Brought to you by

OBESITY, METABOLIC SYNDROME & BEYOND2021

Dr Gary Hudson Specialist Physician

MODULE 4: AETIOLOGY

2

CONTENTS

• Aetiology of obesity

1. Dietary Induced Obesity (DIO)

2. Stress

3. Sleep

4. Inflammation

5. Intestinal microbiome

6. Exercise

7. Hypothyroidism

8. Cushing’s syndrome

9. PCOS = poly cystic ovarian syndrome

10. Iatrogenic

11. Mental health

• Quarantine 15 - new stress in the pandemic

• Summary

• Questions

3

6

10

11

12

13

15

17

20

21

23

25

27

29

30

3

AETIOLOGY OF OBESITY

OBESITY or ABCD (ADIPOSE BASED CHRONIC DISEASE) has been called a neuro-behavioural, genetic-epigenetic, environmental, immune-endocrine medical disease. This complex definition points to all the variants we observe in the presentation of and response to therapy of weight management in different people. The difference of each person specifically relates to their unique combination of aetiologies. There is NO ONE FACTOR that is to blame. One of the first steps in assessing a patient is to find all the contributing factors in order to change them to have a successful outcome.

Most doctors, even specialist endocrinologists, still follow the old thermogenic pattern of:

TOO MANY CALORIES (FOOD) TAKEN IN and TOO LITTLE CALORIES (ENERGY) EXPENDED.

SECTION 4

CALORIESOUT

CALORIESIN

4

The aetiological factors are much more complicated than that.

Factors that promote weight gain include:

1. Aging

2. Gender

3. Race

4. Genetics

5. Socioeconomic status

6. Nutrition

7. Physical activity

8. Medications

9. Sleep

10. Pre-existing medical illnesses.

When looking at groups of people we see certain groups are high risk depending on where they live and work. This has been termed OBESOGENIC ENVIRONMENTS as they promote weight gain often on an epigenetic basis.

Environmental OBESOGENIC factors

1. Family cultures

2. Food access and excess

3. Work and school environments e.g. vending machines.

4. Apps used as well as wearable technologies

5. Behaviour of the individual

5

There is an extensive list for the SECONDARY causes of obesity:

1. Dietary Induced Obesity (DIO) is by far the most common cause

2. Inflammatory conditions especially psoriasis

3. Endocrine disorders such as hypothyroidism, Cushing’s syndrome, insulinoma, PCOS

4. Peri-pregnancy

5. Post-meno and andro-pausal

6. Genetics: Monogenic e.g. Prader-Willi syndrome and Epigenetics e.g. FTO gene

7. CNS conditions especially hypothalamus tumours, trauma, inflammation. Even right sided brain CVA/trauma causing Gourmand syndrome which is an excess craving for gourmet foods

8. Iatrogenic: numerous medications causing weight gain especially psychiatric medications

9. Mental illness with a direct link to schizophrenia, depression and eating disorders

10. Miscellaneous: post cigarette smoking where men can gain on average 3.5kg and women 7 kg!

Most think of obesity in judgmental terms like the 7 deadly sins of Dantes’ Inferno:

Sloth, gluttony, greed, vanity… termed the SALIDRA

The modern sins are the excesses of the subtle S’s:

Sugar, salt, saturated fats, smoking, sedentary, sleeplessness, stress

6

1. DIETARY INDUCED OBESITY (DIO)

It is true that if you gain excess body fat you are definitely eating WRONG! Wrong amount, wrong type, wrong timing…

When it comes to eating, I use the mnemonic for EATING which is

F A T T E R

Frequency, Amount, Type, Timing, Enjoyment, Repeat.

When it comes to exercise, I use the mnemonic

F I T T E R

Frequency, Intensity, Time spent, Type, Enjoyment, Return.

Most people eat more than 700 – 1,000 kilocalories (4,200 kilojoules (kJ)) daily which is our basic food requirement as adults to maintain homeostasis. Our average daily diets contain 2,000 – 3,000 kilocalories (12,600 kJ) per day and so we are always in an excess.

The truism is that if we ate less, we would lose weight but to a level of only 10% weight loss then the weight will plateau due to changes in our metabolic rates further resisting weight loss. This is a called the SET POINT. The highest weight that we are is our PEAK POINT. Our goal weight as adults is the BMI of 24 which is our IDEAL POINT.

