Diabetes mellitus in clinical practice Flashcards
What is Diabetes Mellitus
A group of conditions characterized by high blood glucose & other metabolic and vascular derangements secondary to insufficient insulin action
How can we categorize diabetes mellitus
Type 1
- Insulin-dependent diabetes
- Beta cell destruction-total insulin deficiency
- Type a.) autoimmune
- Type b.) idiopathic ( no markers of autoimmunity)
Type 2
- Non-insulin dependent diabetes
- Impaired insulin action(insulin resistance) & inadequate insulin production(insulin deficiency)
Gestational diabetes
Other specific types
What comes under the phrase ‘other specific types’ of diabetes
- Neonatal
- Genetic defects of insulin secretion
- Genetic defects of insulin action
- Secondary to exocrine pancreatic disease
- Secondary to endocrine disorders
- Secondary to drugs or toxins
- Secondary to infection
- Uncommon forms of immune-mediated diabetes
- Other genetic syndromes sometimes associated with diabetes
How can we categorize the vascular complications of diabetes?
- ) Microvascular complications
2. ) Macrovascular complications
Describe the microvascular complications of diabetes
- Retinopathy
- Nephropathy
- Neuropathy
Describe the macrovascular complications of diabetes
- Cerebrovascular disease
- Ischaemic heart disease
- Peripheral vascular disease
What is the ‘diabetic foot’
- Neuropathy+diabetes+peripheral vascular disease all together causes this
- Presence of several characteristic diabetic foot pathologies such as infection, diabetic foot ulcer,ischemia,gangrene,ulceration and neuropathic osteoarthropathy is called diabetic foot syndrome.
- Due to the peripheral nerve dysfunction associated with diabetes (diabetic neuropathy), patients have a reduced ability to feel pain.
Outline genetic predisposition of T1DM
Haplotypes which suggest predisposition:
HLA-DR3
HLA-DR4
IDDM2
IDDM12
A person with these haplotypes may/ may not develop T1DM depending on whether there’s a precipitating environmental event
-This is because autoimmune diseases are multifactorial
How can we classify neonatal diabetes?
Transient & permanent
Which diabetes arise from genetic defects of beta cell function?
- Neonatal diabetes
- Monogenic diabetes
- Mitochondrial diabetes
What is mitochondrial diabetes associated with?
-Deafness & short stature
What mode of inheritance does mitochondrial diabetes present with
Matrilineal inheritance
What does MIDD stand for?
Maternally inherited diabetes & deafness
What does MELAS stand for?
Mitochondrial Encephalopathy, Lactic acidosis, and Stroke-like episodes
What does MODY stand for?
Maturity onset diabetes of the young
Outline the familial diabetes that are collectively called MODY
- HNF4alpha
- glucokinase
- HNF1alpha
- IPF-1
- HNF-1beta
- Neuro D1
- CarbxylEsterLipase gene
Which diabetes arise from genetic defects in insulin action
- Type a insulin resistance
- Leprechaunism
- Rabson-Meldenhall syndrome
- Lipoatrophic diabetes
Which diabetes arise from diseases of the exocrine pancreas?
- CF
- Haemochromatosis
- Pancreatitis
- Fibrocalculous pancreopathy
- Trauma/pancreatectomy
- Neoplasia
Which endocrine disease can diabetes be secondary to?
- Cushing’s
- Acromegaly
- Phaeochromocytoma
- Glucagonoma
- Hyperthyroidism
- Somatostatinoma
What is phaeochromocytoma?
Too much adrenaline & noradrenaline
Other than some endocrine diseases, what else can diabetes be secondary to?
- Drugs and chemicals eg glucocorticoids,thiazides, IFNalpha
- Infections eg congenital rubella, cytomegalovirus
- Uncommon immune mediated eg insulin autoimmune syndrome, anti-insulin receptor abs, ‘stiff-man’ syndrome
- Other genetic syndromes eg Down’s; Friedrich’s ataxia; Huntington’s, myotonic dystrophy, Prader Willi’s, Turner’s
Which hormones promote proteolysis
- Catecholamines
- Cortisol
- Glucagon
- Cortisol
- GH
What inhibits glycogenolysis?
Insulin
What occurs in the absence of insulin action
- Uncontrolled endogenous glucose production
- Tissue glucose deprivation
- Lipolysis
- Proteolysis
In terms of the physiology of symptoms involved in diabetes, what causes weight loss?
- Proteolysis
- Lipolysis
- Dehydration
In terms of the physiology of symptoms involved in diabetes, what causes nausea?
Ketosis
What is ketosis
A metabolic state characterized by raised level of ketone bodies in the body tissue
In terms of the physiology of symptoms involved in diabetes, what causes hyperventilation?
acidosis
In terms of the physiology of symptoms involved in diabetes, what does dehydration lead to ?
- Hypotension
- Thirst & polydipsia
- Weight loss
In terms of the physiology of symptoms involved in diabetes, what causes dehydration?
- Vasodilation due to ketosis ( which causes acidosis)
- Polyuria ( due to osmotic diuresis)
Hyperglycaemia is due to lack of insulin; in terms of the physiology of symptoms involved in diabetes, what causes osmotic diuresis ?
-osmotic diuresis is caused by glycosuria (which is caused by hyperglycaemia)
In terms of the physiology of symptoms involved in diabetes, what causes infection?
