Diabetes Flashcards
Describe the Regulation of CHO metabolism in non diabetic humans: Fasted
- all glucose comes from liver (and a bit from kidney)
* Breakdown of glycogen
* Gluconeogenesis (utilises 3 carbon precursors to synthesise glucose including lactate, alanine and glycerol) - Glucose is delivered to insulin independent tissues, brain and red blood cells
- Insulin levels are low
- Muscle uses FFA for fuel
- Some processes are very sensitive to insulin, even low insulin levels prevent unrestrained breakdown of fat
Describe the Regulation of CHO metabolism in non diabetic humans: Post feeding
- After feeding (post prandial) - physiological need to dispose of a nutrient load
- Rising glucose (5-10 min after eating) stimulates insulin secretion and suppresses glucagon
- 40% of ingested glucose goes to liver and 60% to periphery, mostly muscle
- Ingested glucose helps to replenish glycogen stores both in liver and muscle
- High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall
what is the Site of insulin and glucagon secretion
pancreas - islets of langerhan
which cell secretes insulin
Beta cell in panceas
which cell secretes glucagon
Alpha cells - pancrease
what are the Key hormonal regulators of carbohydrate metabolism
Insulin
* supresses hepatic glucose output
1. reduces Glycogenolysis and Gluconeogenesis
* Increases glucose uptake into insulin sensitive tissues
* Suppresses lypolysis and breakdown of muscles
Glucagon (counter refulatory)
* Increases hepatic glucose output
1. increasing Glycogenolysis and Gluconeogenesis
* Reduce peripheral glucose uptake
* Stimulate peripheral release of gluconeogenic precursors (glycerol, AAs)
1. Lypolysis and Muscle glycogenolysis + breakdown
Others
* (adrenaline, cortisol, growth hormone have similar effects to glucagon and become relevant in certain disease states, including diabetes)
Describe Diabetes mellitus
- A disorder of carbohydrate metabolism characterised by hyperglycaemia
- Causes morbidity and mortality through
1. Acute hyperglycaemia which if untreated leads to acute metabolic emergencies diabetic ketoacidosis (DKA) and
- hyperosmolar coma (Hyperosmolar Hyperglycaemic State )
Chronic hyperglycaemia leading to tissue complications (macrovascular and microvascular) - Side effects of treatment- hypoglycaemia
What are some Diabetes associated serious complications
Stroke
Diabetic neuropathy
Diabtetic nephropathy
CVD
Diabetic retinopathy
What are the types of diabetes
- Type 1
- Type 2 (inc gestational + caused by meds)
- Maturity onset diabetes of youth (MODY)
- Pancreatic diabetes
- “Endocrine Diabetes” (Acromegaly/Cushings)
What is the Pathogenesis of Type 1 diabetes
- insulin deficiency disease characterised by loss of beta cells (insulin producing) due to autoimmune destruction
- Beta cells express antigens of HLA histocompatability system perhaps in response to an environmental event (?virus)
- Activates a chronic cell mediated immune process leading to chronic ‘insulitis’
Describe Glucose metabolism and Type 1 diabetes
**Failure of insulin secretion leads to
**
* Continued breakdown of liver glycogen
* Unrestrained lipolysis and skeletal muscle breakdown providing gluconeogenic precursors
* Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake
**Rising glucose conc causes increased urinary glucose losses as renal threshold (10mM) is exceeded
**
**Failure to treat with insulin leads to
**
* Increase in circulating glucagon (loss of local increases in insulin within the islets leads to removal of inhibition of glucagon release), further increasing glucose
* perceived ‘stress’ causes increased cortisol and adrenaline
progressive catabolic state and increasing levels of keto
Describe Glucose metabolism and Type 2 diabetes
**A consequence of insulin resistance and progressive failure of insulin secretion (but insulin levels are always detectable)
**
**Impaired insulin action leads to
**
* Reduced muscle and fat uptake after eating
* Failure to suppress lipolysis and high circulating FFAs
* Abnormally high glucose output after a meal
** low levels of insulin prevent muscle catabolism and ketogenesis so profound muscle breakdown and gluconeogenesis are restrained and ketone production is rarely excessive
**
what to Sulphonylureas (gliclazide, glibenclamide) do
- stimulate insulin release by binding to beta-cell receptors
- Improve glycaemic control (1-2% in HbA1c) at the expense of significant weight gain
- Do not prevent the gradual failure of insulin secretion
- Can cause hypoglycaemia (occasionally prolonged and fatal, particularly in the elderly and when renal function is impaired)
What do Thiazolidinediones (pioglitazone - ACTOS) do
- Bind to the nuclear receptor PPAR λ (peroxisome proliferator-activated receptor)
- Activate genes concerned with glucose uptake and utilisation and lipid metabolism
- Improve insulin sensitivity
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