Type 2 Diabetes Mellitus

Question 1

• Is T2 Diabetes common?
• Is it serious?

Answer 1

• Yes - common
• very serious problem

Question 2

Lifetime cost of diabetes in USA is … billion

Answer 2

815 billion dollars

Question 3

What is diabetes mellitus?

Answer 3

A condition where the blood glucose is above an internationally accepted level

Question 4

Diabetes - Diagnostic terms: Usual clinical diagnosis:

• ​Blood:
  
  • Glucose = or > … mmol/l + symptoms
  • Glucose = or > …mmol/l x 2
  • HbA1c = or > 48 mmol/mol (…%)
    
    • Lower value does not exclude diabetes

Answer 4

• Glucose = or > 11.1 mmol/l + symptoms
• Glucose = or > 11.1 mmol/l x 2
• HbA1c = or > 48 mmol/mol (6.5%)
  
  • Lower value does not exclude diabetes

Question 5

Diabetes - Diagnostic terms: 75 Glucose Tolerance Test

• Diabetes Mellitus:
  
  • Fasting plasma glucose = / > … mmol/l
  • 2 hour plasma glucose = / > … mmol/l
• Impaired glucose tolerance
  
  • 2 hour glucose between …-… mmol/l
• Impaired fasting glucose
  
  • fasting glucose between …-… mmol/l

Answer 5

• Diabetes Mellitus:
  
  • Fasting plasma glucose = / > 7 mmol/l
  • 2 hour plasma glucose = / > 11.1 mmol/l
• Impaired glucose tolerance
  
  • 2 hour glucose between 7-11 mmol/l
• Impaired fasting glucose
  
  • fasting glucose between 6-6.9mmol/l

Question 6

What is the gold standard test for diabetes?

Answer 6

75g Glucose Tolerance test

Question 7

What exactly is Type 2 diabetes?

• “A … condition where there is a … cells abnormality resulting in insuffient … to keep the … … normal in the context of … resistance”

Answer 7

“A common condition where there is a Beta cells abnormality resulting in insuffient insulin to keep the blood glucose normal in the context of insulin resistance”

Question 8

What cells are in the pancreas? (shown on histological slide)

Answer 8

Islet cells

Question 9

In the picture the islet cells are stained, what condition does this happen in?

Answer 9

T2 diabetes

Question 10

Cause of B cell problems in Type 2 diabetes

• Genetics
  
  • … (+ / - 60 genes)
• … programming (epigenetics)
  
  • maternal hyper…
  • intrauterine growth …

Answer 10

• Genetics
  
  • polygenic (+ / - 60 genes)
• Fetal programming (epigenetics)
  
  • maternal hyperglycaemia
  • intrauterine growth retardation

Question 11

Type 2 diabetes is seen in a high percentage of …

Answer 11

identical twins

Question 12

Other possible aetiological factors of Type 2 diabetes include… (3)

Answer 12

• old age
• change in the gut microbiota
• glucotoxicity and lipotoxicity (later effects)

Question 13

What is this showing? (what condition)

Answer 13

Type 2 diabetes

Question 14

Why are people insulin resistant?

• relates to …
• Many years of coping to deal with …
• Now, we have plenty of … available

Answer 14

• relates to obesity
• Many years of coping to deal with famine
• Now, we have plenty of calories and food sources available

Question 15

• Fat in the … laid down as it should be = no harm
• If it spills out (‘run out of room’) it spills and becomes … fat

Answer 15

• Fat in the buttocks laid down as it should be = no harm
• If it spills out (‘run out of room’) it spills and becomes visceral fat

Question 16

… fat is a strong risk factor for vascular disease

Answer 16

epicardial fat is a strong risk factor for vascular disease

Question 17

Excess fat in the diabetic … is specific to type … diabates and important in preventing normal … production

Answer 17

Excess fat in the diabetic pancreas is specific to type 2 diabates and important in preventing normal insulin production

Question 18

Ectopic fat - a problem

• It is acting like an … organ producing
  
  • free … …
    
    • causing … resistance
    • … lipids
  • cytokines
    
    • causing … resistance
    • pro … situation
  • pro… factors (PAI1)

Answer 18

• It is acting like an endocrine organ producing
  
  • free fatty acids
    
    • insulin resistance
    • atherogenic lipids
  • cytokines
    
    • insulin resistance
    • pro inflammatory situation
  • procoagulant factors (PAI1)

Question 19

This shows the problems caused by what type of fat?

