The effect of a 12-week low glycaemic index diet on heart disease risk factors and 24 h glycaemic response in healthy middle-aged volunteers at risk of heart disease: a pilot study.

OBJECTIVE: To compare the effects of two energy-restricted healthy diets, one with a low GI and one with a high GI, on heart disease risk factors and weight loss in subjects at risk of heart disease. DESIGN: A 12-week randomized parallel study of low and high GI, healthy eating diets was carried out. SETTING: The study was carried out at the Hammersmith Hospital. SUBJECTS: Eighteen subjects were recruited by advertisement and randomized to one of the two diets. Fourteen completed the study but one was excluded from the final analysis. METHODS: At randomization, subjects were advised to follow the intervention diet for 12 weeks. Before randomization and on completion of the study, anthropometrics, fasting cholesterol and glucose blood tests and 24-h glucose measurements were taken using a continuous glucose monitoring system (CGMS). Statistical analysis was carried out using non-parametric tests. Median (IQR) are presented. RESULTS: A significantly different dietary GI was achieved in the low GI (median: 51.3 (IQR: 51.0-52.0) compared to the high GI (59.3 (59.2-64.0) (P=0.032) group. By week 12, both groups reduced their energy intake by: low GI group: (-)167 ((-)312-(-)123) kcal/day (P=0018) vs high GI group: (-)596 ((-)625-(-)516) (P=0.018) kcal/day, the difference between the groups being significant (P=0.010). However, only the low GI group lost weight ((-)4.0 ((-)4.4-(-)2.4) kg (P=0.018) whereas the high GI group did not significantly change in weight ((-)1.5 ((-)3.6-0.8) kg (P=0.463). By week 12, the low GI group also had a significantly lower 24-h area under the curve (AUC) (7556 (7315-8434) vs 8841 (8424-8846) mmol-h/l (P=0.045) and overnight AUC (2429 (2423-2714) vs 3000 (2805-3072) mmol-h/l (P=0.006) glucose as measured by CGMS. There were no differences in the other heart disease risk factors assessed. CONCLUSIONS: This pilot study provides some evidence that consuming a low GI diet in addition to weight loss and healthy eating may reduce cardiovascular risk. Other potential benefits of GI might have been masked by weight loss in the low GI group. Larger-scale studies need to follow.

Ghrelin enhances appetite and increases food intake in humans.

Ghrelin is a recently identified endogenous ligand for the growth hormone secretagogue receptor. It is synthesized predominantly in the stomach and found in the circulation of healthy humans. Ghrelin has been shown to promote increased food intake, weight gain and adiposity in rodents. The effect of ghrelin on appetite and food intake in man has not been determined. We investigated the effects of intravenous ghrelin (5.0 pmol/kg/min) or saline infusion on appetite and food intake in a randomised double-blind cross-over study in nine healthy volunteers. There was a clear-cut increase in energy consumed by every individual from a free-choice buffet (mean increase 28 +/- 3.9%, p<0.001) during ghrelin compared with saline infusion. Visual analogue scores for appetite were greater during ghrelin compared to saline infusion. Ghrelin had no effect on gastric emptying as assessed by the paracetamol absorption test. Ghrelin is the first circulating hormone demonstrated to stimulate food intake in man. Endogenous ghrelin is a potentially important new regulator of the complex systems controlling food intake and body weight.

Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: evidence for novel influences on body fat distribution.

Visceral obesity is detrimental to health, but the mechanisms controlling body fat distribution are not fully understood. In premenopausal adult females (30 nonobese, 14 obese [body mass index >30 kg/m(2)]), variance in fasting insulin, glucose, insulin/glucose ratio, C-peptide/insulin ratio, triglycerides, and high-density lipoprotein/low-density lipoprotein-cholesterol ratio, were independently influenced by visceral but not total sc or abdominal sc adipose tissue, as measured by whole-body magnetic resonance imaging. Adult females with Prader-Willi syndrome (n = 13) had significantly reduced visceral adiposity, compared with obese controls (visceral/total sc adipose tissue ratio: 0.067 +/- 0.017 vs. 0.108 +/- 0.021), independent of their total adiposity (P < 0.001), or use of exogenous sex steroids. This is in contrast to that expected by their physical inactivity, hypogonadism, adult GH deficiency, and psychiatric problems. Females with Prader-Willi syndrome not receiving sex steroids (n = 8) had significantly reduced fasting insulin, insulin/glucose ratio, and triglycerides and increased C-peptide/insulin ratio, compared with obese controls, adjusting for total (P < 0.05) but not visceral adiposity (P = 0.3-0.6), supporting their association. The cause of the reduced visceral adiposity in Prader-Willi syndrome may reflect novel hormonal, hypothalamic, and/or genetic influences on body fat distribution.

