Diabetes and hypoglycaemia Flashcards
1
Q
Why do we regulate glucose levels?
A
- Regulated at 3-5mM
- Brain and erythrocytes require a continuous supply - avoid deficiency
- High glucose and metabolites cause pathological changes to tissues - e.g. micro/macrovascular disease, neuropathy - avoid excess
2
Q
what are the metabolic effects of insulin?
A
- Muscles - decreases protein breakdown and increases AA uptake
- adipose - increases lipogenesis, decreasing lipolysis
- Liver - increases the uptake of AA, glycogenesis and FA production. Reduces ketogenesis, glycogenolysis and gluconeogenesis
- General tissue - increases glucose uptake
3
Q
What are the main counter regulatory hormones?
A
- Glucagon - secreted by alpha cells of pancreas in response to hypoglycaemia - stimulates glycogenolysis and gluconeogeneis
- Adrenaline - increases glycogenolysis and lipolysis
- GH - increases glycogenolysis and lipolysis
- Cortisol (glucocorticoids) -increases gluconeogenesis
4
Q
What is DM?
A
- Metabolic disorder
- Chronic hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism
- Increased hepatic glucose production and decreased cellular uptake -> hyperglycaemia
- Blood glucose above 10mM exceeds renal threshold -> glycosuria
- Long term complication if not treated correctly -> micro/macrovascular disease
5
Q
What is the prevalence of diabetes?
A
- 422 million globally, estimated to increase
- 3.3million diagnosed in UK in 2014
- Doubled since 1996
- Increased due to poor diet, lack of exercise and also that recording of diabetes has increased
6
Q
How do we diagnose diabetes?
A
- Polyuria (increased urine), polydipsia (increased thirst/drinking) and weight loss (type 1)
- Random plasma glucose >11.1mM
- Fasting plasma glucose >7mM
- OGTT plasma glucose >11.1mM
In the absence of symptoms we test blood samples on two separate days
7
Q
IGT vs IFG?
A
- Impaired glucose tolerance (pre-diabetes) - fasting plasma 6.1-6.9mM, OGTT 7.8-11.1mM
- Impaired fasting glycaemia - not pre-diabetes, but high risk of developing some CVS diseases - fasting plasma <7mM and OGTT <7.8mM
8
Q
How do you carry out an OGTT?
A
- Should be done in patients with IFG, unexplained glycosuria, diagnosis of acromegaly (increased GH = increased glucose)
- 75g oral glucose and test after 2 hrs
- Blood samples collected at 0 and 120 mins after glucose
- Subjects tested fasting after 3 days of normal diet
- If glucose decreases, they may have acromegaly. If this doesn’t decrease, then they’re most likely diabetic
9
Q
What is type 1 diabetes?
A
- Predominantly in children and young adults
- Sudden onset (days/weeks)
- Appearance of symptoms may be preceded by prediabetic period of several months
- Commonest cause is autoimmune destruction of beta-cells
- Interaction between genetic factors and environment - strong link with HLA genes within MHC on Chr6
10
Q
What is the pathogenesis behind type 1 DM?
A
- HLA class II present as foreign and self-antigens to T-cells, initiating an autoimmune response
- Circulating autoantibody to glutamic acid decarboxylase, tyrosine-phosphate-like molecule and islet auto-antigen
- Most common is islet cell antibody
- Destruction of pancreatic beta cells causes hyperglycaemia due to deficiency of insulin and amylin
11
Q
What does amylin do?
A
- glucoregulatory peptide hormone co-secreted with insulin
- lowers blood glucose by slowing gastric emptying and suppressing glucagon output from pancreatic cells
12
Q
What metabolic complications do we get from type 1 DM?
A
- Blood glucose is higher, so there is more water leaving the kidney due to osmosis - excrete lots of urine
- Can get dehydrated from this - leads to mental state changes and confusion -> diabetic coma
- Increased FFA -> increased beta-oxidation -> increased ketone bodies -> ketoacidosis
13
Q
What is type 2 DM?
A
- Slow onset
- Pts middle aged/elderly - risk increases with age
- Strong familiar incidence
- Insulin resistance/ beta-cell dysfunction - may be due to lifestyle factors like obesity and lack of exercise
- Emergency presentation as HONK
14
Q
What is HONK?
