Sulphonylureas

Weight gain, in the range of 3-4 kg over the first 6-12 months of therapy is usual with drugs such as glibenclamide and chlorpropamide, as was seen in the UKPDS. Similar effects are usually seen with newer agents, such as glipizide and gliclazide, although some studies report no weight gain with glipizide, this may be because these studies were of short duration (Simonson et al., 1997 Cefalu et al., 1998). Such drugs should therefore be considered as second-line agents in obese patients with...

Cognitive restructuring

Emotional factors may have considerable impact on a person's dedication to weight change and may be a strong antecedent to overeating or abandoning activity. Negative affect and self-defeating cognitions regarding one's ability to succeed in making behavioural changes may hamper future efforts. Most obese persons have endured many unsuccessful weight loss attempts and this history can fuel maladaptive expectations of future failure if not addressed as a part of comprehensive behavioural...

Genetic basis of obesity in PCOS

Several studies have shown that PCOS is a familial disorder and various features of the syndrome may be differentially inherited (Franks et al., 1997). However, the genetic basis of the syndrome remains controversial. Since then, many studies have revealed that most women with PCOS, both obese and lean, have a degree of insulin resistance and compensatory hyperinsulinaemia, and genes involved in the secretion and action of insulin have been investigated. Molecular studies of the insulin...

Thiazolidinediones

Thiazolidinediones are a relatively new addition to the range of drugs used to treat hyperglycaemia in type 2 diabetes. They are agonists at the peroxisome proliferator activated receptor-y PPARy , a nuclear receptor found predominantly in adipose tissue, the function of which is thought to be regulation of aspects of adipocyte differentiation and adipocyte function Spiegelman, 1998 . These drugs act to sensitize tissues such as adipose tissue and muscle to insulin, via a range of effects that...

Obesity and the risk of type diabetes

Several prospective studies have documented that obesity is probably the most powerful predictor of the development type 2 diabetes Knowler et al., 1981 Colditz et al., 1990 Manson et al., 1992 . However, not every obese subject develops diabetes, i.e. obesity alone is not sufficient to cause type 2 diabetes there are other factors that considerably modify the effect of obesity on diabetes risk. For instance, it is likely that genetic susceptibility to diabetes is a necessary prerequisite for...

Fat or carbohydrate

For the majority of patients diabetic and non-diabetic who have a problem with weight maintenance, targeting fat in the diet is appropriate for the reasons outlined above. This is also the sensible option for Government to adopt as far as population targets are concerned. It must be realized, however, that high carbohydrate intakes can also lead to marked obesity and consequently increase the likelihood of the development of type 2 diabetes. Individual patient therapy may therefore differ from...

References

Adelman RD, Restaino IG, Alon US and Blowey DL 2001 Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents. J Pediatr 138 481-85. American Diabetes Association 2000 Type 2 diabetes in children and adolescents. Diabetes Care 23 381-9. Amiel S, Sherwin R, Simonson D et al. 1986 Impaired insulin action in puberty a contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 315 215-19. Andersen RE, Crespo CJ, Bartlett SJ et al. 1988...

Antiplatelet therapy

Patients with insulin resistance have high levels of circulating PAI-1, a protein that inhibits fibrinolysis. Diabetic platelets show a greater number of GP IIb IIIa receptors and increased tendency to adhesion and aggregation. Endothelial dysfunction results in reduced NO and prostaglandin I2 production with well known antiplatelet aggregation properties and increase level of the pro-aggregatory substances adenosine diphosphate and thromboxane A2 Tschoepe etal., 1990 Aronson et al., 1996 ....

Relapse prevention

The most commonly identified problem in obesity treatment is long-term maintenance of weight loss DePue et al., 1995 Foreyt and Goodrick, 1991 Perri, 1998 . A primary factor known to contribute to adherence with behaviour change strategies and maintenance of weight loss is maintaining episodic long-term contact with treatment providers and or peers Perri et al., 1984, 1986, 1987 . These follow-up contacts can be accomplished with face-to-face meetings, by telephone Lindstrom et al., 1976 , or...

Brent Van Dorsten Introduction

The alarming global increase in the prevalence of overweight and obesity is now a worldwide health epidemic Hill et al., 1995 Popkin and Doak, 1998 Wadden et al., 2002 . Obesity appears closely associated with several major health risks including hypertension, diabetes, high cholesterol, cardiovascular disease, and certain cancers Must et al., 1999 , and may shorten life expectancy in even young adults Fontaine et al., 2003 . A persistent increase in obesity prevalence has been observed in the...

