Dr TAREK NASRALA

• Adipose tissue is divided into two subtypes, white and brown fat. White fat is widely distributed and it represents the primary site of fat metabolism and storage, whereas brown fat is relatively scarce and its main role is to provide body heat, which is essential for newborn babies.

• White adipose tissue is the major energy reserve and its primary function is to store triacylglycerol (TG) in periods of energy excess and to release energy in the form of free fatty acids during energy deprivation

• Adipocytes secrete various factors known to play a role in immunological responses, vascular diseases and appetite regulation

• Leptine is a peptide hormone primarily made and secreted by mature adipocytes, and it has various biological activities, including effects on appetite, food intake and body weight regulation, fertility, reproduction and hematopoiesis.

• Adipose tissue is an important site for estrogen biosynthesis and steroid hormone storage.

• In addition, adipose tissue secretes a variety of peptides, cytokines and complement factors, which act in an autocrine and paracrine manner to regulate adipocyte metabolism and growth, as well as endocrine signals to regulate energy homeostasis.

• Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have a negative effect on health, leading to reduced life expectancy and/or increased health problems

• appetite can be considered as an expression of numerous regulatory processes.

• These processes not only determine the initiation and termination of meals, but also the amount and types of foods consumed, meal length and frequency, and the duration of between-meal intervals

• The Problem

• Diet and physical inactivity are second only to tobacco use in leading causes of death in the US, and the number of deaths related to poor diet and physical inactivity continues to increase

Obesity Co-morbid conditions with high

absolute risk for mortality

• • Metabolic Syndrome

• • Established coronary heart disease

• • Type 2 diabetes

• • Sleep apnea

Conditions exacerbated by obesity

• • Osteoarthritis

• • Gallstones

• • Stress incontinence

• • Gynecological conditions such as amenorrhea and menorrhagia

• • Asthma

Medications that affect weight

• If possible, change medications that can cause weight gain or increased appetite to those that do not promote weight gain. The following may contribute to weight gain:

• • Some antidepressants • • Antipsychotic agents • • Lithium • • Glucocorticoids

• • Progestational hormones

• • Cyproheptadine and possibly other antihistamines

• • Antidiabetes agents: sulfonylureas, thiazolidinediones, insulin

• (Metformin, which increases insulin sensitivity, can decrease appetite slightly.)

• • Antihypertensive agents: beta- and alpha-1 adrenergic receptor blocker

Diet history• The diet history should include what, when and

how much: • • Meals and snacking patterns (number/day and

time of day) • • Portion sizes• • Saturated and trans fat from dairy products

and fatty meats, commercial snack foods and pastries, fried foods and added fats and oils

• • Refined carbohydrates from baked products, desserts, cookies and other sweets

Diet history• Fiber and protective nutrients (potassium,

magnesium and calcium) from fruits, vegetables, legumes, nuts and whole grains

• • Sweetened beverages (juice drinks, soda) and alcohol

• • Major sources of sodium from processed foods, eating out and added salt

• • Frequency of restaurant meals, fast food, take out food. Eating away from home 4 or more times/week is correlated with obesity.

• • Over-the-counter products—vitamin/mineral supplements, herbs and other dietary supplements

Physical activity

Contributes to weight loss

• o Improves lipid profile

• o Reduces blood pressure

• o Improves blood sugar and decreases insulin resistance

• o Reduces risk of cardiovascular disease and overall mortality

• Since the major cause of death in the United States and most other countries is cardiovascular disease, the approach to obesity should be designed to reduce the risks of this problem

• Obesity is a disease of energy storage whose etiology is a cumulatively greater energy intake than is needed for daily activities.

• Fat cell • The extent to which these enlarged cells

produce detrimental health consequences depends on two major factors.

• The first is the mass of fat, which leads to changes in body configuration and resulting reactions (e.g., stigma, osteoarthritis, or sleep apnea).

• The second is the location of the fat cells. The principal detrimental metabolic consequences occur when fat cells enlarge

• Increased intra-abdominal or visceral fat may accentuate this problem

• Inflammatory markers, vascular factors, and leptin from enlarged visceral fat cells causes the primary metabolic derangements, such as diabetes, atherogenic dyslipidemia (decreased HDL cholesterol and increased triglycerides), and release of inflammatory markers such as interleukin 6 (IL-6) and tumor necrosis factor a (TNF-a) or procoagulant factors such as plasminogen activator inhibitor 1 (PAI-1)

Classification and Evaluation of the Overweight Patient

CLINICAL CLASSIFICATION

Anatomy of Adipose Tissue and Fat Distribution

• Obesity is a disease and its pathology lies in the increased size and number of fat cells.

• An anatomic classification of obesity from which a pathologic classification arises is based on the number of adipocytes, on the regional distribution of body fat, or on the characteristics of localized fat deposits

Size and Number of Fat Cells• In adults, the upper limits of the total

number of normal fat cells range from 40,000,000000 to 60,000,000000

• The number of fat cells increases most rapidly during late childhood and puberty, but may increase even in adult life

• The number of fat cells can increase three to five fold when obesity occurs in childhood or adolescence.

Hypertrophic obesity• Enlarged fat cells are the pathologic sign

of obesity.• Enlarged fat cells tend to correlate with

an android or truncal fat distribution, and are often associated with metabolic disorders such as glucose intolerance, dyslipidemia, hypertension, and coronary artery disease.

• These derangements occur because large fat cells secrete more peptides and metabolites, such as IL-6, TNF-a, leptin, and PAI-1. The exception is adiponectin, whose secretion decreases as fat cells enlarges

Hypercellular obesity

• An increase in the number of fat cells usually occurs when obesity develops in childhood.

• Whether it begins in early or middle childhood

• This type of obesity tends to be severe.• Increased numbers of fat cells may also

occur in adult life, and this is to be expected when the body mass index (BMI) is >40 kg/m2

• .

