Diabetes - T1DM, T2DM, HHS & Complications Flashcards
How are blood glucose levels controlled in the body?
Controlled via hormones
Insulin -
- peptide hormone, secreted by the beta cells of the pancreatic islets of Langerhans
- secreted when blood sugar levels increases and facilitates cellular glucose uptake to reduce blood sugar levels ( increases expression of GLUT4 protein channel)
Glucagon -
- polypeptide hormone, secreted by the alpha cells in the islets of langerhans in the tail of the pancreas
- acts to increase blood sugar levels, causes glycolysis of glycogen in liver stores —> glucose
- causes gluconeogenesis to increase glucose levels
Work together to maintain homeostasis
What level is glucose ideally kept at?
Between 4.4. mmol/l - 6.1 mmol/l
What is Type 1 Diabetes Mellitus? What is the pathophysiology?
Type 1 diabetes - chronic condition caused by the pancreas secreting little to no endogenous insulin leading to an insulin deficiency , resulting in hyperglycaemia
Pathophysiology - absolute insulin deficiency due to autoimmune cytotoxic T cell destruction of the pancreatic beta cells, can be triggered by infection/ environment in genetically predisposed patients
What is the epidemiology of T1DM in the UK?
4.7 million people have diabetes in the UK ( both T1&T2) - 8% of these individuals will have type 1 diabetes
How do patients with T1DM present?
Usually presents in adolescents/ children, however can present in older patients “ Latent Autoimmune Diabetes in Adults “ (LADA)
Sudden onset of symptoms including:
Polydipsia and polyuria.
Weight loss due to reduced calorie uptake
Visual blurring from lens swelling.
Genital thrush.
Muscle cramps.
Lethargy
What are the causes of Type 1 DM?
Can be triggered by viruses - Coxsackie B virus, enterovirus
Pancreatic causes: Pancreatitis, trauma, pancreatectomy, destruction ( haemochromatosis, CF - type 3C diabetes- occur secondary to pancreatic diseases)
What are the risk factors associated with T1DM? (4)
Syndromes associated with T1DM - Down’s Syndrome, Turner’s syndrome, Kleinfelters Syndrome
Any other autoimmune conditions -e.g. Addison’s, Grave’s, Hashimoto’s
Family history
Genetics - risks increases in HLA DR3 / DR4 carriers (90% of patients with T1DM carry gene), HLA gene codes for human leukocyte antigen complex which is used to distinguish self from foreign cells
What investigations should be ordered when considering T1DM?
Random blood glucose ( hyperglycaemia - 11 mmol/l is diagnostic with symptoms e.g. polydipsia, polyuria, weight loss)
Blood ketones - to ensure DKA is ruled out
What is the management of T1DM?
- begin insulin therapy ( basal and bolus regime usually)
- Refer to Diabetes specialist to create individual care plan to manage diabetes - this will include
- diabetes education, insulin therapy (injections, regimes & dose adjustment, monitoring ( Libra/ CBG) etc)
- refer patient to DAFNE course - dose adjustment for normal eating
- manage lifestyle issues - diet, exercise, alcohol intake
- refer to diabetes support groups - local & national
- set up annual foot, eye, vision, Urine:albumin excretion and urine tests to prevent complications
- Review HbA1c levels regularly
What are the target HbA1c levels for patients with T1DM? How often should this be checked?
48mmol/mol (6.5%) or lower to minimise the risk of long term vascular disease
Checked every 6 months in controlled diabetes, 3 for uncontrolled
What is reviewed annually in T1DM?
Annual review:
CV: BP, lipids.
Renal: U+E, urine albumin. Microalbuminuria is an early sign of diabetic nephropathy.
Eyes: retinal photography.
Neuropathy testing by clinical examination.
Feet checks.
Ask about erectile dysfunction.
What are the complications of Type 1 DM?
Microvascular:
Neuropathy: glove + stocking, tingle, numb, pain, parasthesia.
Retinopathy (50%): diplopia, blurring.
Nephropathy (25%).
