diabetes type 2 Flashcards
whats the simplified pathophysiology of diabetes type 2?
- repeated glucose and insulin exposure make the cells resistant to insulin
- more insulin is required
- pancreas becomes fatigued and damage from overworked
- insulin output is reduced
how is hyperglaecemia in patients with type 2 diabetes caused, and what complications can it lead to?
- high carb diet
- insulin resistance
- reduced pancreatic function
ALL CAUSE CHRONIC HYPERGLAEMEMIA - this leads to microvascular, macrovascular and infectious complications
what are the non-modifiable risk factors
- Older age
- Ethnicity (Black African or Caribbean and South Asian)
- Family history
what are the modifiable risk factors
- Obesity
- Sedentary lifestyle
- High carbohydrate (particularly sugar) diet
what is the typical clinical presentation of someone with type 2 diabetes?
- Tiredness
- Polyuria and polydipsia (frequent urination and excessive thirst)
- Unintentional weight loss
- Opportunistic infections (e.g., oral thrush)
- Slow wound healing
- Glucose in urine (on a dipstick)
- (acanthosis nigricans - thickening and darkening of skin - insulin resistance)
what does a HbA1c of 42 – 47 mmol/mol indicate?
pre-diabetes
what is the HbA1c is a blood test
reflects the average glucose level over the previous 2-3 months.
what is pre-diabetes and what indicates it
Pre-diabetes is an indication that the patient is heading towards diabetes. They do not fit the full diagnostic criteria but should be educated about the risk of diabetes and lifestyle changes.
An HbA1c of 42 – 47 mmol/mol indicates pre-diabetes.
what is done to diagnose type 2 diabetes?
An HbA1c of 48 mmol/mol or above
The sample is typically repeated after 1 month to confirm the diagnosis (unless there are symptoms or signs of complications).
what are the treatment targets for diabetes?
HbA1c treatment targets:
- 48 mmol/mol for new type 2 diabetics
- 53 mmol/mol for patients requiring more than one antidiabetic medication
The HbA1c is measured every 3 to 6 months until under control and stable.
what is the medical management for type 2 diabetes?
1) first-line - metformin
2) if the patient has QRISK score above 10% consider SGLT-2 inhibitor
3) second-line - metformin add a SGLT-2 inhibitor
4) third-line options are:
- Triple therapy with metformin and SGLT2 and add a DPP-4 or GLP1
5) Insulin therapy (initiated by the specialist diabetic nurses)
what is the role of metformin?
- increases insulin sensitivity
- decreases glucose production by the liver
- doesn’t cause weight gain - can actually cause weight loss
what class of medication is melformin?
biguanide
what are the side effects of metformin?
- Gastrointestinal symptoms, including pain, nausea and diarrhoea (depending on the dose)
- Lactic acidosis (e.g., secondary to acute kidney injury)
what would you suggest to patients on metformin who are experiencing gastrointinestinal side effects?
modified-release metformin
what suffix do SGLT-2 inhibitors end with?
-gliflozin
what is the action of SGLT-2 inhibitors in terms of diabetes type 2?
- the SGLT-2 inhibitor is on proximal tubules of kidneys which rebasorbs glucose from urine into blood
- inhibitors block this to allow more glucose to go into the urine
- reduces blood pressure, leads to weight loss, improves heart failure
when do SGLT2-inhibitors cause hypoglycemia?
when used with insulin or sulfonylureas
what are the side effects of SGLT-2 inhibitors?
- Glycosuria (glucose in the urine)
- Increased urine output and frequency
- Genital and urinary tract infections (e.g., thrush)
- Weight loss
- Diabetic ketoacidosis, notably with only moderately raised glucose
- Lower-limb amputation may be more common in patients on canagliflozin (unclear if this applies to the others)
- Fournier’s gangrene (rare but severe infection of the genitals or perineum)
what does pioglitazone do and what type of drug class is it?
- its a thiazolindinedione
- it increases insulin sensitivity
- it decreases liver production of glucose
what are the notable side effects of pioglitazone?
