Diabetes Flashcards by Mo Hussain

Define Diabetes

Diabetes Mellitus is a set of metabolic disorders in which defects in insulin secretion and/or action leads to Hyperglycaemia and disturbances in carb/protein/fat metabolism

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What are the types of Diabetes?

Type 1 (Insulin Dependant DM)
Type 2 - (Insulin Independant DM)

Maturity Onset Diabetes in the Young (MODY)
Secondary DM
Gestational Diabetes

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What causes Type 1 diabetes?

Its an autoimmune condition in which lymphocytes infiltrate the islets of langerhans causing insulitis (destruction of beta cells that produce insulin)

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Describe the genetic component of Type 1 Diabetes?

Human Leukocyte Antigen (HLA) genes

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How do we treat type 1 diabetes?

Daily insulin injections (as Peptide hormones don’t work orally)

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What causes Type 2 diabetes?

Central Adiposity

> Free FAs in blood
> Decreased Insulin Receptor Sensitivity (Insulin Resistance)

NOrmally the body increases production of insulin to match the resistance, however in people with gene variants that code for Poor high end insulin secretion cant keep up and end up hyperglycaemic

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How do you treat Type 2 Diabetes

1) If you can catch them in a pre-diabetic stage you can restore sensitivity through exercise and diet
2) Oral Hypoglycaemics e.g. Metformin
3) Sulphonylureas
4) Insulin injections

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How do Type 2 Diabetes drugs work?

Oral Hypoglycaemics like metformin antagonise glucagon and inhibit gluconeogenesis to maintain a lower Glc level.

Sulphonylureas close K+ channels in beta cells, stimulating insulin secretion

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Explain the OGTT:

Measure fasting glucose and compare to level 2 hours after ingesting a glucose load.

Normally blood [Glc] returns to normal within 1 hour but diabetics will still be elevated after 2

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At what point in childhood does diabetes present?

At any point but mostly in adolescence

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How do we diagnose childhood onset diabetes?

4Ts:

Tired
Thinner
Thirsty
Toileting more (incl return to day or bed wetting)

Then test with a finger prick glucose test

If suspected refer to a specialist for a same day review

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Why is it so important to diagnose diabetes as quickly as possible?

Undiagnosed children can very easily go into Diabetic Ketoacidosis -> Coma -> Death

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Many children present with diabetes in Diabetic Ketoacidosis, how do we spot this?

N&amp;V
Sweet Ketotic breath
Drowsiness
rapid deep sighing respiration (body is hyperventilating to clear CO2 and so raise the pH)
Coma

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How does diabetes affect the lifespan/mortality rate?

Diabetics have a 5-10 yr reduced life expectancy and twice the mortality rate (5.4% annually)

MIs are the most common cause of death

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What are the long term complications of hyperglycaemia?

DM accelerates Atheroma leading to CAD, MIs & Stroke

Accelerates Arteriolar disease leading to Renal Disease, PVD and blindness

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Explain the mechanism behind which Diabetes accelerates Atheroma

Excess Glc attaches to LDL
LDL can no longer bind to receptors and be cleared in the liver
Hyperlipidaemia occurs

Explain the mechanism by which diabetes causes arteriolar disease?

Normally molecules flux between the blood and subendothelial space.

In DM the high glucose glycosylates Subendothelial collagen and basal lamina proteins resulting in:

1) Collagen binds albumin preventing it from fluxing back out the subendothelial space
2) Basal lamina proteins cross link and accumulate

This causes a build up of proteins in the wall known as the hyaline change

How is Hypoglycaemia an issue for diabetics?

Diabetics who overuse insulin or skip meals can develop hypoglycaemia which if severe enough leads to:

Cognitive Dysfunction
Lethary
Coma
Convulsions
Death

What does uncontrolled diabetes present in the short term?

Thirst (polydipsia)
Tiredness
Polyuria/nocturia
Weight loss
Blurred Vision
Abdominal pain
Dehydration
Can develop into DKA or HHS

What are the methods of testing for Diabetes?

