Weight loss for individuals with type 2 diabetes following a very-low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese. Weight loss produces numerous benefits in T2DM. People with T2DM have difficulty losing and maintaining weight. WHAT THIS STUDY ADDS: Provision of a very-low-calorie diet (VLCD) with group support and behaviour therapy for patients with T2DM is feasible within a community-based setting with trained facilitators. VLCD approaches for weight management in T2DM can achieve more than 90% of weight loss as compared with obese individuals without T2DM. Identification of the need to investigate the full impact of this approach in patients with T2DM by assessing changes in glycaemia, liver function and medication. Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese, and obesity compounds the cardiovascular risk of T2DM. The aim of this retrospective study was twofold: first, to investigate whether a 12-week community-based very-low-calorie diet (VLCD) programme can result in important weight loss; and second, to investigate any potential difference in the weight loss achieved using this community-based approach in individuals with and without T2DM. Three hundred and fifty-five participants with T2DM were matched for age, body mass index (BMI) and gender to participants without T2DM (total cohort comprised 204 males: 506 females (mean ± standard deviation); age (years) 54.0 ± 9.1; BMI (kg m(-2) ) 41.6 ± 8.1; weight (kg) 116.1 ± 25.1). The programme included a daily intake of 550 kcal in addition to group support and behaviour therapy provided by trained facilitators within a community-based setting. After 12 weeks, there was significant weight loss within each group when compared with baseline (T2DM: 115.0 ± 24.4 kg vs. 96.7 ± 21.4 kg, P < 0.0001; non-T2DM: 117.2 ± 25.8 kg vs. 97.3 ± 22.2 kg, P < 0.0001). At 12 weeks, weight change (-18.3 ± 7.3 kg vs. -19.9 ± 7.0 kg, P = 0.012) and BMI change (-6.7 ± 2.9 kg m(-2) vs. -7.1 ± 2.1 kg m(-2) , P = 0.011) were significantly less in the T2DM group when compared with the non-T2DM group. Our results suggest that the use of VLCD approaches for weight management in T2DM can achieve more than 90% of the weight loss seen in obese individuals without T2DM.

The effect of birth weight on clottable and intact fibrinogen levels: a twin study.

Several studies in singletons have found an association between low birth weight and increased plasma concentrations of clotting factors in adult life. Twins provide an opportunity to assess the possible contribution of genetic factors to this association. Forty-four monozygotic and 60 dizygotic same-sex twin pairs aged 19-50 years and 78 singleton controls matched for age, gestational age, gender, maternal age and parity were recruited from an obstetric database. Associations between both adult clottable fibrinogen (measured by the Clauss method) and intact fibrinogen (measured by the immunoprecipitation test), and birth weight were assessed by linear regression with adjustment for current age, gender, smoking and body mass index. Twins were significantly lighter at birth than singleton controls, but did not differ significantly in adult height, weight or fibrinogen levels from the singleton controls. There was a significant inverse association between birth weight and clottable fibrinogen levels among singleton controls [-0.22 g L(-1) kg(-1) (95% CI: -0.41,-0.03), P = 0.03], but not in unpaired twins. For intact fibrinogen there was no significant association with birth weight in either singleton controls or twins. In the within-pair analysis in twins there was a significant inverse association between differences in birth weight and clottable fibrinogen levels in dizygotic twin pairs [-0.34 g L(-1) kg(-1) (95% CI: -0.65,-0.02), P = 0.04], but not in monozygotic twin pairs [-0.12 g L(-1) kg(-1) (95% CI: -0.53, 0.28), P = 0.54]. These results support the possibility that genetic factors may contribute to the association between low birth weight and clottable fibrinogen levels.

Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: UK Multimorbidity Study.

The potential effect of orlistat on cardiovascular co-morbidities may have been previously underestimated. This study assesses the efficacy of orlistat therapy for weight loss and cardiovascular risk factor reduction in obese patients with cardiovascular risk. This was a 54-week, double-blind, randomised, placebo-controlled, parallel group study with 531 patients being randomised. Mean weight loss was significantly greater with orlistat than with placebo (5.8% vs 2.3%; p<0.0001). Orlistat was also associated with significantly greater improvements than placebo in diastolic BP (-5.5 vs -3.1 mmHg; p<0.01), systolic blood pressure (-6.0 vs -2.3 mmHg; p<0.01), oral glucose tolerance test (-0.37 vs +0.09 mmol/l; p<0.05), fasting glucose (-0.19 vs +0.06 mmol/l; p<0.05), total cholesterol (-1.31% vs +3.78%; p<0.0001), LDL-cholesterol (-7.09% vs -0.55%; p<0.0001) and waist circumference (-5.99 vs -2.60 cm; p<0.0001). Orlistat was well tolerated. Orlistat weight loss is associated with improvements in cardiovascular co-morbidities, and hence cardiovascular risk.

Effects of smoking and abstention from smoking on fibrinogen synthesis in humans.

Cigarette smoking and hyperfibrinogenaemia are both significant risk factors for the development of cardiovascular disease. Two studies are described here which aimed to establish the metabolic mechanism responsible for the raised plasma fibrinogen concentration observed in smokers. Chronic smokers had a significantly elevated absolute rate of fibrinogen synthesis (ASR) compared with non-smokers (22.7 +/- 1.3 mg/kg per day versus 16.0 +/- 1.3 mg/kg per day; means +/- S.E.M., P < 0.01), with plasma levels of fibrinogen significantly correlated with fibrinogen synthesis (r = 0.65, P = 0.04). Unlike fibrinogen, plasma albumin concentrations were lower in smokers than in non-smokers (45 +/- 0.4 versus 47 +/- 0.7 g/l, P < 0.05), but there was no difference in rates of albumin synthesis between the two groups. Two weeks cessation from smoking by previously chronic smokers was associated with a rapid and marked fall in plasma fibrinogen concentration (from 3.06 +/- 0.11 g/l to 2.49 +/- 0.14 g/l, P < 0.001), and a significant reduction in ASR (a 33% reduction, from 24.1 +/- 1.7 to 16.1 +/- 1.0 mg/kg per day, P < 0.001). These studies suggest a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking. Moreover, abstention from smoking for a period of only 2 weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration.

An in vitro model of angiogenesis: basic features.

This report describes a model of angiogenesis which develops in admixtures (co-cultures) of human umbilical vein endothelial cells (HUVEC) and human diploid fibroblasts of dermal origin from adult patients. The system does not require the addition of further growth factors other than those normally present in endothelial growth medium (EGM), nor matrix proteins, and cell growth and proliferation are allowed to occur in a standard low (2%) concentration of fetal calf serum. Angiogenesis was specifically stimulated in response to vascular endothelial growth factor (VEGF), resulting in an increased development of structures resembling a microvasculature bed. Alternatively, angiogenesis was inhibited by addition of an excess of neutralising anti-VEGF antibodies, and the anti-angiogenic drugs such as suramin. We briefly show that stimulatory and inhibitory activities can be easily and quickly quantified by image analysis. Tubule formation was confirmed by confocal and electron microscopy, and the development and disposition of these structures within the co-cultures has been analysed immunochemically to show expression of specific endothelial cell determinants, such as PECAM-1. On this and a number of other criteria, the findings validate this in vitro process as a model of in vivo angiogenesis that can be quantified to assay stimulatory and inhibitory agents, signals and drugs.