S7 L2 - Intro to Diabetes Flashcards
What is Diabetes?
How is diabetes diagnosed?
What is Diabetes?
Blood glucose is too high (hyperglycaemia) and over the years leads to damage of the small and large blood vessels causing premature death from cardiovascular diseases
How is diabetes diagnosed?
Plasma glucose concentration -
- Random venous plasma glucose conc: Greater or equal to 11.1mM
or
- Fasting plasma glucose conc: Greater or equal to 7.0mM
- Hb A1c over 48mmol/L (6.5%): Glycated haemoglobin test (shows high glucose levels for up to 3 months)
—- Can’t make the diagnosis from: Glycosuria or stick reading of finger-prick blood alone (but are useful for screening)
Type 1 Diabetes
Relative or absolute insulin deficiency?
Cause
Predisposition?
Signs and symptoms
Late presentation (emergency)
Treatment
Absolute insulin deficiency (absolute – pancreatic beta-cells are destroyed)
Cause: Autoimmune destruction by autoantibodies of beta cells in the pancreas
Individual has a genetic predisposition (HLA DR3 and HLA DR4) for type 1 diabetes and then undergoes some form of environmental trigger
Age of onset: Usually below 30 yrs, but can occur at any age
Signs and Symptoms: Rapid onset (weeks)
Triad - Polyuria (excessive urination), Polydipsia (excessive thirst), weight loss
Also, tiredness, weakness, urogenital infections (e.g. thrush)
Presence of ketones (break down of fats product)
Late presentation – symptoms of ketoacidosis: prostration, hyperventilation, nausea, vomiting, dehydration and abdominal pain
Treatment: Exogenous insulin (subcutaneous)
Ketoacidosis:
- Three components
- Explanation of KA
- Signs and symptoms of KA
Ketoacidosis:
Three components:
Hyperglycaemia, ketonemia (presence of abnormally high ketones in the blood - from ketone body formation), acidosis (H+ associated with the ketones)
Explanation:
The high rates of β-oxidation of fats in the liver coupled to the low insulin/glucagon ratio leads to the production of huge amounts of ketone bodies, such as acetoacetate, acetone and β-hydroxybutyrate. Acetone, is volatile and can be smelled on the patient’s breath. As this ketosis develops, the H+ associated with the ketones produce a metabolic acidosis - keto-acidosis. The features of keto-acidosis are prostration, hyperventilation, nausea, vomiting, dehydration and abdominal pain. Keto-acidosis is a very dangerous condition and it is most important to test for ketones (most conveniently in the urine) when assessing control of diabetes in a patient.
- Presence of ketones in urine = indication for immediate insulin therapy and fluid
- *Neo-natal Diabetes Mellitus:**
- Cause
- Treatment
Cause:
This is different to type 1 diabetes mellitus – different aetiology
Mutations in the pore-forming Kir6.2 subunit or in the regulatory sulfonylurea receptor 1 (SUR1) subunit of the KATP channels in the pancreatic beta cells.
Treatment:
Same as type 1 diabetes mellitus
- *Diabetes Mellutis Type 2**
- Description
- Cause
- Reason to occur
- Symptoms
- Treatment
Description: Relative insulin deficiency
Normal secretion of insulin, but relative peripheral insulin resistance at GLUT4 channels
Cause:
- Defective in insulin receptor mechanism e.g. change in receptor number and/or affinity
- Insulin receptor mutation (?)
- Tissues becoming insulin resistance – insensitive to insulin
Reason to occur: Genetic factors and environmental factor – obesity (particularly abdominal obesity) and sedentary lifestyle
Symptoms: Same as type 1 but much slower onset and less extreme (but not at risk of ketoacidosis). However, may be asymptomatic and be picked up in a health screening.