80% of people who have weight loss due to dietary changes alone are unable to maintain their weight loss due to epigenetic changes that aim for survival and restoration of what is termed our THRIFTY WEIGHT i.e. our comfort weight. Weight loss in our body is seen as illness. We lose weight with wasting disease and we deplete reserves, so the body aims to maintain the weight as much as possible.

Consumption of processed food can produce significant and abrupt weight gains and memory deficits – and in the aging population, rapid memory decline has a greater likelihood of progressing into neurodegenerative diseases such as Alzheimer’s disease.

7

Research is published recently in the Journal Brain, Behavior, and Immunity (reference: Dietary DHA prevents cognitive impairment and inflammatory gene expression in aged male rats fed a diet enriched with refined carbohydrates” by Michael J. Butler, Nicholas P. Deems, Stephanie Muscat, Christopher M. Butt, Martha A. Belury and Ruth M. Barrientos, 20 August 2021) shows that an unhealthy diet triggers inflammation in the aging brain, with a specific focus on the hippocampus and amygdala regions. Even short-term, high-fat high-carbohydrate diets can lead to memory loss and brain inflammation.

DHA, or docosahexaenoic acid, is an omega-3 fatty acid that is present along with eicosapentaenoic acid (EPA) in fish and other seafood. Among DHA’s multiple functions in the brain is a role in fending off an inflammatory response.

The research randomly assigned 3-month-old and 24-month-old male rats to their normal diet (32% calories from protein, 54% from wheat-based complex carbs and 14% from fat), a highly processed diet (19.6% of calories from protein, 63.3% from refined carbs – corn-starch, maltodextrin, and sucrose – and 17.1% from fat), or the same processed diet supplemented with DHA.

Activation of genes linked to a powerful pro-inflammatory protein and other markers of inflammation was significantly elevated in the hippocampus and amygdala of the older rats that ate the processed diet alone compared to young rats on any diet and aged rats that ate the DHA-supplemented processed food.

The amygdala in humans has been implicated in memories associated with emotional (fear and anxiety-producing) events. Both age groups gained a significant amount of weight on the processed diet, with old animals gaining significantly more than the young animals.

8

Our diets and eating habits are often culturally determined. Of all the nutritional plans, the types of diets which are best, pay attention to high fibre and the quality of carbohydrates.

What’s the best diet plan to lose weight? Improve your heart health? Lower your blood sugar? Or reduce the risk of Alzheimer’s Disease. Over 600 different diets have been published from Atkins and South Beach to Weight Watchers, NOOM, Keto, Paleo, Vegan, Whole 30, DASH, MIND, Mediterranean, gluten-free, Banting and more. The most important key factors are:

1. >100 g fibre per day from unprocessed plant-based diet

2. Fermented foods

3. Less cooking, less steps in processing, back to natural state

4. Less salt

5. Less refined sugars

6. More water: 3% body weight especially around times of eating

7. Eat undistracted, chew slower and savour

8. No more quickies - quickly produced, quickly eaten

9. Controlled snacking and drinking

10. Think SUPER FOODS.

9

Figure 1. The graph above demonstrates how rapidly we gain weight from ultra-processed foods.

Figure 2. Within 2 days on a diet just reducing processed foods, there is a weight reduction. Our bodies cannot further metabolise or process already processed foods, so they are simply stored as excess calories in fat tissue.

∆ B

ody

Wei

ght (

kg)

Ultr

a-pr

oces

sed

- Unp

roce

ssed

∆ Energy Intake (kcal/d)Ultra-processed - Unprocessed

-500-2

-1

0

1

2

3

4

5

6

0 500 1000 1500 2000

r=0.8 p<0.0001

Body

Wei

ght C

hang

e (k

g)

Days on Diet

0-1.5

-1

-0.5

0

0.5

1

1.5

2 4 6 8 10 12 14

Ultra-processed Unprocessed

10

2. STRESS

When it comes to stress, we focus on the adrenal gland. In the short term, acute stress triggers the adrenal sympathomimetic system (adrenalin > cortisol) for our FIGHT or FLIGHT decisions. These cause the high heart rate and high BP. Long term mental stress changes sympathomimetic response from the adrenalin fight flight to hypercortisolaemia SUBMIT AND STAY and we become accustomed to this new status quo which leads to decision fatigue and inertia. This stress causes dysregulation LIMBIC system and the CEREBRAL system which interacts with the periventricular ARC area of the hypothalamus and amygdala. The centre of weight control.

