diabetes medicine and pathology Flashcards
Define diabetes mellitus
is a group of distinct chronic diseases that is characterized by the inadequate effect of insulin :
1) absolute inadequacy- type 1
2) relative inadequacy in the context of insulin resistance / decreased insulin action- type 2
This involves a problem w insulin secretion or action or both
Essentially hallmark for both is hyperglycaemia
Define DM type 1
Type 1 a- autoimmune destruction of pancreatic Beta cells leading to absolute insulin deficiency
Type 1b - non autoimmune and more common in ethnic population
What antibodies are present in DM type 1a ?
Insulin autoantibodies
GAD antibodies
Islet cell antibodies
What disease is DM type 1a a/w ?
coeliac disease
other autoimmune disorders ; like thyroid
What is the normal blood glucose level?
70-120 mg/dl
List features of Type 1 diabetes?
shorter history of osmotic symptoms - polyuria, polydipsia etc
typically occurs in a younger age(but not always)
no complications at time of diagnosis
presents in diabetic ketoacidosis
requires lifelong insulin therapy
Describe the clinical findings of DM type 1
clinically silent progression over months, only clinically manifests when 90% of beta cells destroyed which leads to
hyperglycaemia w polyphagia, polydypsia, polyuria, weight loss, blurry vision- acute symptoms
and diabetic ketoacidosis
What is likely to be absent in T1 DM
C peptide- which is an appropriate measurement for secretory aspect of insulin
What is the genetic association for type 1 diabetes?
strong a/w HLA-DR3/DR4 genotypes
monozygotic twins concordance=40-50% thus environmental trigger significant
85% of pts have no affected relative
What are the environmental triggers a/w T1?
viral infection where- viral antigens mimic that of islet cells antigens
breast feeding/weaning
geographical / seasonal variations
timing and nature of triggers may be important
Explain pathogenesis of type 1 diabetes
circulating autoantibodies to islet cell components/antigens >90% of Type 1 pts
autoantibodies may predate the overt type 1 diabetes
this is characterized by lymphocytic inflam of islets- insulinitis
Immunosuppression following diagnosis may decrease damage done to pancreatic beta cells
What is the treatment for T1 diabetes
Basal/Bolus insulin
Mixed insulin
Basal insulin Not - NPH or insulatard Gona- Glargine, Lantus Let- Levemir, Detemir Diabetes- degludac In- insulin tuojeo (my home base)
Bolus All- actrapid (Regular) New- novorapid Hot-humalog Guys-glulisine Find- FiASP (me in the bowling alley)
Mixed insulin
NovoMix 30
7/10 insulatard
3/10 novorapid
Humalog mix 25
3/4 insulatard
1/4 humalog
What are the features of each type of treatment?
Basal insulin
Glargine and levemir both prevent hypoglycaemia at night compared to NPH
levemir given twice
usually given at bed time
Degludac and tuojeo are long acting basal insulins
Basal-bolus regimens
4-5 injections per day
hypoglycaemia and weight gain can occur
Mixed insulin regimens
2 injections daily
inflexible regime
hypoglycaemia can occur
How do you diagnose diabetes mellitus?
Random glucose ≥ 11.1mmol/l with osmotic symptoms or
Fasting glucose ≥ 7.0 mmol/l on 2 occasions or
2 hour glucose value post 75gm oral glucose tolerance test of ≥ 11.1mmol/l or
HbA1c ≥ 6.5% (48mmol/mol)
Define Hba1c
glycated haemoglobin- This is the estimated blood glucose over the span of 3 months
This is due to glucose binding to haemoglobin (valine portion of haemoglobin side chain)
What interferes with the interpretation of Hba1c test?
Hemoglobinopathies, hemolytic or iron deficiency anaemias interfere with interpretation of the test.
What is the aim of treatment for diabetics?