Diet-induced change in fatty acid composition of plasma triacylglycerols is not associated with change in glucagon-like peptide 1 or insulin sensitivity in people with type 2 diabetes.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) have been shown to positively affect blood lipids; however, their comparative effects on insulin sensitivity are unclear. OBJECTIVE: Our objective was to investigate whether chronic intake of MUFAs or PUFAs improves insulin sensitivity in people with type 2 diabetes via stimulation of the endogenous gut hormone glucagon-like peptide 1 [7-36] amide (GLP-1). DESIGN: Nine overweight people with type 2 diabetes received isoenergetic high-MUFA (20.3 +/- 3.5% of total energy) or high-PUFA (13.4 +/- 1. 3%) diets for 24 d in a randomized, double-blind crossover design. RESULTS: Weight and glycemic control remained stable throughout the study. Despite a significant change in the plasma triacylglycerol linoleic-oleic acid ratio (L:O) with both diets (MUFA: from 0.46 +/- 0.03 to 0.29 +/- 0.02, P: < 0.005; PUFA: from 0.36 +/- 0.04 to 0.56 +/- 0.05, P: < 0.05) and the phospholipid L:O (1.7 +/- 0.1 to 2.0 +/- 0.3; P: = 0.04) during consumption of the PUFA diet, this change was not associated with a change in insulin sensitivity, measured by the short-insulin-tolerance test. There was a significant reduction in the ratio of total to HDL cholesterol during consumption of the PUFA diet (5.2 +/- 0.4 compared with 4.7 +/- 0.3; P: = 0.005) but no change with the MUFA diet. There was no change in the fasting or postprandial incremental area under the curve in response to an identical standard test meal for glucose, insulin, triacylglycerol, nonesterified fatty acids, or GLP-1. CONCLUSIONS: Over the 3-wk intervention period, diet-induced change in the triacylglycerol or phospholipid L:O was not associated with either increased stimulation of GLP-1 or a change in insulin sensitivity in people with type 2 diabetes.

A prospective randomised trial to determine the efficacy of a low glycaemic index diet given in addition to healthy eating and weight loss advice in patients with coronary heart disease.

OBJECTIVE: Recent epidemiological and prospective trial evidence suggests that consumption of a low glycaemic index (LGI) diet will reduce coronary risk. We hypothesise that introduction of an LGI diet will improve the metabolic profile of patients who have undergone coronary artery bypass grafting. DESIGN: We conducted a randomised parallel group trial comparing a control group (n=29, age 61.8+/-9 y), who received currently advocated healthy eating dietary advice only, to an intervention group, who received healthy eating advice emphasising LGI carbohydrates (n=26, age 63.6+/-9.4 y) over a 12-week period in free-living patients with coronary heart disease. Outcome measures included fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. RESULTS: A significant lower dietary glycaemic index was achieved in the group assigned to an LGI diet compared to the healthy eating control group (71+/-1 vs 81+/-1); fibre intake was also higher in the LGI group (20+/-1 vs 15+/-1 g). All biochemical markers of glucose and lipid metabolism measured were similar after 12 weeks of the LGI diet or control diet. DISCUSSION: The LGI group achieved a significant LGI and a higher dietary fibre intake. However, there was no measurable significant effect of either the LGI diet or the health eating diet on lipid levels; this may have been hidden by concurrent drug therapy.

The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal.

