Type 1 and Type 2 diabetes

Question 1

What is type 1 diabetes?

Answer 1

inability to produce/secrete insulin due to autoimmune destruction of the beta-cells in the pancreatic islets of Langerhan.

Question 2

What is type 2 diabetes?

Answer 2

a combination of peripheral insulin resistance and inadequate secretion of insulin. It is strongly associated with obesity and the metabolic syndrome.

Question 3

At what age does type 1 diabetes develop?

Answer 3

typically develops in children and adolescents

But condition can develop at any age

Question 4

Which genes are associated with diabetes development?

Answer 4

HLA-DR3- DQ2

HLA-DR4-DQ8

Question 5

Which other autoimmune conditions is type 1 diabetes associated with?

Answer 5

Autoimmune thyroiditis

Graves disease

Coeliac disease

Addison’s disease

Pernicious anaemia

Question 6

Describe the hypotheses behind diabetes development - combination of genetic and environmental factors

Answer 6

genetically susceptible individuals may develop autoantibodies that target the beta-cells in response to an external trigger (e.g. viral infection).

Question 7

Which autoantibody is most commonly found in those with type 1 diabetes?

Answer 7

anti-glutamic acid decarboxylase (anti-GAD) antibody

Question 8

Where is anti-glutamic acid decarboxylase (anti-GAD) antibody found?

Answer 8

enzyme found within beta cells of the pancreas

Question 9

What is the normal range for blood glucose?

Answer 9

3.5-8.0 mmol/L.

Question 10

What are the consequences of decreased insulin concentration in the body?

Answer 10

More glucose is produced by the liver -
Increases glycogenolysis and gluconeogenesis

Decreased glucose uptake
Increased lipolysis

Decreased glucose uptake in adipose tissue and muscle

Decreased protein synthesis and increases protein degradation (increased fat and muscle break down)

Reduced peripheral uptake of glucose to use for energy. Weight loss occurs

Question 11

What happens to the blood sugar when enough insulin is not being produced?

Answer 11

hyperglycaemia - high blood sugar

Question 12

Which acid base disorder is associated with type 1 diabetes and how does it develop?

Answer 12

metabolic acidosis
Body is not obtaning enough enegery as glucose is not being taken up peripheraly and being used for energy

Fatty acids are taken up into hepatocytes and converted into ketone bodies.

Ketone bodies are released back into the circulation and utilised for energy in the form of ATP.

The development of ketosis leads to metabolic acidosis

Question 13

What are the features of Latent-onset autoimmune diabetes in adults?

Answer 13

Type 1 diabetes later in life
autoimmune destruction of beta cells
tends to have a gradual onset.

patients who develop diabetes in adult life with associated ketosis, weight loss, low BMI and family history of autoimmune disease.

Question 14

What are the signs and symptoms of type 1 diabetes?

Answer 14

Symptoms

• lethargy
• polyuria
• polydipsia
• weight loss
• Vomiting

Signs

• Mild-moderate dehydration (dry skin, dry mucous membranes, reduced skin turgor)
• BMI < 25

Question 15

How is type 2 diabetes diagnosed?

Answer 15

classical clinical features are found in the presence of a raised random blood glucose level.

Question 16

Which further tests are conducted on patients suspected with Latent-onset autoimmune diabetes in adults?

Answer 16

c-peptide, genetic testing

Question 17

There are 5 main aspects to the management of type 1 diabetes - name them

Answer 17

Insulin use and regimes

Blood glucose monitoring

Treatment targets

Monitoring for
complications

Education

Question 18

List the different types of insulin used in the treatment of type 1 diabetes

Answer 18

Rapid acting - Novorapid, Lispro

Short acting - Humulin R

Intermediate acting - Humulin I or N

Mixed - Humulin M3
or Humulin 70/30: Mix of short and intermediate-acting insulin

Long acting - Lantus, Levmir

Biphasic - mixture of rapid and intermediate eg Novomix 30

Question 19

What are the 3 main insulin regimes used in patients with type 1 Diabetes?

Answer 19

Basal-bolus regime - rapid- or short-acting insulin before meals and a long-acting preparation for basal requirements.

One, two, or three injections per day regime: - traditionally a biphasic regime with the use of both short-acting and intermediate-acting insulin as separate injections or a mixed product.

Continuous insulin infusion via a pump - supplies rapid- or short-acting insulin. It may be used in patients who are experiencing troubling hypoglycaemic episodes with multiple daily injections regimes.

Question 20

Which of the insulin regimes is used for newly diagnosed patients?

Answer 20

Basal-bolus regime

Question 21

Which of the insulin regimes is used for patients having troubling hypoglycaemia episodes?

Answer 21

Continuous insulin infusion via a pump

Question 22

How often are people with hypoglycaemia required to monitor there blood glucose in a day? When during the day can it be monitored? What is the target blood glucose at monitoring period?