Fat Distribution

Measurement

• Measuring fat distribution is important because increased visceral fat predicts the development of health risks better than total body fat.

• The preferred method is waist circumference, measured according to National Heart, Lung, and Blood Institute/North American Association for the Study of Obesity (NHLBI/NAASO) guidelines

• The subscapular skin fold has also been used to estimate central fat in epidemiologic studies, but is not clinically valuable

• The sagittal diameter, measured as the distance between the surface of the midabdominal skin and the table beneath a recumbent subject has been used as an index of central fat

• More precise estimates of visceral fat can be obtained by computed tomography (CT) or magnetic resonance imaging

• Recent studies show that waist circumference is as good as CT in estimating onset of diabetes

Lipomas and Lipodystrophy

Lipomas

• Localized fat accumulations include single lipomas, multiple lipomas, liposarcomas, and lipodystrophy.

• Lipomas vary in size from 1 cm to more than 15 cm. They can occur in any body region, and represent encapsulated accumulations of fat

• Multiple lipomatosis is an inherited disease transmitted as an autosomal dominant trait

Lipodystrophy

• Lipodystrophy is a loss of body fat in one or more regions of the body.

• It can have genetic causes or it can be acquired

• The clinical features include regional or general decrease in adipose tissue, severe insulin resistance, often with diabetes, markedly elevated triglycerides, and fatty liver

Etiologic Classification

• Neuroendocrine Obesity• Sedentary Lifestyle• Cessation of Smoking• Diet• Genetic and Congenital Disorders• Psychological and Social Factors• Socioeconomic and Ethnic Factors• Drug-Induced Weight Gain

Hypothalamic obesity• Overweight due to hypothalamic injury is rare in

humans

• These brain regions are responsible for integrating metabolic information on nutrient stores provided by leptin with afferent sensory information on food availability

• Hypothalamic overweight in humans may be caused by trauma, tumor, inflammatory disease, surgery in the posterior fossa, or increased intracranial pressure

• The symptoms usually present in one or more of three patterns:

• (i) Headache, vomiting, and diminished vision due to increased intracranial pressure;

• (ii) Impaired endocrine function affecting the reproductive system with amenorrhea or impotence, diabetes insipidus, and thyroid or adrenal insufficiency;

• (iii) Neurologic and physiologic derangements,

• including convulsions, coma, somnolence, and hypothermia or hyperthermia

• ghrelin, a peptide released from the stomach that can stimulate food intake, is decreased in overweight individuals and increased in Prader-Willi syndrome.

• In a group of 16 adolescents with hypothalamic obesity, most due to craniopharyngioma, ghrelin averaged 1345 pg/mL, which was similar to that in 16 overweight adolescents (1399 pg/mL), both of which values were significantly lower than in 16 normal-weight controls (1759 pg/mL)

Hypothyroidism

• Patients with hypothyroidism frequently gain weight because of a generalized slowing of metabolic activity.Some of this gain is fat. However, the weight gain is usually modest and marked obesity is uncommon. Hypothyroidism is common, particularly in older women. In this group, measurement of thyroid-stimulating hormone (TSH) is a valuable diagnostic tool

Cushing’s syndrome

• Obesity is one of the cardinal features of Cushing’s syndrome

• Thus the differential diagnosis of obesity from Cushing’s syndrome and pseudo-Cushing’s syndrome is clinically important for therapeutic decisions. Pseudo Cushing's is a name used for a variety of conditions that distort the dynamics of the hypothalamic-pituitary-adrenal AXIS

• Clinical Findings with Cushing’s SyndromeObesity Amenorrhea

• Asthenia• Hypertension• Virilism• Edema of lower extremities• Plethora• Hemorrhagic manifestations

• Pseudo-Cushing’s includes such things as depression, anxiety disorder, obsessive compulsive disorder, poorly controlled diabetes mellitus, and alcoholism

TEST

• urinary free cortisol, which is the initial screening test, and is considered abnormal if it is more than twice the upper limit of normal

Features of the Polycystic Ovary Syndrome

• Clinical and metabolic components of the polycystic ovary syndrome

• Menstrual abnormalities Amenorrhea or oligomenorrhea• Anovulation , Infertility , Increased risk of miscarriage• Dysfunctional bleeding• Hyperandrogenism, Hirsutism ,Seborrhea and acne • Male pattern of balding , Elevated plasma androgens• Hypothalamic-pituitary abnormalities• Increased LH or LH/FSH ratio , Increased prolactin• Metabolic abnormalities Obesity (10–80%)• Insulin resistance, even in nonobese women• Acanthosis nigricans

• Overweight appears in about half of the women and seems to exaggerate the appearance of the other features,

• Including the insulin resistance that is so characteristic of the syndrome. The insulin resistance and the overweight make diabetes a common association

• Insulin resistance is another characteristic feature of the polycystic ovarian syndrome. In the family study noted

• above, it occurred even when the individuals were not overweight, and it, too, probably reflects the influence of increased androgen on the responses of the insulin signaling system.

• For the pathophysiology of the syndrome, effective treatment might result from inhibiting androgen production or action or enhancing insulin sensitivity.

• Metformin, an insulin-sensitizing drug, improves ovulation. A similar result of reduced insulin resistance is produced by blocking androgen production with spironolactone, flutamide, or buserelin

polycystic ovary syndrome

• The diagnosis can be made if two of the following three features are present and other causes are eliminated.

• Polycystic ovaries on ultrasound examination,

• Elevated testosterone,• Chronic anovulation manifested as

prolonged menstrual periods (oligomenorrhea).

Growth hormone deficiency

• Lean body mass is decreased and fat mass is increased in adults and children who are deficient in growth hormone, compared with those who have normal growth hormone secretion. However, the increase in fat does not produce clinically significant obesity.

