What is Diabetes Mellitus? Flashcards
What is diabetes mellitus?
A group of metabolic diseases of multiple aetiologies characterised by hyperglycaemia together with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both
What are the symptoms of hyperglycaemia?
Polydipsia Polyuria Blurred vision Weight loss Infections
What are the metabolic decompensations of hyperglycaemia?
DKA
HHS
What are the long term complications of hyperglycaemia?
Microvascular: - Retinopathy - Neuropathy - Nephropathy Macrovascular: Stroke, MI, PVD
What fasting venous plasma [Glucose] level is considered high?
> 7mmol/L
What random venous [Glucose] plasma level is considered high?
> 11.1mmol/L
What tests are used to measure blood glucose?
Fasted/Random plasma glucose
Glucose tolerance test
Diagnostic HbA1C
What is considered a high HbA1c?
> 48mmol/L
What is considered a high GTT?
> 11.1mmol/L
What is measured for a GTT?
2hrs after 75g CHO
What is intermediate hyperglycaemia?
Impaired fasting glucose 6.1-7mmol/L
Impaired GTT >7.8/<11mmol/L
HbA1c 42-47mmol/mol
What is the purpose of diabetes diagnostic criteria?
Identifies groups with significantly increased risks of mortality and microvascular complications
Intermediate hyperglycaemia identifies what?
Groups at higher risk of future diabetes and adverse outcomes
What is normoglycaemia?
Glucose levels associated with low risk of developing diabetes and cardiovascular disease
How is diabetes diagnosed?
ONE lab glucose WITH symptoms
TWO lab glucose/HbA1c WITHOUT symptoms
What does HbA1c tell us?
Indication of blood glucose levels over last 8-12 weeks
When can HbA1c not be used for diagnosis?
- Young people
- Current/recent pregnancy
- Short duration of symptoms
- High risk DM acutely ill
- On medication which causes rapid glucose rise
- Acute pancreatic damage/surgery
- Renal failure
- HIV infection
Which drugs cause a rapid rise in glucose? When can they be used?
Corticosteroids
Antipsychotics
Long term (>2months)
What is the breakdown of types of diabetes?
90% type 2
10% type 1
1% other
When does insulin dominate?
In the absorptive state
Which cells secrete insulin?
beta cells
Which cells secrete glucagon?
alpha cells
Insulin inhibits what?
Glycogenolysis and gluconeogenesis in the liver
What is the cause of T1DM?
Postive autoantibodies (anti GAD)
Incidence of diabetes is highest in which age group?
10-19y/os
What is the concordance in T1DM in monozygotic twins?
30-50%
What is the concordance in T1DM if the father has T1DM?
6% risk
What is the concordance in T1DM if the mother has T1DM?
1% risk
What is the concordance in T1DM if the sibling has T1DM?
8% risk
What is the concordance in T1DM if the non-identical twin has T1DM?
10%
What is the concordance in T1DM if both parents have T1DM?
30%
Development of T1DM requires what?
Genetic disposition PLUS:
Trigger
Autoimmunity
What effect does insulin have on adipose tissue?
Reduced lipolysis
What effect does insulin have on the liver?
Reduced glucose production
What effect does insulin have on muscle?
Increased glucose uptake
What is the effect of insulin deficiency on the liver?
Raised glucose production
What is the effect of insulin deficiency on adipose tissue?
Increased lipolysis
What is the effect of insulin deficiency on muscle?
Reduced glucose uptake
Which counter-regulatory hormones are raised in insufficient insulin intake?
Glucagon
Cortisol
Catecholamines
Growth hormones
How does hyperglycaemia lead to impaired renal function?
High osmotic load (glucosuria) leading to loss of water and electrolytes –> consistent dehydration
Increased lipolysis has what negative effect in diabetes?
Increases FFA levels to the liver, increasing gluconeogenesis
Increased ketogenesis
What is the clinical presentation of T1DM?
Thirst Tiredness Polyuria/nocturia Weight loss Blurred vision Abdominal pain SHORT DURATION
How does T1DM present on examination?
Ketones on breath
Dehydration
May have increased RR/HR, H↓TN
Low grade infections
What is the concordance in T2DM if an identical twin has T2DM?
90-100%
What is the concordance in T2DM if one parent has T2DM?
15%
What is the concordance in T2DM if both parents has T2DM?
75%
What is the concordance in T2DM if a sibling has T2DM?
10%
What is the concordance in T2DM if one non-identical twin has T2DM?
10%
What are insulin levels like in T2DM?
Initially high, progressively decrease
How do symptoms present in T2DM?
OFTEN SYMPTOMLESS Thirst Tiredness Polyuria / nocturia Sometimes weight loss Blurred vision Symptoms of complications
Which signs typically present in T2DM?
NOT KETOTIC
Usually overweight
Low grade infections
Micro/macrovascular complications
What are the screening factors for asymptomatic patients in T2DM?
Any TWO of: Overweight FH >30 if Maori/asian >40 if European Previous Hx gestational DM High birth weight baby Inactive lifestyle Previously high [Glc]
Which recognised genetic syndrome causes diabetes?
MODY
Maturity Onset Diabetes in the Young
What is MODY?
Autosomal dominant single gene cause of beta-cell dysfunction
How many diabetes patient have MODY/
5%
Which types of mutations occur in MODY?
Glucokinase mutations
Transcription factor mutations
How does glucokinase diabetes present?
Onset at birth
Stable hyperglycaemia
Diet treatment
Complications rare
What cause transcription factor mutations?
HNF-1alpha
HNF-1beta
HNF-4alpha
How does transcription factor diabetes present?
Adolescence/young adult onset Progressive hyperglycaemia 1/3 diet 1/3 OHA 1/3 insulin Complications frequent
What is the role of glucokinase?
Gluc –> G-6-P
What causes secondary diabetes mellitus?
Drug induced
Pancreatic destruction
Genetic syndromes - DIDMOAD
Endocrine disorders
What are the most common causes of pancreatic damage?
Haemochromatosis
Cystic fibrosis
Chronic pancreatitis
Pancreatectomy
Which endocrine disorders can cause secondary diabetes mellitus?
Cushings syndrome
Acromegaly
Pheochromocytoma
What is gestational diabetes?
Increasing insulin resistance in pregnancy
Developing in 2nd/3rd trimester
Gestational diabetes is more common in who?
FH of T2DM
Overweight and inactive
Which neonatal problems are associated with gestational diabetes?
Macrosomia
Respiratory distress
Neonatal hypoglycaemia
Mothers suffering gestational diabetes are at increased risk of what?
T2DM later in life