Glycated Hemoglobin (HBA1c) < or = 7.0% or < or = 53mmol/mol
Pre-prandial blood glucoses 5 to 7mmol/l
Post-prandial blood glucoses <10mmol/l
No severe hypoglycaemic episodes
Avoid complications of diabetes
Maintain quality of life
Define type 2 diabetes
peripheral tissue resistance to insulin action and an inadequate compensatory release of insulin by pancreatic beta cells - relative insulin deficiency. 83% of cases
What condition(s) are type 2 diabetes a/w ?
metabolic syndrome -visceral obesity, high LDL, low HDL- abnormal lipid profiles, insulin resistance, hypertension. These are major risk factors for cardiovascular disease/atheroma
Other conditions - PCOS, glucose intolerance, Acanthosis nigricans, decreased fibrolytic disease
What increases one’s chances of acquiring type 2 diabetes?
Increase in body fat dose-response relationship
between body fat and insulin resistance
age- tends to be in older pts (but not always)
lack of physical activity
How does T2 DM progress?
Initially due to insulin resistance, the beta cells release more insulin to maintain normal glucose levels (high Cpeptide) . Then it progresses to pre diabetes then overt diabetes w hyperglycaemia.
This hyperglycaemia damages beta cells thus impaired release of insulin from damaged beta cells.This is when diabetes is clinically overt
What accounts for hyperglycaemia in T2 diabetes?
end organ insulin resistance and impaired secretion of insulin
Why does ketoacidosis not occur w T2 DM
This is because even in end stage T2 , insulin is still slightly secreted and a function of insulin is to inhibit formation of ketone bodies
What is the genetic affiliation w T2 DM ?
monozygotic twins have a 90% concordance
polygenic inheritance; insulin resistance genes, insulin secretion genes, Beta cell capacity genes, obesity genes
40% of pts have first degree relatives w DM
What are the environmental factors aw T2 Diabetes?
affluence, obesity, lack of exercise,
increased frequency with increasing age
How does T2D present
T2 DM is a/w chronically high level of glucose so thus microvascular complications more likely, thus complications are present at time of diagnosis. However it can initially be asymptomatic-silent progression- existing many years before it becomes symptomatic.
Osmotic symptoms- polyuria, polydypsia, weight loss, blurred vision, fatigue , infections
Established complications
In regards to screening pts for type 2 , what risk factors are you looking for in order to conduct the screening?
family hx of diabetes, high risk ethnicity, vascular disease, high BMI, abnormal high lipids and blood pressure, habitual physical inactivity,previous pre diabetes, PCOS pt, obstetric hx i.e gestational DM
What is the aim of screening for type 2 diabetics?
To be able to catch the disease in its long progession phase (possibly pre diabetes) and alter its natural history / cease progression to overt diabetes w hyperglycaemia
Is it effective to screen T1 DM
No , not even in high risk siblings
What are the complications a/w diabetes that you screen for?
- Retinopathy (by ophthalmology)
- Nephropathy (urine for microalbuminuria)
- Appropriate foot care (podiatry/chiropody)
- Look for treatable associated risks - clinical examination (blood pressure) and blood tests (lipids)
Describe when to consider MODY (maturity onset diabetes of the young)
- Consider if young and insulin-independent
- Strong family history
- No phenotypic signs of insulin resistance
Where is insulin synthesised? Explain the process.
Insulin is an anabolic hormone that is produced by beta cells of the islet of Langerhans of the endocrine pancreas firstly secreted as pro insulin
Pro insulin is cleaved and is secreted as insulin and C-peptide.
Release of insulin stimulated by rising blood glucose >3.9mmol/l
This is primed by incretin hormones released from L cells of small intestine- > GLP1 which helps reduce work load but increase response of beta cells of pancreas
Explain glucose homeostasis
1) It is made by liver via gluconeogensis
2) Uptake and utilization of glucose by peripheral tissues eg muscle
3) Control of glucose via insulin and counterregulatory hormones eg glucagon,adrenaline , steroids, GH i.e catabolic hormones