OBJECTIVE: To assess whether the addition of viscous fiber at an amount recommended by the US FDA to allow a 'low saturated fat, cholesterol, soluble fiber and coronary heart disease', health claim label on a food package (1.7 g psyllium) and/or fat (30 g sunflower oil and 3 g sodium propionate) to a pasta meal would affect gastric emptying, postprandial glucose, insulin and GLP-1 concentrations. DESIGN: Ten subjects participated in a two-by-two single blind randomized crossover study. Four meals containing 50 g of available carbohydrate were consumed: pasta with or without psyllium enrichment served with a tomato sauce with (520 kcal per meal) and without (240 kcal per meal) fat. Blood samples were taken for 240 min following the meal and all subjects consumed a buffet meal at the end of the study. Gastric emptying was measured using the paracetamol absorption test. Blood was analysed for glucose, insulin, GLP-1. Visual analog scales were used to record feelings of hunger, pleasantness and nausea. RESULTS: The psyllium-enriched pasta had no significant effect on gastric emptying or the incremental area under the curve (IAUC) for GLP-1, insulin or glucose compared with the control pasta. The addition of polyunsaturated fat and sodium propionate significantly increased the IAUC for GLP-1 (P<0.001), delaying gastric emptying (P<0.002), and decreasing glucose (P<0.002). CONCLUSIONS: A dose of 1.7 g psyllium did not evoke measurable effects on gastric emptying, postprandial GLP-1, insulin or glucose metabolism. However the addition of 30 g of oil and 3 g of sodium propionate to the pasta did reduce gastric emptying, increase GLP-1 and reduce glucose and insulin concentrations. While this short-term study may have implications in terms of reducing the risk of diabetes and improving coronary risk factor profiles the long term effects of these nutrients need to be studied.

Plasma glucagon-like peptide-1 (7-36) amide (GLP-1) response to liquid phase, solid phase, and meals of differing lipid composition.

The gut hormone glucagon-like peptide-1 (7-36) amide (GLP-1) is a potent insulin secretagogue. It has been proposed to be a novel treatment for non-insulin-dependent diabetes mellitus (NIDDM). Postprandial plasma GLP-1, insulin, and glucose responses were measured in six healthy volunteers in response to a solid test meal and a liquid meal of identical composition. Responses to three isocaloric soups of identical macronutrient and energy content containing differing degrees of fat saturation were also measured. The liquid form of the meal released significantly more GLP-1 than the solid form (measured by incremental area under the curve 0-180 min: 2.5 nmol.min-1.L-1 [median]; range 1.4-3.7 versus 1.4 nmol.min-1.L-1 [median]; range 0.6-1.8) (P < 0.05) and this occurred earlier (15 min versus 60 min). The incremental area under the curve for insulin was significantly greater following the liquid meal (incremental area under the curve 0-180 min: 18.5 nmol.min-1.L-1 [median]; range 15.9-35.8 versus 17.6 nmol.min-1.L-1 [median]; range 13.7-25.5) (P < 0.05). The glucose response to each meal was not different. The type of fat in the soups produced no significant difference in GLP-1, insulin, or glucose levels. Our findings suggest that the physical form of a meal significantly alters the GLP-1 response, whereas fatty acid saturation has little effect.

Preferential loss of visceral fat following aerobic exercise, measured by magnetic resonance imaging.

The aim of this study was to use whole-body magnetic resonance imaging (MRI) together with biochemical and anthropometric measurements to study the influence of regular moderate exercise with no dietary intervention on adipose tissue distribution in nonobese healthy women. We found significant decreases in both total (28.86+/-2.24 vs. 27.00+/-2.27 liters, P < 0.05) and regional fat depots (visceral fat: 1.68+/-0.21 vs. 1.26+/-0.18 liters, P < 0.01) using whole-body MRI despite no significant change in body weight, body mass index, or the waist-to-hip ratio. Interestingly, no changes in body fat content were found using anthropometry or impedance. There was a significant increase in high density lipoprotein cholesterol (1.58+/-0.06 vs. 1.66+/-0.08 mmol/L P < 0.02) following exercise although there were no changes in other blood lipids such as triglycerides. In summary, moderate aerobic exercise over a period of 6 mon resulted in a preferential loss in visceral fat in nonobese healthy women, and this may help to explain some of the health benefits associated with regular and moderate physical activity.

Vulnerable patients with a fractured neck of femur: nutritional status and support in hospital.

