Topic 5 - Diabetes and Obesity

Question 1

What stress and support do those with diabetes and obesity have?

Answer 1

Stress of the day to day management of their disease and the mental load this can have.
Diabetic patients are well supported by diabetic nurse, GMP, podiatrists, ophthalmologist etc. Obese patients don’t have same level of support.

Question 2

What energy source does the brain use?

Answer 2

Glucose - 80mg/minute.

If glucose isn’t present, uses ketones (lipids).

Question 3

How much glucose do your peripheral tissues use?

Answer 3

50mg/minute at rest.

During exertion it increases.

Question 4

How is glucose transported into cells?

Answer 4

Facilitated diffusion using GLUT-4 uniporter transporters. The co-transporter is sodium ions so you may hear them referred to as SGLT - sodium glucose transporters.

GLUT-3: not insulin dependent, found in neuronal cells - brain and nerve tissue
GLUT-4: insulin-dependent. Insulin has to bind to it to open the transporter up to allow glucose to enter the cell.

Question 5

Is fasting a binary term?

Answer 5

No. It’s a gradient. So as you get more and more glucose depletion, more and more ketones are synthesised.

Question 6

What are ketones synthesised from and how can it be used?

Answer 6

Synthesised from fatty acids.

They can cross the blood-brain barrier and be used as an adjunct and replacement for glucose in fasting states.

Question 7

Talk about what happens when food and drink is digested and the anabolic and catabolic pathways.

Answer 7

When carbs are digested, they become glucose. You can use that glucose for use now at the cells or for storage in tissues for later. Insulin is used to allow storage of glucose in tissues in the form of glycogen. This is the anabolic pathway.

When stored in the tissue, at rest, glucagon works to release glucose for use to raise the sugar levels in the blood. This can be between meals or at night. This is part of the catabolic pathway.

At times of physical or surgical stress, epinephrine (adrenaline) and cortisol work to release glucose from stored tissue. This is part of the catabolic pathway.

Question 8

What is the stored form of glucose called and where is it stored?

Can it be mobilised into blood glucose from these stores? What’s the process that does this?

Answer 8

Glycogen
Stored in liver and muscles

In the liver, it can be converted into liver glucose and then blood glucose for use in the bloodstream through the process of glycogenolysis.
In the muscles, it can be converted into muscle glucose and used only for muscles, not in the bloodstream.

Question 9

Define glycogen

Answer 9

A polysaccharide of glucose

Question 10

Define anabolic and catabolic pathway

Answer 10

Anabolic pathway - the pathway of insulin storing glucose in tissues

Catabolic pathway - the pathway of releasing glucose from stored forms for use. This includes cortisol, epinephrine and glucagon.

Question 11

How can you synthesise new glucose?

Answer 11

From lipid digestion into fatty acids, then into triglycerides, and then into glycerol.
That, along with pyruvate lactate and amino acids can be used in gluconeogenesis to produce new glucose.

Question 12

Define diabetes mellitus.

Answer 12

A group of disorders characterised by persistently raised blood glucose levels.

Question 13

What are the causes of diabetes mellitus?

Answer 13

It can be caused by a lack of insulin, inability to respond to insulin, or combination of both.

Question 14

Why must you be careful when referring to something as diabetes?

Answer 14

There is also a condition called diabetes insipidus which is unrelated to glucose levels.

Question 15

What are the four types of diabetes mellitus?

Answer 15

Type 1 DM

Type 2 DM

Gestational diabetes mellitus

Other specific types of diabetes mellitus:

• Monogenic defect - a single gene defect which could encode for insulin resulting in diabetes. Could be associated with genetic conditions like Down’s Syndrome or Turner’s syndrome.
• Drug-induced DM. Like long term corticosteroid treatment.
• Secondary to pathological conditions like pancreatitis or trauma.
• Secondary to iatrogenic causes like pancreatic surgery (after pt has pancreatic cancer and it’s been removed so can’t produce insulin anymore).

Question 16

The pancreas has both endocrine and exocrine functions. What does this mean?

Answer 16

Endocrine - production of insulin.

Exocrine - production of digestive enzymes that are secreted into the duodenum

Question 17

What is Type 1 diabetes? How is it caused?

Answer 17

T-cell mediated destruction of beta-cells in Islets of Langerhans in the pancreas. These cells normally produce insulin. When it reaches 90% destruction, symptoms occur.

Question 18

Does Type 1 DM have a rapid onset or not?

