Diabetes

Question 1

What are the symptoms and consequences of hyperglycemia?

Answer 1

Polyuria
Thirst
Weight loss
Fatigue

Neuropathy
Nephropathy
Heart disease
Cataracts and blindness
Diabetic coma
Death

Question 2

What are the symptoms and consequences of hypoglycemia?

Answer 2

Irritability and fatigue
Food cravings
Headaches
Dizziness
Shaking
Confusion

Loss of consciousness
Accidents amd injury
Weight gain
Reduced IQ
Brain abnormalities

Question 3

Describe insulin signalling

Answer 3

Insulin/IGF-1 Receptor tyrosine kinase
Recruits the IRS family of proteins
Activate Ras, Mek, Erk for general gene expression
Activates PI3K, AKT pathway to increase glucose transporter insertion in the membrane
AKT and PKC pathways increase glucose metabolism

Question 4

What are the metabolic effects of insulin?

Answer 4

Increase glucose uptake and conversion to glycogen and triglyceride, glycolysis, increase amino acid uptake and protein synthesis

Question 5

Describe insulin and glucagon

Answer 5

Insulin secreted by the beta cells in the islets of Langerhans
Promotes secretion of glycogen and lowers blood sugar
Glucagon has an antagonistic action to insulin, secreted by the alpha cells
Secreted in response to low blood sugar

Question 6

Describe the actions of glucagon on the cell

Answer 6

GPCR➡ cAMP➡ PKA
Increases pyruvate and glycogen conversion to glucose
Promotes gluconeogenesis, glycogenolysis, ketogenesis, lipolysis
Inhibits lipogenesis

Question 7

Describe some of the other hormones involved in glucose homeostasis

Answer 7

Glucagon-like peptide 1 (GLP1)- alternative proteolytic processing in intestinal L cells (not alpha cells) of proglucagon 
Adrenaline
Glucocortcoids
Somatostatin
Growth hormone

Question 8

Describe type 1 diabetes mellitus

Answer 8

5-10% of cases
Beta cells selectively destroyed
Complete lack of insulin
Childhood onset
Genetic component
HLA genes are major risk factors
Environmental trigger unknown: causes beta cell lysis and T cell mediated autoimmune response
Viral infections, parental age, stress
Acute presentation with keto acidosis

Question 9

Describe type 2 diabetes mellitus

Answer 9

85-95% of cases
Insulin resistance amd beta cell failure
Strongly associated with obesity
Residual insulin so ketosis is rare
Often present with diabetic complication
Part of the metabolic syndrome- diabetes, obesity, hypertension, hyperlipidaemia
Insulin resistance- liver, skeletal muscle fat, reduced uptake of glucose from blood leads to dyslipidaemia and platelet aggregation
Impaired insulin secretion- initial increase to offset resistance followed by progressive deterioration
Substantial genetic component

Question 10

Describe diabetes diagnosis

Answer 10

Fasting plasma glucose >/= 7mmol/l

Oral glucose tolerance test >/= 11.1mmol/l

Question 11

What are the complications of diabetes?

Answer 11

Hypoglycemia
Ketoacidosis- build up of ketone bodies in blood lowers pH
Micro vascular complications- retinopathy- areas of hypoxia in retina leads to progressive blindness, nephropathy- protein urea, neuropathy- degenerative disorders of peripheral nerves can lead to ulcers, gangrene and amputation
Macrovascular- due to lipid disorders promotes atherosclerosis

Question 12

Describe diabetes treatment

Answer 12

Multiple daily injections of insulin- mealtime, short acting, with carbohydrate counting
Metformin- insulin sensitiser, no hypoglycemia or weight loss, SE- nausea, GI effects, lactic acidosis
Blocks gluconeogenesis by liver and increases glucose uptake by muscle via AMP kinase
Sulphonylureas- Gliclazide, stimulates insulin release, quick onset and effective in early type 2, SE- hypoglycemia, weight gain
Incretin-based- GLP1 stimulates glucose dependent insulin secretion to avoid hypoglycemia
SGLT2 inhibitors- sodium-glucose cotransporter 2 inhibitors- inhibit glucose reabsorption in PCT
Phlorizin- naturally occurong inhibitor