -0.68, P < 0.001); the average degree of fatty-acid unsaturation (r = -0.61, P < 0.001); and the ratio of the percentage of C20:4 n-6 fatty acids to the percentage of C20:3 n-6 fatty acids (r = -0.55, P < 0.01), an index of fatty-acid desaturase activity. In the normal men, insulin sensitivity was positively correlated with the percentage of arachidonic acid in muscle (r = 0.76, P < 0.01), the total percentage of C20-22 polyunsaturated fatty acids (r = 0.76, P < 0.01), the average degree of fatty-acid unsaturation (r = 0.62, P < 0.05), and the ratio of C20:4 n-6 to C20:3 n-6 (rho = 0.76, P = 0.007). CONCLUSIONS Decreased insulin sensitivity is associated with decreased concentrations of polyunsaturated fatty acids in skeletal-muscle phospholipids, raising the possibility that changes in the fatty-acid composition of muscles modulate the action of insulin.
Diabetes | 1996
David G Carey; Arthur Jenkins; Lesley V. Campbell; Judith Freund; Donald J. Chisholm
Insulin resistance appears to be central to obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) obesity, in nonobese women, the relationship between abdominal fat and insulin resistance is unknown. By measuring regional adiposity with dual-energy X-ray absorptiometry and insulin sensitivity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean ± SE body BMI of 26.7 ± 0.9 kg/m2 and differing risk factors for NIDDM, we found a strong negative relationship between central abdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-body insulin sensitivity (r = −0.89, P < 0.0001) and nonoxidative glucose disposal (r = −0.77, P < 0.001), independent of total adiposity, family history of NIDDM, and past gestational diabetes. There was a large variation in insulin sensitivity, with a similar variation in central fat, even in those whose BMI was <25 kg/m2. Abdominal fat had a significantly stronger relationship with insulin sensitivity than peripheral nonabdominal fat (r2 = 0.79 vs. 0.44), and higher levels were associated with increased fasting nonesterified fatty acids, lipid oxidation, and hepatic glucose output. Because 79% of the variance in insulin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.
Diabetologia | 1996
L. H. Storlien; Louise A. Baur; A. D. Kriketos; D. A. Pan; Gregory J. Cooney; Arthur Jenkins; G. D. Calvert; Lesley V. Campbell
The history of research into the relationship between dietary fat intake and impaired insulin action has its origin in the work of Himsworth approximately 60 years ago [1, 2]. In a series of pioneering studies using crude indices of insulin action and limited subject numbers (only one in an often quoted paper!), Himsworth linked high levels of fat intake with insulin resistance, and conversely, improved insulin action with predominantly carbohydrate diet. However, the link was tenuous and really apparent only at the extreme ends of the dietary spectrum (<20 or > 80 % of calories as fat). These studies, flawed as they were, influenced the field enormously in the absence of any significant work in the area for a remarkable period of time. The conclusions reached by Himsworth were reinforced to some extent by misuse of glucose tolerance data that showed deteriorations following periods on diets extremely low in carbohydrate (< 50 g/day) and improvement on liquid formula diets providing a remarkably high percentage (75-85 %) of calories from carbohydrate [3-5]. It was really not until the 1980 s that the development of acceptable techniques for the measurement of insulin action in vivo allowed the relationship between dietary fat intake and insulin action to be accurately assessed. These studies have essentially been confined to investigations in rodents and humans.
Obesity Reviews | 2011
Evelyn Smith; Phillipa Hay; Lesley V. Campbell; Julian N. Trollor
Recent research suggests that increased adiposity is associated with poor cognitive performance, independently of associated medical conditions. The evidence regarding this relationship is examined in this review article. A relatively consistent finding across the lifespan is that obesity is associated with cognitive deficits, especially in executive function, in children, adolescents and adults. However, as illustrated by contradictory studies, the relationship between obesity and cognition is uncertain in the elderly, partly because of inaccuracy of body mass index as a measure of adiposity as body composition changes with aging. This review further discusses whether obesity is a cause or a consequence of these cognitive deficits, acknowledging the possible bidirectional relationship. The possible effects of increased adiposity on the brain are summarized. Our investigations suggest that weight gain results, at least in part, from a neurological predisposition characterized by reduced executive function, and in turn obesity itself has a compounding negative impact on the brain via mechanisms currently attributed to low‐grade systemic inflammation, elevated lipids and/or insulin resistance. The possible role of cognitive remediation treatment strategies to prevent and/or treat obesity is discussed.
