The Role of Diet in Disease Prevention and Management

Global Impact of Diet-Related Risks

• Cardiovascular Disease (CVD) Mortality: Diet-related risks are responsible for approximately $10 \text{ million}$ deaths globally, accounting for $52\%$ of all CVD deaths worldwide.

• Risk Factors Classification:     * Unmodifiable Risk Factors: Factors that cannot be changed by the individual:         * Age.         * Gender.         * Genetic factors.         * Race and ethnicity.     * Modifiable Risk Factors: Lifestyle and physiological factors that can be influenced:         * Hypertension (high blood pressure).         * Hyperlipidemia (high blood lipids).         * Obesity.         * Unhealthy foods (e.g., sugary cereals).         * Alcohol intake.         * Cigarette smoking.

Malnutrition: Deficiency and Global Trends

• Global Statistics:     * Underweight individuals: $0.484 \text{ billion}$.     * Overweight individuals: $3.427 \text{ billion}$.

• Causes of Malnutrition Worldwide:     * Lack of food/access to high-quality food.     * Poverty, war, and drought.     * Lack of land and overpopulation.     * Lack of knowledge regarding proper nutrition.     * Decline in breast feeding.     * The ‘McDonalds’ factor (proliferation of unhealthy, processed fast foods).

• Specific Deficiency Diseases:     * Starvation: General lack of food intake.     * Protein/Energy Malnutrition: Lack of macronutrients.     * Rickets & Osteomalacia: Deficiency in $Ca^{2+}$ (Calcium) and Vitamin D.     * Scurvy: Deficiency in Vitamin C.     * Xerophthalmia: Deficiency in Vitamin A.     * Beriberi: Deficiency in Thiamin (Vitamin B1).     * Pellagra: Deficiency in Niacin.     * Pernicious Anaemia: Deficiency in Vitamin $B_{12}$.     * Anaemia: Deficiency in $Fe$ (Iron).     * Goitre: Deficiency in $I_2$ (Iodine).

• Malnutrition in Developing Countries:     * Kwashiorkor: Primarily a protein deficiency. Characteristics include pitted oedema (swelling). Typically affects children in their $2^{nd}$ to $3^{rd}$ year of life.     * Marasmus: General energy/calorie deficiency. Typically affects infants around $12 \text{ months}$ of age.     * Scale: Several million new cases occur annually.

Malnutrition and Starvation in the UK

• Primary Causes:     * Lack of good quality food due to poverty or lack of education.     * Secondary to disease processes ($2^{\circ}$): Diarrhoea, anorexia (related to cancer or anorexia nervosa).

• Clinical Prevalence:     * $40\%$ of hospital patients are malnourished.     * Malnutrition levels increase after $2 \text{ weeks}$ in hospital, particularly in surgical patients.     * Contributing factors: Severity of illness, complications, and inadequate nutrient repletion.     * In many cases, Intravenous (I/V) dextrose and electrolytes may be the sole nutrient support provided.

• Clinical Signs of Starvation:     * Emaciation: Bony protrusions, low body weight, thin skin that is dry and pigmented.     * Psychological/Systemic: Apathy, amenorrhoea (absence of menstruation), and anaemia.     * Metabolic: Lowered basal metabolic rate ($BMR$), leading to hypothermia.     * Organ Failure: Cardio-respiratory failure and oedema.     * Biochemical: Various biochemical imbalances.

Mental Health and Eating Disorders

• Co-occurring Disorders:     * $97\%$ of people hospitalized for an eating disorder have at least one co-occurring mental health disorder.     * $94\%$ suffer from mood disorders like major depression.     * $69\%$ of patients with anorexia nervosa also have Obsessive-Compulsive Disorder (OCD).     * $81\%$ of people with bulimia nervosa have an anxiety disorder.     * $1/3$ of people with Binge Eating Disorder (BED) are diagnosed with major depression.     * $1/4$ of people with an eating disorder have symptoms of Post-Traumatic Stress Disorder (PTSD).

