Diabetes Flashcards
What is the hormonal response to hypoglycaemia?
Decrease insulin, glucagon release, adrenaline release - giving symptoms of hypos
What is the pathophysiology behind the microvascular disease of diabetes?
Endothelial cells take up glucose (not dependent on insulin to do so) and form more surface glycoproteins. This thickens the basement membrane
What is the most common site affected by diabetic neuropathic arthopathy?
The foot - Charcot foot.
60% tarsometatarsal joints
30% Metatarsophalangeal joints 10% ankle
What are clinical features of LADA?
- age of onset <25 kg/m2
- personal or family history of autoimmune disease
The presence of two or more criteria had a 90 percent sensitivity and 71 percent specificity for identifying patients positive for anti-GAD antibodies.
What is the best test to distinguish T1DM from T2DM?
IA-2 and anti-GAD antibodies
- if one or more positive then diagnosis of T1DM is assumed
What is an example of a GLP-1 agonist?
Liraglutide
Exenatide
Activates GLP-1 receptors which stimulates insulin secretion
May increase medullary thyroid cancer - contraindicated in MEN2
What is gluconeogenesis?
Generation of glucose in the liver from non-carbohydrate substances (pyruvate, lactate, glycerol, amino acids)
What is glycolysis?
Conversion of glucose to pyruvate - provides energy in form of ATP
What is glycogenolysis?
Breakdown of glycogen to G-6-P
G6P is a substrate for glucose formation
What is glycogenesis?
Glycogen synthesis - where glucose molecules are added to chains of glycogen for storage
What is ketogenesis?
Formation of ketones from fatty acid breakdown, occurs withing mitochondria in liver
Fatty acids are broken down by b-oxidation to acetyl Coa which in starving states is made into ketone bodies from HMG-CoA
What is c-peptide?
Protein secreted with insulin by pancreatic beta-cells but is cleared more slowly therefore easier to measure - can help with discrimination of endogenous vs exogenous insulin administration
What is the process of insulin secretion?
- triggered by BSL greater than 3.9
- glucose transported into cell by GLUT 1 receptor
- metabolised to g6p to generate ATP
- ATP inhibits K channel inducing cell depolarisation which opens calcium dependant channels
- insulin released from granules
What are incretins and there role?
Peptides released from neuroendocrine cells of GI tract after food ingestion
E.g. GLP-1 released from all cells mad stimulates insulin secretion in an insulin dependant manner and also suppresses glucagon secretion, slows gastric emptying, increases insulin sensitivity, decreases food intake)
Describe how insulin exerts action?
Released in the bloodstream, 50% degraded by liver, rest continues in blood stream
Binds to insulin receptor stimulating tyrosine kinase activity triggering widespread cell signalling
Activation of P13K pathway stimulates translocation of GLUT4 to cell surface allowing glucose uptake by skeletal muscle and fat
What are some anabolic effects of insulin?
Storage of triglycerides in adipose tissues
Increases glucose transport to fat and muscle
Increases glycolysis in fat and muscle
Stimulates glycogen synthesis
Inhibits glycogenolysis, gluconeofemesis, lipolysis, ketogenesis
Where is glucagon secreted from?
Pancreatic alpha cells
Major susceptibility genes for type 1 diabetes?
HLA DR3 and DR4
What are some examples of islet cell antibodies?
Glutamic acid decarboxylase (GAD)
IA-2
ZnT8
Antibodies are found in 85%
What are some types of MODY?
MODY 1 - HNF4alpha MODY 2 - glycokinase MODY 3 - HNF1alpha MODY 4 - IPF1 MODY 5 - HNF 1 beta
Diagnosis of diabetes?
Fasting glucose greater then 7.0
HbA1c greater then 6.5%
Symptoms of hyperglycemia and fasting glucose greater then 11.1
Oral glucose tolerance test - glucose greater then 11.1 after challenge
What is the definition of MODY?
Non insulin dependant diabetes at age less then 25
Usually autosomal dominant transmission with lack of autoantibodies
What is LADA?
Latent autoimmune diabetes of adulthood
Patients aged 30-75 who have positive autoantibodies, usually have a period of insulin independence but progress to insulin within 6 years
5 distinguishing features of LADA fro type 2 diabetes?
Younger Symptomatic onset BMI less than 25 Autoimmune history Family history
Diagnosis of impaired glucose tolerance?
Fasting glucose 5.6-6.9
OGTT 7.8- 11
HBA1c 5.7-6.4