Circulation | 2004
Jerry R. Greenfield; Katherine Samaras; Arthur Jenkins; Paul J. Kelly; Tim D. Spector; J. Ruth Gallimore; Mark B. Pepys; Lesley V. Campbell
Background—C-reactive protein (CRP) values predict atherothrombotic cardiovascular disease and type 2 diabetes mellitus. Associations between CRP and obesity, predominantly assessed anthropometrically, may partly explain these observations. Previous studies have been unable to control for genetic influences on CRP and obesity. The aim of this study was to examine the relationship between CRP and accurately measured body fat, lipids, apolipoproteins, blood pressure, and environmental and behavioral factors, independent of genetic influences. Methods and Results—One hundred ninety-four healthy female twins (age 57.2±7 years) were studied after excluding pairs with CRP values >10 mg/L. Total body fat and central abdominal fat (CAF) were measured by dual-energy x-ray absorptiometry. CRP concentration was strongly related to surrogate and direct measures of body fat (r =0.31 to 0.54, P <0.001), diastolic blood pressure (r =0.20, P =0.003), and lipid and apolipoprotein levels (r =0.21 to 0.51, P <0.008). Light-to-moderate alcohol consumers and nonusers of hormone replacement therapy (HRT) had lower CRP levels than abstainers and HRT users, respectively. In stepwise multiple regression analysis, CAF, triglycerides, apolipoprotein B, and HRT use explained 46% of the variance in circulating CRP. In analyses controlling for genetic influences in monozygotic twins, within-pair differences in CRP were associated with within-pair differences in total body fat (r =0.39, P <0.001), CAF (r =0.34, P =0.002), diastolic blood pressure (r =0.24, P =0.03), apolipoprotein AI (r =−0.33, P =0.01), HDL cholesterol (r =−0.42, P =0.001), and triglycerides (r =0.35, P =0.007). Conclusions—CRP was strongly related to total and central abdominal obesity, blood pressure, and lipid levels, independent of genetic influences. These relationships are likely to contribute significantly to prospective associations between CRP and type 2 diabetes and coronary events.
Diabetes Care | 1998
Tania P. Markovic; Arthur Jenkins; Lesley V. Campbell; Stuart M. Furler; Edward W. Kraegen; Donald J. Chisholm
OBJECTIVE To examine the mechanisms by which weight loss improves glycemic control in overweight subjects with NIDDM, particularly the relationships between energy restriction, improvement in insulin sensitivity, andregional and overall adipose tissue loss. RESEARCH DESIGN AND METHODS Hyperinsulinemic glucose clamps wereperformed in 20 subjects (BMI = 32.0 ± 0.5 [SEM] kg/m2, age = 48.4 ± 2.7 years) with normal glucose tolerance (NGT) (n = 10) or mild NIDDM (n = 10) before and on the 4th (d4) and 28th (d28) days of a reduced-energy (1,100 ± 250 [SD] kcal/day) formula diet. Body composition changes were assessed by dual energy x-ray absorptiometry and insulin secretory changes were measured by insulin response to intravenous glucose before and after weight loss. RESULTS In both groups, energy restriction (d4) reduced fasting plasma glucose (FPG) (ΔFPG: NGT = −0.4 ± 0.2 mmol/1 and NIDDM = −1.1 ± 0.03 mmol/1, P = 0.002), which was independently related to reduced carbohydrate intake (partial r = 0.64, P = 0.003). There was a marked d4 increase in percent of insulin suppression of hepatic glucose output(HGO) in both groups (ΔHGO suppression: NGT = 28 ± 15% and NIDDM = 32 ± 8%, P = 0.002). By d28, with 6.3 ± 0.4 kg weight loss, FPG was further reduced (d4 vs. d28) in NIDDM only (P = 0.05), and insulin sensitivity increased in both groups (P = 0.02). Only loss of abdominal fat related to improvements in FPG (r = 0.51, P = 0.03) and insulin sensitivity afterweight loss (r = 0.48, P = 0.05). In contrast to insulin action, there were only small changes in insulin secretion. CONCLUSIONS Both energy restriction and weight loss have beneficial effects on insulin action and glycemic control in obesity and mild NIDDM. The effect of energy restriction is related to changes in individual macronutrients, whereas weight loss effects relate to changes in abdominal fat.
