Diabetes & Obesity Flashcards
Can glucose be converted to fat?
Yup, glucose is broken down during glycolysis to form pyruvate and ultimately acetyl-CoA
Acetyl-CoA can be converted to Malonyl-CoA (Acetyl-CoA carboxylase) - which can then enter fatty acid metabolism, resulting in the formation of fatty acids.
What are the risk factors for type II diabetes?
What is the link between the microbiome and obesity?
Two common gut microbe phyla are Bacteroidetes and Firmicutes
- Firmicutes generate more harvestable energy - increases energy uptake
- Firmicutes more common in microbiome of obese people
Microbiome from obese and lean mice was transplanted into germ-free lean mice
- Mice given obese microbiome had greater weight gain
- Mice given obese microbiome stored more fat and became insulin resistance even when calorie-intake kept the same
Transfer a phenotype by transferring bacteria/microbiome
How does diabetes mellitus (both type 1 and 2) present?
Patients can have either…
1. Asymptomatic hyperglycaemia (normally associated with T2)
2. Symptomatic hyperglycaemia (normally associated with T1) - results in..
- Polyuria, polydipsia. Thirst
- Fatigue
- Recurrent infections – inhibits function of inflammatory cells
- Weight loss (type 1)
How is a diagnosis for diabetes made?
Different measurments that can be taken…
1. Random plasma glucose or 2 hours after a 75g glucose load > 11.1 mmol/L
2. Fasting plasma glucose equal or greater than 7.0 mmol/L
3. Haemoglobin A1c equal or greater than 48 mmol/mol
In asymptomatic patients you need two investigations separated in time
What results are required for a pre-diabetes diagnosis?
Impaired glucose tolerance = fasting plasma glucose ≤ 7.0 mmol/L and 2 hour glucose after a 75 g glucose load 7.8-11.1 mmol/L
Impaired fasting glucose = fasting glucose ≥ 6.1 and ≤ 7.0 mmol/L
What is Haemoglobin A1c? How is it used?
Haemoglobin A1c - measures the levels of hemoglobin glycosylation - higher blood sugar across time = higher levels of glycosylation
Important to remember that HbA1c takes time to become elevated as reaction is slow
HbA1c often used to monitor response to treatment.
Reference range 20-42 mmol/mol
42-48 = pre-diabetic
>48 = diabetic
How do type 1 and type 2 diabetes differ in terms of…
1. Weight loss
2. Ketonuria
3. Time course of symptoms
4. Severity of symptoms
5. Family history
6. Age
What is the standard treatment for type 1 diabetes?
Destruction of pancreatic beta cells - Insulin deficient
Hence, patients requires insulin therapy
- Common to have a basal long-acting insulin combined with meal insulin boluses of short-acting insulin (basal-bolus)
- Continuous subcutaneous insulin pumps
Outline the pathogenesis of type 2 diabetes.
In type 2 diabetes we observe both insulin resistance and impaired beta cell dysfunction
Complex metabolic abnormalities contribute to hyperglycaemia…
1. Liver
2. Kidney
3. Gut
4. Brain
What treatments are used for type-2 diabetes?
Lifestyle advice
1. Nutritional advice
2. Weight loss advice-aim to lose 5-10% of original weight - Group based weight loss often best
3. Exercise
4. Stop smoking
5. Reduce alcohol
Initial treatment is with metformin - mechanism not fully understood, but it appears to…
- Sensitizes insulin action
- Opposes action of glucagon
- Reduced hepatic gluconeogenesis
- Increase glucose uptake by muscle
- Causes weight loss
- Importantly does not cause hypoglycaemia
Most common side effect is GI upset
Monitor HbA1c- aim for 48 mmol/mol (reference range 20-42)
Second line treatment - SGLT2 inhibitor (flozins)- e.g. canagliflozin - inhibit reabsorption of glucose in the kidney
What are the complications associated with diabetes?
- Hypertension
- Kidney disease
- Retinopathy
- Cardiovascular disease
- Neuropathy - Peripheral neuropathy & Autonomic neuropathy
- Infections
Outline metformins mechanism of action.
- Inhibition of liver gluconeogenesis - inhibits glucagon effects on liver
- Improved skeletal muscle glucose uptake
- Increase glucagon-like peptide 1 (GLP-1) levels - GLP-1 increases insulin secretion and reduces glucagon secretion
- Main site of action is probably the mitochondrion
What are examples of other drugs that are for treating type 2 diabetes?
What is sulphonylureas mechanism of action - DM T2?
Names - Gliclazide, Glipizide
Action - Stimulate insulin secretion
Side effects - Cause hypoglycaemia and weight gain
What is GLP-1 receptor agonists (GLP-1-RAs)mechanism of action - DM T2?
Examples - Liraglutide, exenatide, dulaglutide
Action - Potentiate nutrient-induced insulin secretion and reduce glucagon secretion
Other Effects
Slows gastric emptying
Decreases appetite
Causes weight loss
Low risk of hypoglycaemia