BACKGROUND AND AIM: Malnutrition has serious consequences for recovery and increases the risk of complications in hospital patients. Fractured neck of femur (NOF) patients may be particularly at risk because of their old age and frail state of health. We conducted an observational study to evaluate the nutritional state and the nutritional support, which was provided to this group during their stay in hospital. METHODS: Twenty-five consecutive people admitted to an orthopaedic ward with a fractured NOF at Charing Cross Hospital, London were recruited. Anthropometric measures, biochemical indices, 3 days dietary intake and dietetic referral rates were collected. RESULTS: Patients had a significantly lower body mass index (BMI) compared with the mean BMI for sex and age in an elderly UK population (21.97 +/- 1.06 versus 26.73 +/- 0.03 kg m(-2); P < 0.005). They took just 58.6% of their energy requirements in hospital (4219 +/- 319 versus 7199 +/- 202 kJ mean(-1) daily intake over 3 days in week 2). Using the hospitals own nutritional risk assessment tool 56% of patients were found to be at risk of malnutrition on admission, which increased to 68% after 2-3 weeks. Of these 64% were referred to a dietitian and were given nutritional supplements. Nutritional assessment revealed that their nutritional status worsened during stay. CONCLUSIONS: This group of patients with fractured NOF is likely to be malnourished on admission and to show a rapid deterioration in its nutrition status during admission. Energy needs were not met in up to 50% of patients. These results reinforce the need to screen, supplement and monitor fractured NOF patients.

Treating obesity: a follow-up study. Can the stages of change model be used as a postal screening tool?

AIMS: We have previously shown that although a postal questionnaire based on the stages of change model (SCQ) failed to distinguish outpatients most likely to lose weight, it appeared to influence attendance rates. We therefore audited attendance upon receiving a pre-appointment SCQ in the post and compared this to previous standard practice in 1996. METHODOLOGY AND RESULTS: Seventy-eight obese outpatients (BMI 36.7 +/- 6.7 kg m-2, age 43 +/- 15 years) (mean +/- SD) were included. Twenty-nine per cent of patients failed to return an SCQ and were not sent an appointment and therefore did not block dietetic time. Eleven per cent returned an SCQ but did not attend (DNA) visit 1, whilst 21% attended visit 1 but DNA visit 2. Thirty-nine per cent attended both appointments and lost a significant amount of weight (105 +/- 23 vs. 103.2 +/- 23 kg, P < 0.0001) in 4 weeks. There was no difference in SCQ results between groups. Overall attendance rate at initial and follow-up appointments increased by 11%, while DNA rates fell by 20% compared with the 1996 audit. CONCLUSION: The SCQ has sifted out one in four patients who previously DNA an initial dietetic outpatient appointment. This has reduced waiting-list time as appointments are only book on return on the SCQ form, increased effective use of dietetic time through increased attendance rates, and lowered the DNA rate of follow-up appointments.

Proglucagon-derived peptides in intestinal epithelial proliferation: glucagon-like peptide-2 is a major mediator of intestinal epithelial proliferation in rats.

Proglucagon-derived peptides have been implicated in the control of intestinal mucosal cell division. To investigate the actions of these peptides on intestinal cell proliferation, different doses of enteroglucagon, oxyntomodulin, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were tested in male Wistar rats maintained on total parenteral nutrition. Crypt cell proliferation was assessed by the analysis of arrested metaphases in microdissected crypts. Enteroglucagon and oxyntomodulin had no effect on intestinal weight or cell proliferation. GLP-1 had a slight effect on stomach and small intestinal weights and on epithelial cell proliferation in the small and large intestines. GLP-2 infusion dose-dependently increased the weights of the stomach, small intestine, colon, and cecum and increased crypt cell proliferation in the small and large intestines of parenterally fed rats. In orally fed animals, GLP-2 increased intestinal weight but had little effect on proliferation. Therefore, of the proglucagon-derived peptides, GLP-2 appears to be a major mediator of intestinal epithelial proliferation.

Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers.

Exendin-4 is a long-acting potent agonist of the glucagon-like peptide 1 (GLP-1) receptor and may be useful in the treatment of type 2 diabetes and obesity. We examined the effects of an intravenous infusion of exendin-4 (0.05 pmol. kg(-1). min(-1)) compared with a control saline infusion in healthy volunteers. Exendin-4 reduced fasting plasma glucose levels and reduced the peak change of postprandial glucose from baseline (exendin-4, 1.5 +/- 0.3 vs. saline, 2.2 +/- 0.3 mmol/l, P < 0.05). Gastric emptying was delayed, as measured by the paracetamol absorption method. Volunteers consumed 19% fewer calories at a free-choice buffet lunch with exendin-4 (exendin-4, 867 +/- 79 vs. saline 1,075 +/- 93 kcal, P = 0.012), without reported side effects. Thus our results are in accord with the possibility that exendin-4 may be a potential treatment for type 2 diabetes, particularly for obese patients, because it acts to reduce plasma glucose at least partly by a delay in gastric emptying, as well as by reducing calorie intake.