Hyperglycaemia
State the symptoms associated with microvascular diabetic complications
- Numbness,pain,tingling hands & feet
- abormal sweating
- gastroparesis
- Diarrhoea
- Postural dizziness
- Erectile dysfunction
- Incontinence
- Pain,weakness (wasting)
- Diplopia
- Pain, tingling, weakness(may get carpal tunnel)
What is Carpal tunnel?
-A medical condition due to compression of the median nerve as it travels through the wrist at the carpal tunnel. -Main symptoms are pain, numbness and tingling in the thumb, index finger, middle finger and the thumb side of the ring fingers.
Define diplopia
double vision
How do we diagnose diabetes?
- Typical symptoms of hyperglycaemia
- Unequivocally high blood glucose concentration or HbA1c
- Venous plasma glucose> 11.1mmol/L or HbA1c>/= 48mmol/mol(6.5% or over)
What HbA1c level do we class as having diabetes
- 5% or more
i. e 48mmol/mol
What is HbA1c
- Glycated haemoglobin; a form of haemoglobin that is covalently bound to glucose
- Tells you your average blood glucose levels over the last 6-12 weeks
- Red blood cells have a lifespan of 120days so this works
- The HbA1c value, which is measured in mmol/mol, should not be confused with a blood glucose level which is measured in mmol/l
- Needs to be done by healthcare professionals
- Measured via venous blood draw
What is the normal Hba1c level in non-diabetics
- Normal= between 4% and 5.6%
- Levels between 5.7% and 6.4% mean there’s a greater chance of getting diabetes
- Levels of 6.5% or greater means you have diabetes
- We set these figures at these levels cos these are the levels in which the microvascular complications start to happen
How do we diagnose diabetes in the absence of typical symptoms
On 2 separate occasions (& days) there must be:
-Abnormal blood glucose
-Abnormally high amount of glucose on circulating proteins (HbA1c)
-any of:
HbA1c>/= 6.5%
Fasting venous plasma glucose>/=7mmol/l
Random or 2h post 75g glucose load>/=11.1mmol/l
How can we define pre-diabetes
- Borderline area at which HbA1c level isn’t completely normal but it is not yet high enough to be classed as diabetes
- Here they have an increased risk of developing microvascular complications & and an increased risk of developing diabetes
- Levels between 6.1% and 6.4%( 43-47mmol/mol)
- Impaired glucose tolerance
- Fasting venous plasma glucose< 7 and 2h post 75g glucose load >/=7.8 and <11.1mmol/l
- Impaired fasting glucose
- Fasting venous plasma glucose 6.1-6.9mmol/L
Describe how the oral glucose tolerance test is performed
- 180g CHO for 3days ebfore
- Overnight fast
- Sedentary during test
- Fasting venous plasma glucose
- 75g anyhdrous glucose over 5min
- 2 hour venous plasma glucose
Can we use the same diagnostic criteria for the values giving for venous plasma glucose, whole blood and capillary blood glucose
No because glucose concentrations are different in different samples
What are the clinical features of T1DM
- Insulin deficient
- Ketosis prone
- HLA markers
- Autoimmune
- Onset peak in adolescence
- Weight loss
What are the clinical features of T2DM
- Insulin resistant & deficient
- Not ketosis prone
- Polygenic
- S Asians> Africans & Caribbeans> Europids
- Increases with ageing ( younger in ethnic groups with high prevalence)
- Associated with obesity
What are the aims of management of diabetes ?
- Remove symptoms of uncontrolled diabetes
- Avoid diabetes emergencies
- Reduce risk of development/progression of complications of diabetes
- Early detection & effective management of complications
- Avoid adverse effects on QOL ( related to diabetes or its treatment)
What are the modifiable risk factors for long term diabetes complications
- Glycaemic control
- Hypertension
- Lipid profile/dyslipidaemia
- Smoking
- Exercise
- Diet
- Obesity/overweight
What are the non-modifiable risk factors for long term diabetes complications
- Age
- Gender
- Family history
- Ethnicity
Explain a ‘hard endpoint’ in a clinical trial
-An outcome important to patients
-Death
-MI
-Stroke
-Blindness
-Renal failure
-Amputation
This does not need to be measured
Explain a ‘surrogate endpoint’ in a clinical trial
- Biomarker intended to substitute for a hard endpoint
- Risk factors/causal factors: eg BP, lipids, HbA1c
- Subclinical indicators: eg retinal morphology
- Correlated factors: eg C reactive protein (for CVD)
What is the ‘glucocentric view’ in diabetes
-The view that blood glucose is the cause of diabetes
What does UKPDS stand for
UK prospective diabetes study
What are sulphonyureas?
A class of oral medications that control blood sugar levels in patients with type 2 diabetes by stimulating the production of insulin in the pancreas and increasing the effectiveness of insulin in the body
What landmark trials took place for diabetes
UKPDS
- 20 year study
- > 5000people newly diagnosed with T2DM
- RCT
- Intensive group: sulphonyurea or insulin later metformin
- Conventional treatment (diet,drugs if hyperglycaemic symptoms/ FPG>15
DCCT (Diabetes Control and Complications Trial )
- 1447 people with T1DM
- Randomised to intensive or conventional insulin therapy
- Followed for mean 6.5years
What is the normal blood glucose level
- Tested while fasting should be between 3.9 and 7.1 mmol/L
- In a healthy adult male of 75 kg with a blood volume of 5 liters, a blood glucose level of 5.5 mmol/L