Introduction

The epidemic of obesity afflicting the USA and much of the developed world represents one of the most serious threats to the health of our species. Bariatric surgery Gk baros weight, iatrikos the art of healing is a rapidly evolving branch of surgical science, which aims to induce substantial weight loss in those whose obesity places them at significant risk of developing serious health problems. For most diseases, this risk does not become acute until individuals are more than 50 per cent...

How to identify obesity genes

The ultimate goal of obesity genetics is to identify a gene defect found exclusively in obese patients producing a functional variant for example with altered or absent protein function, the so-called 'smoking gun' . The approaches that may be used in the attempt to identify such mutations depend to a large extent on what is known a priori about the function of the normal protein product. If there is knowledge that an abnormal protein product is capable of causing obesity or counteracting it ,...

Contents

1 Changing Epidemiology of Obesity - Implications for Diabetes 1 Assessment of obesity in epidemiological studies 1 The epidemiological link between obesity and diabetes 3 Factors modifying the relationship between obesity and diabetes 5 2 The Genetics of Human Obesity 13 Victor J. Lawrence and Tahseen Choudhury Why has the genetics of obesity been difficult to study 13 How much of obesity is genetic 15 Is there a major gene for obesity 17 How to identify obesity genes 18 3 Lifestyle...

Pathological causes of obesity

Genetic and endocrine abnormalities are rare causes of obesity in childhood. However, they are important to mention as many parents of obese children are convinced that their child has an underlying 'hormonal' problem and this belief can be a significant barrier to the lifestyle changes that need to be made when tackling childhood obesity. The clinical features of these genetic and endocrine disorders are highlighted in Table 12.2. Children with simple obesity tend to be tall for their age as...

Franks Et Al Hum Reprod 1997 12 2641-8

Arcaro G, et al. 1999 Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity. Int J Obes 23 936-42. Azziz R, Ehrmann D, Legro RS et al. 2001 O'Keefe M, Ghazzi MN. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 86 1626-32. Balen A 1999 . Pathogenesis of polycystic ovary syndrome - the enigma unravels Lancet 354 966-7. Barbieri RL, Makris A, Randall...

The approach to dietary prescription

The initial approach to the patient and the initial emphasis on diet and dietary alterations are of extreme importance. This may be the only advice the patient remembers, and first approaches to dietary intervention are liable to provide the best outcomes relative to both improved control and weight loss in the overweight obese diabetic. The restriction of single nutrients such as sugar, is not advised but dietary habits in general should be discussed, as well as the modification and reduction...

Carlton B Cooke

Professor of Medicine and Consultant Physician, Dept of Medicine Diabetes Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK Senior Lecturer in Paediatric Endocrinology, Dept of Endocrinology, Diabetic Home Care Unit, The Children's Hospital NHS Trust, Steelhouse Lane, Birmingham B4 6NH, UK Consultant in Clinical Biochemistry and Metabolic Medicine, The Robert Gorden University, School of Life Sciences, St. Andrew Street, Aberdeen, AB25 1HG, UK Park House Medical Centre, 61 Burton...

The Malmo feasibility study Eriksson and Lindgarde

The feasibility of diet and exercise intervention in 217 men with IGT was assessed in the Malmo feasibility study. The effect of exercise and diet was compared to a reference group with no intervention. The reference group consisted of men who themselves decided not to join the intervention programme. Thus, the groups were not assigned at random. By the end of the 5-year study period 10.6 per cent of the intervention group and 28.6 per cent of the reference group had developed diabetes. Thus,...

Development of obesityrelated type diabetes

Weight increases, particularly in the adipose tissue depots when the amount of energy calories consumed exceed energy used for exercise and metabolic processes. This is known as 'positive energy balance' and the excess is stored as white adipose tissue Frayn et al., 1995 Gregoire et al., 1998 . It terms of the development of type 2 diabetes, this is largely observed as excessive consumption of nutrients, which are high in caloric content. Both excess consumption of macronutrients such as...

The epidemiological link between obesity and diabetes

The link between obesity prevalence and rates of diabetes in different populations was demonstrated by West with an increase in the prevalence of type 2 Figure 1.1 Prevalence of obesity in the UK from 1980 to 1997 from Joint Health Surveys Unit on behalf of the Department of Health 1999. 80 90 100 110 120 Percentage standard weight mean Figure 1.2 Graph showing the relationship between the prevalence of diabetes predominantly type 2 diabetes and body weight in 10 representative populations....

Lipogenesis

Lipogenesis Lipolysis

Lipogenesis describes the process by which triglycerides circulating in the blood are hydrolysed to form NEFAs, which can be taken up by adipocytes and re-esterified in the form of intracellular triglycerides. NEFA are transported bound to albumin. However, cholesterol, triglycerides and phospholipids are transported as one of six different forms of lipoprotein complexes three of which are the very-low density lipoproteins VLDL , low-density lipoproteins LDL and high-density lipoproteins HDL ....