• Growth hormone replacement reduces body fat and visceral fat

• Treatment of acromegaly, which lowers growth hormone, increases body fat and visceral fat.

• Growth hormone selectively decreases visceral fat.

• The gradual decline in growth hormone with age may be one reason for the increase in visceral fat with age

Drug-Induced Weight Gain

• Several drugs can cause weight gain, including a variety of psychoactive agents and hormones.

• The degree of weight gain is usually limited to 10 kg or less, but occasionally patients treated with high dose corticosteroid, with psychoactive drugs, or with valproate may gain more

• The tricyclic antidepressant amitriptyline is a common culprit and may also increase the preference for carbohydrates.

• Lithium also has been implicated in weight gain.

• Two antiepileptic drugs, valproate and carbamazepine, which act on the N-methyl-D-aspartate (glutamate) receptor, cause weight gain in up to 50% of patients

• The serotonin antagonist cyproheptadine is associated with weight gain.

• Glucocorticoids cause fat accumulation on the neck and trunk, similar to that seen in patients with Cushing’s syndrome.

• These changes occur mostly in patients taking>10 mg/day of prednisone or its equivalent.

• Megestrol acetate is a progestin used in women with breast cancer and in patients with AIDS to increase appetite and induce

• weight gain. • The increase in weight is caused by fat.

• Insulin stimulates appetite, probably through intermittent hypoglycemia as the most likely mechanism.

• Weight gain occurs not only in patients with diabetes treated with insulin but also in patients treated with sulfonylureas, which enhance endogenous insulin release, and with glitazones, which act on the peroxisome proliferator–activated receptor (PPAR- ) to increase insulin sensitivity

• the effect of insulin was dose-dependent.

Cessation of Smoking

Weight gain is very common when people stop smoking and is at least partly mediated by nicotine withdrawal. Weight gain of 1 to 2 kg in the first few weeks is often followed by an additional 2- to 3-kg weight gain over the next four to six months. Average weight gain is 4 to 5 kg, but can be much greater

Sedentary Lifestyle

A sedentary lifestyle lowers energy expenditure and promotes weight gain In children there is a graded increase in BMI as the number of hours of television watching increases

The number of automobiles is related to the degree of obesity in adults

Observations illustrate the importance of decreased energy expenditure in the pathogenesis

of weight gain .

The highest frequency of overweight occurs in men in sedentary occupations .

Estimates of energy intake and energy expenditure in Great Britain suggest that reduced energy expenditure is more important than increased food intake in causing obesity

Diet

The amount of energy intake relative to energy expenditure is the central reason for the development of obesity.

However, diet composition also may be variably important in its pathogenesis

Overeating

Voluntary overeating (repeated ingestion of energy exceeding daily energy needs) can increase body weight in normal-weight men and women.

progressive hyperphagic overweight

Number of patients who begin to become overweight in childhood have unrelenting weight gain.

This can only mean that month by month and year by year their intake is exceeding their energy expenditure.

Since more energy is required as we get heavier, this must mean that they have steadily increasing intakes of food.

Dietary fat intake

Epidemiologic data suggest that a high fat diet is associated with obesity.The capacity to store glucose as glycogen in liver and muscle is limited Fat stores, which are more than 100 times the daily intake of fat

The small storage capacity for glucose as glycogen in liver and muscle, as opposed to very large storage for fat in adipocytes, makes eating carbohydrates to provide glucose a more important physiologic need that may lead to overeating when dietary carbohydrate is limited and carbohydrate oxidation cannot be reduced sufficiently

• Dietary carbohydrate and fiber• When the consumption of sugar and body

weight is examined there is usually an inverse relationship

• Consumption of sugar-sweetened beverages in children may enhance the risk of more rapid weight gain

• Men eating more fiber had lower body weight

Dietary calciumSince there are no major concerns regarding adverse events, and calcium can be beneficial to bone health, there would be no disadvantage in increasing calcium and vitamin D intake modestly

Frequency of eating•The relationship between the frequency of meals and the development of overweight is unsettled•When normal subjects eat several small mealsa day, serum cholesterol concentrations are lower than when they eat a few large meals a day.•Similarly, mean blood glucose concentrations are lower when meals are frequent

Restrained eatingA pattern of conscious limitation of food intake is called restrained eatingGreater increases in restraint correlate with greater weight loss, but also with higher risk of lapse or loss of control and overeatingpeople with higher levels of conscious control maintain lower weight

Binge-eating disorderBinge-eating disorder is a psychiatric illness characterized by uncontrolled episodes of eating, usually in the eveningThe patient may respond to treatment with drugs that modulate serotonin

Night-eating syndromeNight-eating syndrome is the consumption of at least 25% of energy between the evening meal and the next morning, and awakening during the night to eat three or more times per week

Psychologic and Social Factors

• Psychologic factors in the development of obesity are widely recognized, although attempts to define a specific personality type that causes obesity have been unsuccessful

Socioeconomic and Ethnic Factors

• Obesity is more prevalent in lower socioeconomic groups in the United States and other developed countries

• the higher prevalence of overweight in women, suggests important interactions of

• gender with many factors that influence body fat and fat distribution.

• The reason for this association is not known.

Genetic and Congenital Disorders

• Monogenic causes of excess body fat or fat distribution

• These include• leptin deficiency, a leptin receptor defect, a defect in

the processing of proopiomelanocortin (POMC), a defect in proconvertase 1 (PC 1), a defect in TSH-b, and a defect in PPAR-g. Although these defects are relatively rare, they

• show the powerful effects that some genes have on the deposition of body fat

Polygenic causes of excess body fat

• The more common genetic factors involved in obesity regulate the distribution of body fat, the metabolic rate and its response to exercise and diet, and the control of feeding and food preferences

Predictors of Weight Gain• Infant of diabetic mother or mother who smoked• Overweight parents• Overweight in childhood• Lower education or income group• Cessation of smoking• Sedentary lifestyle• Low metabolic rate• Lack of maternal knowledge of child’s sweets eating habits• Recent marriage• Multiple births

Adult Women

• Most overweight women gain their excess weight after puberty.