- Weight gain
- Heart failure
- Increased risk of bone fractures
- A small increase in the risk of bladder cancer
which drugs used to manage diabetes type 2 can cause hypoglycemia?
- metformin - NO
- SGLT-2 - YES
- pioglitazone - NO
- sulfony;ureas - YES
- DPP-4 inhibitors and GLP-1 mimetics - NO
whats the role of sulfonyureas?
- stimulate insulin release from the pancreas
what are the side effects of sulfonylureas?
- weight gain
- hypoglycemia
whats the role of and what type of drug are DPP-4 inhibitors and GLP-1 mimetics?
Incretins (GLP-1) are hormones produced by the gastrointestinal tract. They are secreted in response to large meals and act to reduce blood sugar by:
Increasing insulin secretion
Inhibiting glucagon production
Slowing absorption by the gastrointestinal tract
incretins are inhibited by DPP-4
so these drugs allow more incretins
what are the side effects of DPP-4 inhibitors?
- Headaches
- Low risk of acute pancreatitis
how do GLP-1 mimetics work and how is it administered?
- imitate the action of GLP-1
- subcutaneous injections
what are the notable side effects of GLP-1 mimetics?
- Reduced appetite
- Weight loss
- Gastrointestinal symptoms, including discomfort, nausea and diarrhoea
what are the different types of insulin, wht ratio are they administrated at and after how much time do they begin working?
Insulin is usually initiated and managed by diabetic specialist nurses.
Rapid-acting insulins (e.g., NovoRapid) start working after around 10 minutes and last about 4 hours.
Short-acting insulins (e.g., Actrapid) start working in around 30 minutes and last about 8 hours.
Intermediate-acting insulins (e.g., Humulin I) start working in around 1 hour and last about 16 hours.
Long-acting insulins (e.g., Levemir and Lantus) start working in around 1 hour and last about 24 hours or longer.
Combinations insulins contain a rapid-acting and intermediate-acting insulin. In brackets is the ratio of rapid-acting to intermediate-acting insulin:
Humalog 25 (25:75)
Humalog 50 (50:50)
Novomix 30 (30:70)
what are the key complications of type 2 diabetes?
microvascular:
- Diabetic retinopathy
- diabetic neuropathy
- diabetic nephropathy
macrovascular:
- cardiovascular disease
- Diabetic foot
other:
- Gastroparesis (slow emptying of the stomach)
- Hyperosmolar hyperglycemic state
- Infections (e.g., periodontitis, thrush and infected ulcers)
- DKA
what is used to control hypertension in those with type 2 diabtees?
ACE inhibitors
at what point are ACE inhibitors administered to type 2 diabetics?
ACE inhibitors are started in type 2 diabetics with chronic kidney disease when the albumin-to-creatinine ratio (ACR) is above 3 mg/mmol (as opposed to 30 mg/mmol in patients without diabetes).
when are SGLT-2 inhibitors started on type 2 diabetics?
SGLT-2 inhibitors are started in type 2 diabetics with chronic kidney disease when the albumin-to-creatinine ratio (ACR) is above 30 mg/mmol (in addition to the ACE inhibitor).
when are phosphodiesterase-5 inhibitors started on type 2 diabetics?
erectile dysfunction
what are the 4 options for neuropathic pain?
- Amitriptyline – a tricyclic antidepressant
- Duloxetine – an SNRI antidepressant
- Gabapentin – an anticonvulsant
- Pregabalin – an anticonvulsant
explain what is hyperosmolar hyperglycemic state, its presentation and how its treated?
It is characterised by hyperosmolality (water loss leads to very concentrated blood), high sugar levels (hyperglycaemia) and the absence of ketones, distinguishing it from ketoacidosis.
It presents with polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension and confusion.
It is a medical emergency with high mortality. Involve experienced seniors early. Treatment is with IV fluids and careful monitoring.