Answer 19

ectopic fat

Question 20

Study - looking at CVS disease - 3 patients

• P1 - Individual of normal body weight - not much visceral. CVS issues at follow up?
• P2 - Lots of non visceral fat - fat in places designed to be lad down (some visceral fat) CVS issues at follow up?
• P3 - lots of visceral fat - (also ectopic fat in abdomen) - also fat around muscle - CVS issues at follow up?

Answer 20

• P1 - Individual of normal body weight - not much visceral. CVS issues at follow up? - no
• P2 - Lots of non visceral fat - fat in places designed to be lad down (some visceral fat) CVS issues at follow up? - no
• P3 - lots of visceral fat (ectopic fat in abdomen) - also fat around muscle - CVS issues at follow up? - yes - risk of developing hypoglycaemia because of their insulin resistance and this also compounds the whole situation

Question 21

This graph shows people with … syndrome vs people without it

Answer 21

metabolic syndrome

Question 22

Metabolic syndrome: other associations

• Fatty liver disease with …
• Hepatocellular carcinoma and intrahepatic cholangiocarcinoma
• Chronic … disease
• Polycystic … …
• …-disordered breathing
• Hyperuricemia and g…
• An increased risk of … decline and …

Answer 22

• Fatty liver disease with steatosis
• Hepatocellular carcinoma and intrahepatic cholangiocarcinoma
• Chronic kidney disease
• PCOS - polycystic ovarian syndrome
• Sleep-disordered breathing
• Hyperuricemia and gout
• An increased risk of cognitive decline and dementia

Question 23

Diagnosis of metabolic syndrome and insulin resistance

• Important physical sign is what?
• How do we measure it?

Answer 23

Important physical sign is what? - substantial abdominal obesity - measure and record via waist circumference

Question 24

Type 2 diabetes - UK prevalence 2017 (Diabetes UK)

• … million persons + … million at risk

Answer 24

4.6 million persons + 12.3 million at risk

Question 25

Adult obesity in england - risen from ...% in 1993 to ...% in 2016

Answer 25

Adult obesity in england - risen from **15**% in 1993 to **26**% in 2016

Question 26

The age group most likely to be overweight or obese is age ...-..., but only by a small margin

Answer 26

The age group most likely to be overweight or obese is age **55-64** but only by a small margin

Question 27

_Prevalence of overweight and obesity: (20 march 2018)_ * above ...% among from 45 upwards

Answer 27

above **70**% among from 45 upwards

Question 28

What is this graph showing? (increasing ... in young people)

Answer 28

What is this graph showing? (increasing **obesity** in young people)

Question 29

_Nurses health study (JCEM 2002 87:2784) - Diabetes_ * ...% Type 2 diabetes attributed to ... * BMI \> ... * Lack of ... * ... diet

Answer 29

* **96**% Type 2 diabetes attributed to ... * BMI \> **23** * Lack of **exercise** * **Unhealthy** diet

Question 30

Type 2 diabetes is not "... diabetes" it's "... ..." diabetes

Answer 30

Type 2 diabetes is not "**mild diabetes**" it's "**very bad" diabetes**

Question 31

_Type 2 diabetes - what's the problem?_ * ... side effects / morbidity related * ...glucaemia per se * Dysregulation of Lipid ... * High levels of ... cytokines * High levels of Free ... * Increased susceptibility to ...