Diabetic Medicine | 1991
Barth R; Lesley V. Campbell; S. Allen; J. J. Jupp; Donald J. Chisholm
Despite the established role of foot care education in diabetes management, reports evaluating such interventions are rare. The effectiveness of an intensive foot care intervention programme and a conventional one were therefore compared in Type 2 diabetes. The intensive group showed significantly greater improvements than the conventional group in foot care knowledge (p < 0.001), compliance with the recommended foot care routine (p = 0.012), and compliance with the initial advice to consult a podiatrist (other than the project podiatrist) for further treatment (p = 0.008). At the first follow‐up visit the intensive group also showed a significantly greater reduction in the number of foot problems requiring treatment than the conventional group.
Diabetes Care | 1994
Lesley V. Campbell; Priscilla E Marmot; Jenny A Dyer; Mark Borkman; L. H. Storlien
OBJECTIVE To examine the dietary preferences of and metabolic effects in patients with non-insulin-dependent diabetes mellitus (NIDDM) of a home-prepared high-monounsamrated fat (HM) diet compared with the recommended high-carbohydrate (CHO) diet. RESEARCH DESIGN AND METHODS Ten men with mild NIDDM prepared HM and high-CHO diets at home alternately and in random order for 2 weeks each with a minimum 1-week washout. Before and after each diet, 24-h urine glucose, fasting lipids, fructosamine, and 6-h profiles of glucose, insulin, and triglycerides were measured. Dietary preferences were assessed by questionnaire. RESULTS In the HM diet, patients consumed 40% of energy intake as CHO and 38% as fat (21% monounsaturated) compared with 52 and 24%, respectively, in the high-CHO diet, with equal dietary fiber content. Body weight and total energy intake were similar in both. The HM diet resulted in significantly lower 24-h urinary glucose excretion, fasting triglyceride, and mean profile glucose levels. The fructosamine levels, the fasting total, low-density lipoprotein, and high-density lipoprotein cholesterol, and the prandial triglyceride concentrations did not differ significantly as a result of the diets. The two diets did not differ in ratings for overall acceptance, taste, cost, ease of preparation, variety, or satiety. CONCLUSIONS Prepared at home, the HM diet was, in the short-term, metabolically better in some aspects than the currently recommended diet for NIDDM. It also provided a palatable alternative.
Metabolism-clinical and Experimental | 2003
Ann M. Poynten; Seng Khee Gan; Adamandia D. Kriketos; Anthony J. O’Sullivan; John Kelly; Bronwyn A. Ellis; Donald J. Chisholm; Lesley V. Campbell
Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 +/- 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by (1)H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P =.03) and nonoxidative glucose disposal (P <.01) and increased fasting NEFAs (P =.01). The decrease in GIR related significantly to the increase in fasting NEFAs (r(2) =.30, P =.03). The intrasubject increase in basal and clamp fat oxidation correlated with the decrease in GIR (r(2) =.45, P <.01 and r(2) =.63, P <.01). There were no significant changes in muscle LCACoA, TG, or IMCL content. Therefore, induction of insulin resistance by NA occurs with increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content.
International Journal of Obesity | 2003
Philip W. Peake; Adamandia D. Kriketos; Gareth Denyer; Lesley V. Campbell; John A. Charlesworth
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.