The brain is the central hub of weight control. 90% of the 2,000 genes that control weight are focused in the brain. The balance between anorexia (not eating) and orexia (eating) or hyper-phagia (excess eating) lies in this fragile area.

Remember the balance between Ghrelin vs Leptin, Insulin and cortisol vs GLP-1 and GLP-2 and the central role of MC4 receptor (MC4R).

The dove tail between stress and sleep is therefore vital.

11

3. SLEEP

SLEEP DEPRIVATION is associated with lowered leptin levels, raised ghrelin levels and higher eating at night and rapid increase in BMI. Night shift workers have a higher BMI than day working colleges.

Sleep disturbances account for 30% of weight gain. < 5hrs per night is harmful, the ideal duration is 7- 8 hours. Excess sleep also harmful (> 9 hours) as is daytime sleeping in adults. A u-shaped curve therefore exists for ideal sleep time. In the first phase of sleep latency phase one should initiate sleep within 10-15 minutes of repose. Blue-light stimulates the awake centre and prevents this first stage of sleep. Duration of sleep is more important than quality of sleep.

Within one hour of sleep our growth hormone peaks, our testosterone peaks and cortisol and adrenalin and insulin drop. Leptin peaks and ghrelin drops. This creates the perfect calm milieu for weight loss as opposed to the chaotic daytime perfect storm of weight gain. Sleep deprivation raises nocturnal cortisol levels and there is a loss of cortisol diurnal biorhythm causing a Cushing’s syndrome.

Sleep is important to slow heart rate, lower BP, deeper slower breathing. This is termed NIGHT DIPPING. Loss of this dipping is one of the major aetiological factors in hypertension and cardiac disease is sleep apnoea.

We must be asleep in dark room, no blue light stimulation, no white noise from between 22h00 - 05h00 when the cortisol levels are at their lowest.

Sleep deprivation is a sign of our modern times. Spiegel et al Annals of Internal medicine 2004. Patients were assessed after 48 hours of sleep deprivation and found to have a 25% increased hunger due to ghrelin peak levels and there was a drop in leptin levels and increased cortisol and insulin levels. They had an increase in cravings, mainly for quick low nutritional carbohydrates as the brain only sees and uses glucose as fuel for brain activity.

12

4. INFLAMMATION

Classic immune-metabolic syndromes include HYPOTHYROIDISM caused mainly by Hashimoto’s thyroiditis. DIABETES MELLITUS by anti-GAD antibodies, SLE, rheumatoid arthritis and especially PSORIASIS.

Chronic inflammation stimulates macrophages which are intrinsically linked to adipocytes and gut lymph nodes. They trigger oxidative stress due to inflammation and promote more abnormal fat distribution and WAT (white adipose tissue) remodelling and fat cell hypoxia. (see Module #3 Pathophysiology of obesity)

As we get older and fatter, our allergic responses become more inflammatory. B lymphocyte response change to a more T cell lymphocyte-based response.

In autoimmune diseases a newly identified lymphocyte called the X-lymphocytes cell that cross between T and B cells and adipocytes.

Inflammatory, and possibly infective, aetiology exist for obesity. Adipose tissue is known to be a repository of various cytokines, especially interleukin-6 and tumour necrosis factor alpha. There is an association between obesity and a high-normal level of plasma pro-calcitonin, a dependent variable that reflects a state of infection!

In COVID-19 disease the adipocyte is a reservoir for the corona virus.

Adenovirus-36 infection is associated with obesity. The prevalence of adenovirus-36 infection is 20-30% in people who are obese, versus 5% in people who are not obese.

Post appendectomy there is an increase in weight. This is due to a change in the gut bacteria. The appendix is the nursery hub for our good bacteria

and once it is removed, we are prone to the over-growth of “bad” bacteria IBS, inflammatory bowel disease and obesity! Post

cholecystectomy also causes weight gain with the changes of bile salts concentrations which are essential is controlling fatty

acids in the bowel.