Random Glucose tests
Fasting Glucose Tests
Oral Glucose tolerance Test
HbA1c blood test

What is HbA1c?

Glycated Haemoglobin

Sugar in the blood binds to haemoglobin, the amount that does is directly proportional to the total amount of Glucose.
So HbA1c levels reflect the level of glucose in the blood over the last 10-14 days

What are the diagnostic criteria for Diabetes?

Two Diagnostic tests without symptoms

Or 1 diagnostic tests with symptoms

What values would make a diagnostic test +ve for diabetes?

Fasting glucose > 7mmol/l
Random glucose >11.1mmol/l
OGTT >11.1mmol/l after 2 hours
HbA1C >48mmol/mol

When can we not use an HbA1c test?

Anything that effects the haemoglobin level e.g.:

Pregnancy
Acute illnesses
Renal failure
very recent pancreatic damage/removal
HIV
Meds that cause short term glucose spikes e.g. CCS
Children

A diagnostic test for people with diabetes require showing they are hyperglycaemic, but what is intermediate hyperglycaemia?

Intermediate hyperglycaemia is where glucose/HbA1c levels are raised but don't meet the threshold for diabetes. These people are considered high risk for diabetes, CVD and associated complications

As we've seen Hyperglycaemia can accelerate large and small vessel arterial disease, retinopathy, neuropathy and nephropathy but what are its short term complications?

Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycaemia State (HHS)

Define Diabetic Ketoacidosis?

Low levels of insulin cause a high level of Fatty Acids in the blood. They're converted to Ketone bodies in the liver to be used for energy Causes acidosis of the blood leading to: - N&V - Sweet Ketotic breath - Drowsiness - Rapid deep sighing respiration (hyperventilation) - Weakness, confusion -> Coma - Polyuria

Define Hyperosmolar Hyperglycaemic State

High blood sugar levels resulting in a high osmolarity of blood without significant ketoacidosis. ``` More common in Type 2, it leads to: - Dehydration Weakness - Leg cramps - Visual problems - Altered Consciousness ```

What is MODY?

An autosomal dominant genetic syndrome making up 5% of diabetics, thus important to check for FH of diabetes. Basically a single gene defect leads to impaired B-cell function. It looks like Type 2 but presents in young people

What are the sub-types of MODY?

Depends on the kind of mutation: ``` Glucokinase mutations # Onset at Birth # Stable hyperglycaemia # Treated with diet # Rare complications ``` ``` Transcription Factor Mutations # Adolescent onset # Progressive Hyperglycaemia # Treated with diet, oral hypoglycaemics and insulin # Frequent complications ```

What is Secondary Diabetes Mellitus?

DM brought on by: - Drugs e.g. CCS - Pancreatic destruction/removal - Genetic syndromes - Endocrine disorders e.g pheochromocytoma, cushings or acromegaly

What is gestational diabetes?

Increased insulin resistance brought on by pregnancy Associated with FH of type 2, being overwight and inactive. It also increases risk of Type 2.

What does gestational diabetes cause regarding the baby?

- Foetal Macrosomia (big baby) - Neonatal Respiratory arrest - Neonatal Hypoglycaemia

In short how does diabetes present?

- thirst - Tired - Polyuria/nocturia - Weight loss - Blurred vision - Abdominal pain - Dehydration - Low grade infections e.g. thrush If they've reached DKA: - Ketotic breath - N&V - Hyperventilation - Tachypnoea/tachycardia Type 2 diabetics are rarely ketotic but are usually overweight. They are also more likely to present with complications, having had long-term low grade diabetes

What are the treatments for diabetes?

Exact treaments depend on the type: Type 1 - Insulin Type 2: - if you catch them in the prediabetic stage try to restore sensitivity through exercise/diet - Oral hypoglycaemics - Sulponyureas - Insulin

Describe how Oral Hypoglycaemics (OHG) & Sulphonyureas work?

OHG e.g. metformin: - Inhibits gluconeogenesis and antagonizes glucagon Sulphonyureas: - Close ATP-dependant K+ channels in beta cells, stimulating Ca2+ entry and so insulin vesicle exocytosis