Answer 31

* **Serious** side effects / morbidity related * **Hyper**glycaemia per se * Dysregulation of Lipid **Metabolism** * High levels of **proinflammatory** cytokines * High levels of Free **radicals** * Increased susceptibility to **infections**

Question 32

Microvascular damage to small blood vessels in the eye and the retina - leading to haemorrhages and exudate - macula - enables you to see clearly - if these get into centre person may lose vision * What condition may this happen in? * Why does this happen?

Answer 32

* What condition may this happen in? - **Type 2 diabetes** * Why does this happen? - **blood glucose too high for too long**

Question 33

* ... shown in the image are much more common in individuals with ... * There is an increased generation of polyols from ... * 1% reduction in ... reduces ... risk by 19%

Answer 33

* **Cataracts - common in diabetes** * There is an increased generation of polyols from **glucose** * 1% reduction in **HBA1c** reduces **cataract** risk by 19%

Question 34

* Renal disease in type ... diabetes * result of blood glucose being ...

Answer 34

* Renal disease in type **2** diabetes * result of blood glucose being **too high for too long**

Question 35

Another tissue which is damaged in T2 diabetes is the ... - longest ones suffer most - these are where? what develops? Do you notice it easily?

Answer 35

* Another tissue which is damaged in T2 diabetes are the **nerves - longest ones suffer most - in the feet** * **develop neuropathic ulcer** * **dont always notice it**

Question 36

Another problem with blood sugar being too high for too long in T2 diabetes is ... of connective tissue

Answer 36

Another problem with blood sugar being too high for too long in T2 diabetes is **glucosylation** of connective tissue

Question 37

_Bone in T2 diabetes_ * Mechanically ... * increased fractures x ... * in spite of normal bone ...

Answer 37

* Mechanically **weaker** * increased fractures **x 2** * in spite of normal bone **density**

Question 38

Treatment of hyperglycaemia reduces ... disease

Answer 38

**microvascular disease**

Question 39

Treatment of hyperglycaemia reduces larger blood vessel diseases such as .... and .... by a much smaller amount

Answer 39

Treatment of hyperglycaemia reduces larger blood vessel diseases such as **stroke** and **myocardial infarction** by a much smaller amount

Question 40

The major cause of death of people with T2 diabetes is what?

Answer 40

heart attacks

Question 41

_Type 2 diabetes - UKPDS study - prevention of complications_ * Long term follow up showed that good glycemic control reduces both ... and .... complications

Answer 41

**micro and macrovascular complications reduced**

Question 42

_Why do people with T2 diabetes have heart attacks?_ * Many people with diabetes have a lot of these inflammatory type .... particles circulating (more than those with normal BG) * 'Bad' cholesterol (called ...) - when you glycosalate it - with high BG this happens - becomes more ...genic and pro-... * Good cholesterol - known as ... - is lower in these individuals

Answer 42

* Many people with diabetes have a lot of these inflammaotry type **lipoprotein** particles circulating (more than those with normal BG) * **Low density lipoprotein**'bad' cholesterol - glycosalate - with high BG this happens - becomes more **atherogenic** and **pro**-**inflammatory** * 'Good' cholesterol - **HDL** - lower in these individuals

Question 43

_Atherosclerotic lesion - how does a MI happen?_ * ... plaque - if stable what happens? * If you have pro-inflammatory like proteins and other inflammatory substances being produced by the ... fat - inflammatory reaction inside the plaque - dissolves the cap - pro inflammatory material leaks into ... ... causing blood ... * How do we fix this?

Answer 43

* atheromatous plaque - if stable what happens? - **not much** * If you have pro-inflammatory like proteins and other inflammatory substances being produced by the **ectopic** fat - inflammatory reaction inside the plaque - dissolves the cap - nasty pro inflammatory material leaks into **coronary artery** causing blood **clot** * **Give clot blusters - restore blood flow and prevent MI**

Question 45

Large blood vessels in feet are affected by pro-inflammatory process (in T2 Diabetes) * What disease?