13

We need a diversity of over 20 trillion species of bacteria for symbiotic health from production of vitamin K to the absorption of macro- and micro-nutrients to the reduction of inflammation to the production of serotonin.

Hippocrates said that all diseases originate in the gut and Cicero said that we are what we eat.

Changes in our diet, cooking methods and processing of foods have changed the microbiota flora of our guts. We eat less raw natural foods and our diets are lower in fibre and higher in salts and sugars. Microwaving and plastic containers especially with BPA, kill our good bacteria.

5. INTESTINAL MICROBIOME

14

Antibiotic use and abuse especially in farming where it is used to fatten livestock. Antibiotics are associated with the metabolic syndrome and cardiac disease e.g. azithromycin and inflammation, especially tendonitis such as first-generation quinolones e.g. ciprofloxacin and they are also contra indicated to be prescribed with ACE inhibitors and ARB’s because they cause acute renal damage due to their inflammatory induction.

Once again antibiotic stewardship is brought into question. Not every infection needs an antibiotic. Azithromycin in out-patient COVID-19 has shown no benefits.

The use of Pre- and Probiotics is debatable, but the best foods are fermented foods such as yoghurts, cheeses, pickling, kefir, cottage cheese, buchu, sour milk, vinegar…

Higher rates of Caesarean sections cause new-borns to have weaker gut microbiota due to the sterile process of delivery and it is advisable that all babies at birth are given maternal vaginal and anal swabs orally, to increase their bacterial biodiversity and reduce atopy. The higher rates of C-sections has caused the spike in obesity and atopy in modern day children.

Is Faecal transplantation therefore a therapeutic option for obesity as it is in inflammatory bowel disease?

One of the benefits of BARIATRIC SURGERY is the change in gut flora post operation.

There is also the debate about the continuous use of PPI’s proton pump inhibitors causing gastric acid changes and possible bacterial overgrowth as well as the role that helicobacter pylori plays in obesity.

15

6. EXERCISE

Most of our work is much less labour intensive. With computerisation you find yourself sitting and staying in one position for hours exposed to blue light. Especially now in the pandemic with lockdowns and more than 40% of the workforce working from home. We have become more sedentary and we sit in traffic, sit at work, sit on couch at home. Someone remarked homo erectus is now homo siticus? Sitting is the new sugar and the loss of skeletal exercise has profound impact on our health.

The lower our skeletal muscle efforts and the lower our energy expenditure and the shorter our lives (the SHIFT trial showed that fitness and a slow pulse rate will get you to 98 years of age and beyond).

Despite digital monitoring (apps and wearable technologies), we actually move less than the arbitrary 10,000 steps per day. We should engage in a minimum of 30 minutes of activity, 3 times a week of walking more than 3km at a time: 30/3/3.

The less we move the more fat builds up between the muscle fibres. This forms a type of myopathy and less physical tensile strength like wagu beef! This is a form of insulin resistance. Think of those people with huge triceps and legs with limb fat.

Remember the mnemonic F I T T E R

Frequency, Intensity, Type, Timing, Enjoyment and Return.

16

We can only do so much exercise beyond a certain point and there will be no change in our metabolism, this is termed CONSTRAINED. Our V-Q max respiratory quotient and MET have a plateau.

Activity: Energy ratio that is constrained actually starts to drop down after a period of time.

(Pantzer H et al Genetic Biology 2016 :26(3))

We must have a balance between resistant anaerobic exercise and endurance aerobic. But all in all we must keep moving.

Pulse monitoring usually aids our intensity:

220 - age in years and 85% of that level sustained for 20-30 minutes.

Rule of thumb you should double your resting heart rate! The night after exercise, you have higher levels growth hormone and leptin and less cortisol and insulin. Exercise also increases GLP-1 levels and is essential to reverse fatty liver disease and inflammation.

17

7. HYPOTHYROIDISM

500 million people in the world are affected by hypothyroidism. Very little endemic iodine deficiency exists due to supplementation. Most people are under-diagnosed especially, a vulnerable group of men >60 years of age! Normal TSH is 0.3-3! Once your TSH is over 3 you have sub-clinical hypothyroidism. Most malignancies in cold nodules have TSH levels of around 4.5. The ratio of free T4 : free T3 is 5:1.

