Diabetes Mellitus Type II Flashcards
What is the cause of the osmotic symptoms in diabetes?
The body’s need to dilute the high sugar levels in the blood with extra water
What are the osmotic symptoms of diabetes?
Increased thirst
Frequent micturition
What effect does the increase in osmotic substance in the blood have on the circulation?
It reduces it
Why do diabetics often suffer lethargy and reduced concentration?
High or low blood glucose levels - both are to do with an imbalance of blood glucose and amount of / effectiveness of circulating insulin
What is the role of insulin?
To transport glucose from the blood and to cells for energy
What is the primary difference between type 1 and type 2 diabetes?
Type 1 - inefficient production of insulin
Type 2 - ineffective use of circulating insulin / reduced sensitivity to it (largely due to increased level of glucose, insulin levels not enough)
What are the key risk factors for type 2 diabetes?
Sedentary lifestyle High fat sugary diet Raised BMI Smoking Drinking alcohol
What is considered a normal fasting sugar level?
</= 6mmol/L
What fasting glucose level is consistent with prediabetes?
6.1-7 mmol/L
What fasting glucose level is consistent with diabetes?
> 7.0 mmol/L
Why is testing HbA1C more useful clinically than fasting glucose?
It gives a longer term impression of blood glucose levels (average over past 8-12 weeks)
What does HbA1C test?
Glycated haemoglobin
What lifestyle changes should a type II diabetic make?
Dietary - reduce fat and sugar intake
Smoking cessation
Exercise more / lose weight
List some of the more serious consequences of poorly controlled blood glucose in a diabetic.
Diabetic retinopathy
Cellulitis / ulcers / gangrene / sensory peripheral neuropathy / amputation
Coronary artery disease
MI (mostly due to inadequate blood supply)
If diabetic vascular disease is suspected what investigation most likely to be useful?
Angiography
If arterial stenosis is recognised what can be done to improve blood flow and reduce further risk of ischaemia?
Percutaneous Coronary Investigation (angioplasty)
A Random Plasma Glucose (RPG) of between 7.8 and 11.0 mmol/L is indicative of what?
Impaired glucose tolerance (pre-diabetes)
A RPG result of more than what is indicative of diabetes?
11.1
What is considered a normal fasting plasma glucose?
< 6.1
What fasting glucose result is indicative of diabetes?
> 7 mmol/L
Impaired glucose tolerance is indicated by a fasting glucose of?
Between 6.1 and 7.0 mmol/L
What does OGTT stand for?
Oral Glucose Tolerance Test, it is a good test for pre-diabetes and insulin resistance (drink high glucose drink and have blood tests at certain intervals after)
What does the HbA1c test demonstrate?
It gives a picture if the average levels of glycosylated haemoglobin over a 3-4 month period (the average lifespan of a RBC)
What % of the HbA1c result relates to the glycosylated haemoglobin levels for the previous 4 weeks?
50%
What factors affect HbA1c?
Haemolysis (reduced RBC survival so falsely low result) Renal impairment Iron deficient anaemia Pregnancy Blood transfusion
Name the 4 main types of diabetes
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Secondary diabetes (pancreatic damage, hepatic cirrhosis, endocrine)
Gestational diabetes
What 2 organs are associated with glucose production?
The liver (~75%) The kidneys (~20%)
What are the main 2 anatomical factors which contribute to glucose homeostasis?
Liver production and skeletal muscle use
By which process is the majority of glucose produced by the liver created?
Glycogenolysis
By what process is glucose produce in the kidneys? (And to a lesser extent than glycogenolysis in the liver)
Gluconeogenesis
Define glycogenolysis
The breakdown of glycogen to form glucose
Define gluconeogenesis
The production of glucose and glycogen using non-glucose precursors i.e. Fats and proteins
What affect does glucagon have in the blood?
It releases glucose into the blood (therefore increasing blood glucose)
What is glycogen?
The principle storage form of glucose in human cells
highest concentration in the liver with many in skeletal cells and some in kidneys, few in brain
How much of the glucose filtered by the kidneys is reabsorbed by them?
Nearly all of it!
What are the main 4 type of hormones involved in glucose homeostasis?
Insulin
Glucagon
Incretin
Glucocorticoids (e.g. GH and cortisol)
Where is insulin produced and what is its role in glucose homeostasis?
Beta cells of the pancreas (found in the Islets of Langerhans); released during digestion and removes glucose from the blood (carrying them to cells for utilisation)
Where is glucagon produced and what is its role in glucose homeostasis?
Produced in the alpha cells of the pancreas (found in the Islets of Langerhans). It is released in response to low glucose levels and stimulates glycogenolysis and gluconeogenesis as well as breakdown of triglycerides (stored fat)
List 5 functions of insulin.
1) enhances peripheral glucose uptake
2) inhibits glycogen breakdown in liver
3) enhances storage of glucose as glycogen
4) increases protein synthesis
5) increase triglyceride storage
Name the other 4 counterregulatory hormones to insulin besides glucagon.
Growth Hormone
Cortisol
Adrenaline
Noradrenaline
Persistent elevation of counterregulatory hormones will have what affect on a person?
It can reduce their sensitivity to insulin
If there was an insufficiency in counterregulatory hormones what would occur once insulin acted?
Hypoglycaemia
Briefly describe the process of how glucose stimulates insulin secretion
Glucose binds to GLUT-2 receptor on pancreatic Beta cell > glycolysis occurs in the cell releasing ATP > ATP sensitive K+ channels on the cell close causing depolarisation > Ca++ channels open > Ca++ influx > insulin released via exocytosis
NB sulphonylureas act on Beta cells in similar way)
Briefly, how does preproinsulin become insulin?
Preproinsulin enters the rough ER > part of this peptide cleaved off in rough ER lumen to become proinsulin > at Golgi App. cleaved again to become insulin. Then released via exocytosis when stimulated by the NS / glucose
Which of the 2 insulin release phases is missing of deficient in type 2 diabetes?
1st phase (immediately after eating)
What are incretins and what do they do?
They are GI hormones which stimulate a decrease in blood glucose levels by increasing the amount of insulin released from Beta cells of the Islet of Langerhans
Name the main 2 incretins
GLP-1 and GIP (GLP-1 more important)
What enzyme inactivates GLP-1 and GIP down?
Dipeptidyl peptidase-4 (DPP-4)
What results from decreased incretins in type 2 diabetes?
Decreased insulin and increased glucagon > Increased blood glucose which can’t be utilised > glycogen breakdown in liver > protein breakdown in skeletal muscles > reducing weight and adipose tissues breakdown into ketones
In normal physiology what prevents glucose being excreted in urine?
After glucose is filtered through the glomerulus it is then reabsorbed back into the circulation by SGLT2 in the proximal tubule
Ancanthosis is what?
A hardening/thickening of the skin that appears darker than the healthy skin. It can be a sign of diabetes (more specifically insulin resistance) - associated with obesity. Can also be associated with Cushing’s or polycystic ovary syndrome
