Diabetes Mellitus and its Complications Flashcards
What are the classical symptoms of both types of diabetes?
Polyuria, polydipsia, polyphagia, and weight loss
Give three hormonal causes of diabetes and their mechanisms.
- Growth hormone excess - direct effect of growth hormone is prodiabetic -> increased lipolysis, increased gluconeogenesis, and decreased peripheral glucose uptake (explains why hyperglycemia inhibits it)
- Cortisol / exogenous steroids - prolonged steroid use or hypercortisolism is diabetogenic
- Prolonged epinephrine / stress -> increased glucose levels
Describe the mechanism of the symptoms seen in severe insulin insensitivity (Type 2) or insulin deficiency (Type 1)?
Unopposed glucagon -> hyperglycemia, proteolysis for gluconeogenesis
Hyperglycemia -> increased plasma osmolality -> polydipsia
Hyperglycemia -> osmotic diuresis (exceed tubular maximum) -> polyuria and hypovolemia -> dehydration
Proteolysis and weight loss -> polyphagia
What type of acid base imbalance occurs in insulin deficiency and why? What will the patient do to compensate?
- Increased lipolysis -> ketogenesis, since liver thinks brain is starving (can’t get glucose in). Ketones are anions.
- Circulation failure and tissue ischemia -> due to hypovolemia -> serum lactate levels increase -> further anion gap metabolic acidosis
Patient will be vomiting and breathing very rapidly / deeply (Kussmaul respirations)
What are the changes in the kidney which occur due to diabetes? Grossly / microscopically.
Nephropathy -> diffuse / nodular glomerulosclerosis
Nonenzymatic glycation of small vessels (hyaline arteriolosclerosis) takes its toll
Efferent arterioles affected first -> glomerular hyperfiltration with microalbuminia -> nephrOTIC syndrome
Kimmelstiel-Wilson nodules will form in glomeruli
Eventually involves both afferent and efferent arterioles, leading to systemic hypertension
How does sorbitol play a role in the pathogenesis of diabetes? What tissues lack the appropriate enzymes and how does this manifest?
Sorbitol pathway uses aldose reductase to capture glucose in cells, and then sorbital DH to regenerate fructose
LuRKS are tissues with insufficient sorbitol dehydrogenase to get rid of sorbitol if it is at high levels.
Sorbital is an osmotic agent which causes damage.
L = Lens = Cataracts
R = Retina = Retinopathy
K = Kidneys = Nephropathy (some contribution)
S = Schwann Cells = peripheral neuropathy
What are the consequences of the large vessel non-enzymatic glycation in diabetes? What is the most common cause of death in diabetes?
Atherosclerosis - most important, increases strokes and MIs
Coronary artery disease
Peripheral vascular occlusive disease with gangrene -> common cause of limb amputations
Most common cause of death in diabetes is MI
How are nerves typically affected in diabetes?
Neuropathy - motor loss, sensory (glove and stocking distrubution) loss, and autonomic degeneration
-> remember gastroparesis and nocturnal fecal incontinence due to loss of internal anal sphincter ind iabetes
What is the diagnostic cutoff for HbA1c in diabetes and what is the treatment goal?
> 6.5% is likely diabetes, goal is 7% for control (reflects average blood glucose over 3 months)
How can the diagnosis of diabetes be made via random glucose and fasting glucose?
Random glucose > 200 mg/dL
Fasting glucose > 126 mg/dL after 8 hours of fasting
What is the glucose tolerance test and what is diagnostic for diabetes?
Give the patient 75g of glucose in water
If glucose is >200 mg/dL 2 hours after consumption, patient has diabetes
Are type 1 / type 2 diabetes insulin requiring or dependent?
Type 1 - always insulin dependent -> will die without
Type 2 - may be insulin requiring or not at all, typically not dependent -> will not die without.
Which type of diabetes has a stronger genetic predisposition, and what HLA’s predipose you?
Type 2 diabetes has a stronger genetic predisposition than Type 1
HLA-DR3 and DR4 are associated with Type 1 diabetes though.
Think type 1 and not 2, associated with 3 and 4 “1,2,3,4”
What gets diabetic ketoacidosis and what tends to precipitate it?
Usually Type 1 diabetics, because type 2 diabetics have some basal endogenous insulin which suppresses lipolysis (no ketone bodies will be generated). Can happen in type 2 diabetics with total beta cell failure.
Precipitated by stress (i.e. infection)
What are the signs and symptoms of DKA?
DKA is Deadly
D - delirium / psychosis (from decreased brain perfusion due to hypovolemia)
K - Kussmaul respirations - deep / rapid breathing
A - abdominal pain, nausea / vomiting
D - Dehydration
Fruity odor can be smelled on breath due to exhaled acetone
Will DKA present with hyperkalemia or hypokalemia? What is the overall treatment?
Hyperkalemia -> insulin is required to bring K+ into cells, and acidosis prevents Na/H exchanger from running, so K+ cannot be brought into cells as well.
Treatment is IV fluids, insulin AND K+
-> although they are hyperkalemic, their total body K+ is low due to diuresis. Insulin will restore their intracellular K+, causing hypokalemia
What are the life-threatening complications of DKA?
- Rhizopus infection (mucormycosis)
- Cardiac arrhythmias - due to hyperkalemia
- Cerebral edema - due to too rapid correction of hyperglycemia
What can be seen in the pancreatic islets in Type 1 vs Type 2 diabetes?
Type 1 - T lymphocytic infiltration -> autoimmune destruction
Type 2 - amyloidosis - accumulation of AE amyloid from overproduction of insulin + amylin. Actual protein that accumulates is amylin.
What is the life-threatening condition analogous to DKA seen commonly in Type 2 diabetics? What is the cause?
Hyperosmolar hyperglycemic nonketotic syndrome (HHNS)
Seen in Type 2 diabetics with limited ability to drink
-> a state of profound hyperglycemia-induced dehydration
What is the pathogenesis of HHNS?
Hyperglycemia -> excessive osmotic diuresis -> dehydration
Serum osmolality will become very high (low water, glucose >500 mg/dL)
-> hypotension, neurological deficits, and coma.
Will acidosis classically be seen in HHNS? What is the treatment?
Classically no, since ketone production is inhibited by presence of insulin.
Treatment is aggressive IV fluids and insulin therapy
What is the mechanism by which insulin resistance during pregnancy is thought to arise? Why does this occur?
Human placental lactogen (HPL) is produced, which induces insulin resistance. Insulin resistance allows blood glucose levels to be slightly elevated to let the baby use glucose to develop.
It also stimulates lipolysis, allowing the mother to use ketone bodies for energy.
How does maternal diabetes occur? When does it occur?
Human placental lactogen normally also stimulates an increase in insulin levels in the mother, to prevent diabetes. If the pancreatic beta cells cannot produce sufficient levels of insulin, maternal diabetes mellitus occurs
Occurs during 2nd or 3rd trimester, usually during the first pregnancy
What are the possible fetal consequences of uncontrolled maternal diabetes?
Fetal anomalies due to hyperglycemia-induced oxidative stress.
- Heart - transposition of the great arteries, ASD / VSD
- CNS - neural tube defects
- Large for gestational age (macrosomia)
- Intrauterine growth retardation (if there is placental insufficiency due to vascular disease)
- Caudal regression syndrome