Primary causes are the most common causes that directly involve the thyroid gland e.g. Hashimoto’s thyroiditis, post I-131 radiation, radiation, infections, thyroidectomies.

Secondary causes involve the pituitary gland with decreased TSH. Here you cannot use TSH levels, T4:T3 is essential in diagnosis.

Tertiary causes are often related to medication e.g. amiodarone.

When testing, one must do at least three tests: TSH, Free T4 and Free T3.

Every thyroid should have a sonar done. On therapy TSH should be 0.1-1 and for thyroid cancer 0.

Sub-clinical hypothyroidism has a low T3 and may have increased reverse T3.

Underactive thyroid function also causes:

• Raised MCV

• Lower sodium

• Increased lipids

• Increased CPK

• Increased serum creatinine

18

Low thyroid causes slowing of physiological and mental activity. The presentation is widespread and often missed. Cold intolerance and fatigue and bradycardia, dry coarse skin, alopecia, loss lateral eyebrows, nail changes. Thickened tongue, fullness in throat, dysphagia, hoarseness. Depression, pseudo dementia, loss ankle reflexes. Oligo-menorrhea and infertility. Puffiness especially peri-orbital and pretibial myxedema.

Medication to avoid in hypothyroidism: -

• Amiodarone

• INF alpha

• IL-2

• Thalidomide

• Lithium

• Stavudine

• Rifampicin

• Phenytoin

• Ethionamide

• Flax seed

19

When treating using replacement levothyroxine, the starting dose 1.6ug /kg. This alters for the elderly, osteoporotic or tachyarrhythmia. Amount of thyroid used is to suppress TSH to <1 in primary hypothyroidism. In pregnancy the dose increases monthly 1.8ug/kg to prevent cretinism.

The question always remains when to use T3?

• Symptomatic despite levothyroxine dose

• Free T4:free T3 ratio 5:1

• when using androgens and oestrogens

• Raised reverse T3 levels

• Subclinical hypothyroidism

• GIT Helicobacter Pylori gastritis

• Coeliac disease

20

8. CUSHING'S SYNDROME

An excess of cortisol in both primary disease that is pituitary based with raised CRH and non-suppressible ACTH, secondary syndrome with adrenal disease and tertiary with exogenous administration of cortisol. Indirect factors are high stresses, high inflammation, high allergies and sleep deprivation. These are the most common causes.

Cortisol levels can be measured using cortisol at 08h00 or at midnight. The peak and the dip of cortisol diurnal rhythm. This can be measured in both blood or saliva.

If high androgens are also measured, then you must check for a tumour of adrenal glands. Also if ACTH doesn’t allow for natural cortisol suppression. High cortisol directly causes uncontrolled hypertension and high glucose levels with visceral fat deposits.

It is a difficult condition to treat as it is very insidious and even after adrenal surgery, 50% of patients still have high cortisol levels.

You can indirectly block the cortisol by using anti-fungal medication e.g. ketoconazole. Or directly block using Mifepristone. Spironolactone is used for the mineralo-cortisone side.

21

9. PCOS = POLY CYSTIC OVARIAN SYNDROME

PCOS has a dual presentation and by definition it is a hormonal imbalance with anovulation and/or hyper-androgenicity. It is both an INSULIN RESISTANT and hyper-STEROIDOGENESIS condition.

PCOS is one of the most common endocrine disorders with more than 20% of females (i.e. 1/5) showing PCOS polymorphology but only 7% of the population have the true genetic disease.

PCOS is directly associated with obesity, and this weight change is dependent on insulin resistance in 40% and the remaining 60% due to abnormal steroidogenesis. In females, a high hormonal level results in a higher weight! This is opposite to male patients who often have hypogonadism.

In PCOS full metabolic syndrome is common from an early age in puberty. Sleep apnoea is 5-10 fold increased which is often not diagnosed in young females.

The P* H* O classification is newer approach to PCOS aimed at presentation and management.

P = phenotype, H = hirsutism and O = oligomenorrhea.

