Chronic Diabetes Complications Introduction

Chronic complications of diabetes

  • Macrovascular complications: IHD, stroke
    • Diabetes is a risk factor in atherosclerosis
  • Microvascular complications (diabetes specific - not seen in the abscence of hyperglycaemia):
    • Neuropathy
    • Nephropathy
    • Retinopathy
  • Cognitive dysfunction/dementia
  • Erectile dysfunction
  • Psychiatric complications

Screening for complications

At patient's yearly diabetic review:
  • Digital retinal screening
  • Foot risk assessment
  • Urine albumin-to-creatinine ratio and serum creatinine

Pathophysiology of microvascular complications

  • In normal patients glucose is completely oxidized via glycolysis and the TCA cycle
  • When faced with excess glucose, glycolytic flux is high but mitochondria can't keep up
  • Alternative glucose metabolism pathways are used which, in excess, can be harmful

Formation of advanced glycation end products (AGE)

  • When a wide variety of proteins are exposed to increase glucose concentrations, glucose binds irreversibly to the protein to form AGE
  • AGEs cause tissue injury and inflammation via stimulation of pro-inflammatory factors, such as complement and cytokines

Increased flux of glucose through the sorbitol-polyol pathway

  • Glucose + aldose reductase → sorbitol
  • Sorbitol and fructose accumulate which cause changes in vascular permeability (osmotic damage), cell proliferation and capillary structure via stimulation of protein kinase C and TGF-β

Increased flux of glucose through other pathways

  • NADPH oxidase generated via pentose phosphate pathway - generates ROS
  • UDP-GlcNAC generated via hexosamine pathway - causes inflammation and fibrosis
  • Diacyl glycerol activates protein kinase C - protein kinase C can activate NF-KB which is thought to be active in the kidneys causing nephropathy