Answer 22

At least four times a day

On waking: fasting blood glucose 5–7 mmol/L

Before meals: blood glucose 4–7 mmol/L

Post meals: test after 90 minutes, blood glucose 5–9 mmol/L

Can also measure it before bed instead of in the morning

Question 23

Under which conditions may a patient be required to monitor there blood glucose more than 4 times daily

Answer 23

porting activities, pregnancy and in those with hypoglycaemic episodes.

Question 24

What is used to monitor the long term control of blood glucose? How often should the test be conducted?

Answer 24

HbA1c - glycated haemoglobin, indicative of the average blood glucose over 3 months

It should be repeated every 3-6 months to assess glycaemic control.

Question 25

What should the target HbA1c be? When may a higher target be required?

Answer 25

HbA1c < 48 mmol/L (6.5%). Higher threshold? hypoglycaemic episodes, occupation and co-morbidities.

Question 26

How often should patients obtain a diabetic complications review. What is assessed during these reviews?

Answer 26

At least once a year- more often if required Assessment of injection site - fat accumilation Retinopathy review - screening Nephropathy review - renal function (eGFR) and albumin:creatinine ratio (ACR) Diabetic foot review (neuropathy) - full examination including footwear, monofilament assessment of neuropathy, vascular assessment +/- dopplers. Cardiovascular risks - optimisation of blood pressure, lipids, weight, smoking and others Thyroid disease - Blood tests

Question 27

Which Retinopathy complications are associated with diabetes?

Answer 27

Non prolifertaive - Dilation of the retina veins and microaneurysms which can cause internal hemorrhaging and oedema in the retina. Oedema in the central retina is the main cause of vision loss in this case - Dot and blot haemorrhages - Hard exudates - Cotton wool spots - Venous beading (pre- proliferative) Proliferative Fragile, new blood vessels form near the optic disk and grow on the vitreous chamber and elsewhere in the retina. They can bleed, reduce vision and lead to separation and detachment of areas of the retina - new vessels at the disc and elsewhere - fibrosis - traction retinal detachment Maculopathy - Exudates - Oedema

Question 28

Which Nephropathy complications are associated with diabetes?

Answer 28

Disease of the kidney involving damage to the blood vessels in the glomerulus is characterised by proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis First sign = microalbuminuria, which can be assessed with an albumin:creatinine ratio (ACR). An ACR 3 - 30 mg/mmol is suggestive of microalbuminuria

Question 29

Which neuropathy complications are associated with diabetes?

Answer 29

Damage to the nerve fibres and blood vessels supplying nerves - Peripheral It causes pain or loss of feeling in the hands, arms, feet, and legs It causes pain in thighs and hips and weakness in legs - It can cause changes in digestion, bowel (gastric paresis) and bladder control problems, and erectile dysfunction It can affect any nerve in the body and it causes pain or weakness Symmetrical polyneuropathy: typically a peripheral neuropathy that occurs in the leg secondary to loss of vibration, pain and temperature sensation. Mononeuropathy: damage to a single cranial or peripheral nerve (e.g. third nerve palsy). Diabetic amyotrophy: a spectrum of disease affecting the lumbosacral plexus leading to symmetrical pain, weakness and wasting in the proximal muscles of the leg. Autonomic neuropathy: a spectrum of conditions related to damage of the autonomic nervous system, which can effect multiple systems.

Question 30

Which Cardiovascular complications are associated with diabetes?

Answer 30

- Increases risk of atherosclerosis plaque formation - Tissue nutrient and oxygen supply to heart and brain and extremities is compromised - Cerebrovascular disease (stroke) - Heart Disease (Myocardial infarction, congestive heart failure) - Peripheral vascular disease (ulceration, gangrene and amputation

Question 31

In the context of type 1 diabetes what does the term sick day rules mean?

Answer 31

Understanding what to do during intercurrent illnesses is essential in patients with T1DM to prevent poor glycemic control and potential ketoacidosis.

Question 32

List 5 sick day rules

Answer 32

Continue insulin therapy, alterations may be required, advice from a specialist may be sought Increase frequency of blood glucose monitoring Consider ketone monitoring Maintain good hydration and when possible a normal meal pattern, meals may be replaced by carbohydrate based drinks Seek urgent medical attention if unable to tolerate oral intake, drowsy or sustained vomiting

Question 33

Which Diabetic foot problems /complications are associated with diabetes?

Answer 33

Due to loss of sensation and poor blood supply, patients are at risk of a number of complications including diabetic ulcers, secondary infection (e.g. cellulitis, osteomyelitis), skin necrosis and eventually amputation. Charcot’s joint - results from loss of sensation and subsequent repeated micro-trauma to the foot. Typically mid foot. Microtrauma in the presence of poor peripheral blood flow leads to remodelling, swelling and distortion of the whole joint.

Question 34

Which skin infections are those with diabetes prone to?

Answer 34

staphylococcal skin abcesses, oral or genital candidiasis

Question 35

Which symptoms are associated with typ2 2 diabetes?