Macrovascular :
MI, cerebrovascular events , Peripheral Vascular disease
Others:
Diabetic foot, a combination of vasculopathy and neuropathy.
Commoner in type 1: DKA, hypoglycaemia
Long-term prognosis for type 1 diabetes:
Life expectancy is reduced by around 10 years, with most early death due to CVD.
What is Type 2 Diabetes Mellitus?
Type 2 Diabetes Mellitus is a condition characterised by hyperglycaemia secondary to insulin resistance and a relative lack of insulin.
What is the pathophysiology of T2DM?
Characterised by defect in both insulin sensitivity and insulin secretion
Insulin resistance occurs at peripheral tissues ( skeletal muscle, adipose tissue, liver) —> reduced glucose uptake —> impaired inhibition of hepatic glucose output
Initially - hyperinsulinaemia to compensate for resistance to maintain glucose concentrations within normal ranges - phase known as Impaired glucose tolerance / Impaired fasting glucose- unique window for lifestyle intervention
Eventually this leads to B cell exhaustion resulting in reduced insulin secretion and rises in glucose levels as it is unable to enter the cells
What is the epidemiology of T2DM in the UK?
4.9 million patients in the UK with diabetes, approx. 90% of these patients will have type 2
What is the clinical presentation of T2DM?
Type 2 - more insidious & subtle onset, usually occurs in older patients ( over 40 years old)
Symptoms:
Polydipsia and polyuria.
Visual blurring from lens swelling.
Unintentional weight loss
Genital thrush. ( opportunistic infections)
Slow healing
Muscle cramps.
Lethargy. In some cases of type 2, this may be the only symptom initially.
Most signs are rare at presentation ( seen in more advanced disease) , except for neuropathy:
Neuro: peripheral neuropathy (found in 50% of type 2 at diagnosis), postural ↓BP from dysautonomia, Romberg’s +ve from dorsal column disease.
Eyes: xanthelasma, retinopathy, ophthalmoplegia from mononeuritis multiplex.
Mouth: candida.
Legs: ulcers, necrobiosis lipoidica.
It may also present with complications e.g. HHS (type 2).
What are the risk factors of Type 2 Diabetes Mellitus?
Obesity
Lack of exercise
Poor diet
Demographic: age, male, Asian.
Alcohol use
Genetic factors - family history.
PCOS
Often preceded by ‘pre-diabetes’: impaired glucose tolerance (7.8-11 random glucose) or impaired fasting glucose (6.1-6.9 fasting glucose).
What are the causes of T2DM?
Lifestyle factors - inactivity, poor diet ( high sugar —> insulin resistance), obesity
Genetic factors - polygenic disease
What risk factors are associated with T2DM?
Obesity
Metabolic syndrome- central obesity, HTN, Hyperlipidaemia
Inactivity
Family history ( genetic predisposition)
Race - Asian, black, Hispanic & Native American - more likely to develop than Caucasian
PCOS
Age
Alcohol use
What investigations should be considered when diagnosing Type 2 diabetes?
HbA1c test - 6.5% and above is diagnostic
Random blood glucose - 11.1 mmol/L or more with symptoms (+)
Urine dip stick - check for glycosuria
Oral glucose tolerance test - performed in the morning prior to breakfast, take a baseline fasting glucose result then consuming a 75g glucose drink and measured CBG 2 hours later - if result is over 11 mmol/L - diabetes
What is the management of pre diabetics ? What values are diagnostic of pre-diabetes?
If pre-diabetic - recommend lifestyle interventions
- lose weight
- exercise
- stop smoking
HbA1c – 42-47 mmol/mol
Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l
Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
What values are diagnostic of type 2 diabetes?
HbA1c > 48 mmol/mol ( 6.5%)
Random Glucose > 11 mmol/l
Fasting Glucose > 7 mmol/l
OGTT 2 hour result > 11 mmol/l
What is the management of type 2 diabetes?