Advantages of basal insulin in T2DM (3)
- Patient adjusts insulin themselves, based on fasting glucose measurements
- Carries on with oral therapy, combination therapy is common
- Less risk of hypoglycaemia at night
Advantages of premixed insulin in diabetes (2)
- Both basal and prandial together
- Can cover insulin requirements though most of the day
Clinical presentation of T2DM (6)
- Obese hypertensive older patient
- Polydipsia
- Nocturia
- Polyuria
- Glycosuria
- Recurrent thrush
Diagnosis of T2DM (2)
- Same as T1DM (RPG >11.1, FPG >7, HbA1c >48)
- Prediabetes exists this time
Disadvantages of basal insulin in T2DM (2)
- Doesn’t cover meals
- Best used with long-acting insulin analogues (expensive)
Disadvantages of pre-mixed insulin (3)
- Requires consistent meal and exercise pattern
- Cannot seperately titrate individual insulin components
- Increased risk of nocturnal and fasting hypoglycaemia
Epidemiology of T2DM (3)
- Presents later on in life (usually 30+ years)
- Males > females
- People of Asian, African and Afro-Carribean ethnicity are 2-4x more likely to develop T2DM than white people
First treatment for Type 2 diabetes and prediabetes before drugs
Lifestyle change - diet, exercise, modify RFs
Last line of treatment for T2DM if all else fails
Insulin treatment
Main complication of T2DM
hyperosmolic state
Pathophysiology of T2DM (3)
- Peripheral insulin resistance with partial insulin deficiency
- Decreased GLUT4 expression - impaired insulin secretion
- Lipid and beta amyloid deposits in pancreas, progressive b cell damage
Prediabetic states and levels (3)
FBG: 6.1-6.9
2nd post prandial: 7.8-11.0
HbA1c: 42-47 (6.0-6.4%)
Risk factors for T2DM (7)
- Genetic link (stronger than T1DM)
- Obesity
- Alcohol excess
- Hypertension
- Gestational diabetes
- PCOS
- Drugs: corticosteroids, thiazides
Signs of T2DM (4)
- Acanthosis nigricans (fig.1)
- Glove and stocking sensory loss
- Diabetic retinopathy
- Diabetic foot disease
Why are thiazolidinediones (pioglitazone) not commonly given as a diabetic drug? (3)
- Increase weight
- Increase risk of heart failure
- Increase risk of fractures
hyperosmolar hyperglycemic state
- extremely high blood sugar
- extreme dehydration
- frequent urination as the body tries to get rid of excess glucose
- weakness and fatigue
- confusion or altered mental state - from light confusion to coma
- vision changes - blurred
- rapid heart rate - tachycardia
- low blood pressure - hypotension
hypoglycaemia diagnosis
Blood glucose test (typically <70 mg/dL or <3.9 mmol/L)
Symptoms relief after glucose intake confirms diagnosis
The role of bariatric surgery to treat obesity
consist of:
- gastric bypass
- sleeve gastrectomy
- adjustable gastric band
mechanism:
- restrict food intake
- alter gut hormones to control apetite
benefits:
- weight loss
- remission of type 2 diabetes, hypertension and slepp apnea
considerations:
- requires lifestyle changes post-surgery
- risks
- complications
monogenic diabetes
maturity-onset diabetes of the young (MODY) - dominant
neonatal diabetes mellitus (NDM)
drug-induced diabetes
Certain medications can induce diabetes, including:
Glucocorticoids: Used for inflammation and immune suppression.
Thiazides: Used for hypertension.
Beta-Blockers: Used for heart conditions.
Atypical Antipsychotics: Used for psychiatric disorders.
endocrine causes for diabetes
Diabetes can also result from other endocrine disorders, such as:
Cushing’s Syndrome: Excess cortisol production.
Acromegaly: Excess growth hormone production.
Hyperthyroidism: Excess thyroid hormone production.
Pheochromocytoma: A tumor of the adrenal gland that produces excess adrenaline
enzymes of exocrine pancreas
amylase - carbs
lipase - fats
proteases - trypsin and chymotrypsin - proteins