• Anorexia Nervosa:     * Signs: Distorted self-image, intense fear of weight gain, restricted food intake, significant weight loss, fatigue, dizziness/fainting, muscle weakness.     * Death Rate: $10\%$ after $10 \text{ years}$; $20\%$ after $20 \text{ years}$.     * Causes of Early Death: Heart issues, refeeding syndrome, endocrine disorders, gastrointestinal disease, and suicide.

• Bulimia Nervosa:     * Symptoms: Frequent bathroom visits, excessive exercising, preoccupation with body image, feeling out of control, guilt/shame about eating, and social withdrawal.     * Physical Signs: Intentional vomiting, swollen cheeks/jawline, bloodshot eyes, dehydration, acid reflux, and scars/calluses on knuckles.

Cardiovascular Disease and Lipoprotein Theory

• Key Medical Terms:     * Atherosclerosis: Often called ‘hardening of the arteries’; the formation of plaque composed of cholesterol, fat, fibrous tissue, and calcium salts.     * Vascular Disease: Endothelial damage that causes thrombosis (blood clotting).     * Coronary Thrombosis: A blood clot, often occurring because of existing atherosclerosis.

• Lipoprotein Theory:     * High-Density Lipoproteins (HDL): Known as ‘good’ cholesterol. They carry cholesterol from tissues back to the liver for breakdown. Normal levels are $30-80 \text{ mg/l}$; levels above $75 \text{ mg/l}$ are considered protective.     * Low-Density Lipoproteins (LDL): Known as ‘bad’ cholesterol. They carry two-thirds of total plasma cholesterol to the cells. The ratio of LDL to HDL is critical for health.

• LDL Regulation:     * Cells have LDL receptors to remove them from the blood.     * A decrease in the number of receptors leads to increased LDL in the blood.     * High-fat diets reduce the number of receptors in the liver (down-regulation).

• Familial Hypercholesterolaemia:     * A genetic disease where a single gene defect results in defective LDL receptors.     * It is a dominant trait.     * Heterozygous form: Presents as a heart attack around age $35+$.     * Homozygous form: More severe; heart attacks can occur before age $20$.     * Elevated LDL levels in these patients are often resistant to dietary intervention.

Dietary Interventions and Pharmacotherapy for CHD

• Nutritional Recommendations to Lower LDL:     * Total Fat: Should be less than $30\%$ of total energy intake.     * Saturated Fat: Reduce to less than $10\%$ of dietary energy.     * Polyunsaturated Fatty Acids (PUFA): Increase to $3-7\%$ of dietary energy. High PUFA diets have higher antioxidant content.     * Trans Fatty Acids: Reduce intake (found primarily in hydrogenated vegetable oils).     * Monounsaturated Fatty Acids (MUFA): Resistant to lipid peroxidation. Intakes of $10-18\%$ cis MUFA improve lipid profiles, insulin sensitivity, and glycaemic control in Type II diabetes.

• Statins (HMG CoA Reductase Inhibitors):     * Mechanism: Statins inhibit the enzyme HMG CoA Reductase, which converts 3-hydroxy-3-methylglutaryl CoA (HMG CoA) into mevalonate, a precursor to cholesterol.     * Benefits: Can reduce bad cholesterol by up to $50\%$. They help prevent up to $2\%$ of heart events in most people (rising to $7\%$ in vulnerable patients).     * Cost: Manufacturing costs are as low as $2p$ per pill.     * Risk Reduction: Approximately $21\%$ relative risk reduction per $mmol/L$ of LDL reduction. A $2 \text{ mmol/L}$ reduction leads to a $∼40\%$ risk reduction.

• Other Mediators:     * Antioxidants: Prevent the oxidation of lipids; lipid peroxidation otherwise leads to LDL uptake by macrophages in the endothelium.     * Microbiota: Bacteria break down choline and carnitine into trimethylamine (TMA), then trimethylamine-N-oxide (TMAO), which may increase heart disease risk.     * Homocysteine: Folate and Vitamin $B_{12}$ are coenzymes in methylation; deficiencies cause elevated homocysteine, a risk factor for CHD.

