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Flashcards in Diabetes Deck (130)
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What is diabetes mellitus?

genetic predisposition and an autoimmune process causing gradual destruction of the beta cells of the pancreas, leading to no insulin production

deficiency or deminished effectiveness of endogenous insulin, hyperglycemic, deranged metabolism and causing microvascular problems


What are the different types of DM?

type 1 - failure to produce sufficient insulin
type 2 - the body's resistance to insulin
gestational - high blood glucose levels during pregnancy, causing risk to mother and foetus
maturity onset diabetes of the young - monogenetic defects of B cell function (impaired insulin secretion), appearing as mild hyperglycaemia at a young age, autosomal dominant
secondary - from pancreatic disease,cystic fibrosis, cushing's, acromegaly, thiazide diuretics, corticosteroids, congenital lipodystrophy, acanthosis nigricans, wolframs syndrome


What is the pre diabetic phase?

where auto immunity has been developed but no clinically apparent insulin dependency, insulin autoantibodies can be developed in genetically predisposed

triggered by viruses, dietary factors, enviromental toxins, emotional or physical stress, early cessation of breast feeding


Risk factors for type 1 diabetes?

10% have family history, associated with HLA DR3 and DR4 and islet cell antibodies, Caucasian, North Europe, Scandinavian, 30-50% concordance in twins, associated with other auto immune disease, eventual dissapearnace of C peptide, 6q determines islet sensitivity to damage


At what age does type 1 DM usually present itself?

juvenile onset, but can occur at any age


When does type 2 DM usually occur?

over 30, but becoming increasingly common in children and adolescents, polygenic disorder


Risk factors for type 2 DM?

excess body weight, physical inactivity, alcohol, south asia, history of gestational diabetes, impaired glucose tolerance, impaired fasting glucose, drug therapy, low fibre, hyglycaemic index diet, metabolic syndrome, polycystic ovarian syndrome, family history, male, elderly


Pathophysiology of type 2 DM?

the genetic form has mutations of the insulin receptor and structural alterations of the insulin molecule so patients gradually become insulin resistant and beta cells fail to secrete enough insulin and beta cell mass is reduced to 50% of normal, the C peptide persists


How do all DM present?

polyuria, polydipsia, lethargy, boils, glycosuria, blurred vision, thirst, signs of micro and macrovascular disease, pruritus, frequent and recurrent infections


Symptoms only in type 1 DM?

weight loss, dehydration, ketonuria, acetone breath, Kussmaul breathing, nausea, vomiting, hyperventilation, acute with short duration of symptoms


Symptoms only in type 2 DM?

acute and chronic complications, subacute with a longer duration of symptoms


Diagnosis of DM?

2 fasting venous plasma glucose - >7mmol/L
random plasma glucose and symptoms >11.1mmol/L
HbA1c >6.5% (48mmol/mol)
Fasting plasma glucose 11.1mmol/L
impaired fasting glucose 5.6-6.9mmol/L


Management of DM?

educate, self management, healthy diet, weight loss, smoking cessation, regular exercise, low sugar, high starch, glucose control, glucose and HbA1c monitoring, early detection, monitor complications, global assessment of cardiovascular risk, antidiabetic agents


Treatment of type 2 diabetes?

oral hypoglycemic agents, along with diet and lifestyle changes to get good glyaemic control


Function of insulin?

regulated carb and fat metabolism affecting the liver, muscle and fat tissue, causing glucose uptake

inhibits the release of glucagon and blocks fat being used as an energy source

stores excess energy

promotes the uptake of glucose from the blood into the liver and the conversion of glucose into glycogen and glucose to acetyl coA to triglyceroles into VLDL to be stored triglycerol in adipose tissue


Where is insulin synthesized?

in the pancreas, in the beta cells of the islets of Langerhan


What is insulin synthesized from and how?

synthesized from the preproinsulin, moves into the endoplasmic reticulum and then converted into proinsulin precursor by proteolytic enzymes known as prohormone convertases and exoprotease carboxypeptite E

splits the proinsulin precursor into A, B and C, A and B are joined by diastole bonds to make insulin and the C peptide helps G protein membrane


When is insulin released?

in response to increased blood glucose levels and then it is sustained with the slow release of newly formed vesicles, triggered independently of sugar


What stimulates insulin release?

GLUT 2 carries glucose into the beta cells, stimulating insulin release


How does insulin affect amino acids?

uptake of amino acids from the blood stream to the liver

then causes proteinogenesis and protein synthesis


How does insulin affect fat?

promotes storage of fat in skeletal muscle as fatty acids

synthesis of triglycerol

stores excess energy


What is the insulin receptor?

a tyroxin kinase receptor made up of 2 beta, 2 alpha and 2 tyroxin kinase (an enzyme which is usually inactive) subunits


When does tyroxin kinas become active?

when it has a phosphate group coming off it

insulin binds to the alpha subunits of the insulin receptor, causing the tyroxin kinase to become phosphorylated to be activated


What happens when the insulin receptor (tyroxin kinase) is activated?

intracellular effects of insulin occur from IRS-1 stimulation

promotes growth, gene expression, glycogen synthesis, fat synthesis, protein synthesis, increased glucose transporter expression (GLUT2 in liver and GLUT4 in muscle), so there is an uptake of glucose into the liver


What causes insulin resistance?

insulin cannot bind to tyroxin kinase receptor so there is not an increase of GLUT2 receptors so glucose remains in the blood steam


What happens to glucose in the liver?

stored as glycogen or converted to fats and turned into VLDLs and transported into adipose tissue


How does insulin affect blood glucose levels?

decreases them


What effect does insulin have on enzymes?

inhibits glycogen phosphorylase into glucose and then promotes hexokinase and glycogen synthase to form glycogen, increased glucose transporters to liver and muscle, stimulate ribosome activity to make proteins and inhibits protein degradation and increase glycolysis for fat synthesis, and prevents beta oxidation


After lifestyle changes, what is the first medication used for type 2 diabetes treatment and how does it work?

Biguanides e.g. metformin - phosphorylates GLUT4 to increase glucose transport uptake and reduces glucose production from the liver, sensitizing target tissues to insulin


Why is metformin more effective in type 2 diabetes, and only used in type 1 if overweight?

it can only act in the presence of endogenous insulin so needs residual functioning pancreatic islet cells