Lecture 8.1: Type 1 and 2 Diabetes Mellitus Flashcards
What is Diabetes Mellitus?
A disease in which the body’s ability to produce or. respond to the hormone
insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood
Type 1 Diabetes
Occurs when body is unable to produce enough insulin
Tends to develop at young age
Cannot be prevented
Require insulin therapy
Type 2 Diabetes
Occurs due to insulin resistance
Tends to develop at an older age
Can be prevented with lifestyle changes
Can be managed with lifestyle modifications alone is diagnosed early
Diabetes Symptoms: Type 1 and 2
Frequent urination
Increased thirst and hunger
Unintentional weight loss
Fatigue
Blurry vision
Sores/wounds heal slowly
Numbness/tingling in arms and feet
Prediabetes
Means you have a “higher than normal” blood sugar level
It’s not high enough to be considered type 2 diabetes, but without lifestyle changes, adults and children with prediabetes are more likely to develop type 2 diabetes
Characteristics of Blood Glucose Regulation Disorders
• Chronic hyperglycaemia
• Long-term clinical complications
• Elevated glucose levels in urine
• Patients are thirsty
Diagnosis of Diabetes Mellitus
How is glucose used?
• Taken up by cells to be used as energy for all organs
• Liver and muscle metabolise glucose to glycogen
• When glycogen stores full
• Liver metabolises glucose to triacylglycerols
• Carried to adipose tissue as VLDLs for storage
Why would blood glucose rise to abnormal levels?
• Glucose remains in the blood. Not taken up by tissues. Hyperglycaemia.
This is because of:
• Lack of insulin (relative or absolute)
• Or ineffective insulin
• The body is essentially starved of glucose
How would Hyperglycaemia present?: Osmotic Effects
Polyuria
Dehydration
Thirst (polydipsia)
Glycosuria
Opportunistic Infections (thrush, UTIs)
How would Hyperglycaemia present?: Metabolic Impact
Inadequate Energy Utilisation (wasting)
Lethargy
Catabolic Crisis
Diabetic KetoAcidosis (DKA)
“Melting of flesh into urine”
When does ketogenesis start?
Mitochondrial oxaloacetate depleted
Acetyl CoA reacts with itself to form acetoacetate and 3-hydroxybutyrate (ketone bodies)
Body is in desperate need for fuel source
Hyperosmolar Hyperglycaemic State
• HHS, used to be called HONK (HyperOsmolar Non-Ketotic State)
• Very high levels of solute in the blood affecting the osmotic balance
• Resulting in severe dehydration
• Water lost in urine
• Water from cells of body tissues (including brain) drawn out into blood
• High risk of blood clots
Long-term effects of hyperglycaemia (2)
Glycation of proteins (Glucose reacts non-enzymatically with free amino groups in cellular and extracellular proteins)
Formation of Reactive Oxygen Species (ROS) (free radicals: damaging lipids, proteins and DNA)
Effects of Glycation of Proteins
“Sticky” Blood
Causing microvascular damage/stiffened vessels:
• Neuropathy
• Retinopathy
• Nephropathy
• Hypertension
Formation of Reactive Oxygen Species (ROS)
Contribute to vascular damage
Beta cells thought to be particularly prone to enhanced oxidative phosphorylation, causing oxidative stress and loss of β cell function.
A vicious circle…
Diabetic Peripheral Neuropathy
Peripheral neuropathy is nerve damage caused by chronically high blood sugar and diabetes
It leads to numbness, loss of sensation, and sometimes pain in your feet, legs, or hands
Diabetic Retinopathy
Issue at the back of the eye (retina)
At first, diabetic retinopathy might cause no symptoms or only mild vision problems but may eventually lead to partial or complete blindness
Diabetic Nephropathy
Kidney damage caused by diabetes
Damage blood vessels in the kidneys as well as nephrons so they don’t work as well as they should
Many people with diabetes also develop high blood pressure, which can damage kidneys too
Macrovascular complications of Diabetes
Cerebrovascular, cardiovascular, peripheral vascular disease
– Stroke
– Heart Attack
– Intermittent Claudication
– Gangrene
Cost of Diabetes
Diabetes accounts for about 10% of the NHS budget and 80% of these costs are due to complications
Diabetes will increase the cost of social care; an amputation significantly impacts a person’s ability to look after themselves independently
Why the rapid increase in prevalence of Diabetes?
• Obesity
• Longevity
• Unsatisfactory Diets
• Sedentary Lifestyle
• Urbanisation & Economic Development
Diagnosis: Haemoglobin A1C
Glycated plasma proteins causing ‘sticky’ blood
HbA1C is a commonly measured glycated protein, minor component of haemoglobin
Level of HbA1C tells us cumulative exposure to plasma glucose concentration, over last 120 days
Most reliably demonstrate 8 week average glucose control
Diagnosis
Diagnosis
Treatments for Type 1 Diabetes
Insulin Injection
Treatments for Type 2 Diabetes: Excluding Non-Insulin Therapies
• Lifestyle
• Insulin
Treatments for Type 2 Diabetes: Non-Insulin Therapies
Insulin sensitizers
Insulin secretagogues:
• Biguanides (metformin)
• Sulphonylureas
• Thiazolidinediones (rosiglitazone)
• GLP1 analogues
• DPP4 inhibitors
• α-glucosidase inhibitors
• SGLT2s
Latrogenic Risks: Hypoglycaemia
• Emergency, so treat immediately
• Brain damage
• Cardiac arrest
• Coma
• Death
How do we monitor patients with diabetes? (6)
• Wellbeing
• Educate and empower to monitor own diabetes
• Glucose control - capillary blood glucose testing vs urine glucose testing
• HbA1c – glycated haemoglobin
• Other vascular risk factors – BP, lipids, smoking, exercise, diet
• Surveillance for complications
