Type II DM Flashcards
Type II DM
-pathophysiology
- body makes insulin but the tissues do not response well to it
- insulin resistance: excess adipose tissue –> free fatty acids + adipokines = inflammation
- increase insulin production
- beta cell hyperplasia and hypertrophy
- normoglycemia
- beta cells secrete amylin
- amylin builds up
- hypoplasia and hypertrophy of beta cells
- insulin levels decrease
- hypergylcemia
Type II DM
- symptoms (4)
- complications (7)
-polyphagia, polyuria, polydipsia, glycosuria
- hyaline atherosclerosis,
- thickened b.m in capillaries = hypoxia
- atherosclerosis
- retinopathy
- nephrotic syndrome
- diabetic neuropathy - decreased sensation in toes and fingers
- ulcers –> poor nerve supply + nerve damage
Diabetic ketoacidosis is less common in DM type I or II?
Type II DM because some insulin is still being produced
Main targets DM treatment (3)
- glycemic control - HbA1c
- cholesterol
- BP
Serum insulin and C-peptide levels in DM I and II
DM I –> lower levels
DM II –> high or normal levels
Cases when hypoglycemia can develop (2)
- if dose of insulin is too high
- if medications given directly stimulate insulin secretion without reacting with plasma glucose –> only medications like that: Sulphonylureas and Glinides
Metformin
- mode of action
- can it be used together with insulin therapy?
- clinical utility
- contraindications
- side effects
- decrease hepatic glucose production and increase insulin-mediated peripheral glucose uptake
- yes
- first line - can be combined with any other medication
- doest not cause hypoglycemia or weight gain
-contraindicated if eGFR <30 ml/min
- diarrhea, abdominal discomfort
- lactic acidosis - if prescribed improperly
- vit B12 deficiency
Metformin
-recommendations to decrease side effects (4)
- start first dose in the evening before going to bed
- start from the smallest dose –> if patient is tolerant –> increase dose
- increase dose to maximum tolerated OR maximum therapeutic dose
- titration period may take up to 1 month
Sulphonylureas
- mode of action
- clinical utility
- contraindications
- side effects (2)
- increase endogenous insulin secretion by binding to pancreatic beta cells and triggering a cascade of intracellular events (does not react to plasma glucose levels)
- can be combined with any other medication but risk of hypoglycemia will increase
- if eGFR <30 ml/min
- hypoglycemia and weight gain
Glinides
- mode of action
- difference when compared to Sulphonylureas
- side effects (2)
- increase insulin secretion by binding to pancreatic beta cells and triggering a cascade of intracellular events
- stimulation of insulin secretion is more rapid and short lasting
- hypoglycemia and weight gain
Alpha-glucosidase inhibitors
- mode of action
- side effects
- inhibit enzymes that degrade oligosaccharides and disaccharides in the small intestine
- flatulence and abdominal discomfort
Thiazolidinedione
- mode of action
- clinical utility
- side effects (3)
- decrease insulin resistance by increasing the sensitivity of muscle and adipose cells to insulin and suppressing hepatic glucose production
- does not cause hypoglycemia, maximal clinical effect is expected in a few weeks after starting
- weight gain, edema, increased LDL
- may exacerbate or precipitate CHF
- increased risk of myocardial events
Thiazolidinedione
- contraindications (2)
- can it be used together with insulin?
- patients with abnormal liver function
- increased risk for bladder cancer
-no, it increases the risk of fluid retention specially in patients with heart failure
The incretin system
- plays a key role in regulation of post-meal glucose
- incretin effect –> increases beta cell response to oral glucose –> a greater insulin release than when the same amount of glucose is given IV
- increase C-peptide levels after oral glucose load
The incretin system
-Glucagon- like peptide (GLP-1) - function (7)
- increases insulin secretion in a glucose dependent manner
- enhances glucose-dependent insulin secretion and decrease postprandial glucagon secretion
- increase glucose uptake by peripheral tissue and decrease hepatic glucose production = decrease blood glucose in fasting and postprandial states
- promotes satiety and reduces appetite
- helps regulate gastric emptying
- enhances B cell proliferation
- secreted by intestinal L-cells
GLP-1 is mot responsive to…?
Actions are mediated via…?
-Lipids and amino acids
- GLP-1R
- receptors are expressed in beta cells
- when activated –> activates cAMP and protein kinase A dependent and independent actions
DPP-4 inhibitors
- mode of action
- clinical utility (3)
- cannot be used in combination with…?
