Diabetes Mellitus Flashcards
Insulin action on glucose, protein and fat?
Glucose : Decrease HGO
-Increase muscle uptake
Protein : decrease proteolysis
Fat : decrease lipolysis
decrease ketogenesis
GLUT 4 transporter characteristics?
Common in myocytes and adipocytes
Highly insulin responsive
Lies in vesicles
Recruited and enhanced by insulin
7 fold increases glucose uptake
Effects of insulin on Muscle cell metabolism?
Fed state: inhibits protein –> gluconeogenic AAs
* Cortisol also aids this inhibition
Fasting state: stimulates gluconeogenic AAs production
* GH, IGF-1 also aids this pathway
AAs can leave cell once created to create glucose
Effects of Insulin and Glucagon on the Liver?
Fed state : inhibits gluconeogenesis of AAs to glucose and promotes AAs to turn into proteins = decreasing HGO
Fasting state : Glucagon stimulates AAs to be transported into hepatocytes, protein –> AAs conversion and Gluconeogensis into glucose
* Gluconeogenesis aided by Cortisol = increased HGO
Effects of Insulin on Triglycerides
LPL enzyme breaks them down into fatty acids and glycerol.
This relies on insulin activating the enzyme
Fed state: Insulin Stimulated glucose uptake by transporters into adipocytes –> NEFAs
Insulin then stimulates NEFAs –> triglycerides
Fasting state: Insulin Inhibits triglyceride breakdown into NEFAs
* GH and Cortisol promotes Triglycerides –> Glycerol + NEFAs
How does blood circulation aid insulin release quickly?
Due to Hepatic Portal vein connecting gut to liver directly = can detect increased glucose levels
Can HGO increase due to lipid metabolism?
Gluconeogenesis can occur by triglycerides
Glycerol can travel in or Hepatocyte triglycerides can be converted to Glycerol-3P –> Glucose
What are the cerebral energy type requirements?
Glucose primarily
Or ketone bodies
In a fasting state, what does glucagon encourage in liver? (Fatty Acyl - CoA)
NEFAs transported into hepatocytes
Glucagon stimulates fatty Acyl-CoA –> Ketone bodies ( Acetyl CoA/ Acetoacetate/ Acetone + 3 OH-B ) == Ketone bodies released from liver
- in the fed state insulin inhibits ketone body production
What is Hepatic Glycogenolysis?
The generation of glucose from stored glycogen in liver during fast state:
Glucose –> Glucose-6-P –> Glycogen ( this is stored by insulin )
Glucagon stimulates Glucose-6-P production from Glycogen which turns to Glucose = Increased HGO
Can muscle cells release glucose?
No, glycogen created will be used in the muscle cell by conversion to glucose, then to Acetyl CoA = Oxidative phosphorylation ( Carbon dioxide release )
*GH also inhibits glucose uptake alongside Glucagon during Fasting
In a fasted state what happens to
NEFA levels?
Amino acid levels?
- Triglycerides lysis increased so NEFA increase
- Increase at first by increased proteolysis then decrease when prolonged fast
What occurs in the Fed state?
Stops HGO Increase Glycogen Decrease gluconeogenesis Increase protein synthesis Decrease proteolysis Increase Lipogenesis
How do diagnose Diabetes Mellitus?
High levels of glucose
Fasting glucose : 7+
Random glucose : 11.1+
Oral glucose tolerance test:
2-hour glucose
- HbA1c test
Need two positive tests to diagnose or 1 test and symptoms
Characteristics of type 1 diabetes?
- Autoimmune condition
- Absolute insulin deficiency
Diabetic ketoacidosis : serious acute compilation due to increased ketone bodies
Clinical presentation of Type 1 diabetes?
- Weight loss
- Hyperglycaemia
- Glycosuria with osmotic symptoms
- Ketones in bood and urine
Diagnostic tests : (tell you more likely to be type 1 )
- Antibodies GAD, IA2
- low C-peptide
- Presence of ketones
- Need to watch out for other autoimmune diseases that can occur or already have
What happens when too much insulin is administered?
No glucose hepatic output
Muscle glucose input
What are counterregulatory responses to hypoglycaemia?
- increased Glucagon
- increased Catecholamines
- increased Cortisol
- increased Growth hormone
= Increased HGO + Lipolysis
Impaired awareness of hypoglycaemia due to loss of counterregulatory response until it is very low
Symptoms and signs of hypoglycaemia?
(Autonomic) Sweating Pallor Palpitations Shaking
(Neuroglycopenic) •Slurred speech •Poor vision •Confusion •Seizures •Loss of consciousness
Characteristics of type 2 Diabetes?
Insulin resistance resides in liver, muscle and adipose tissue
*Have enough insulin to suppress ketogenesis and proteolysis
( you can have insulin resistance before having diabetes)
What pathways are activated by insulin - which one is affected by insulin resistance?
P13K-Akt pathway ( metabolic action ) = this is where insulin resistance occurs
MAPK pathways ( growth and proliferation
Presentation of symptoms of type 2 diabetes?
- Hyperglycaemia
- Overweight
- UTI due to glucose in urine
- Less osmotic symptoms
- Complications
- Insulin resistance
- Later insulin deficiency
- Dyslipidaemia (disturbances in fat metabolism cause changes in the concentrations of lipids in the blood)
What are the risk factors for type 2 diabetes?
Age, PCOS, high BMI, Family History, Ethnicity, Inactivity
Complications caused by diabetes?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular
Dietary recommendations?
- Total calories control
- Reduce calories as fat and refined carbs
- Increase complex carb calories
- …
How is type 1 managed?
- Exogenous insulin (basal-bolus regime)
- Self-monitoring of glucose
- Structured education
- Technology
How is type 2 managed?
- Diet
- Oral medication
- Structured education
- May need insulin later
How is type 2 managed?
- Diet
- Oral medication
- Structured education
- May need insulin later
What are the medical terms for the following:
Feeling thirsty:
Passing urine frequently:
Getting up at night to pass urine:
Painful when it pees:
- Polydipsia
- Polyuria ( glucose in urine = can lead to UTI )
- Nocturia
- Dysuria ( due to UTI )