22

Cholesterol is converted to steroids and in PCOS there’s increased androgenic steroids and pregnenolone via CYP11alpha. This raises cortisol and therefore they have Cushingoid features.

4 SUBTYPES described using the ROTTERDAM criteria: -

1. PHO = full syndrome weight, oligo-menorrhea, and hirsutism with insulin resistance with metabolic syndrome in 50%

2. PH = normal menstrual cycle but weight and hirsutism high.

3. PO = oligomenorrhea with no hirsutism

4. HO = oligomenorrhea and hirsutism, no insulin resistance.

Diagnostic marker in the blood is a LOW SBG = sex binding globulin due to high steroid levels.

70% inherited pattern, but the difficulty is the phenotypic heterogenicity regarding the Rotterdam criteria. It is termed more Oligo-genetic

1. FTO the first described obesity gene has a minor alelle rs 9939609 in 455 PCOS (Diabetologia 2008) and is associated with a raised BMI

2. PPARƴ is the marker for insulin resistance, they often have a low vitamin D level

3. TCF7L2 is linked to beta cell dysfunction and raises insulin which can cause type 2 diabetes mellitus

4. CYP 19, 11α 5α indicates raised androgens

GWAS genome study showed 16 variants in PCOS 3 loci 2p163, 2p21,9p333

Associated with the FSHϐgene, Gonadotropin gene, Gutter4 gene of insulin

23

10. IATROGENIC

Just like central focused genes and diseases of the brain, so most of the centrally acting medications are to blame for weight gain.

1. Anti-epileptics: -

• Valproate

• Carbamazepine

• Phenytoin

2. Anti-depressants: -

• SSRI Trans fluoxetine e.g. (citalopram)

• Amitriptyline TCA

• Tetracyclic Mirtazapine

• SNRIs (venlafaxine)

3. Anti-psychotics: -

• Olanzapine

• Trazadone

• Risperidone

• Fluoxetine

• Lithium

4. Sedating Antihistamines: -

• Cyproheptadine

• Chlorpheniramine

• Promethazine

• Loratadine

24

5. Anti-inflammatories: -

• NSAIDS: diclofenac

• Cortisone

• Cyclosporine A

6. Anti-hypertensives: -

• Thiazide diuretics

• Beta blockers especially first generation no ISA e.g. propranolol

7. ARVs: -

• Stavudine

• Non-nucleotide reverse transcriptase inhibitors

• Protease inhibitors

8. Steroids and anti-diabetic medications: -

• Cortisone

• Insulin

• GH excess

• Sulphonylureas

• Oestrogens

• Progesterone

• Anabolic steroids.

25

11. MENTAL HEALTH

There is a direct link with depression and obesity. The highest weight gains are found in schizophrenia where there is a shared genetic link on TCF7L2 and of cause the use of anti-psychotic medications. Depression is often linked to eating disorders and colloquially termed MODD FOOD. Where dopamine and serotonin are elevated using food as an anti-depressant. Food addiction is common. Most anti-depressants affect weight gain and the sleep disturbances with depression also add to this pseudo-Cushingoid situation.

Surprisingly after bariatric surgery, 33% of patient have severe depression. Is it the link to gut production of serotonin?

Figure 3 describes the link between obesity and depression the cyclical nature in which patients feel trapped.

26

A recent study showed that hypercortisolism is associated with recurrent affective disorders, which increases the risk for metabolic disorders and cardiovascular risk factors such as obesity, overweight, large waist, high low-density lipoprotein (LDL) levels, and low high-density lipoprotein (HDL) levels.

Severely obese children (BMI at or above 120% of the 95th percentile) between ages 2 and 5 years were more likely to have the following characteristics:

• Being African American (odds ratio [OR]: 1.7) or Hispanic (OR: 2.3) USA studies

• In South Africa, African and biracial girls

• Engage in more than 4 hours of screen time (OR: 2.0)

• Coming from households characterized by a lower level of educational achievement (OR: 2.4)

• Coming from a single-parent household (OR: 2.0)

• Coming from a household living in poverty (OR: 2.1)

• In addition, children in this age group who had never been breastfeed were at higher risk of severe obesity (OR: 1.9)

• Underlying childhood ADD and depression

• Stresses of obesogenic environments.