Lifestyle modification - lose weight, exercise, improved diet ( low glycaemic, high fibre) , stop smoking
Optimise other risk factors - prescribe statins to modify hyperlipidaemia, start BP medication if indicated to prevent CV disease
Medical -
First line
- Biguanide - Metformin 500mg
- increases insulin sensitivity & decreases gluconeogenesis
2nd line: add other therapies depending on individual patient factors & drug tolerance
sulfonylurea ( gliclazide) - stimulate insulin release form pancreas
Pioglitazone (thiazolidinedione) - increases insulin sensitivity & decreases gluconeogenesis
DPP-4 inhibitor - (sitagliptin), inhibits DPP-4 & ergo increases GLP-1 ( hormone produced by GI tract - act to reduce blood sugars after a large meal is ingested)
SGLT-2 inhibitor - (dapaglifozin) - increase glucoseuria
What are the complications of type 2 diabetes?
Microvascular:
Neuropathy: glove + stocking, tingle, numb, pain, parasthesia.
Retinopathy (50%): diplopia, blurring.
Nephropathy (25%).
Macrovascular:
MI , cerebrovascular events, Peripheral vascular disease
Others:
Diabetic foot, a combination of vasculopathy and neuropathy.
Commoner in type 2: hyperosmolar hyperglycaemic state.
What is Diabetic Ketoacidosis?
Diabetic ketoacidosis occurs when there is a decreased insulin supply ( i.e. an insulin deficiency) or an increased insulin demand ( e.g. due to illness). This leads to reduced glucose uptake into cells, reducing ATP production leading to ketogenesis & electrolyte imbalances. Usually occurs in type 1 diabetics
What are the causes of DKA?(6)
6 I’s:
-low Insulin
- Infections - pneumonia, UTI’s, Cellulitis
- Inflammatory - pancreatitis, cholecystitis
- Intoxication - Alcohol, Cocaine, Methamphetemines
- Infarction - MI’s, Stroke
- Iatrogenic - corticosteroids ( increases blood glucose levels which increases insulin demand), surgery ( requires wound healing —> more glucose needed ergo more insulin needed)
What is the pathophysiology of DKA?
less insulin, reduces glucose uptake into cells —> hyperglycaemia, reduced ATP production
Causes beta-fatty acid oxidation to create ACoA —> ketogenesis —> ketone bodies ( acetoacetate, beta-hydroxybutryate)
Ketone bodies enter blood stream and release protons —> ketoacidosis
Ketones stimulate the emetic centre of the medulla —> nausea and vomiting
Why does DKA cause hyperkalaemia? What does the hyperkalaemia cause?
Ketoacidosis - causes H+ ions in Extracellular fluid to move into the intracellular fluid, this removes potassium from the intracellular fluid into the extracellular fluid ( via a H+/K+ pump), causes potassium to accumulate in ECF
K+ also builds up in ECF as Na+/K+ pumps are stimulated by insulin, and due to insulin deficiency, they are not stimulated, leading to high K+ ECF levels
Total body potassium decreases, however, the excess potassium in the ECF can enter the blood stream leading to hyperkalaemia
Hyperkalaemia —> arrhythmias ( palpitations / chest pain), alters peristaltic function of small intestine —> ileus —> abdo pain
Why do patients with DKA present with an increased resp rate?
Increased resp rate - to reduce acidosis by increasing CO2 loss —> Kussmauls Respiration ( deep and rapid respiration), also to get rid of acetone form ketone bodies ( fruity breath odour)
What is the presentation of someone with DKA?
Polyuria
Polydipsia
Nausea and vomiting
Acetone smell to their breath
Dehydration and subsequent hypotension
Altered Consciousness
They may have symptoms of an underlying trigger (i.e. sepsis)
What investigations are needed to diagnose DKA?
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)- Blood glucose
Ketosis (i.e. blood ketones > 3 mmol/l) - Blood ketones
Acidosis (i.e. pH < 7.3) - ABG/VBG
What additional investigations can you order in DKA?
U&Es - Electrolytes
VBG
FBC
Urinanalysis
CXR
ECG
MSU
Blood cultures
MI screen