A
- Metabolic complication of type 2
- Severe hyperglycaemia, severe dehydration from increased urination, increased plasma osmolarity
- No ketosis, minimal acidosis
- Impaired consciousness
- Death if untreated
15
Q
How do we monitor glycaemic control?
A
- Aim to prevent complications or avoid hypoglycaemia
- Self-monitoring - capillary blood measurement; urine analysis - gives indication of blood glucose conc above renal threshold
- 3-4 months - blood HbA1c (glycated Hb, covalent linkage of glucose to residue in Hb)
- urinary albumin - index risk of progression to nephropathy
16
Q
What is the stepwise treatment for type 2?
A
- Diet and exercise
- oral monotherapy (metformin)
- Oral combination (Sulphonylureas, Gliptins, GLP-1 analogues)
- Insulin and/or oral agents
17
Q
What are the long term complications from DM?
A
- Microvascular - retinopathy, nephropathy, neuropathy
- Macrovascular disease - related to atherosclerosis, heart attack and stroke. Affects the endothelial cells -> can lead to hardening of the blood vessels
18
Q
How can they reduce CV risk?
A
- Attain normal weight and waist circumference
- Eat less fat and salt
- Exercise
- Stop smoking
- HbA1c <7%
- BP target <130/80mmHg
- Total cholesterol <4mM, LDL <2mM
19
Q
What is hypoglycaemia?
A
- Plasma glucose <2.5mM
- Results in energy failure and neurological damage
- dangerous because glucose is a vital fuel for the brain - only ketones can substitute as last resort
20
Q
What can cause hypoglycaemia?
A
- Insulinoma
- Inherited metabolic disorders - glycogen storage diseases, galactosaemia, hereditary fructose intolerance
- Drugs - Sulphonylureas, insulin, alcohol abuse
- Endocrine disease - cortisol disorder
- Others - severe liver disease, non-pancreatic tumours, postgastrectomy, renal disease
21
Q
What is an insulinoma?
A
- Tumour in beta cells of pancreas
- Symptoms - fasting hypoglycaemia, inappropriate high insulin conc when plasma glucose is low.
- C-peptide should be measured - synthesis of insulin will increase, the amount of C-peptide cleaved will also increase. If C-peptide is low, it wont be insulinoma
22
Q
What is glycogen storage disease type 1?
A
- G-6-phosphatase deficiency
- AR disease
- glucose synthesis from glycogen or gluconeogenesis is blocked
- presents in early infancy; severe fasting hypoglycaemia as only source of glucose is dietary carbohydrate
- accumulation of glycogen causes hepatomegaly; inability to produce glucose from lactate -> acidosis
- Give uncooked cornstarch for slow release of glucose
23
Q
What is galactosaemia?
A
- Caused by defects on 3 enzymes - most common is galactose-1-phosphate uridyl transferase deficiency
- AR disorder
- Deficiency of Gal-1-PUT impairs conversion of gal-1-p to g-1-p; gal-1-p accumulates in liver (toxic)
- Hypoglycaemia and vomiting/diarrhoea after starting milk feeds
- Galactose excreted in urine
- treat by excluding galactose from diet
24
Q
What is hereditary fructose intolerance?
A
- AR disorder
- Deficiency of fructose-1-phosphate adolase B
- Ingested fructose accumulates inhibiting glycogenolysis at the phosphorylase step - cant make glyceraldehyde (glycolysis) or dihydroxyacetone-P (gluconeogenesis)
- Severe hypoglycaemia and vomiting after ingesting fruit or sweetened foods
- Fructosuria
- Avoid ingestion of fructose or sucrose
25
Q
What is benign fructose intolerance?
A
- Absence of fructokinase
- cant convert fructose to f-1-p
26
Q
What is the response to falling glucose levels in fasting?
A
- Suppression of insulin release, limiting glucose uptake into non-cerebral tissues
- Secretion of glucagon, nor-/adrenaline, cortisol and GH to raise glucose level
- Stimulate hepatic gluconeogenesis, glycogenolysis and FA oxidation
27
Q
What are the symptoms of hypoglycaemia?
A
- Neurogenic - triggered by falling glucose levels, activated by ANS and mediated by sympathoadrenal release of catecholamies and Ach. Causes mood changes, trembling, paleness, sweating, dizziness, blurred vision, headaches, tiredness, hunger.
- Neuroglycopaenia - glucose deprivation of neurones. Causes confusion, difficulty speaking, ataxia, seizures, coma, death
