Diabetes 2 Flashcards
What is DIDMOAD (Wolfram Syndrome)?
Diabetes Insipidus, DM, Optic atrophy, Deafness, neuro anomalies
How does Bardet-Biedl Syndrom usually present?
Very obese, polydactyly, hypogonadal, visual impairment, hearing impairment, mental retardation, DM, consanguineous parents
What are some associated AI conditions of T1DM?
Thyroid disease, coeliac, pernicious anaemia, addison’s, IgA deficiency. Rare-AI polyglandular syndrome (Type 1 and 2), AIRE mutations, IPEX syndrome
What is Type 2 Polyglandular Endocrinopathy?
Most common polyglandular failure syndrome. Can include conditions such as T1DM, addisons, vitiligo, primary hypogonadism/thyroidism, coeliac
What is Type 1 Polyglandular Endocrinopathy?
Polyglandular syndrome in which multiple endocrine glands dysfunction. Autosomal recessive condition, associated with mild immune deficiency (Muco-cutaneous candidiasis), any associated condition in Type 2, primary hypoparathyroidism, pernicious anaemia, alopecia
What causes insulin resistance?
Ectopic fat accumulation and increase FFA circulation, increase inflammatory mediators, reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport
What occurs due to insulin resistance leading to a decline in beta cell function?
Glucotoxicity and lipotoxicity (due to elevated FFA, TG)
Does an apple or pear weight distribution have a higher risk of T2DM and CVD?
Apple
What is the therapy staircase in T2DM?
Diet and exercise, oral monotherapy, oral combination, injectable and oral therapy
What are some traditional oral anti-hyperglycaemic agents?
Biguanides-metformin. Sulphonylureas-glicazide, glibenclamide, glimeparide. Thiazolidinediones-pioglitazone
What are some of the effects of metformin?
Hyperglycaemia management-reduces HbA1c by 15-20mmol/l, hypoglycaemia (not when monotherapy), weight effect (can reduce it), prevention of micro/macrovascular complications
What are some adverse effects of metformin?
GI S/Es-anorexia, nausea, vomiting, diarrhoea, abdo pain, taste disturbance. Interference with vitB12 and folic acid absorption, lactic acidosis (can be fatal), liver failure/toxcity, rash, renal toxicity
What is the 1st line agent for T2DM?
Metformin
What is a sulphonylurea?
An insulin secretagogue. 1st gen (rarely used)-chlorpropramide, tolbutamide. 2nd gen (shorter acting)- glicazide, glipizide, glibenclamide/glyburide, glimepiride
What are the effects of the SUs?
Hyperglycaemia management-reduces HbA1c, results in more rapid reduction in hyperglycaemia than insulin sensitisers, (concern with beta cell demise acceleration). Prevention of microvascular complications, not macrovascular
What are the adverse effects of the SUs?
Hypoglycaemia, wt gain, GI upset, headache, rarely hypersensitivity, blood dyscrasias and liver dysfunction. Avoid in severe renal/hepatic failure
When should SUs be considered?
After metformin or in those intolerant of metformin
What kind of drug are the Thiazolidinediones (TZDs)?
PPAR gamma agonists
What are the effects of the TZDs?
Hyperglycaemia management-reduces HbA1c. Hypoglycaemia (not if used without SU). Wt increase, heart failure, improvement in microalbuminuria, prevention of macrovascular complications
What are therapies based on incretins?
GLP-1 receptor agonists- exenatide, exendin, liraglutide, lixisenatide, DPP-IV inhibitors-vildagliptin, sitagliptin, saxagliptin, linagliptin
What are the benefits of GLP-1 receptor agonists?
Promote insulin secretion from pancreas without hypoglycaemia, suppress glucagon (increased in T2DM), decrease gastric emptying-early satiety, act on hypothalamus-reduce appetite-resulting wt loss
What are the downsides of GLP-1 receptor agonists?
Nausea-resolves in most, injectable, pancreatitis, pancreatic cancer
What are the benefits of DPP4 inhibitors?
Promote insulin secretion from pancreas without hypoglycaemia, suppress glucagon (increased in T2DM), weight neutral
What are the side effects of DPP4 inhibitors?
Very limited S/Es, pancreatitis, pancreatic cancer
What are some SGLT2 inhibitors?
Dapa/cana/empa-gliflozin
What do SGLT inhibitors do?
Decrease uptake of sugar by about 1/4- increase sugar in urine
What are the downsides to SGLT inhibitors?
Sugar in urine can lead to thrush, possible increase in UTIs
How is insulin given more commonly in T2DM?
Basal insulin- insulin is given if people fail on non-insulin therapies. Once daily NPH insulin is added to metformin (+-SU)
What inheritance does MODY exhibit?
Autosomal dominant
Is MODY insulin or non-insulin dependent?
Non-insulin
What is the common age of onset of MODY?
Usually before 25yo
What are the types and proportions of different MODY mutations?
Glucokinase mutation 14%, transcription factor (HNF1…) 75%, MODY x 11%
How do glucokinase mutations causing MODY present and how are they treated?
At birth, stable hyperglycaemia, complications are rare. Diet based treatment
How do transcriptiion factor mutations causing MODY present and how are they treated?
Adolescence/young adult onset, progressive hyperglycaemia, frequent complications. Treatment is 1/3 diet, OHA, insulin
Describe transient neonatal dm (TNDM)
Type of DM at birth that is not permanent. Considered to be a type of MODY
Describe permanent neonatal diabetes (PNDM)
Diabetes usually diagnosed 0-6wks. Lifelong insulin treatment
To what drug are HNF1alpha mutations causing MODY sensitive to?
SU’s
What channel mutation can cause neonatal diabetes?
Katp channel mutation
What are some examples of types of insulin?
Rapid, short, intermediate, long acting.Also rapid intermediate/short intermediate mixture
What insulin regimen should all/most of T1DM patients be on?
Basal bolus
What is the disadvantage of twice daily insulin regimen?
It does not mimic physiological insulin secretion
What is the BG target pre-meal regarding insulin treatment?
3.9-7.2mmol/l
What is the BG target 1-2hrs after beginning of meal regarding insulin treatment?
Less than 8mmol/l
What are the key difference between insulin analogues and historic soluble insulin??
Faster onset (10-15 mins opposed to 30-60), peak action at 60-90mins rather than 2-4hrs, duration of 4-5 hours rather than 5-8
Should T1DM patients be on an analogue or isophane basal insulin usually?
Analogue
What does an insulin pump do?
Provides continuous administration of short acting insulin subcut. Background dictated by basal rate, manually activated bolus to cover meals
How is glycated haemoglobin (HbA1c) formed?
By non-enzymatic glycation of hg on exposure to glucose
Over what period of time is HbA1c a measure of average BG?
6-8wks
What factors effect insulin absorption/action?
Pen accuracy, leakage, temperature, injection site and depth, exercise
What checks should be employed to reduce risk in insulin injection?
Check site for lipohypertrophy, check needle