Answer 18

Yes, can get diagnosed in childhood or late teens, depending on when the 90% point is reached. But once you reach it, clinical symptoms rapidly onset.

Question 19

What are some key clinical signs of Type 1 DM?

Answer 19

• Polyuria: excessive urination because of increased glucose in urine so kidneys can’t retain water and this leads to fluid depletion and you become dehydrated
• Polydypsia: excessive thirst
• Weight loss: without insulin, glucose can’t be stored in the body, so muscles have to use catabolic pathways and energy from fat stores is used.
• Fatigue: extreme fatigue as very little ketone is produced but a lot of effort goes into producing it

Question 20

Test

Question 21

How is type 1 and type 2 DM monitored?

Answer 21

Finger prick test is a measure of capillary blood glucose at that time.
HbA1c is a measure of glycated Hb (Hb becomes glycated in presence of sugar). This is done every 90 days - 3 months as that’s the lifespan of RBCs.

Question 22

What should the target of HbA1c be?

Answer 22

Below 48mmol/mol or 6.5%.

Question 23

What is diabetic ketoacidosis (DKA)?

Answer 23

A complication of type 1 DM. When your body is producing ketones (catabolic pathway), these are acidic and can make your body’s pH lower, leading to metabolic acidosis. Is fatal if untreated.

Question 24

What are the clinical signs of DKA?

Answer 24

• Confusion
• Rapid deterioration
• Vomiting, diorrhoea, abdominal pain and shaking
• Diminished consciousness (termed diabetic coma). They have no insulin so no glucose and just ketones so really acidic.
• Kussmaul breathing or air-hunger
• Patients have fruity or acetone smelling breaths because of the ketones.

Question 25

What can cause DKA?

Who should you suspect DKA in?

Answer 25

• Binge drinking
• Missed insulin doses (e.g. due to dental pain, not eating etc so don’t take insulin).
• Infection (glucose levels rise but without insulin they’re not going anywhere).
• Surgery

Suspect DKA in a known diabetic patient who’s significantly hyperglycaemic (over 11mmol) with symptoms of DKA.

Question 26

What advice should you give to patients to avoid DKA?

Answer 26

Still eat something even if it’s a sugary drink, take insulin doses and monitor finger-prick test more often.

Question 27

What is a complication that can occur with Type 2 diabetes mellitus and what are the signs of it?

Answer 27

HHS (Hyperosmolar Hyperglycaemic State) - signs are similar to DKA. Finger prick test will say ‘high’ as it has a limit and in these patients it can be well over 30mmol.

Question 28

How should you treat pts with DKA or HHS?

Answer 28

Emergency put them in ambulance and send to hospital.

Question 29

What is type 2 DM and what are the causes?

Answer 29

Type 2 DM is when a person is hyperglycaemic due to an inability to respond to insulin appropriately, and later on in the disease, dysfunction of b-cells in the Islets of Langerhans.

It can’t respond to insulin because of failure of intracellular signalling pathways. Normally insulin binds to GLUT-4 and the transporter opens to let glucose into the cell. Here, this doesn’t open and so glucose can not be taken up by the muscle and fat cells.

The dysfunction of b-cells means there’s a deregulation in the normal homeostatic mechanisms that control insulin production. So can have a lot or can have too little.

When there’s not enough insulin, this means it can’t suppress liver’s production of glucose. So overall there’s rising levels of glucose and reduced uptake of glucose so overall higher net levels of glucose.

Question 30

What is the onset like in type 2 DM?

Answer 30

Insidious onset and can evolve over many years

Question 31

What are the risk factors for type 2 DM?

Answer 31

• Obesity. 80x more likely to develop type 2 DM than someone with BMI <23.
• Ethnicity
• Family history. Obesogenic environment.
• History of gestational diabetes can increase mother’s and child’s risk of type 2 DM.
• Diet.
• Other things like steroid use.

Question 32

Define gestational diabetes.

Why is the incidence increasing? Who is it prevalent in?

Answer 32

Gestational diabetes is diabetes that occurs or is first recognised in pregnancy.

Incidence increasing bc of obese mothers and also people getting pregnant later in life.

More prevalent in Asians than caucasians.

Question 33

Is there a particular part of pregnancy when gestational diabetes is more likely?

Answer 33

Second half of diabetes when insulin resistance develops.

Question 34

What are the risks of gestational diabetes?