• This weight gain may be precipitated by a number of events, including pregnancy, oral contraceptive therapy, and menopause

Pregnancy

• Weight gain during pregnancy, and the effect of pregnancy on subsequent weight gain, are important events in the weight gain history of women

• A few women gain considerable weight during pregnancy, occasionally >50 kg

Oral contraceptives

• Oral contraceptive use may initiate weight gain in some women, although this effect is diminished with the low dose estrogen pills

• The typical weight gain in the pill user group was only 0.5 kg, but the small weight gain in these women was attributable to the accumulation of fat, not body water

Menopause

• Weight gain and changes in fat distribution occur after menopause.

• The decline in estrogen and progesterone

• secretion alters fat cell biology so that central fat deposition increases.

• Estrogen replacement therapy does not prevent the weight gain, although it may minimize fat redistribution

Adult Men

• The transition from an active lifestyle during the teens and early 20s to a more sedentary lifestyle thereafter is associated with weight gain in many men.

• The rise in body weight continues through the adult years until the sixth decade. After ages 55 to 64, relative weight remains stable and then begins to decline

Facts

• Body weight varies throughout the day as food is eaten and then metabolized. Body weight also varies from day to day, week to week, and over longer intervals.

• Understanding these fluctuations and their relationship to more significant weight cycling related to dieting and regain (yo-yo dieting) is important in understanding obesity

Facts

• Adults under age 55 years tend to gain weight, and those over 55 tend to lose it (134).

• The youngest adults gain the most weight, and the oldest adults lose the most.

• Women have significantly greater variation in their weight over 10 years than do men

• Most researchers agree that weight cycling neither necessarily increases body fat, nor adversely affects blood pressure, glucose metabolism, or lipid concentrations.

CLINICAL EVALUATION OF OVERWEIGHT

PATIENTS

Clinical Information from Interview• Are members of your family overweight?• Do your parents or grandparents have• diabetes?• Do you have diabetes?• Do you have high blood pressure?• Do you take thyroid hormone?• Have you gained 20 lb or more (10 kg) since age 20 yr?• Do you fall asleep easily during the day?• Do you exercise regularly?• Do you have gallstone or gall bladder disease?• Do you take medications regularly? If so, specify• Are you depressed?• FOR WOMEN: Do you have normal menstrual periods?

Clinical Evaluation• Step 1: Physical Measurements

• Vital signs

• As part of any clinical encounter the nurse or physician should measure several vital signs including height, weight (calculate BMI), waist circumference, pulse, blood pressure and, if indicated by the patient’s complaints, temperature

BMI

• Accurate measurement of height and weight, which are used to calculate the BMI, is the initial step in the clinical assessment of the patient.

• This index is calculated as the body weight (kg) divided by the stature [height (cm)] squared (wt/ht 2)

Step 2: Measure Waist Circumference

• Waist circumference is the most practical clinical alternative approach to assessing visceral fat.

• Waist circumference is measured with a flexible tape placed horizontally at the level of the superior iliac crest

• Tracking the change in waist circumference is a good tool for following the progress of weight loss

Other Physical Aspects of Obesity

• A number of physical features of an obese individual may help identify a specific cause for the individual’s problem.

• Features of the hypothalamic syndrome . Cushing’s syndrome

• Polycystic ovarian disease is a common cause of obesity in younger women.

• Among the various genetic diseases that produce obesity, Prader-Willi is the most common.

• It includes hypotonia, mental retardation, and sexual immaturity, and can usually be recognized clinically.

•

• Detection of acanthosis nigricans should suggest significant insulin resistance. This is a clinical finding of increased, very dark pigmentation in the folds of the neck, along the

• exterior surface of the distal extremities, and over the knuckles.

• It may signify increased insulin resistance or malignancy, and these possibilities should be evaluated

Diet Composition

• MACRONUTRIENTS

• Dietary Fat

• Protein

• Carbohydrate

Dietary Fat

• Fatty acids are divided into two basic categories: saturated and unsaturated

• Saturated fat is generally solid at room temperature and is most commonly found in animal sources (e.g., fat in whole milk, cheese, and butter).

• Monounsaturated and polyunsaturated fats are examples of unsaturated fats

Dietary Fat

• Sources of

• Monounsaturated fats include olive, canola (rapeseed), peanut oils, nuts, and avocados

• Polyunsaturated fats can be found in corn, soybean, sunflower, safflower, and flaxseed oil, as well as fish

Dietary Fat

• High saturated and trans fat intake can raise low-density cholesterol levels and increase the risk for cardiovascular disease

• Two polyunsaturated fatty acids, linoleic acid and linolenic acid, are considered essential because the body cannot produce them.

• Consumption of approximately 4% of total

• energy intake from plant oils (e.g., about one tablespoon of oil) will prevent essential fatty acid deficiency

Dietary Fat• Dietary fat can affect body weight regulation in

a variety of ways. First, dietary fat (9 kcal/g) has more than double the energy of carbohydrate and protein

• This is the underlying concept behind low-fat diets, reduced-fat foods, and drugs that inhibit fat absorption

Dietary Fat• Second, dietary fat is palatable.

• Good taste enhances the enjoyment of eating, it can undermine weight control

• Flavor and taste are strong mediators of food intake

• Intake of palatable high-fat foods can lead to overconsumption without appropriate compensation.