• Prevention Checklist:     * High intake of fruit, vegetables, wholemeal bread, and pulses.     * Moderate intake of nuts (especially walnuts).     * Unsaturated cis oils (Vitamin E source).     * Regular fish consumption (including oily fish).     * Salt intake below $6 \text{ g/day}$ (as salt increases blood volume and BP).

Obesity Epidemic and Clinical Consequences

• BMI Classification:     * Underweight: <18.5     * Normal: $18.5-24.9$     * Overweight: $25-29.9$     * Obese: $30-34.9$     * Extremely Obese: 35<     * Formula: $\text{BMI} = \frac{\text{Weight (kg)}}{\text{Height (m)}^2}$

• Global Obesity (OECD): The USA has the highest rates, followed by Mexico and England. Rates are projected to continue rising through $2030$.

• Effects of Obesity:     * Mental Health: Depression and body image issues.     * Respiratory: Sleep apnea.     * Organ Function: Liver disease (fat buildup/failure), gallbladder issues (stones), kidney failure (related to chronic kidney disease/CKD).     * Skeletal: Joint pain, weakened muscles, and bone fractures.     * Reproductive: Infertility and pregnancy complications.     * Cardiovascular: Stroke, heart attack ($40\%$ higher risk in obese individuals vs $10\%$ for non-obese for cardiovascular disease).     * Cancer: Endometrial, post-menopausal breast, bowel (men), liver, kidney, colon, and pancreatic cancers.

• Economic Impact: UK medical costs rise per capita as BMI increases: from $\pounds 805$ for BMI <25 to $\pounds 1,493$ for BMI $\ge 40$ (an $86\%$ increase).

• The Obesogenic Environment: Factors contributing to obesity include:     * Exogenous: Advertising, favorable pricing for high-energy foods, lack of cycle routes/school facilities, passive indoor entertainment.     * Host Factors: Genetics, parental weight, breastfeeding practices, and household cooking skills.

• Obesity Treatment Strategy:     * Target weight loss: $400-800 \text{ g}$ per week.     * Energy deficit: $500-1000 \text{ kcal/day}$.     * Note: Purely dietary approaches often fail due to poor compliance and a drop in metabolic rate post-weight loss.

Diabetes Mellitus

• Disorder of Glucose Homeostasis: Characterized by hyperglycaemia; also affects fat and protein metabolism.

• Types:     * Type I: Juvenile onset; complete lack of insulin.     * Type II (NIDDM): Mature onset; insensitivity of cells to insulin and reduced cellular uptake of glucose.

• NHS Burden: Costs $\pounds 10.7 \text{ billion/year}$, utilizing $6\%$ of the total NHS budget.

• Global Projections (2019 to 2045):     * World: $463 \text{ million}$ ($2019$) to $700 \text{ million}$ ($2045$) - a $51\%$ increase.     * Highest regional increase: Africa ($143\%$ increase projected).     * Western Pacific: $1 \text{ in 3}$ adults with diabetes lives in this region.

• Blood Glucose Regulation (Pancreatic Feedback):     * High blood sugar: Stimulates insulin release from the pancreas -> glucose uptake by tissues and glycogen formation in the liver -> lowers blood sugar.     * Low blood sugar: Stimulates glucagon release -> stimulates glycogen breakdown into glucose -> raises blood sugar.

• Diabetes and Weight Loss Medications:     * SGLT-2 Inhibitors: Sodium-Glucose Cotransporter-2 inhibitors are used for glucose control and are also cardioprotective.     * Incretins (GLP-1 & GIP): Hormones from the small intestine that stimulate insulin, slow gastric emptying (preventing spikes), and increase satiety.     * Specific Drugs:         * Orlistat: Lipase inhibitor (prevents fat absorption).         * Liraglutide & Semaglutide: GLP-1 receptor agonists.         * Tirzepatide: GIP analogue/GLP-1 receptor agonist.         * Qsymia: Amphetamine/anti-convulsant (currently banned).         * Setmelanotide: For patients with rare gene mutations (e.g., POMC).