Answer 45

What disease? - Peripheral vascular disease

Question 46

_Type 2 Diabetes - what to do?_ * ... the diabetes * Improve the ... * Reduce the CVS risk factors (which are... 4) * ... for complication + ... early

Answer 46

* **Prevent** the diabetes * Improve the **hyperglycaemia** * Reduce the CVS risk factors (which are... 4) * **Dyslipemia** * **Hypertension** * **Smoking** * **Obesity** * **Screen** for complication + **treat** early

Question 47

Treating Type 2 diabetes - Stage 1 is changing peoples ... * How?

Answer 47

Treating Type 2 diabetes - Stage 1 is changing peoples **lifestyle** * **Via diet (less food, more healthy food), exercise (walk dog etc)**

Question 48

Telling Diabetes patients to eat better and exercise is not enough - what has been developed to support them?

Answer 48

* **Diabetes eduaction programmes e.g. Desmond**

Question 49

_Type 2 Diabetes & Macrovascular Disease_ * Prevention / Treatment * Lifestyle manouvres (3 things, which are ...) * Treatment of ... (3) * Use of ... (drug) * if known, or very high risk for CAD

Answer 49

* Prevention / Treatment * Lifestyle manouvres (3 things, which are **diet/exercise/smoking)** * Treatment of: * **Dyslipaemia** * **with statins** * **Hypertension** * **Hyperglycemia** * Use of **aspirin** (drug) * if known, or very high risk for CAD

Question 50

_Type 2 diabetes - Screening to enable early treatment_ * Eyes: * ... photography * ... treatment when required * Kidneys: * Measure urine ... (EMU) * Control Blood Pressure & ... * ... inhibitors & ARBs * Feet: * Screen for ...pathy & ... disease

Answer 50

* Eyes: * **Retinal** photography * **Laser** treatment when required * Kidneys: * Measure urine **albumin** (EMU) * Control Blood Pressure & **Glucose** * **ACE** inhibitors & ARBs * Feet: * Screen for **Neuropathy** & **Vascular** disease

Question 51

* What is this device for (left)? (Screening for...) * What about right device? * How often should we examine this area?

Answer 51

* **Microfilament** - screen for Neuropathy (use on feet) * Right - feel pedal pulses - absent - check with handheld **doppler** - if absent pulses and peripheral vascular disease - at risk for ulcers and amputation - serious coronary artery disease * How often should we examine this area - **feet examined once a year - avoid these issues**

Question 52

_Type 2 Diabetes - Goals_ * ... modification * Screen for ... * Special ... for complications * check 3 things: (which parts of body?) * HbA1c ... % (48-55 mmol/mol) * Blood pressure of around ...-.../80 * LDL * Non HDL cholesterol

Answer 52

* **Lifestyle** modification * Screen for **complications** * Special **clinics** for complications * **foot, renal, eye** * HbA1c **6.5-7.5** % (48-55 mmol/mol) * BP **120-140**/80 * LDL \<**2.0** mmol/l * Non HDL cholesterol \<**2.78**

Question 53

_Treating Type 2 Diabetes_ * Pharmacological interventions * Reduce ... resistance * Increase ... production/ secretion * Provide ... replacement * Metabolic/ Obesity ... * Sleeve ... * ... en Y Bypass * ... Band

Answer 53

* Pharmacological interventions * Reduce **Insulin** resistance * Increase **Insulin** production/ secretion * Provide **Insulin** replacement * Metabolic/ Obesity **Surgery** * Sleeve **Gastrectomy** * **Roux** en Y Bypass * **Gastric** Band

Question 54

_Treating Type 2 Diabetes - Goals must be tailored to the individual_ * Elderly * Less ... treatment * Avoid ... * ... women * Tight control

Answer 54

* Elderly * Less **aggressive** treatment * Avoid **hypoglycaemia** * **Pregnant** women * Tight conttrol

Question 55

Treating Type 2 Diabetes - Goals must be tailored to the individual - what particular groups of individuals (2)

Answer 55

* **Elderly** * **Pregnant women**