Endo 16 - T2DM Flashcards
T2DM is not ketosis prone. What tissues are often damaged long term in T2DM?
Retina, kidney, nerves, artery
What is the fasted blood glucose threshold for T2DM
> 7mmol (over 6 = “impaired fasting glucose”
2 hr glucose > 11.1 = T2DM
Diabetes is the most common cause of what in the UK?
Blindness in working age people, renal replacement therapy and amputation
T2DM gene mutations are associated with?
Intrauterine growth restriction
Describe MODY
Several hereditary forms of MODY. MODY is autosomal dominant
It causes ineffective pancreatic Beta cell insulin production - and mutations of transcription factor genes, glucokinase gene
Positive Family history, not commonly linked to obesity
Specific treatment depending on type of MODY
Only diabetes causes microvascular complications (as in, macrovascular complications may arise from other things but Diabetes will give microvascular complications)
Y
Intrauterine environment is key. Studies have shown what?
Infant birth weight and birth weight at a young age predicts diabetes risk
Describe the metabolism and presentation of T2DM
- Heterogeneous
- Obesity
- Insulin resistance and insulin secretion deficit (but which came first)
- Hyperglycaemia and dyslipidaemia
- Acute and chronic complications
Describe insulin secretion in T2DM
Insulin secretion is in 2 phases, 1st phase (sharply right after meal) and 2nd phase (after meal)
Insulin secretion deteriorates with T2DM / Impaired Glucose Tolerance (IGT)
Also, T2DM/IGT = impaired glucose uptake by muscle and more HGO (as less inhibition by insulin)
Insulin is meant to switch off lipolysis (no need to breakdown fat after we’ve eaten). But insulin resistance may cause problems - e.g. atheroma formation.. How
In adipocyte - lipolysis not switched off due to insulin resistance.
- Triglyceride broken down into glycerol and non-esterified FA.
- Both glycerol + NEFA travel to liver —> NEFA becomes VLDL-TG and glycerol contributes to glucose production (via gluconeogenesis).
- Consequence - increased small dense VLDL in blood - increased risk of atheroma, etc. Also increased HGO (+ gluconeogenesis) = increased plasma glucose. Impaired uptake of glucose to muscle means glucose remains in blood
Central/omental fat is more dangerous than peripheral fat.
Yah
Gut microbiota perturbations ARE ASSOCIATED (not causative) with T2DM. How
Bacterial lipopolysaccharides ferment to short chain FA, bacteria also may modulate bile acids
Inflammation may arise - which signals metabolic pathways
All diabetics drugs, except Metformin, cause
Weight gain (e.g. insulin)
Describe T2DM diabetes presentation
- Osmotic symptoms
- Infections
- Screening test
- Nearly 50% present with complication - e.g.acute: hyperosmolar coma, chronic: IHD, retinopathy
What are the microvascular complications of T2DM
- Retinopathy
- Nephropathy
- Neuropathy
What are the macrovascular complications of T2DM
- IHD
- Cerebrovascular
- Renal artery stenosis
- PVD
What are the metabolic complications of T2DM
- Lactic acidosis
2. Hyperosmolar
What can treatment of T2DM cause
Hypoglycaemia
What is monitored in the treatment of T2DM
- Weight
- Glycaemia
- BP
- Dyslipidaemia
How is weight managed/treated in T2DM
Education, diet control (increase complex carbs, increase unsaturated fat as proportion of fat and increase soluble fibre).
Orlistat (GI lipase inhibitor)
How is glycaemia treated/managed in T2DM
- Metformin/insulin (though insulin may increase weight)
- Sulphonylureas / metaglinides (increase insulin secretion from pancreas)
- alpha-glucosidase inhibitor (increases time taken to absorb glucose - bypassing the 1st phase insulin secretion problem)
- Thiazolidinediones
Describe metformin
It is a biguanide insulin sensitiser - p much prescribed in anyone
Reduces insulin resistance (reduced HGO, increased peripheral glucose disposal)
GI SEs
Not used if severe liver, cardiac or mild renal failure
How do B cells work?
How does Glibenclamide (sulphonylurea) work
- Glucose enters B cell –> metabolised (by glucokinase) and produces ATP
- ATP produced inactivates ATP sensitive K channel, which triggers VGCC to open —> influx of Ca causes insulin secretion
- Glibenclamide (sulphonylurea) binds to and blocks the ATP sensitive K channel –> No K efflux so cell depolarises –> activates VGCCs —> Ca influx and insulin release
Used in lean T2DM patients where diet hasn’t worked - will cause weight gain
What is acarbose and how does it work
It is an alpha-glucosidase inhibitor - prolongs absorption of oligosaccharides
This allows insulin secretion to cope (as defective first phase secretion)
May cause flatus (gas)
Describe thiazolidinediones
e.g. Pioglitazone
It is a peroxisome proliferator-activated receptor agonist (PPAR-gamma)
It allows insulin to work better (insulin sensitiser) - causes weight gain but PERIPHERAL and NOT OMENTAL
Improved in glycaemia and lipids
What does GLP-1 do?
Stimulates insulin, suppresses glucagon
Increases satiety
It is secreted in response to nutrients in the gut (from L cells)
Causes weight loss, not gain
GLP-1 are often given in conjunction with Gliptins (DPPG-4 inhibitors) in T2DM. What are gliptins
BUT GLP-1 more effective than gliptins/DPPG-4 inhibitors
They are DPPG-4 inhibitors - they increase the half life of exogenous GLP-1
How do SGLT2 inhibitors work, give an example
They work in the PCT of the kidney - decrease glucose reabsorption (by inhibiting Na/Glu cotransporter) –> increased glycosuria/polydipsia
They reduce HbA1c, may also reduce all causes of mortality (including heart failure)
e.g. Empaglifozin
Which other aspects are treated in T2DM
- BP
2. Diabetic dyslipidaemia