Ectopic fat storage fat content in obesity

Positive energy balance produces an excess of triglyceride with storage in the liver Ryysy et al., 2000 and skeletal muscle Goodpaster and Kelley, 1998 Goodpaster et al., 1997, 2000 Shulman, 2000 which is subsequently followed by insulin resistance, glucose, intolerance and diabetes. This similar effect is also observed in patients with lipodystrophy characterized by a severe reduction in adipose tissue with increased triglyceride storage in the liver and skeletal muscle Robbins et al., 1979,...

Exercise tolerance and cardiorespiratory fitness in overweight and obese adults and children

There is very little data published on the exercise tolerance of obese adults. We tested 19 obese adults 4 males and 15 females aged 40.3 13.5 years for exercise tolerance Gately et al., 1997 . Mean body mass and BMI of the group was 112.6 18.9 and 37.9 10.6 kg m, respectively. Exercise tolerance was assessed using the treadmill walking test protocol developed for the Allied Dunbar National Fitness Survey ADNFS Activity and Health Research, 1992 . Exercise tolerance was low as identified by a...

Restrictivemalabsorptive procedures

There are two types of operation that utilize a combination of restricted gastric size and a variable degree of small intestinal bypass to achieve superior weight loss. The Roux en Y gastric bypass Figure 11.3 is the most widely performed operation for weight reduction in the USA. Creating a 15-ml gastric pouch beneath the gastro-oesophageal junction induces a similar degree of gastric restriction to the VBG and laparoscopic band. However, after gastric bypass, food is separated from digestive...

Abnormalities of menstrual cycle and infertility

PCOS is the commonest cause 78 per cent of anovulatory in infertility Hull, 1987 . It was demonstrated that menstrual abnormalities are more frequent in obese than non-obese PCOS women Kiddy et al., 1990 . In addition, it was shown that a reduced incidence of pregnancy and inadequate response to pharmacological treatments to induce ovulation may be more common in obese PCOS women Galtier-Dereure et al., 1997 . Insulin resistance and accompanying hyperinsulinaemia, which can increase amount of...

Diabetes as a foregut disease

The gut secretes insulinotropic hormones called incretins which stimulate i -cell production of insulin in response to food, especially carbohydrate, entering the foregut. The principle incretins are glucagons, glucagon-like peptide-1 GLP-1 and glucose-dependant insulinotropic peptide GIP Kellum et al., 1990 Creutzfeldt and Nauck, 1992 Gutnaik et al, 1992 Holst, 1994 . Any disturbance of this 'enteroinsular axis' following surgical diversion of food into the more distal small intestine could...

Physical activity and obesity

Exercise is the most variable component of energy expenditure it is therefore clear to see why exercise has been adopted as a component to treat overweight and obesity. Indeed, exercise or physical activity is promoted within a range of guidelines for the prevention and treatment of overweight and obesity WHO, 1997 NIH, 1998 . Understanding the impact of physical activity and exercise on obesity and associated variables is important, as an increase in physical activity not only has significant...

The Diabetes Prevention Program DPP The Diabetes Prevention Program Research Group Knowler et al The Diabetes

The Diabetes Prevention Program was a multicentre randomized clinical trial carried out in the United States. It compared the efficacy and safety of three interventions an intensive lifestyle intervention, or standard lifestyle recommendations combined with metformin or placebo. The study focused on high-risk individuals n 3234 with IGT who also had slightly elevated fasting plasma glucose gt 5.5 mmol l . The original closing date of the study was planned to be in year 2002. However, the study...

Jonathan Webber John PH Wilding

Associate Specialist, Diabetes and Endocrinology, Birmingham Heartlands and Solihull NHS Trust Teaching , Birmingham, UK Department of Public Health, University of Helsinki, and Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland Department of Public Health, University of Helsinki, and Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute,...

Liquid meal replacements

Despite their historical public popularity, liquid meal replacements have received little empirical attention until the recent past. Ditschuneit et al. 1999 conducted a study in which 100 patients received nutrition consultation and random assignment for three months to either a 1200-1500 kcal day self-selected diet or an isoenergetic diet in which two meals and two snacks per day were replaced by SlimFast products. After the initial 3-month treatment period, both groups were prescribed a...

Sudhesh Kumar

Professor of Medicine, Diabetes amp Metabolism, Warwick Medical School, University of Warwick, UK Copyright 2004 John Wiley amp Sons Ltd, The Atrium, Southern Gate, Chichester, Email for orders and customer service enquiries cs-books wiley.co.uk Visit our Home Page on www.wileyeurope.com or www.wiley.com All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording,...