Answer 34

• Macrosomia. Big foetus. This can result in stillbirth, miscarriage or early infant death.
• Macrosomia also means there’s a higher likelihood of mother needing emergency C-section or having a traumatic birth
• Pre-eclampsia

Question 35

Can gestational diabetes resolve after pregnancy?

Answer 35

Yes, but the mum is still 7x more likely to develop type 2 DM later in life.

Question 36

What is the impact of chronic DM?

Answer 36

1. Microvascular disease
   - Capillary endothelial damage and basement membrane thickening
   - Retinopathy
   - Neuropathy
   - Nephropathy
2. Macrovascular disease.
   - Accelerated atherosclorosis
   - CVD, cerebrovascular disease and peripheral arterial disease
3. Metabolic complications
   - DKA
   - Dyslipidaemia

Question 37

Can wound healing be varied?

Answer 37

Varies from strongly affected to not affected at all

Question 38

Causes of poor wound healing in DM?

Answer 38

Impaired immune function because neutrophils act abnormally. They don’t do the stop, drop and roll.

The high glucose concentration is also optimal for fungi and bacterial infections to take hold. Can result in amputations.

Question 39

How does DM affect oral health?

Answer 39

• Periodontal (salivary gland function and impaired immune response can result in perio disease. Bi directional relationship and level of control affects perio and vice versa).
• Xerostomia (altered quality and quantity of saliva due to microvascular and autonomic neuropathies, and dehydration from increased glucose leading to reduced saliva, as well as side effect of drugs)
• Fungal infections - poor wound healing so candida can take hold
• Sialosis - uninflammatory asymptomatic enlargement of the major salivary gland, normally the parotid gland
• Adverse taste due to metformin

Question 40

What are two types of drugs used in managing type 1 DM?

Answer 40

Short acting insulin after each meal to help bring the carb levels down. E.g. humalog.
Long acting insulin taken morning and night to ensure there’s no dramatic peaks and troughs e.g. lantus.

Question 41

How can you manage type 2 DM?

Answer 41

Weight loss through diet and exercise.

• Biguanides e.g. Metformin. These only work in the presence of insulin, so you’ve got to be secreting some insulin for these to work. They lower plasma glucose levels by increasing peripheral utilisation of glucose and decreasing gluconeogenesis.
• Gliptins e.g. sitagliptin inhibit an enzyme called DPP-4, which plays a major role in glucose metabolism. They also indirectly stimulate more insulin production and reduce glucagon secretion.
• Sulphonylureas e.g. Gliclazide augment insulin secretion - they stimulate the pancreas to produce more insulin. These are ones you do need to be aware of. If a patient takes their sulphonylurea in the morning and they miss their meal because they’re nervous of coming to the dentist or they have toothache, they can get quite profound hypoglycaemia from that because they’ve produced more insulin but they haven’t had anything to eat, so it’s just going to keep dropping their blood sugar levels. It’s not normally to a level where the patients are put at harm but it’s not ideal.
• a-glucosidase inhibitors. Not strictly an oral hypoglycaemic agent but they reduce carbohydrate absorption by the gut. Unfortunately, the carbohydrates then ferment in the gut so the abdominal side effects can be a challenge for these patients.
• Glitazones like pioglitazone enhance the effects of endogenous insulin, but fluid retention can be a problem, so they tend not to give it to patients with heart failure or renal impairment, which can be quite a significant number of patients with type 2 diabetes.
• Meglitinides like rapaglinide are glucose regulators that enhacnce insulin secretion (so like gliclazide be careful about skipping meals). They are glucose regulators and they have quite a rapid onset of action but a short duration, so they’re kind of used like how short-acting insulin is used.

Question 42

What technological advancements are there in glucose monitoring?

Answer 42

Libre - cannula under skin, measures CBG and sends info to app.
Insulin pump - delivers basal rate of insulin in cannula under the skin. Can hold 300 units of insulin which lasts 2-3 days. Can supplement with additional boluses of insulin after meals.

Have to rotate cannula sites to avoid lipidystrophy.

Question 43

Define obesity.

Answer 43

BMI 30+

Overweight is 25-30.

Question 44

Is BMI an accurate tool?

Answer 44

Yeah - the problem about muscle etc. only applies for bodybuilders more than regular people.

Question 45

What other measurement could you do as well as BMI?

Answer 45

Waist circumference - central fat deposition has a correlation with health issues.

Question 46

How do people get obese?