• High-fat preloads have been shown to increase the amount of fat consumed at a subsequent meal

Protein

• Protein is a unique macronutrient • It provides the body with a usable form of nitrogen. • Nitrogen is found in amino acids, the building• blocks of protein. • The amino acids that are consumed from food are

used to synthesize a variety of proteins that have diverse functions in the body (i.e., enzymes, hormones, structural components, and antibodies)

Protein• As with some fatty acids, the body cannot produce

certain amino acids; therefore, they are considered essential and must be obtained from the diet.

• Protein requirements vary as a function of one’s age and health status.

• Protein equilibrium can be achieved on average by consuming 0.8 g of protein per kg of body weight per day.

• Requirements are generally greater for infants, children, adolescents, pregnant and lactating women, and athletes

Protein• Protein appears to be an important promoter

• of satiety, excessive consumption can be associated with increased intake of saturated fat and cholesterol, if lean meat and meat products, low-fat dairy products, and vegetarian foods such as beans and lentils are not consumed.

• High protein intake also poses the risk of reduced consumption of carbohydrate-rich foods including whole grains, fruits, and vegetables, which are good sources of fiber, vitamins, and minerals

Carbohydrate• Like fat, various forms of carbohydrate exist in food.

• Sugars (e.g., glucose, fructose, sucrose) are the simplest forms of carbohydrate.

• More complex carbohydrates are both digestible (i.e., multiple glucose units linked together like starch) and indigestible (i.e., fiber).

• Carbohydrates play an important role in inducing satiety.

• However, the primary function of dietary carbohydrate is to provide energy. Certain cells use glucose for energy exclusively (e.g., red blood cells and brain cells)

• Like dietary fat, carbohydrate can positively and negatively affect weight regulation.

• Increased intake of fiber rich foods can promote satiety;

• however, excess intake of digestible carbohydrate, like any other macronutrient, results in energy storage in adipose tissue

EFFECTS OF MACRONUTRIENTS ON SATIETY

• Hunger is one of many factors that influences food consumption, it is an important factor in terms of weight control.

• An individual who is satisfied will be more likely to limit food intake and maintain body weight than one who is constantly hungry

• Foods high in protein, fiber, and water content were more satiating than foods high in fat

• High fat test foods were associated with higher daily fat and energy intakes than carbohydrate rich test foods

• beverages promote obesity not only by providing added calories but also by their poor ability to promote compensatory responses and satiety

• Studies suggest that lowering the energy density, particularly by incorporating water into a food or recipe (as opposed to simply drinking water with a meal), is a more effective strategy for reducing food intake than altering the proportion of macronutrients in a meal

Examples

Lower-Fat Diets• Very Low Fat Diets• Diets that provide <10% fat are defined as very low fat

diets• Pritikin and Ornish diets are examples of very low fat

diets• The Ornish diet is a plant-based diet and therefore

encourages consumption of high complex carbohydrate, high-fiber foods (e.g., fruits, vegetables, whole grains), beans, soy, moderate amounts of reduced-fat dairy, eggs, and limited amounts of sugar and white flour

• the very low fat diets strongly discourage consumption of foods containing high amounts of refined carbohydrate and/or fat such as sugar, high-fructose corn syrup, white flour, and rice

Low-Fat Diets

• The guidelines are based on the premise that a low-fat (20–30%), high-carbohydrate (55–60%) diet results in optimal health

• reduction of dietary fat content from 40% to 25% to 30% of energy intake under ad libitum conditions produces a 2- to 4-kg weight loss

• consumption of a low-fat, low-calorie diet, in the context of intensive group and/or individual counseling and physical activity, is an effective strategy for weight management

• low-fat diets are associated with health benefits, such as reduced incidence of diabetes and improved control of hypertension

Implementation of lower fat diets and safety considerations

• If fat is reduced from 40% to 10% to 30% of energy intake and protein is held constant at 15%, the percentage of carbohydrate consumed increases from 45% to 55% to 75%

• replacing fat with fiber-rich carbohydrates, also known to delay nutrient absorption, may be an effective strategy for managing appetite

• achieved by increasing intake of whole grain bread and pasta, brown or wild rice, beans, and vegetables, and replacing highly refined carbohydrate containing foods like sugary cereals, instant oatmeal, and low-fat/high-calorie baked goods with whole grain cereal, steel cut oatmeal, and fruit for dessert

• Few safety concerns emerge with low-fat• diets; • Reducing fat intake below 4% of total energy

intake may increase risk of essential fatty acid deficiency.

• Unless increased gradually, very high fiber diets may result in gastrointestinal distress.

• The efficacy of very low fat diets for long-term weight management remains uncertain

Moderate-Fat Diets• Mediterranean diets are considered moderate-fat

diets because they generally contain over 30% of total calories from fat

• A traditional Mediterranean diet is rich in natural whole foods and relies heavily on foods from plant sources like fruits, vegetables, legumes, breads and grains, and nuts and seeds.

• These plant foods along with olive oil and low-to-moderate amounts of cheese, and yogurt, are consumed daily

• red meat, fish, chicken, and eggs are consumed on a weekly basis. The diet is low in saturated and trans fat due to limited intakes of butter, red meat, and processed foods.

• Fresh or dried fruit with nuts is viewed as a typical daily dessert rather than commercially baked foods

HIGH-PROTEIN DIETS

• intakes of 25% total energy or greater or of 1.6 g/kg/day can be considered high.

• The Zone diet (30% protein, 40% carbohydrate, and 30% fat) is an example of a high-protein diet

• In addition to weight loss, there was a greater reduction in waist circumference, waist-to-hip ratio, and intra-abdominal adipose tissue even after weight was regained

LOW-CARBOHYDRATE DIETS• Low-carbohydrate encourage consumption of

controlled amounts of nutrient-dense carbohydrate-containing foods (i.e., vegetables, fruits, and whole grain products) and eliminate intake of carbohydrate-containing foods based on refined carbohydrate (i.e., white bread, rice, pasta, cookies, and chips).

