Complications of diabetes Flashcards
Micro vascularisation complications (4)
- Ophthalmogical
- renal
- neurological
- lower extremity
Macro vascularisation complication
Cardiovascular
Acute complications of diabetes mellitus
Diabetic keto acidosis (type 1)
Nonketotic hyperosmolar syndrome (NKHS - type 2)
Chronic complications of diabetes mellitus
VASCULAR
- Micro = nephropathy, retinopathy, neuropathy
- Macro = cardiovascular, cerebrovascular, peripheral vascualr
NON - VASCULAR
- Sexual dysfunction
- Skin manifestation
- Gum infection
- Cataracts
- Glaucoma
What are the 3 major mechanisms underlying the hyperglycemic damage in diabetes mellitus
- Protein glycosylation
- Up regulation of polyol pathway
- Dyslipidemia
Polyol pathway
- Glucose entry into most cells of body is insulin dependent EXCEPT vascular endothelium in the retina, kidney, nervous system
- Glucose in tissue can be metabolised to sorbitol
- normal glucose => little glucose entering polyol pathway (aldose reductase has low affinity for glucose)
- hyperglycemia => excess glucose enters the polyol pathway (excess sorbitol pathway)
- Depletion of NADPH & nitric oxide in endothelial cells => increased oxidative stress - cell damage
Compound associated with 30% of Neural Tube Defects
Ionositol - diminished in excess sorbitol production
Link between type 2 diabetes mellitus and CVD
Increased risk of CVD with type 2 diabetes mellitus
Dyslipidemia - macrovascular disease: what does it cause
MACROVASCULAR ATHEROSCLEROSIS
- Increased coronary, cerebral, peripheral artery diseases
- Increased LDL and Triglycerides, decreased HDL
- Reduced fibrinolytic activity
CONSEQUENCES OF ARTERIAL INSUFFICIENCY/OBSTRUCTION
- MI
- Stroke
- Peripheral arterial disease (gangrene)
** SD LDL => upregulation of hepatic lipases - directly related to MIs and peripheral arterial diseases
Physiological consequences of protein glycosylation
PROLONGED HYPERGLYCEMIA
- Covalent binding of glucose to various proteins
- Advanced glycosylation end products
- Hb (RBCs are freely permeable to glucose - O2 won’t bind to glycosylated Hb), collagen in BV wall & BVs become leaky
ALTERED PROTEIN FUNCTION
- Altered charge - highly reactive - oxidative stress
- Altered structure, resistant to proteolysis
- Induction of cytokines, trap macromolecules (LDL etc)
- Diabetic retinopathy, nephropathy, neuropathy
What happens in diabetic retinopathy
Vessel basement mebrane deterioration
Ischemia, microhemorrhages
What happens in diabetic nephropathy
Basement membrane thickening
Hyperfiltration, increase glomerular pressure
Progress microalbuminuria -> proteinuria, eventually end-stage renal disease
What is sensory neuropathy
Loss of sensation
Abnormal sensation
Pain in hands and/or feet
Can progress to partial or complete loss of sensitivity to touch and temp
High risk of injury without pain
Autonomic neuropathy
Regulates sweating and perfusion to the limb
Loss of autonomic control inhibits thermoregulatory function and sweating
Results in dry, scaly and stiff skin that is prone to cracking and allows a portal of entry for bacteria
Hyperosmotic Hyperglycemic Non-Ketotic Syndrome (HHNS)
- Insulin
- Hyperglycemia
- Enough insulin to prevent ketosis but not enough to prevent hyperglycemia
- Extreme hyperglycemia without acidosis
- Poor glucose uptake and increase in hepatic glucose
- Enough insulin to suppress ketone synthesis
- Extreme hyperglycemia => severe electrolyte and fluid loss
- Vascular collapse
Diabetic KetoAcidosis (DKA) of DM
- Caused by
- Effect on blood:
- glucose
- pH
- bicarbonate
- ketone conc
- electrolytes
- Complete lack of insulin - unrestrained lipolysis and ketone synthesis
- Blood glucose > 250 mg/dL
- Blood pH < 7.3
- Blood bicarbonate < 15mEq/L
- Ketones present in blood and urine - BETAHYDROXYBUTYRATE => increase in production of ROS and may lead to decreased egg survival (infertility)
- Electrolyte abnormalities (Na, K, Cl, HCO3-)
What happens in beta oxidation
Breakdown of FAs to provide energy
Acetyl CoA generated enters Krebs Cycle
Impact of excess lipolysis (source of energy for diabetics) on beta oxidation
Vast amounts of beta oxidation in liver
- Liver uses little Acetyl CoA
Condensation of 2….
Acetyl CoA molecules
=> formation of acetoacetic acid - release of CoA
Exits hepatocytes easily
Enters tissues - reformed into Acetyl CoA
Used for energy
What is acetoacetic acid converted to
Acetoacetic acid is converted to ketones
- Beta-hydroxybutyric acid/acetone
Ketone levels in blood increase - tissue use limited // OXALOACETATE (this combines with Acetyl CoA in TCA Cycle but as diabetics can’t metabolise CHOs, limits acetyl CoA entry to krebs cycle)
Ketones build up
Severe acidosis with acetone breath
Decreases blood pH, HCO3-, Hb avidity for O2
Hypoxic coma &/or tachycardia
Diagnostic criteria for diabetes and impaired glucose regulation
Glucose tolerance test
What is gestational diabetes
Form of glucose intolerance diagnosed in some women in pregnancy
(normal for a pregnant woman to become less sensitive to insulin)
Occurs more frequently among obese women and women with a family history of diabetes
Women have increased chance of having/developing type 2 diabetes
7 secondary causes of diabetes mellitus
- Acromegaly
- Cushing syndrome
- Thyrotoxicosis
- Pheochromocytoma
- Chronic pancreatitis
- Cancer
- Drug induced hyperglycemia
Beta blockers
Inhibit insulin secretion
Calcium channel blockers
Inhibit secretion of insulin
Corticosteroids
Cause peripheral insulin resistance and gluconeogenesis
Protease inhibitors
Inhibit the conversion of proinsulin -> insulin
Thiazide diuretics
Inhibit insulin secretion due to hypokalemia
Also cause increased insulin resistance due to increase FFA mobilisation
