DM: Complications Flashcards
What are the microvascular complications of DM? (3)
Retinopathy, nephropathy, neuropathy
What are the macrovascular complications of DM? (3)
Coronary heart disease, peripheral arterial disease, cerebrovascular disease
What are some of the nonvascular complications of DM?
Infections, skin changes, hearing loss, GI, GU, cataracts, glaucoma, etc
Which trial provided definitive proof that reduction in chronic hyperglycemia can prevent many complications of type 1 DM, and that intensive diabetes management substantially lowers HbA1c compared to conventional management?
Diabetes Control and Complications Trial (DCCT)
Type 1 DM
Which trial followed up the participants of the DCCT which showed that the initial separation in glycemic control disappeared on the subsequent follow-up of >18 years?
Epidemiology of Diabetes Intervention and Complications (EDIC) trial
The DCCT trial showed the improvement of glycemic control reduced the following complications by how much?
a. retinopathy
b. albuminuria
c. nephropathy
d. neuropathy
e. cardiovascular events
a. retinopathy - 47% reduction (7.7 additional years of vision)
b. albuminuria - 39% reduction
c. nephropathy - 54% reduction (5.8 additional years free from ESRD)
d. neuropathy - 60% reduction (5.6 years free from lower extremity amputations)
e. cardiovascular events - 42-57% reduction
Which trial showed that improved glycemic control reduced the complications of type 2 DM?
United Kingdom Prospective Diabetes Study (UKPDS)
Type 2 DM
The UKPDS showed that each percentage point reduction in HbA1c was associated with a ___% reduction in microvascular complications.
35%
Which trial studied Japanese individuals with type 2 DM randomized to either intensive glycemic control or standard therapy with insulin?
Kumamoto study
Legacy effect or Metabolic memory refers to
The positive impact of a period of improved glycemic control on later disease
Hypotheses on how DM complications develop
- Hyperglycemia leads to epigenetic changes that influence gene expression in affected cells
- Chronic hyperglycemia leads to formation of advanced glycosylation products which bind to specific cell surface receptor and/or the nonezymatic glycosylation of intra- and extracellular proteins, leading to cross-linking of proteins, accelerated atherosclerosis, glomerular dysfunction, endothelial dysfunction, and altered extracellular matrix composition
- Increases glucose metabolism via the sorbitol pathway related to enzyme aldose reductase
- Increases the formation of diacylglycerol, leading to activation of protein kinase C, which alters the transcription of genes
- Increases the flux through the hexosamine pathway, which generates fructose-6-phosphate, a substrate for O-linked glycosylation and proteoglycan production
Characteristics of nonproliferative diabetic retinopathy
Appears late in the first decade or early in the second decade of the disease
Retinal vascular microaneurysm, blot hemorrhages, and cotton-wool spots
Hallmark of proliferative diabetic retinopathy
Neovascularization
Most effective therapy for diabetic retinopathy
Prevention (intensive glycemic and blood pressure control)
Which medicine can reduce the progression of retinopathy?
Fenofibrate
True or false: Aspirin therapy (650mg/d) appears to influence the natural history of diabetic retinopathy.
False
How many percent of patients with diabetes develop diabetic nephropathy?
20-40% (hence there are additional genetic or environmental susceptibility factors)
Diabetic kidney disease refers to _______ and _________.
- Albuminuria
2. Reduced GFR (<60 ml/min/1.73m2)