27

QUARANTINE 15 - NEW STRESS IN THE PANDEMICThe COVID-19 pandemic began with overwhelming uncertainty for much of the general population. The government-imposed lockdowns have led to major lifestyle changes for individuals around the world. With the high risk for disease transmissibility in social settings, people were instructed to stay indoors and practice social distancing. Following a rapid shift to virtual jobs, trips to the workplace had quickly turned into frequent trips to the fridge.

People were unable to keep up with usual physical activity during the time spent at home. The accessibility and convenience of frequent snacking increased.

With the onset of the pandemic, rates of depression and other mental health disorders are also on the rise. A common feature of depressive disorders is an increase in carbohydrate and sugar craving and consumption, which is a major risk factor for the onset of obesity. The two diseases share multiple features, and with the chronic nature of obesity, patients with comorbid obesity and depression generally have a worsened course of illness.

28

Nearly 80% of primary care physicians prescribe antidepressants as a first-line treatment option. As such, there is an increase in mental health diagnoses during the pandemic with an increase in antidepressant prescriptions Commonly prescribed antidepressants may contribute to weight gain.

Clinically significant anti-depressive effects may also be reached through physical activity. Data suggests that regular exercise may be efficacious in reducing mild to moderate symptoms of depression.

High-intensity exercise is found to be associated with improvements in executive functioning and working memory tasks, while all forms of exercise, regardless of intensity, help improve attention, visual memory, and spatial planning.

29

SUMMARY

When looking at the complexity of aetiological factors I have created a 10-pronged approach. You can count them on the digits of your hands.

1. What is your diet “F A T T E R ?”

2. What is your exercise “F I T T E R ?”

3. What is your sleeping pattern?

4. What are your stresses or moods?

5. What medication do you take?

6. What allergies do you have?

7. What inflammation do you have?

8. What are the hormones like?

9. What is the family history?

10. What is your gut like?

30

QUESTIONS:1. In the cause of obesity:a) Only one cause is normally foundb) Sleep deprivation plays a large rolec) Diet is the main factor more than 60%d) Aerobic exercise is essential as it helps 80% weight losse) All medications are safe to use when trying to lose weight.

2. Diet induced weight loss includes:a) Eating 6 meals a dayb) No intermittent fasting allowedc) Eating after midnightd) Low fibre diete) Drinking water: 3% body weight daily.

3. With regards to sleep:a) Sleep apnoea is a high risk for cardiac arrhythmiasb) Minimum of 4 hours a night is important c) Quality sleep more important that quantityd) Sleep deprivation reduces ghrelin levelse) Night time increase in BP is essential.

4. In exercise:a) 90 minutes daily recommendedb) Only weight training is beneficial c) Heart rate must at least double during exercised) Ongoing exercise increase weight loss without a plateaue) Exercise damages the body and therefore raises your cortisol levels.

5. Chronic inflammation:a) Causes increase in Interleukin -6 and TNF alphab) Increase cortisol levelsc) Linked to psoriasis d) None of the abovee) All of the above.

31

6. PCOS is associated with:a) Low SBG and low LHb) Only caused by insulin resistancec) Must always have menstrual irregularitiesd) Very rare condition e) Has a monogenic inheritance pattern.

7. Hypothyroidism:a) Primary hypothyroidism has a low TSH levelb) Reverse T3 is a form of subclinical hypothyroidismc) Levothyroxine is given at 50ug daily for all patientsd) Poses no risk for cardiac disease e) Sonography not essential.

8. In Cushing’s syndrome:a) Tumours of the pituitary are malignantb) ACTH suppression test causes an increase in cortisol levels c) Glucose levels are often very lowd) Surgery helps only 50% of patients e) Causes generalized subcutaneous fat deposition.

9. ARV medication causes:a) Weight loss in patientsb) Have no effect on metabolic syndromec) Can cause weight gain and increased risk diabetes mellitusd) Result in macrophage depletione) No renal disease and so renal function test are not needed.

10. When looking to aetiology of weight gain: -a) All Anti-epileptics cause weight lossb) All Anti-depressants help with weight lossc) All Anti-histamines help with weight lossd) None of the abovee) All of the above.

Brought to you by