Type 1 diabetes mellitus

Question 1

What is type 1 diabetes?

Answer 1

An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
The resultant hyperglycaemia requires life-long insulin treatment

Question 2

Why is the dichotomy of diabetes untrue?

Answer 2

There is significant overlap in the ways of presentation e.g Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)

Question 3

When does type 1 diabetes present?

Answer 3

Traditionally thought to be childhood/ early adu;thoos but it can present at any age.

Question 4

How does Type 1 diabetes develop?

Answer 4

Genetic predisposition
Immune Activation - Potential precipitating event ( e.g viral infection)
Immune Response - Development of single autoantibody
beta-cell mass degradation
progressive loss of insulin release
Overt diabetes; C-peptide present
No C-Peptide present

Question 5

Why is the immune basis important?

Answer 5

Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically
Immune modulation offers the possibility of novel treatments
Not there yet

Question 6

Describe the immunology in Type 1 diabetes?

Answer 6

Defect in both innate and active immune system.Primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
Exacerbated by release of pro-inflammatory cytokines
Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity

Question 7

Can people with type 1 Diabetes produce insulin?

Answer 7

Some have been found to be able to produce a small amount, but not enough to substitute the need for insulin therapy.

Question 8

What mediates genetic susceptibility for type 1 diabetes?

Answer 8

HLA-DR Allele

Question 9

What are possible environmental factors for Type 1 diabetes precipitation?

Answer 9

Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota

Question 10

What Pancreatic autoantibodies can you measure to confirm type 1 diabetes?

Answer 10

Detectable in the sera of people with Type 1 diabetes at diagnosis.
Not generally needed for diagnosis in most cases
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)

Question 11

What are the symptoms of type 1 diabetes?

Answer 11

polyuria
nocturia
polydipsia
Blurring of vision
Recurrent infections
Weight loss
Fatigue

Question 12

What are the signs of type 1 diabetes?

Answer 12

dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria

Question 13

What affects the diagnosis of type 1 diabetes?

Answer 13

Diagnosis is based on clinical features and presence of ketones.

Question 14

What happens when you don’t have enough insulin?

Answer 14

Breakdown of muscle protein
Increase glucose output from the liver
Break down fat cells (lipolysis)

Question 15

What ketone bodies can lead to diabetic ketoacidosis?

Answer 15

Acetyl CoA
Acetoacetate
Acetone + 3OH-B

Question 16

What are the main aims of treatment in type 1 diabetes

Answer 16

Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications

Question 17

Why do you lose weight in type 1 diabetes?

Answer 17

Osmotic diuresis
become dehydrated
anything you eat cant be used due to lack of insulin

Question 18

Is type 1 diabetes monogenic or polygenic?

Answer 18

Polygenic - susceptibility spread amongst many genes

Question 19

Why do you get blurred vision in type 1 diabetes?

Answer 19

High glucose in the eyeball, water moves in to dilute increased solute concentration.

Question 20

What are the acute complications of type 1 diabetes?

Answer 20

Diabetes ketoacidosis
Uncontrolled Hyperglycaemia
Hypoglycaemia

Question 21

What are the chronic microvascular complications of type 1 diabetes?

Answer 21

Retinopathy
Neuropathy
Nephropathy

Question 22

What are the chronic macrovascular complications of type 1 diabetes?

Answer 22

Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease

Question 23

What are the 4 tenets of type 1 diabetes treatment?

Answer 23

Insulin Treatment
Dietary support / structured educations
Technology
Transplantation

Question 24

What are the 3 features of insulins physiological profile?

Answer 24

Basal insulin has a flat profile
Insulin is never completely supressed
Prandial peak has two phases

Question 25

What are the short acting types of insulin?

Answer 25

``` Human insulin – exact molecular replicate of human insulin (actrapid) Insulin analogue (Lispro, Aspart, Glulisine) ```

Question 26

What are the long-acting types of insulin?

Answer 26

``` Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH) Insulin analogue (Glargine, Determir, Degludec) ```

Question 27

Describe Insulin pump therapy?

Answer 27

Continuous delivery of short-acting insulin analogue e.g. novorapid via pump Delivery of insulin into subcutaneous space Programme the device to deliver fixed units / hour throughout the day (basal) Actively bolus for meals

Question 28

What are the dietary principles for patients with type 1 diabetes?

Answer 28

Where possible, substitute refined carbohydrate containing foods (sugary / high glycemic index) with complex carbohydrates (starchy / low glycemic index)

Question 29

What is the artificial pancreas?

Answer 29

Real time glucose sensor, with an algorithm to use glucose value to calculate insulin requirement.

Question 30

What are the two types of transplantation?

Answer 30

Islet cell transplants Isolate human islets from pancreas of deceased donor Transplant into hepatic portal vein Requires life-long immunosuppression Simultaneous pancreas and kidney transplantBetter survival of pancreas graft when transplanted with kidneys Requires life-long immunosuppression

Question 31

How do we monitor glucose levels?

Answer 31

HbA1c

Question 32

Why do we measure Hb1Ac?

Answer 32

Reflect last 3 months (red blood cell lifespan) of glycaemia Biased to the 30 days preceding measurement Glycated NOT glycosylated (enzymatic) Therefore linear relationship Irreversible reaction Glycated haemoglobin

Question 33

What guides insulin doses?

Answer 33

Using self-monitoring of blood glucose results at home and HbA1c results every 3-4 months Based on results, increase or decrease insulin doses

Question 34

What is the diagnosis for diabetic ketoacidosis?

Answer 34

pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L

Question 35

What is the threshold hold for hypoglycaemia?

Answer 35

<3.6 mmol/L

Question 36

When does hypoglycaemia become a problem?

Answer 36

Excessive frequency Impaired awareness (unable to detect low blood glucose) Nocturnal hypoglycaemia Recurrent severe hypoglycaemia

Question 37

What are the risks of hypoglycaemia?

Answer 37

``` Seizure / coma/ death (dead in bed) Impacts on emotional well-being Impacts on driving Impacts on day to day function Impacts on cognition ```

Question 38

What are risk factors for hypoglycaemia?

Answer 38

``` Exercise Missed meals Inappropriate insulin regime Alcohol intake Lower HbA1c Lack of training around dose-adjustment for meals ```

Question 39

What is the acute management for hypoglycaemia?

Answer 39

Alert - Oral Carbs Drowsy - Buccal glucose Unconscious - IV glucose

Question 40

What is the treatment for Diabetic ketoacidosis?

Answer 40

Antiemetic IV fluids for dehydration through a drip Insulin to supress ketogenesis