• Consumption of foods that do not contain carbohydrate (i.e., meats, poultry, fish, as well as butter and oil) is not restricted, the emphasis is on moderation and quality rather than quantity

THYROID HORMONES AND DERIVATIVES

Thyroid hormones are the physiological controllers of basal metabolism.

Hypothyroid and hyperthyroid states are associated with predictable changes in energy expenditure and in body weight and composition.

Mean body weight and fat mass are normally decreased by 15% in hyperthyroidism, and hypothyroid patients weigh 15% to 30% more than in their euthyroid states.

Normal physiological variations in T3 concentrations have also been shown to be responsible for differences between individuals in daily energy expenditure as much as 150 kcal/day , and a low T3 level is a risk factor for subsequent weight gain

Moreover, among obese subjects, 20% have overt or subclinical hypothyroidism.

Thyroid hormones have been used to treat obesity for more than a century

Selective agonists at the TR b have been developed and have been shown in animal models to have fewer side effects than T 3

Leptin

• humans, with a genetic deficiency in the adipocyte-derived hormone leptin or its receptor, exhibit extreme obesity

• A recent study of Hukshorn et al. did not find any effect of subcutaneous pegylated recombinant native human leptin treatment on body fat, energy expenditure, or substrate utilization in obese men

Ephedrine/Caffeine

• ephedrine (E) as monotherapy decreases body fat in obese subjects by a combined action of suppression of appetite and stimulation of energy expenditure

• Adenosine antagonists such as caffeine (C) potentiate the thermogenic and clinical effects

• Dose-response studies found that the combination of ephedrine 20 mg and caffeine 200 mg produced the best synergistic effect on thermogenesis

• The clinical studies of E & C clearly show that the compound is effective in the treatment of obesity for up to one year

• Waluga et al. concluded that E & C had no undesirable effects on cardiovascular function in obese subjects

• A hypothetical cardiovascular safety concern could be raised by the combination of E & C and exercise

b -Adrenoceptor Agonists b2-Agonists such as terbutaline and salbutamol, are used

in the treatment of asthma, but they have been shown to be thermogenic, to increase insulin mediated glucose disposal, and to increase the ratio of T3 to T4

b 2 -adrenoceptor stimulate repartitioning in man with reduction of fat mass and increase in the lean tissue mass

The clinical value for obesity treatment is limited due to the effect on heart rate, tremor, and the uterus.

Other Drugs with Thermogenic Properties

Hormones such as testosterone and growth hormone have been used to treat obesity, and it is likely that both have thermogenic effects

Due to serious side effects its use is restricted hormone-deficient patients

capsaicin from hot chilies polyphenols from green tea

HISTAMINE AND ITS RECEPTORS

• H 1 receptor• the H 1 receptor mediates the histamine-induced

contraction of smooth musculature and mediates the effects of the histamine released from mast cells in allergic reactions

• in the hypothalamus it is responsible for the inhibitory effects on food intake

• H 1 receptor probably is involved in body weight regulation

• H 2 Receptor

• There is no evidence that the H 2 receptor is of importance in the histaminergic regulation of food intake or body weight

• H 3 receptor

• This histamine receptor is a major player in the histaminergic system’s regulation of food intake and body weight

• H 4 receptor

• It is not considered to be of importance in mediating any of histamine’s effects on food intake and metabolism

Serotonin and Other Orexigenic andAnorexigenic Pathways

• Serotonin was linked to the control of food intake and feeding behavior 30 years ago

• Serotonergic releasers and reuptake inhibitors such as fenfluramine, D -fenfluramine; selective serotonin reuptake inhibitors (SSRIs) such as sertraline and fluoxetine; and sibutramine (a noradrenergic and 5-HT reuptake inhibitor) have all been shown to adjust feeding behavior

• Fluoxetine study in obese participants 60 mg/ Day significantly more weight was lost in the drug condition than the control

• Used in Disorders characterized by binge eating• the 5-HT 1B receptor, sumatriptan, a novel• 5-HT 1B/1D receptor agonist, has also been

shown to produce a significant reduction in food intake in healthy women

Herbal and Alternative Approaches to Obesity

HERBAL THERMOGENIC AIDS

• Herbal Caffeine and Ephedrine

• Herbal ephedra remains the one efficacious dietary herbal supplement for the treatment of obesity

• Herbal dietary supplements containing caffeine 20 or 60 mg with ephedrine 10 or 24 mg were shown to increase oxygen consumption acutely in man compared to placebo using a ventilated hood system

• Ephedrine products were sold without a prescription for the treatment of asthma with a recommended dosage up to 150 mg/ day.

• Caffeine is sold without a prescription as a stimulant with a recommended dose of up to 1600 mg/day

• One of the concerns regarding herbal caffeine and ephedrine, is the lack of uniform quality.

• levels of active ingredients is not universal.• Most of the products contain many other herbal ingredients.• These other ingredients had no proven efficacy or safety for

treating obesity, and raised issues of potential drug interactions

• The adverse events associated with herbal caffeine and ephedrine were hypertension, palpitations, tachycardia, stroke, and seizures

• Three billion doses of ephedra containing dietary herbal supplements were sold in 1999, equivalent to one adverse event per 70 million doses.