- side effects (3)
- prolong the effects of GLP-1 and GIP on alpha and beta cells leading to increased insulin secretion and decreased glucagon secretion
- does not cause hypoglycemia, can be combined with any other medication, very good for elderly patients, dose should be reduced in renal insufficiency
- GLP-1RA because they work on the same system (incretin system)
- upper respiratory tract infection, nasopharyngitis and headache
GLP-1RA
- mode of action
- clinical utility (4)
- contraindication
- side effects (4)
- mimic the effects of endogenous GLP-1 by activating GLP-1 receptors throughout the body
- they are synthetic incretins
- increase insulin, decrease glucagon, slow gastric emptying
- increase glucose uptake by peripheral tissue, decrease hepatic glucose production
- low risk of hypoglycemia, weight reduction, reduction in postprandial glucose excursions ,injectable (requires training)
- eGFR <15 ml/min
- nausea, vomiting, diarrhea, risk of acute pancreatitis,
The role of kidney in glucose handling (4)
- kidney reabsorbs and recirculates glucose
- 90% - reabsorbed in proximal tubule (S1 segment) - facilitate by SGLT2
- 10% - reabsorbed in proximal tubule (S3 segment) - facilitate by SGLT1
- minimal or no glucose excretion in urine
The role of SGLT
- SGLT1 (2)
- SGLT2 (3)
SGLT1
- main uptake mechanism for glucose and galactose in the intestine
- high-affinity, low-capacity transporter
SGLT2
- in the brush-border membrane of the proximal renal tubular cells in the S1 + S2 segment
- responsible for around 90% of the total renal glucose re-absorption
- low-affinity, high-capacity transporter
SGLT2 inhibitors
- mode of action
- clinical utility (4)
- contraindication
- side effects (3)
- reduce renal tubular glucose reabsorption = reduce blood glucose without stimulating insulin release
- can be combined with any other medication, low risk of hypoglycemia, weight loss, BP reduction
- eGFR <45 ml/min
- genital and urinary tract infections
- risk of normoglycemic ketoacidosis
- volume depletion, hypovolemia and hypotension
If a patient with type II DM is a high risk patient OR has established ASCVD, CKD or HF, consider add which drugs?
- GLF-RA or SGLT2 inhibitors
- irrespectively of baseline or individualized HbA1c
GLP-1 RA recommendations
For patients with type 2 diabetes and established:
- atherosclerotic CV disease with prior MI,
- ischemic stroke,
- unstable angina with ECG changes
- other MACE (major adverse cardiac events)
basically –> if Atherosclerotic cardiovascular disease (ASCVD) predominates
SGLT-2 recommendations
For patients with type 2 diabetes:
- with or without established atherosclerotic CVC but with HF,
- with foot ulcers or at high risk for amputation,
- to prevent the progression of CKd, HF, MACE and CV death
basically –> if heart failure (HF) or chronic kidney disease (CKD) predominates
When to start insulin therapy in type II diabetes patients?
When combinations with oral medications become ineffective - when HbA1c levels >10%-12
Blood glucose levels are very high >16.7-19,9 mmol/l
OR
In urgent situations –> ex: pneumonia, MI, stroke, ketoacidosis
OR
If there is evidence of ongoing catabolism (weight loss)
How to choose the HbA1c target?
If diabetes diagnosed for the first time, healthy patients –> less than 6.5%
Elderly patient with cardiovascular risk factors –> 7.0-7.5%
the closer we are to normal HbA1c as a healthy person, the higher the risk of hypoglycemia
Diabetic nephropathy
- reduction of GFR + protein in urine
- necessary to analyze the albumin to creatinine ratio in urine
Normal GFR - 90 or higher
Kidney failure - less than 15
Normal albumin in urine - <30 mg/g
Severe high albumin in urine - >300 mg/g
Hyperglycemic hyperosmolar state (HHS)
-pathophysiology
-extremely high blood sugar + high osmolarity (too much pee)
- increase glucose levels
- water leaves cells and enters blood vessels
- urination increases
- severe dehydration
Hyperglycemic hyperosmolar state (HHS)
-diagnosis (4)
- absence of ketones
- plasma osmolarity >320
- increase enzymes - albumin, amylase, creatinine kinase
- plasma glucose >600 mg/dl
Hyperglycemic hyperosmolar state (HHS)
-treatment
- fluid replacement before insulin to avoid circulatory collapse
- electrolyte hemostasis
- treat underlying disease
- airway management
How to calculate plasma osmolarity?
2 Na + glucose + urea
normal - 285-295
Which condition is more dangerous DKA or HHS?
HHS because patients are most of time unconscious and elderly people which usually have concomitant diseases.
HHS most common cause of death
Brain edema
Most effective GLP-1RA
Semaglutide
How to choose HbA1c target?
- diabetes diagnosed for the 1st time –> less than 6.5%
- elderly patient + risk factors –> 7.0-7.5%
- healthy patient –> less than 6.5%
- short life expectancy –> above 7.0%
the closer we are to normal HbA1c as a healthy person –> the higher the risk of hypoglycemia
