Type II DM

Question 1

Type II DM

-pathophysiology

Answer 1

• body makes insulin but the tissues do not response well to it
• insulin resistance: excess adipose tissue –> free fatty acids + adipokines = inflammation

1. increase insulin production
2. beta cell hyperplasia and hypertrophy
3. normoglycemia
4. beta cells secrete amylin
5. amylin builds up
6. hypoplasia and hypertrophy of beta cells
7. insulin levels decrease
8. hypergylcemia

Question 2

Type II DM

• symptoms (4)
• complications (7)

Answer 2

-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

Question 3

Diabetic ketoacidosis is less common in DM type I or II?

Answer 3

Type II DM because some insulin is still being produced

Question 4

Main targets DM treatment (3)

Answer 4

1. glycemic control - HbA1c
2. cholesterol
3. BP

Question 5

Serum insulin and C-peptide levels in DM I and II

Answer 5

DM I –> lower levels

DM II –> high or normal levels

Question 6

Cases when hypoglycemia can develop (2)

Answer 6

1. if dose of insulin is too high
2. if medications given directly stimulate insulin secretion without reacting with plasma glucose –> only medications like that: Sulphonylureas and Glinides

Question 7

Metformin

• mode of action
• can it be used together with insulin therapy?
• clinical utility
• contraindications
• side effects

Answer 7

• 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

Question 8

Metformin

-recommendations to decrease side effects (4)

Answer 8

• 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

Question 9

Sulphonylureas

• mode of action
• clinical utility
• contraindications
• side effects (2)

Answer 9

• 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

Question 10

Glinides

• mode of action
• difference when compared to Sulphonylureas
• side effects (2)

Answer 10

• 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

Question 11

Alpha-glucosidase inhibitors

• mode of action
• side effects

Answer 11

• inhibit enzymes that degrade oligosaccharides and disaccharides in the small intestine
• flatulence and abdominal discomfort

Question 12

Thiazolidinedione

• mode of action
• clinical utility
• side effects (3)

Answer 12

• 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

Question 13

Thiazolidinedione

• contraindications (2)
• can it be used together with insulin?

Answer 13

• patients with abnormal liver function
• increased risk for bladder cancer

-no, it increases the risk of fluid retention specially in patients with heart failure

Question 14

The incretin system

Answer 14

• 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

Question 15

The incretin system

-Glucagon- like peptide (GLP-1) - function (7)

Answer 15

• 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

Question 16

GLP-1 is mot responsive to…?

Actions are mediated via…?

Answer 16

-Lipids and amino acids

• GLP-1R
• receptors are expressed in beta cells
• when activated –> activates cAMP and protein kinase A dependent and independent actions

Question 17

DPP-4 inhibitors

• mode of action
• clinical utility (3)
• cannot be used in combination with…?
• side effects (3)

Answer 17

• 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

Question 18

GLP-1RA

• mode of action
• clinical utility (4)
• contraindication
• side effects (4)

Answer 18

• 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,

Question 19

The role of kidney in glucose handling (4)

Answer 19

• 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

Question 20

The role of SGLT

• SGLT1 (2)
• SGLT2 (3)

Answer 20

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

Question 21

SGLT2 inhibitors

• mode of action
• clinical utility (4)
• contraindication
• side effects (3)

Answer 21

• 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

Question 22

If a patient with type II DM is a high risk patient OR has established ASCVD, CKD or HF, consider add which drugs?

Answer 22

• GLF-RA or SGLT2 inhibitors

- irrespectively of baseline or individualized HbA1c

Question 23

GLP-1 RA recommendations

Answer 23

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

Question 24

SGLT-2 recommendations

Answer 24

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

Question 25

When to start insulin therapy in type II diabetes patients?

Answer 25

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)

Question 26

How to choose the HbA1c target?

Answer 26

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

Question 27

Diabetic nephropathy

Answer 27

- 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

Question 28

Hyperglycemic hyperosmolar state (HHS) | -pathophysiology

Answer 28

-extremely high blood sugar + high osmolarity (too much pee) 1. increase glucose levels 2. water leaves cells and enters blood vessels 3. urination increases 4. severe dehydration

Question 29

Hyperglycemic hyperosmolar state (HHS) | -diagnosis (4)

Answer 29

- absence of ketones - plasma osmolarity >320 - increase enzymes - albumin, amylase, creatinine kinase - plasma glucose >600 mg/dl

Question 30

Hyperglycemic hyperosmolar state (HHS) | -treatment

Answer 30

- fluid replacement before insulin to avoid circulatory collapse - electrolyte hemostasis - treat underlying disease - airway management

Question 31

How to calculate plasma osmolarity?

Answer 31

2 Na + glucose + urea normal - 285-295

Question 32

Which condition is more dangerous DKA or HHS?

Answer 32

HHS because patients are most of time unconscious and elderly people which usually have concomitant diseases.

Question 33

HHS most common cause of death

Answer 33

Brain edema

Question 34

Most effective GLP-1RA

Answer 34

Semaglutide

Question 35

How to choose HbA1c target?

Answer 35

- 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