Answer 46

High fat and calorie dense diets, alongside/or physical inactivity.
3500 calories + puts on one pound of fat.

Question 47

What holds more calories - fat or carbs?

Answer 47

Fat

Question 48

Why is a small amount of fat necessary?

Answer 48

Vitamins A D E K are fat-soluble so stored in fat and absorbed in fat

Question 49

What is BMR?

Answer 49

The amount of calories you need at rest to function

Question 50

What is the management strategy for obese people?

Answer 50

Not putting on any more weight
Modest reductions in weight - can be difficult on joints and bones and the fact that 3500 calories need to be burnt for 1 pound to come off
Bariatric surgery - surgical sleeves to make the stomach smaller

Question 51

Factors that cause obesity?

Answer 51

Lack of physical activity - Netflix, supermarkets, office jobs
Diet - high fat high calorie dense, more processed food at supermarket, social outing
Other factors - genetics, smoking, medications

Question 52

What are some health implications of obesity?

Answer 52

There are multiple health implications with obesity.

• Reduced life expectancy. If you’re obesity grade 1 (BMI of 30), that will reduce your life expectancy by 7 years, up to obesity grade 3 which is formerly known as morbidly obese, that can be up to 13 years).
• having obesity can make you more likely to have type 2 DM, particularly Asian people are at much greater risk than Caucasians or black people
• Hypertension, heart failure and stroke (covered in cardiovascular lec)
• Coronary Heart Disease (covered in cardiovascular lec)
• Dyspnoea is shortness of breath. This is multifaceted so a physical restriction of weight on the thorax, particularly when you’re lying down, will limit the expansion, and abdominal mass will impede your diaphragm, and both of these will restrict your ability to inflate your lungs so restricts your ability to breath. There’s more oxygen demands by having increased tissue demands - so by having more fat, your oxygen demands are increased too.
• Obstructive Sleep Apnoea - obesity puts you at significant risk of this. OSA is repeated collapses of the upper airway (of the pharynx) which occludes the airway for 10-15 seconds, or longer, during sleep. This means a person never feels like they’ve had a good nights sleep and subsequently have increased fatigue levels during the day. The knock on effects of being tired all day means you’re less likely to want to eat well and go to the gym etc. so it can have a lot of effect on a person’s day to day life.
• There are psychosocial effects too, so things like anxiety, depression and low self-esteem are all really prevalent in obese people. They also face discrimination in education, in the workplace (where obese people actually tend to earn less than non-obese people). In healthcare, it’s not uncommon that someone will go into their GP with a problem completely unrelated to their weight and the GP may say have you considered weight loss - it’s in the patient’s best interest, but the patient went in for something completely different and weight loss shouldn’t be the first thing addressed. Also social relationships can be profoundly impacted. All of this has an impact on the psychology.
• Osteoarthritis - the weight of the body being increased has got a significant effect on the supporting skeleton, which has not got bigger but has stayed the same. The hips and the knees and the ankles are taking a lot more wear and tear. If you think about obesity, the cut off point can be 140kg for someone who’s at grade 3 cut off point - that’s double the average of our average 70kg man. The skeleton isn’t getting any bigger so the body is bearing double its expected weight.
• Stress urinary incontinence - it’s much more prevalent in women. It’s when you basically wee a bit when you laugh. It’s essentially increased mass like abdominal fat and pressure on the bladder.
• Menstrual dysfunction and reduced fertility are issues too
• Cancer (it’s only some cancers)
  It’s about 10% of all cancers in non-smokers and 30% of endometrial cancers. But it’s also got a notable correlation with hormone-related tumours like breast and prostate cancer, and other cancers like colon, renal and pancreatic cancers too.
• Gastro-oesophageal reflux - tends to do with the abdominal mass when the patient lies down and the weight of their abdominal mass compresses their organs. It can compress the stomach and cause reflux up through the oesophageal spincter (?).
• Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis- we’ll talk more about this in the hepatic and renal lecture. Obese people are more likely to have it.

Question 53

How should you think about obesity in dentistry?

Answer 53

• access to the building
• safe weight limit of dental chairs (usually 22stone/140kg)
• excess soft tissue around the head and neck
• prescribing drugs
• long procedures may lead to pressure sores
• increased prevalence of GORD
• Sedation and GA may be more difficult

Medical emergencies:

• IM needles may not reach muscle
• Difficult to provide effective CPR (moving patient, anatomical landmarks)
• Airway management and IV access can be difficult