• By comparison, ibuprofen produced one adverse event, mostly gastrointestinal, per 25 million 200-mg doses sold

Green Tea• Green tea prepared by heating or steaming the

leaves of Camellia sinensis is widely consumed on a regular basis throughout Asia

• Black tea is made by allowing the green tea leaves to auto-oxidize enzymatically leading to the conversion of a large percentage of green tea catechins to theaflavins

• A green tea extract containing both catechins and caffeine was more potent in stimulating brown adipose tissue thermogenesis than equimolar concentrations of caffeine alone

• Catechins from green tea inhibit catechol-O-methyl transferase at the level of the fat cell, the hormone that degrades norepinephrine

• While the caffeine it contains slows the breakdown of cyclic AMP by inhibiting phosphodiesterase

• The evidence for catechins giving weight loss is weak and dependent, in part, upon the level of chronic caffeine intake in long term weight lose

Synephrine from Citrus aurantium• the Seville orange contains indirect acting

• b-sympathomimetics including synephrine, hordenine, octopamine, tyramine, and N-methyltyramine

• Women have a lower thermic effect of food than men,

• C. aurantium increases this thermic effect 29% in women, but not in men

Capsaicin and Analogs

• Capsaicin stimulates calcium influx to visceral adipose tissue through the vanilloid type-1 receptor and prevents adipogenesis

• Capsaicin has been shown to increase satiety and energy expenditure in human

• The effect seems to be greater when the capsaicin is contained in food such as tomato juice rather than in capsules

• A product containing 0.4 mg of capsaicin, 625 mg of green tea, and 800 mg of chicken essence gave a decrease in body fat and an increase in energy expenditure over a two-week treatment period

• Another combination product contained capsaicin 1.2 mg, L –tyrosine 1218 mg, caffeine 302 mg, and calcium carbonate 3890 mg daily

• Capsiate is a nonpungent capsaicin analog that is found in the CH-19 sweet red pepper cultivar

• Evodiamine is a nonpungent vanilloid receptor agonist that comes from the fruit of the Evodia rutaecarpa

• Raspberry ketone is similar in structure to capsaicin, prevents fatty liver, improves obesity, and increases norepinephrine-induced lipolysis in white adipocytes

• Fucoxanthin is a major carotenoid found in edible seaweed

• 1,3-Diacylglycerol oil, a cooking oil used to reduce body fat in Japan

• 1,3-Diacylglycerol has been shown to increase fat oxidation and to decrease hunger (52). 1,3-Diacylglycerol also decreases total body fat, subcutaneous fat, and visceral fat

• 1,3-Diacylglycerol is present in various vegetable oils in small amounts

G. cambogia (Hydroxycitric Acid)

500 mg of G. cambogia extract was combined with 100 mg of chromium picolinate taken t.i.d

HCA is also sold as an herbal supplement containing the calcium salt for which the dose is 3 g/day as a treatment for obesity

Cissus quadrangularis

• C. quadrangularis standardized to 2.5% phytosterols and 15% soluble plant fibers combined with green tea extract (22% epigallocatechin gallate and 40% caffeine), niacin bound chromium, selenium (0.5% L -selenomethionine), pyridoxine, folic acid, and cyanocobalamin

Guggul

• An herbal preparation made from the sticky gum of various myrrh trees that has been alleged to aid in lowering serum cholesterol.

• "A number of studies have substantiated the cholesterol lowering properties of guggul and its ability to raise metabolism by activating sluggish thyroid function.

Evening Primrose Oil

• Evening primrose oil contains g-linolenic acid and has been proposed as a treatment for obesity

• Some believe that evening primrose oil is effective in the treatment of obesity but not true

Hoodia gordonii

• is a cactus that grows in Africa

• It has been eaten by bushmen to decrease appetite and thirst on long treks across the desert

• Caralluma fimbriata

• C. fimbriata is an edible cactus, like Hoodia, and was used by Indians to suppress appetite

Pyruvate

• Pyruvate or mixtures of pyruvate and dihydroxyacetone at 15% to 20% of dietary calories accelerate weight loss on a calorie-restricted diet and slow weight regain after weight loss

• Pyruvate sold as a dietary herbal supplement is sold as a calcium salt and is taken at 3 to 6 g/day for weight loss

Yohimbine

• One study randomized 20 subjects to yohimbine 20 mg/day or a placebo and a 1000 kcal/day diet.

• Over the three-week study the yohimbine group lost 3.55 kg compared to 2.21 kg in the placebo group

Dehydroepiandrosterone (DHEA)• They originate in the adrenal gland and gonads and are

weak androgens and has been sold as a dietary supplement for weight loss.

• The reduction of endogenous DHEA production with aging and with malnutrition or illness has suggested that DHEA may be more effective in elderly obese females

• Studies suggest that DHEA may have a positive impact on insulin sensitivity, but its effect on body fat or body weight in humans is minimal and clinically insignificant.

Chromium Picolinate

• Gained popularity for both weightlifters and people desiring weight loss

• Although chromium picolinate 200 and 400 mg/day has no effect upon body composition in humans, it has a significant effect on lipids, blood pressure, and glucose tolerance and as such is not helpful for the treatment of obesity

Calcium• Nearly 20 years ago, McCarron et al. reported that there

was a negative relationship between BMI and dietary calcium intake

• Shapses et al., however, gave trends toward weight loss with 1 g/day calcium supplement for six months of 0.8 kg of weight and 1 kg of fat Thus, there appears to be an effect of calcium and particularly dairy calcium to reduce body weight, but the magnitude of this effect appears controversial.

• There are no major concerns regarding adverse events due to supplementation with dairy calcium.

Topical Fat Reduction• Local application of substances to the fat cells

that stimulate the lipolytic process have the potential to reduce the size of the treated fat cells.

• Using one thigh as a control, isoproterenol injections (a b-receptor stimulator), forskolin ointment (a direct stimulator of adenylate cyclase), yohimbine ointment (an a-2 receptor inhibitor), and aminophylline (an inhibitor of phosphodiesterase and the adenosine receptor) gave more girth loss from the treated than the control thigh.

