DM complications - Overview

Question 1

DM is the leading cause of:

Answer 1

• New blindness in adults
• Renal failure
• Nontraumatic lower extremity amputation

Question 2

Diabetes-associated complications related to hyperglycemia usually do not appear until ____

Answer 2

The second decade of hyperglycemia

• Note:*
• In contrast, diabetes-associated CHD risk, related in part to insulin resistance, may develop before hyperglycemia is established

Question 3

Diabetes-related complications can be divided into:

Answer 3

• Vascular
  
  • Microvascular complications are diabetes-specific
  • Macrovascular complications have pathophysiologic features that are both shared with the general population and diabetes-specific
• Non-vascular

Question 4

Examples of non-vascular complications

Answer 4

• Infections
• Skin changes
• Hearing loss

Question 5

Microvascular and macrovascular complications

Answer 5

• Microvascular
  
  • Retinopathy
  • Neuropathy
  • Nephropathy
• Macrovascular
  
  • Coronary heart disease [CHD]
  • Peripheral arterial disease [PAD]
  • Cerebrovascular disease

Question 6

The microvascular complications of both type 1 and type 2 DM result from ____

Answer 6

Chronic hyperglycemia

• Note:*
• Evidence implicating a causative role for chronic hyperglycemia in the development of macrovascular complications is less conclusive

Question 7

CHD events and mortality rate are ____ times greater in patients with type 2 DM and correlate with fasting and postprandial plasma glucose levels as well the hemoglobin A1c (HbA1c)

Answer 7

Two to four

Question 8

Summary of the features of diabetes-related complications

Answer 8

1. (Duration and degree of hyperglycemia correlate with complications
2. Intensive glycemic control is beneficial in all forms of DM
3. Blood pressure control is critical, especially in type 2 DM
4. Survival in patients with type 1 DM is improving, and diabetesrelated complications are declining
5. Not all individuals with diabetes develop diabetes-related complications

Question 9

Mechanism(s) by which chronic hyperglycemia leads to diverse cellular and organ dysfunction

Answer 9

• Unknown
• An emerging hypothesis
  
  • Hyperglycemia leads to epigenetic changes that influence gene expression in affected cells
• Other hypotheses:
  
  • Chronic hyperglycemia leads to formation of advanced glycosylation end products (AGEs; e.g., pentosidine, glucosepane, and carboxymethyllysine) which bind to specific cell surface receptor and/or the nonenzymatic glycosylation of intra- and extracellular proteins, leading to cross-linking of proteins, accelerated atherosclerosis, glomerular dysfunction, endothelial dysfunction, and altered extracellular matrix composition
  • Hyperglycemia: (1) increases glucose metabolism via the sorbitol pathway related to the enzyme aldose reductase; (2) increases the formation of diacylglycerol, leading to activation of protein kinase C, which alters the transcription of genes for fibronectin, type IV collagen, contractile proteins, and extracellular matrix proteins in endothelial cells and neurons; and/or (3) increases the flux through the hexosamine pathway, which generates fructose-6- phosphate, a substrate for O-linked glycosylation and proteoglycan production, leading to altered function by glycosylation of proteins such as endothelial nitric oxide synthase