11. Appetite and Weight Flashcards
obesity health risks
6% UK deaths metabolic syndrome/type 2 diabetes CV disease liver disease cancer reproductive dysfunction joint problems psychological morbidity
metabolic syndrome
constellation of closely associated CV risk factors:
visceral obesity
dyslipidaemia
hyperglycaemia
hypertension
underlying mechanism = insulin resistance
pathophysiology of metabolic syndrome
increased free fatty acids (lipolysis of visceral fat, gluconeogenesis, dyslipidaemia)
pro-inflammatory cytokines - TNF alpha, IL-6
insulin resistance
decreased GLUT-4 expression
decreased tyrosine kinase activity
type 2 diabetes risks
age
obesity
family history
ethnicity
why is type 2 diabetes prevalence increasing?
ageing population
increased obesity prevalence (+diagnosed younger)
better detection /diagnosis
obesity and cardiovascular disease
metabolic disease + increased: blood volume and viscosity vascular resistance hypertension left ventricular hypertrophy coronary artery disease stroke
obesity and respiratory system
obstructive sleep apnoea
hypoxia/hypercapnia
pulmonary hypertension - right heart failure
accidents
obesity and GI/liver
non-alcoholic fatty liver
non-alcoholic steatohepatitis - may progress to cirrhosis, portal hypertension, hepatocellular cancer
gallstones
reflux
obesity and cancer
~10% cancer deaths in non smokers
breast, endometrial, oesophagus, colon, renal, thyroid
obesity - mechanisms of increased cancer
increased insulin
increased free IFG-1
increased oestrogen
adipocytokines
obesity and reproductive system
PCOS - oligonmenorrhoea, hirsutism, sub fertility, insulin resistance
male hypogonadism
adverse pregnancy outcomes
obesity and joints
osteoarthritis
gout
aetiology of obesity
genetic factors
environmental factors
programming
gut microbiome
genetic causes of obesity
rare - obesity associated syndromes, Prader-Willi, Bardet-Biedl
common - polygenic, susceptibility genes
+ hypothyroidism, Cushing’s
diet and obesity
high fat, high sugar
coca-colanisation of developing world
socio-economic factors
obesity and physical activity
20-50% total energy expenditure
obesity prevalence related to proxy measures: car ownership, TV viewing
socioeconomic factors
foetal programming
‘programming’: stimuli at critical periods have persistent biological effects
stressors: undernutrition, trace elements
mechanism: epigenetic modification
life course model
factors operating at every stage of life affect health outcomes later in life
pathway of risk between events and health outcomes
worst outcome: low birth weight, excessive weight gain in infancy, adult obesity
gut microbiome
integral to host homeostasis - absorption, reabsorption
influenced by diet: high fat high fibre
influence disease risk: obesity, type 2 diabetes
regulation of appetite and weight
slow acting hormones that regulate weight
rapid acting peptides that regulate meal sizes
slow acting hormones
regulate body weight
leptin insulin
signal body fat % to hypothalamus - decrease food intake and increase energy expenditure
rapid acting peptides
regulate meal sizes cholecystokinin (CCK) - reduce eating ghrelin - increase eating PYY - reduce eating act via hypothalamus
arcuate nucleus in hypothalamus
accelerator neurons neuropeptide Y: increases eating agouti-related peptide (ArRP): blocks melanocortin receptor brake neutrons: POMC neurone melanocortin peptides: decrease eating
leptin in mice
deficiency - mouse models of obesity
leptin treatment reduces obesity in leptin-deficient mice
leptin in humans
starvation single: permissive effect ion puberty/reproduction
deficiency/mutation of receptors = rare
usually: increased leptin concentration with increased fat, ?leptin resistant, ?decreased leptin CNS transport
treatment
lifestyle modification
pharmacological
surgical
public health/social
lifestyle modification - diet
500-1000kcal energy deficiency
low energy density: decreased saturated fat and sugar, increased fruit and veg
decrease portion sizes and snacking
structured meals/meal replacement
lifestyle modification - physical activity
exercise 7 days a week
regardless of weight loss, exercise increases health
VLCD and type 2 diabetes
primary care programme
patients with type 2 diabetes
initial total diet replacement with formula
stepped food reintroduction
long term maintenance with structured support
46% induced remission if type 2 diabetes
lifestyle modification usual targets and problems
10% weight loss, 1-2lb per week
‘yo-yo’ dieting - regain weight loss
obesogenic environment
weight loss: results in increased hunger and decreased satiety
pharmacological therapy
orlistat
metformin
orlistat mechanism
binds and inhibits lipases in lumen of gut
prevents hydrolysis of dietary fat into absorbalblke free fatty acids/glycerol
excrete ~1/3 dietary fat
orlistat adverse effects
flatulence, oily faecal leakage, diarrhoea
reduced absorption of fat soluble vitamins
(supplement)
metformin
best first line for obese patients with type 2 diabetes (all other oral hypoglycaemic agents and insulin cause weight gain)
recommended by NICE for prevention of type 2 diabetes in high risk adults
problems with pharmacological treatment
can only increase 3-4 fold proportion of patients who achieve 5% weight loss
weight regained after treatment stops
surgical treatments
laparoscopic adjustable banding
roux-en-Y gastric bypass
laparoscopic adjustable banding
restrictive only
inject/withdraw saline to adjust band diameter
roux-en-Y gastric bypass
restrictive
malabsorptive
alterations in but hormones and bile acid flow contribute to weight loss
micronutrient deficiencies - supplemented with iron, B12, folate, calcium, vitamin D
dumping syndrome - GI/vasomotor symptoms
endocrine factors important in effects
increased satiety is key
advantages of weight loss surgery
weight loss: 25-30%
resolves/improves comorbidities
saves costs
disadvantages of weight loss surgery
preoperative mortality/morbidity
long term follow up
some weight regain
expense