Treatment:
1. Lifestyle change – calorie control and exercise. WEIGHT LOSS - If remove fat around pancreas, can really help to normalise beta-cell function, also reducing amount of liver fat content, can lead to a return of normal insulin sensitivity
2. Medication
e.g. Metformin (Metformin inhibits hepatic gluconeogenesis. This would act to lower plasma glucose which is the desired effect in a patient with Type 2 diabetes)
e.g. Sulphonylurea: increase insulin release from remaining beta cells and reduces insulin resistance
3. Bariatric surgery
4. Insulin
Complication: Same as Type 1 Diabetes Mellitus
- *Complications of Diabetes Mellutis (Type 1 and Type 2)**
- Urgent complication (Type 1 only)
- Macrovascular complications
- Microvascular complication
Uregent complication (Type 1 only)
Ketoacidosis
- *Macrovascular complications:**
- Increased risk of stroke
- Increased risk of myocardial infarction
- Poor circulation to the periphery – particularly the feet
- *Microvascular complications:**
- Diabetic eye disease: Visual problems due to the changes in osmotic effects of glucose (glaucoma). Most significantly, damage to the blood vessels in the retina, can lead to blindness. Damaged blood vessels may leak and form protein exudate on the retina or they can rupture and cause bleeding in the eye. Also, new vessels may form (proliferative retinopathy). These vessels are weak and can easily bleed.
- Diabetic kidney disease (nephropathy): Damage to the glomeruli, poor blood supply because of changes to blood vessels, damage from infections…
- Diabetic neuropathy: Diabetes damages to peripheral nerves includes loss of sensation and changes due to alteration in function of the autonomic nervous system
- Diabetic feet: Poor blood supply, damage to the nerves, increased risk of infection all make feet particularly vulnerable.
Quiz:
- What does HbA1c show?
- Why does insulin have to be taken subcutaneously rather than orally?
- Why is their sugar in the urine (in uncontrolled DM)? Why increased thirst?
What does HbA1c show?
This is formed by glycation. Glycation is the non-enzymatic random process that disrupts protein structure and function. If protein (Hb) is in contact with high concentration of glucose for prolonged periods of time, they will become covalently bonded to glucose by the process of glycation.
Why does insulin have to be taken subcutaneously rather than orally?
Insulin is a peptide hormone so would be broken down in the gastrointestinal tract to its constituent amino acids (rendering it inactive) if it were to be taken orally.
Why is their sugar in the urine (in uncontrolled diabetes mellitus)? Why increased thirst?
hyperglycaemia -> above renal threshold -> glucosuria -> polyuria -> increased thirst -> polydipsia
Lack of insulin has caused plasma glucose to increase. Under normal conditions all the glucose removed in the glomerulus is reabsorbed in the proximal convoluted tubule. If the blood glucose level increases, as in diabetes mellitus, the capacity of the convoluted tubule to reabsorb glucose is exceeded (i.e. the renal threshold for glucose is exceeded) and glucose appears in urine. For glucose this threshold is a plasma concentration of around 10 mmol/L. The extra glucose in the nephron tubule due places an extra osmotic load on the nephron meaning that less water is reabsorbed to maintain the isosmotic character of this section of the nephron. This extra water remains with the glucose in the nephron tubule and is excreted as copious urine (polyuria). As excreting more water, become dehydrated, so have increased thirst.
Quiz cont.
- How can you tell that the pancreas has completely stopped producing insulin?
- Does bio-synthesised insulin have C-peptide
How can you tell the pancreas has completely stopped producing any insulin?
Plasma C-peptide levels - As C-peptide is released with insulin in equimolar amounts, its level in plasma is a useful marker of endogenous insulin release. Measurement of plasma C-peptide levels in patients receiving insulin can therefore be used to monitor any endogenous insulin secretion because medical preparations of insulin to be used as a drug for injection into patients does not contain any C-peptide.
Does bio-synthesised insulin have C-peptide?
Connecting peptide (C-peptide) is cleaved from proinsulin during the biosynthesis of insulin and is released in equimolar amounts to insulin from pancreatic β cells. However, commercial insulin preparations for injection just contain insulin (no C-peptide is added to the preparation). For this reason measuring C-peptide can give an indication of any residual endogenous insulin secreting capacity of a diabetic receiving insulin injections since any C-peptide must have come from endogenous insulin synthesis rather than injected insulin.
- *Metabolic Syndrome**
- Two main causes of this disease
- Description of the syndrome
- Diagnostic criteria
Two main causes of this disease:
Insulin resistance and abdominal obesity
Description:
Metabolic syndrome is a cluster of the most dangerous risk factors associated with cardiovascular disease (CVS DISEASE FOCUSED):
- diabetes
- raised fasting plasma glucose
- abdominal obesity
- high cholesterol
- high BP
= INCREASE in CARDIOVASCULAR risk
Diagnosis criteria:
- Waist measurement >94cm for men and >80cm for women
Plus two of the following:
- raised triglyceride
- reduced HDL cholesterol
- raised blood pressure
- raised fasting glucose
