Diabetes and its treatment Flashcards
What do alpha cells make?
glucagon
What do beta cells make?
insulin
What do delta cells make?
somatostatin
What contributes to glucose in the blood?
Food and Liver
What takes up glucose from the blood?
Muscle and kidney (and liver)
When does blood glucose peak throughout the day? (which would then normally be followed by insulin release)
Post prandial (roughly 8am, 1pm and 7 pm)
What is diabetes?
Metabolic disorder characterised by chronic hyperglycemia resulting from defects in inslin sceretion, insulin action or both
What would result in lack of insulin?
Reduced production
Insulin cant get to the cell to work
What happens when there is no insulin released?
The liver releases more glucose
The muscle cannot take much so the kidneys uptake the glucose
How is diabetes diagnosed?
High blood glucose and symptoms, Hb test (but this doestn detect young people with rapid onset as it looks at the previous 3 months)
What vessels are affected by retinopathy and arterial disease?
Retinopathy - microvessels
Arterial disease - macrovessels
What is HbA1c?
glycated haemoglobin. It is a measurement of diabetes management over 2 - 3 months.
What affects HbA1c?
renal failure - changes the cells ability to bind glucose
thalassaemia - abnormal Hb which binds to glucose more strongly
When can HbA1c be inaccurate?
Abnormally high caused by persistent HbF (thalassaemia)
Low caused by haemolysis or increased red cell turnover (blood loss)
What is the blood glucose level of a diabetic when fasting and 2 hrs after meal?
fasting >7mmol/L
post 2 hrs >11.1mmol/L
What is IGF ? (almost diabetes)
Impaired glucose fasting. (Pre-type 1 diabetes)
Unknown cause
50% risk of diabetes
Treat with healthy diet, yearly glucose checks
What is IGT? (almost diabetes)
Impaired glucose tolerance (Pre-type 2 diabetes)
Cause is insulin resistance
50% risk of diabetes
Increased risk of heart disease
Treat with diabetic diest, yearly glucose checks and treat cardiac risk factors
Prevent progression with exercise and weight loss
Other than type 1 and 2, what is the other form of diabetes?
Gestational
Name 3 classifications of diabetes?
INSULIN DEFICIENCY - auto-immue destruction of pancreas
INSULIN RESISTANCE - unknown cause related to obesity, receptor abnormalities, excessive hormone
GESTATIONAL
Describe type 1 diabetes mellitus?
Less cells in the pancreas, cant make insulin Incidence 1/10,000 Often younger with weight loss M>F Cause is genetic and environmental
How does type 1 diabetes mellitus present?
Polyuria Thirst weight loss dehrydration (wee 5-8L/day) ketoacidosis coma
What are the 2 new delivery systems for insulin?
INSULIN PUMP - continuous insulin given, less hypos, less insulin, but high cost
INHALED INSULIN - small trials, only 1/10 dose absorbed, long term safety unkown
Describe an islet cell transplant?
Islets taken from donor pancreas
Isolate islets of langerhans
infusion of islets which go to the portal vein
Describe a pancreas transplant?
Donor donates pancreas and duodenum
What happens if pt needs a short operation?
Half the normal morning dose
First on the list
Monitor symptoms
Cover antibiotics
What happens if pt needs a long operation?
Needs to be in hospital
First on the list
Iv, glucose and K+
cover with antibiotics
Describe type 2 diabetes?
Insulin resistance so glucose does not go into cell
Incidence 1/1000
Often older with weight gain
M=F
Cause is genetic and environment (more genetic though)
What is the link between birth weight and insulin resistance?
Increased birth weight = increased risk resistance
decreased body weight = increased insulin sensitivity
Increased BMI = increased rate type 2 diabetes
How does type 2 diabetes present?
Non symptomatic
Metabolic - thirst, polyuria
Non metabolic - comlications: blurred vision, CVA, peripheral neuropathy, angina, MI, UTI, foot ulcers
How do we treat type 2 diabetes? (in order of stage)
IF THIN - diet, exercise, sulphonylureas, metformin, insulin
IF FAT - diet, exercise, weight loss, metformin, sulphylureas, insulin
What action do sulphonylureas have?
Increased insulin release from pancreas
What are the side effects of sulphonylureas?
egs tolbutamide, glibenclamide, glicazide
hypoglycaemia, weight gain, nausea, anorexia, vomiting, alcoholic, skin rash
What is the action of metformin?
Suppresses glucose production by the liver
What are the side effects of metformin?
nausea, vomiting, diarrhoea, VitB12 malabsorption, lactic acidosis
What is the action of thiazolidinediones?
Increased insulin sensitivity. Increase muscle and decreases secretion from the liver
What are the side effects of thiazolidinediones?
eg rosilitizone
Hypoglycaemia, liver damage, fluid retention, weight gain
What drugs decrease absorption?
Alpha glucosidase inhibitors (acarbase) - flatulence, no hypo, slow glucose absorption Lipase inhibitors (orlistat) - weight loss, decreased cholesterol, flatulence, no hypo, omhobots pancreatic and gastric lipase
What is GLP -1?
Glucagon like peptide 1
Diabetics dont produce as much GLP -1
When is GLP - 1 secreted?
On the ingestion of food
What are the effects of GLP - 1?
BETA CELLS - enhances glucose dependant insulin secretion in pancreas
ALPHA CELLS - suppressed postprandial glucagon secretion
LIVER - reduced hepatic glucose output
STOMACH - slows the rate of gastric emptying
BRAIN - promotes satisfaction and decreases apetite
What are the 2 incretin based therapies?
- DPP - 4 inhibitors - protect native GLP -1 from inactivation by DPP-4
(eg sitagliptin, vildagliptin, alogliptin) - GLP - 1 receptor agonists - mimic native GLP - 1
(eg exenatide, liroglutide, lixisematide)
What is exenatide?
A GLP - 1 receptor agonist. It is resistant to DPP-IV degradation. Given subcutaneously
Decreases HbA1c
Augments glucose stimulating insulin secretion, slows gastric emptying, suppresses innapropriately increased glucagon
Which two organs play large roles in managing diabetes?
Gut and kidney
Describe the normal glucose handling of the kidney?
80% glucose is reabsorbed by SGLT2
10% glucose reabsorbed by SGLT1
Minimal glucose excreted in urine
What is the action of dapagliflozin?
stops reabsorption by SGLT2 in the renal proximal tubule so more glucose secreted in urine
Secondary benefit of weight loss
What 2 classes of treatment can be used for diabetes?
Insulin dependent mechanisms - glucose utilisation
Insulin independent mechanisms - glucose excretion
What are the insulin dependent mechanisms? (glucose utilisation)
Insulin sensitisers - thiazolidinediones, metformin
Insulin releasers - sulphonylureas, meglitinides
Insulin replacement - insulin
What are the insulin independant mechanisms? (glucose excretion)
SLGT-2 inhibition - dapagliflozin
GLP - 1 and DDPIV - increase insulin release
What is gestational diabetes?
Mother has increased glucose which crosses the placenta so the baby produces insulin and this controls its own glucose. But insulin is a growth factor so the baby gets other complications and increased risk of still birth.
When is gestational diabetes prone?
2nd and 3rd trimester
What is the treatment for gestational diabetes?
85% diet
15% diet and insulin
What are the complications associated with gestational diabetes?
Still births, large baby, death for mother
What is the chance that a mother who experiences gestational diabetes will have diabetes in the future?
50% diabetic in next 5 yrs
15% diabetic in next pregnancy
