Diabetes mellitus Flashcards
Compare and contrast LADA vs MODY.
LADA - latent autoimmune diabetes in adults; a type of type 1 diabetes which is diagnosed later than the typical onset of type 1 (and so commonly mistaken for T1DM). Progress to insulin requirement within 6 years; may have other autoimmune conditions and have antibodies and low C-peptide.
MODY - maturity onset diabetes of the young; a type of T2DM but commonly mistaken for type 1 as onset is early but there are no antibodies present and usually no insulin requirement. Usually family history present as monogenic autosomal dominant inheritance.
Define type 2 diabetes.
Common disorder characterised by insulin resistance and relative insulin deficiency. Most patients are asymptomatic and are diagnosed through screening (abnormal fasting plasma glucose, haemoglobin A1c, and/or oral glucose tolerance test)
Define type 1 diabetes mellitus.
Characterised by absolute insulin deficiency. Most cases result from autoimmune pancreatic beta-cell destruction in genetically susceptible individuals. Usually presents with acute symptoms or ketoacidosis in childhood or adolescence. Lifelong insulin therapy is required.
Broadly describe diabetes mellitus.
DM results from lack, or reduced effectiveness, of endogenous insulin. Hyperglycaemia is one aspect of a far-reaching metabolic derangement, which causes serious microvascular or macrovascular problems.
So think of DM as a vascular disease: adopt a holistic approach and consider other cardiovascular risk factors too.
How common is type 1 DM? Who is usually affected?
- Type 1 diabetes accounts for about 5% to 10% of all patients with diabetes
- Most commonly diagnosed diabetes of youth (under 20 years of age) and causes ≥85% of all diabetes cases in this age
- Geographical variation - more common in Europeans and less common in Asians
- Worldwide, incidence is increasing by 3% every year, although the reasons for this are unclear
- Affects M&F equally
What is the cause of type 1 DM?
Insulin deficiency from autoimmune destruction of insulin-secreting pancreatic β cells
Associated with other autoimmune diseases (>90% HLA DR3± DR4). Concordance is only ~30% in identical twins, indicating environmental influence.
Four genes are important: one (6q) determines islet sensitivity to damage (eg from viruses or cross-reactivity from cows’ milk-induced antibodies).
Latent autoimmune diabetes of adults (LADA) is a form of type 1 DM, with slower progression to insulin dependence in later life.
What are the causes of type 2 DM? What types exist?
(non-insulin-dependent DM)
↓insulin secretion ± ↑insulin resistance.
- It is associated with obesity, lack of exercise, calorie and alcohol excess.
- ≳80% concordance in identical twins, indicating stronger genetic influence than in type 1 DM.
- Typically progresses from a preliminary phase of IGT or IFG. (This is a unique window for lifestyle intervention.)
- Maturity onset diabetes of the young (MODY) is a rare autosomal dominant form of type 2 DM affecting young people.
How common is type 2 DM? Who is usually affected?
- At ‘epidemic’ levels in many places, mainly due to lifestyle but also due to better diagnosis and improved longevity. Trends in incidence rate of diabetes has plateaued and now appears to be decreasing.
- 90% of cases of diabetes are type 2
- Higher prevalence in Asians, men and the elderly (up to 18%)
- Most are over 40yrs, but teenagers are becoming affected
What is impaired glucose tolerance?
- IGT is fasting plasma glucose <7mmol/L
- and OGTT 2hr glucose _>7.8mmol/L but <11.1mmol/L (_7.8-11.1mmol/L)
What is impaired fasting glucose?
IFG is fasting plasma glucose between 6.1-7.0mmol/L (but not including these numbers)
Do an OGTT to exclude DM.
What is a normal, pre-diabetic and diabetic HbA1c level?
normal - <42mmol/mol
pre-diabetic - 43-47 mmol/mol
diabetic - >47mmol/mol
What is the difference between IFG and IGT>
- IGT - post-prandial glucose regulation
- IFG - fasting glucose regulation
Lower incidence of progression to DM in IFG than IGT. If IFG and HbA1c at high end of normal range then incidence of DM is 25%.
Name some unusual causes of DM.
Steroids - anti HIV drugs, newer antipsychotics
Pancreatic - pancreatitis, surgery (if >90% removed), trauma, pancreatic destruction (haemochromatosis, cystic fibrosis), cancer.
Cushing’s disease - acromegaly, phaeochromocytoma, hyperthyroidism, pregnancy
Other - congenital lipodystrophy, glycogen storage disroders
Define metabolic syndrome (syndrome x).
Definition from International Diabetes Federation:
- central obesity (BMI>30, or ↑waist circ, ethnic-specific values)…
…plus two of:
- BP≥130/85,
- triglycerides ≥1.7mmol/L,
- HDL≤1.03♂/1.29♀mmol/L,
- fasting glucose ≥5.6mmol/L
- or type2 DM.
~20% are affected; weight, genetics, and insulin resistance important in aetiology. Vascular events—but probably not beyond the combined effect of individual risk factors.
What is the WHO criteria for diagnosis of DM?
- Symptoms of hyperglycaemia (e.g. polyuria, polydipsia, unexplained weight loss, visual blurring, genital thrush, lethargy)
- AND raised venous glucose detected once - fasting >7mmol/L or random >11.1mmol/L
OR
- Raised venous glucose on 2 separate occassions - fasting >7mmol/L, random >11.1mmol/L OR OGTT 2hr value >11.1mmol/L
OR
- HbA1c >47mmol/mol (avoid in pregnancy, children, type 1 DM, haemoglobinopathies)
- Try to do a blood glucose each time you’re taking blood - non systematic but better than urine tests which have high false -ve rate.*
Name 4 differences between type 1 and type 2 DM.
Type 1 - usually weight loss, persistent hyperglycaemia despite diet and medication; autoantibodies (islet cell antibbodies ICA and anti-glutamic acid decarboxylase GAD antibodies), ketonuria.
When should you suspect LADA?
Type 2 - not always old, ketotic, poor response to hypoglycaemics (and slim with FH of autoimmunity) think of LADA and measure islet cell antibodies.
Summarise the management of type 2 DM.
List the 4 types of diabetic retinopathy.
Background retinopathy - microaneurysms (dots), haemorrhages (blots), hard exudates (lipid deposits)
Pre-proliferative retinopathy - cotton-wool spots (e.g. infarcts), haemorrhages, venous beading
Proliferative retinopathy - new vessels form
Maculopathy - hard to see in early stages but suspect if reducedd acuity. Caused by high retinal blold flow caused by hyperglycaemia. New vessels near disc, proliferate, bleed and fibrose and can detach retina. Capillary pericyte damage.
