ENDOCRINOLOGY Flashcards
What is the normal blood glucose range for a healthy person:
- fasting
- post meal
Fasting 4 - 5.9 (or 5.4 ish)
Post meal can go up to 7.8
Think of this as approx 2 mmol range from 4 that roughly doubles post meal
What is the diagnostic blood sugar range for diabetes
Fasting >7 mmol/l
Post meal >11.1 mmol/l
7/11
What is the blood sugar range for pre-diabetes
Impaired fasting glucose: 6.1 - 7 mmol/l
Impaired glucose tolerance: 7.8 - 11 mmol/l (glucose challenge 75 mg)
Describe the pathology of Diabetes mellitus type 1
Autoimmune - autoantibodies against beta cells in islets of langerhans
Islet cell antibodies - ICA
Anti-glutamic acid decarboxylase (GAD) antibodies
Depleted beta cells = no insulin production (get down to around 10% at diagnosis)
No insulin = glucagon dominant state
=Increase gluconeogenesis (exacerbates hyperglycemia, as no insulin to clear)
=glycosuria
=Increase lipolysis, beta oxidation of fats, ketogenesis
Because there is so little insulin, you get unregulated ketogenesis
=Ketoacidosis
=Ketouria
DKA
Treatment - Insulin
Describe the pathology of type 2 diabetes
- Impaired insulin secretion (possibly bc of fat deposits in pancreas and liver)
- Insulin resistance across cells
Low insulin = glycogen dominant state
=gluconeogenesis (but glucose cant be cleared as cells resistant)
=increase lipolysis BUT bc some baseline insulin, do go into DKA, as insulin still has some regulatory effect
Insulin resistance
=Cant clear glucose
=Glycouria
NO ketouria
Treatment: Metformin, and possibly insulin if production is bad
Think of this one as being driven by physiological mechanisms that have the potential to be reversed
List some differences in the pathology of type 1 and type 2 DM
1: ketouria + glucouria; autoimmine, beta cell destruction, associated with other autoimmune diseases; HLA DR3, DR4 associated (90%)
2: glucouria only, physiological, caused by obesity, lack of exercise, calorie and alcohol excess. Reversible
What autoantibodies are associated with type 1 diabetes
Islet cell antibodies
GAD antibodies - Anti glutamic acid decarboxylase
Risk factors for type 1 diabetes
HLA DR3, DR4 positive
Other autoimmune disease - hypothyroid
Inheritance risk:
if a mother has the condition, the risk of developing it is about 2%
If a father has the condition, the risk of developing it is about 8%
if both parents have the condition, the risk of developing it is up to 30%
if a brother or sister develops the condition, the risk of developing it is 10%
(rising to 15% for a non-identical twin and 40% for an identical twin).
Risk factors for type 2 diabetes
Obesity Lack of exercise Alcohol excess High calorie intake 80% concordance in identical twins Pre-diabetes - progresses from this Gestational diabetes
Asian men
What does cortisol do to insulin
Counteracts it
This is why steroids can cause diabetes
Atypical causes of diabetes
Steroids, HIV meds, antipsychotics
Pancreatitis, pancreas surgery
Cushing’s, acromegaly, hyperthroidism, pregnancy
What is metabolic syndrome
BMI >30 or high waist circumference - central obesity Plus two of the following: BP >135/85 Triglycerides >1.7 mmol/L HDL - hyperlipidemia Pre-diabetes Diabetes
obesity + signs of cardiovascular disease (hypertension, hyperlipidemia etc) + diabetes
What are the typical symptoms of type 1 diabetes
Polyuria - osmotic diuresis Thirst - osmotically driven, not bc of fluid loss Weight loss Fatigue Blurred vision Pruritis vulvae - vaginal candidiasis Chest infections Hunger - lack of useable energy source
Signs of DKA
Drowsiness
Unexplained vomitting
Dehydration
+type 1 diabetes symptoms
Symptoms: develop over days polyuria and polydipsia nausea and vomiting weight loss weakness abdominal pain (confused with surgical abdomen) Drowsiness / confusion
Signs: hyperventilation (Kussmaul breathing) dehydration (average fluid loss 5-6 litres) hypotension Tachycardia coma
Difference in presentation of type 1 and 2 diabetes
Type 1 acute onset, may present in ketoacidosis
Type 2 insidious onset - pt may be asymptomatic at diagnosis - very rare to present in ketoacidosis, may present with complications instead of classic symptoms - eg vision changes
Type 1 - bloods will show autoantibodies, ICA, GAD; HLA D3 and D4 associated
Type 1 often starts before puberty, or younger pt
Type 2 over 30
Flags for type 1 diabetes
Short history (Weeks) of symptoms
Weight loss
Ketouria
What happens if you dont treat ketoacidosis
Absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones
Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume
Ketones (weak organic acids) cause anorexia and vomiting
Vicious circle of increasing dehydration, hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death
What are the diagnostic features of DKA
Hyperglycaemia (plasma glucose usually <50 mmol/l)
Raised plasma ketones (urine ketones > 2+)
Metabolic acidosis – plasma bicarbonate < 15 mmol/l
Hyperglycaemia
Ketones
Acidosis
NB - K+ will be high on presentation as K+ leaves cell to counteract acidity, but will fall when treat with insulin so need to treat this
What is the treatment of DKA
rehydration (3L first 3 hrs) insulin (inhibits lipolysis, ketogenesis, acidosis, reduces hepatic glucose production, increase tissue glucose uptake) replacement of electrolytes (K+) treat underlying cause Treatment must be started without delay Follow DKA protocol in hospital
List some of the complications of DKA
cerebral oedema (deterioration in conscious level) children more at risk
adult respiratory distress syndrome
thromboembolism – venous and arterial
aspiration pneumonia (in drowsy/comatose patients)
death
What is the normal range for HbA1c
<42
Outline the treatment for type 1 diabetes
Basal-bolus insulin regime
Basal long-acting insulin at night to cover hypoglycemia through the night
x3 short-acting insulin pre or post meal during the day
Benefits:
Its flexible to the patients life as they can control they insulin dose based on their meal (carb content) and when they eat, or alter according to exercise
Disadvantages:
It is arduous - pt has to actively manage their blood sugars and cannot miss any injections
They also need to match their dose to their carb load - requires checking carbohydrate content and matching
Risk of weight gain
Must still have plan for hypo
Outline the treatment for type 2 diabetes
- Diet, exercise, weight loss (aim is to improve insulin sensitivity)
- Metformin on its own (inhibits glyconeogenesis from liver, to reduce glucose load - improves insulin sensitivity)
- Metformin + second line drug to improve insulin sensitivity/ secretion
DPP4 inhibitors - Gliptin (inhibit the breakdown of incretin)
Sulphaylurea
Pioglitazone - Triple therapy: Metformin + 2 others
- Insulin therapy
