Diabetes Complications -Malchoff Flashcards
Diabetes: a syndrome with multiple causes characterized these two things
- increased peripheral catabolism
- increased glucose production by the liver
Type of defect in Type 1 vs. Type 2
Type 1: autoimmune destruction of beta cells
Type 2: polygenic/epigenic/environmental causes leading to increased resistant to insulin and progressive pancreatic beta-cell failure
Diabetec definitions for:
- Fasting plasma glucose (mg/dl)
- 2 hr post 75 g of glucose
- A1C
if two tests are not conrcordant in an individual, the tests are repated and worser nuber is accepted/considered correct
- Fasting (mg/dl): >126
- 2 hr post 75 g of glucose: >200
- A1C >/= 6.5
hemoglobin A1C
- what is it
- what does it indicate
- glycated hemoglobin: glucose gets attached to RBC by glycation (non-enzymatic process); the more glucose around, the more glycated hemoglobin, the higher the A1C
- indicates blood glucose for 100 days (life span of RBC-might be affected if spleen is removed, causing RBCs to last longer)
6% A1C level corresponse to what mean serum glucose level? (in mg/dl)
6% = 126 mg/dl
List the 3 main (overarching) complications of diabetes
- Ketoacidosis, hyperosmolar coma
- Microvascular disease
- Macrovascular disease
Major macrovascular disease in diabetes complications
-subsets of this
ATHEROSCLEROSIS
- MI
- CVA
- Peripheral vascular disease (gangrene, renal artery stenosis)
*these mechanisms aren’t understood very well yet*
3 main types of microvascular disease caused by diabetes complications
1) neuropathy
2) retinopathy
3) nephropathy
mortality vs. morbidity in diabetes
Mortality: macrovascular disease (MI, CVA)
Morbidity: microvascular disease (nephro-, neuro-, retinopathy)
- Diabetes
- Impaired fasting glucose (pre-DM)
- normal
Which are positive in microvascular vs macrovascular in terms of risk based?
Diabetes is positive for both, but only macrovascular is also positive in IFG (normal is negative in both)
best type of control for complications in Type 2 DM
Blood pressure control
bigger bang for buck: statistically significant for percent reduction in microvascular, macrovascular, and death
Results of cumulate incidence of Mi + CVA in type 1 DM: conventional vs intensive therapy for 6.5 years
Intensive therapy had slightly lower incidences, but not that amazing compared to conventional
LDL control reduces atherosclerotic cardiovascular disease. Which drugs work? (include their MOA)
- Statins: HMG CoA reductase inhibitors, decrease cholesterol synthesis, lower LDL cholesteraol
- Fibrates: PPAR-alpha agonists (promotes uptake and catabolism of FAs), decrease VLDL synthesis
Ezetimibe MAY NOT AFFECT ASCVD (reduces GI cholesterol absoprtion)
Study about niacin
While niacin raises HDL by 30%, it fails to prevent ASCVD
Study about N-3 Fatty Acids (omega-3)
they decrease TG by 15 mg/dL, but fail to prevent ASCVD or ASCVD death in diabetic patients
Treatment rational for macrovascular disease prevention (3)
- BP control (<140/<80)
- LDL cholesterol and TG control (< 100 mg/dl)
- Blood sugar control (<7.0%)
A1C levels in patients with established coronary artery disease
Probably harmful for A1C to be <6.5% due to hypoglycemia.
Studies show that this can actually kill pt due to hypoglycemic episodes: if you have atherosclerosis in the heart and you have a hypoglycemic episode, you release catecholamines which will constrict your coronary arteries even more, potentially causing MI, arrythmia, death.
Retinopathy (3) and comments on its effects/therapy
- microaneurysms
- hemorrhages
- exudates
does not threaten vision, no directed retinal therapy required, BP and DM control delay/prevent progression
What are microaneurysms? Why do they develo?
Microaneurysms are aneurysms of capillaries:
- high glucose concentrations hurt the pericytes that line retinal capillaries
- pericytes die
- microaneurysms are first step of DM retinopathy
What type of retinopathy threatens vision? What is treatment?
Proliferative Retinopathy
- growth of new vessels
- bleeding threatens vision
- laser panretinal photocoagulation causes regression/prevents blindness
- scatter treatment over wider area of retina: laser heat to seal/destroy leaky blood vessels
Proliferative Retinopathy and vascular endothelial growth factor
-describe the process of damage to new proliferation and the treatment
microvascular damage –> decreased retinal oxygen + nutrient delivery –> increased growth factor production –> proliferation of new blood vessels
injections of intra-vitreous VEGF antibody (Bevacizumab) caused rapid improvement after 1 week
What is macular edema?
What does it cause, what doesn’t it cause?
Is it treatable?
- swelling or thickening of the eye under the macula
- causes decreased acuity, but DOES NOT cause blindness (think about when youre underwater, blurry AF but you can still see…)
- treatable with VEGF inhibitors (injected directly into the vitreous)
What two problems with the eye do not response to improved blood sugar control?
- proliferative retinopathy
- macular edema
What is the leading cause of dialysis?
Diabetic nephropathy