Answer 35

- polyuria - polydipsia - nocturia - weight loss - fatigue - blurred vision - pruritis - recurrent urinary or genitourinary infections

Question 36

Name the 4 tests used in the diagnosis of diabetes

Answer 36

Fasting plasma glucose (FPG) Random plasma glucose (RPG) 75 gram oral glucose tolerance test (OGTT) Haemoglobin A1c (HbA1c, glycated haemoglobin)

Question 37

What is the difference in diagnosiing diabetes in someone with symptoms and in someone without?

Answer 37

for an individual who has no symptoms, two diagnostic tests are required (eg 2x FPG, or HbA1c, but only one abnormal OGTT is required) One diagnostic test is enough to diagnose diabetes for someone with symptoms

Question 38

What is the difference in diagnosing diabetes in someone with symptoms and in someone without?

Answer 38

For an individual who has no symptoms, two diagnostic tests are required (e.g. 2x FPG, or HbA1c, but only one abnormal OGTT is required) One diagnostic test is enough to diagnose diabetes for someone with symptoms

Question 39

For each test used in diagnosing diabetes, state which values are normal, abnormal, and indicative of impaired glucose tolerance (IGT)

Answer 39

Fasting plasma glucose N = <6.0 DM = >7.0 IGT = <7.0 Impaired fasting glucose = 6.1-6.9 Random blood glucose N = <7.8 DM = >11.1 HbA1c N = <42 (5.9%) DM = > 48 (6.5) IGT = 42-47 (6.0-6.4) 2H plasma glucose N = <7.8 DM = >11.1 IGT = 7.8-11.0 IFG = <7.8

Question 40

For each test used in diagnosing diabetes, state which values are normal, abnormal, and indicative of impaired glucose tolerance (IGT)

Answer 40

Fasting plasma glucose N = <6.0 DM = >7.0 IGT = <7.0 Impaired fasting glucose = 6.1-6.9 Random blood glucose N = <7.8 DM = >11.1 HbA1c N = <42 (5.9%) DM = > 48 (6.5) IGT = 42-47 (6.0-6.4) 2H plasma glucose (OGTT) N = <7.8 DM = >11.1 IGT = 7.8-11.0 IFG = <7.8

Question 41

Which endocrine disease can cause diabetes?

Answer 41

Acromegaly - excess growth hormone Cushing’s syndrome - excess cortisol Glucagonoma - excess glucagon Phaechromocytoma - excess catecholamines Hyperthyroidism - excess thyroid hormone Conn’s syndrome- excess aldosterone

Question 42

Which drugs can cause diabetes?

Answer 42

Glucocorticoids b-blockers Thiazide diuretics Tacrolimus (used in transplantation – may cause “New Onset Diabetes after Transplantation” [NODAT]) Atypical anti-psychotics – eg. olanzapine, risperidone, clozapine

Question 43

Which infections can cause type 2 diabetes?

Answer 43

Congenital rubella Cytomegalovirus others

Question 44

What does the term glucose toxicity mean with regards to type 2 diabetes?

Answer 44

When hyperglycaemia enhances insulin resistance and b- cell failure (unable to produce as much insulin) in type 2 diabetes High glucose = poorer B cell function so less insulin secretion

Question 45

What are thrifty genes?

Answer 45

Genes,which favour that favour fat storage and / or insulin resistance help us in times of famine May be overly activated in diabetes

Question 46

How do fat cells contribute to insulin resistance?

Answer 46

pro-inflammatory cytokines from adipocytes contribute to insulin resistance

Question 47

In type 2 diabetes, what happens to the mass of beta cells and alpha cells?

Answer 47

b-cell mass is relatively preserved a-cell population increased – leads to excess glucagon relative to insulin

Question 48

Later on with type 2 diabetes, which protein is deposited in the pancreas which lings diabetes to dementia?

Answer 48

Amyloid peptide deposition in the pancreatic islets occurs late in the disease

Question 49

List the 5 main factors associated with metabolic syndrome?

Answer 49

- Central Obesity - Low HDL Concentration - High Triglyceride - High Blood pressure - increased Fasting glucose

Question 50

Which individuals should be screened for type 2 diabetes?

Answer 50

- Over weight people - Strong family history of diabetes - History of gestational diabetes - Ethnic minorities ▪ South Asian – 6x increased risk ▪Afro-Caribbean – 2x increased risk Individuals with known vascular disease - Coronary Heart Disease, - Peripheral Vascular Disease, - Cerebrovascular disease - Patients on steroids / atypical anti-psychotic therapy / transplants Unexplained foot ulcers / recurrent candida / skin abscesses

Question 51

When can using HbA1cot diagnose diabetes be problematic?

Answer 51

conditions interrupting erythropoiesis (e.g. EPO use, iron-deficiency), haemoglobin structure issues (e.g. haemoglobinopathies), glycation issues (e.g. CKD, alcoholism), red cell survival (e.g. haemolysis, splenectomy)

Question 52

What are the 3 main injection sites for insulin? List in order of fastest absorption site to slowest

Answer 52

Abdomen Thighs Buttocks