AMINO ACIDS AND NEUROTRANSMITTER MODULATION

• 5-Hydroxytryptophan• Changes in plasma amino acid levels can modify

food intake by affecting the brain availability of neurotransmitter precursors

• 5-HTP at a dose of 8 mg/kg/day• Glucomannan, water-soluble fiber

supplemented at 20 g/day over eight weeks gave a 5.5 lb. weight loss with no prescribed diet

Chitosan

• The product has a molecular weight of more than a million Daltons, and is designed to bind to intestinal lipids including cholesterol and triglycerides

• Chitosan 3 g/day

PHYSICAL AGENTS

• Jaw Wiring

• Jaw wiring has been used for the treatment of obesity since the 1970s

• The mean weight loss was 25.3 kg in six months which is comparable to obesity surgery over the same period of time

• Waist Cord

• The maintenance of large weight losses using the waist cord is achievable with diet-induced weight loss.

• The waist cord is believed to provide a feedback signal whenever weight gain occurs, triggering behaviors designed to result in prevention of weight gain

Criteria for a healthy weight loss diet

• • Usual calorie intake reduced by 500-1000 calories/day with a minimum intake of

• 1000-1200 calories/day • • High fiber (25 gm/day) from whole grains,

fruits, vegetables, and legumes • • Minimum 5 servings fruits and vegetables/day • • Protein not >15-20% calories • • Total fat not >25-30% calories and saturated fat

not >10% calories • • Increased physical activity up to one hour on

most days

Increased physical activity• • Long-term goal—Accumulate at least 30 minutes or more of

moderate intensity • physical activity on most, and preferably all, days of the week. • • Caloric expenditure will vary with intensity of the activity and body

weight. • Obese individuals may achieve a moderate intensity at lower levels

due to the • work load of excess weight and low cardiorespiratory fitness. • • An hour a day is recommended to prevent weight gain with aging

and 60-90 • minutes may be necessary to sustain weight loss, but this amount of

physical • activity is unrealistic for many patients

Increased physical activity

• A more realistic goal for physically unfit patents is to start with 10 minutes every

• other day and increase slowly to 30-45 minutes on most, and preferably all,

• days to expend 100-200 calories daily. Walking is practical because of safety

• and accessibility. • • Physical activity may be intermittent throughout the day

or all at one time. • • Limit sedentary time (TV, computer) to <2 hours/day. • • More active patients may want to determine their target

heart rate when • exercising

Examples of Moderate Intensity Physical Activity

• Walking 1 ¾ miles in 35 minutes (20 minute mile) • Bicycling 5 miles in 30 minutes • Water aerobics for 30 minutes • Swimming laps for 20 minutes • Dancing fast (social) for 30 minutes • Shoveling snow for 15 minutes • Gardening 30-45 minutes • Raking leaves for 30 minutes • Washing windows or floors for 45-60 minutes • *Roughly equivalent to expending 150 calories

• Consume an average of 1400 calories/day (24% calories from fat)

• • Do not eat extremely low carbohydrate diets • • Eat breakfast • • Expend about 400 cal/day, equivalent to

walking 4 miles, in physical activity. • Walking is the most frequently cited physical

activity. • • Have positive coping skills and self-efficacy

“I am concerned your extra weight has increased your blood

pressure and risk for a heart attack. Even a small weight loss

will decrease your risk.”

“Losing weight may also make it easier to find clothes you like

or participate in activities you enjoy.

Set realistic expectations for weight loss

• • 10% reduction in body weight reduces health risks related to obesity.

• • 1-2 lb loss/week can be achieved with a 500-1000 calorie deficit/day.

• • For most patients this means a daily calorie intake of 1200-1600 calories/day.

• • Six months is a reasonable time to expect a 10% weight loss.

What to say for patients not ready to make diet or physical activity

changes• Discuss personal risks and benefits of change.

You might say: • “Your BMI is higher than recommended for good

health. • Weight loss will reduce your risk of chronic

diseases like heart disease and diabetes, and will reduce stress on your joints, making it

• easier for you to do the activities that you enjoy.

What to say for patients not ready to make diet or physical activity

changes• Even a small weight loss would help and

you might be able to cut down on the amount of medicine you have to take.

• I’d like to help you when you are ready

•

• WEIGHT (Kg; lbs) BMI • (kg/m2• ) 45kg 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 125 130 • cm. in. 99lbs 110 121 132 143 154 165 176 187 198 209 220 231 242 253 264 275

286 • 155cm 61 18½ 21 23 25 27 29 31 33 35½ 37½ 39½ 41½ 43½ 46 48 50 52 54 • 160 63 17½ 19½ 21½ 23½ 25½ 27 29 31 33 35 37 39 41 43 45 47 49 51 • 165 65 16½ 18½ 20 22 24 26 27½ 29½ 31 33 35 36½ 38½ 40½ 42 44 46 48 • 170 67 15½ 17 19 21 22½ 24 26 27½ 29½ 31 33 34½ 36 38 40 41½ 43 45 • 175 69 14½ 16 18 19½ 21 23 24½ 26 28 29½ 31 32½ 34½ 36 37½ 39 41 42½ • 180 71 14 15½ 17 18½ 20 21½ 23 24½ 26 28 29 31 32½ 34 35½ 37 38½ 40 • HEIGHT (Cm; inches) • 185 73 13 14½ 16 17½ 19 20½ 22 23½ 25 26 28 29 30½ 32 33½ 35 36½ 38 • Underweight = <18.5kg/m2• ; Normal = 18.5-24.9kg/m2• ; Overweight = 25-29.9kg/m2• ; Obese = ≥30kg/m2 • Waist Circumference: k <94cm ideal,• >102cm high risk; l <80cm ideal, • >88cm high risk {better risk predictor than BMI!}