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Diabetes - Overview of the Complications of Diabetes

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Overview

Diabetes is characterised by the following long-term complications.
   
 
  Microvascular     Macrovascular  
           
  Retinopathy     Coronary heart disease  
  Blindness      Angina, MI, CCF  
  Nephropathy       Peripheral vascular disease  
  Microalbuminuria, Proteinuria,     Foot ulcers & limb amputation/s  
  Neuropathy     Cerbrovascular disease  
  Peripheral & Autonomic       Transient Ischaemic Attack/s  
  Neuropathy, Mononeuritis     Stroke  
  Multiplex.        
   
 

The prevalence of both micro & macrovascular complications increase with the duration of diabetes.   After 10 years one or more microvascular complications are present in over 50% of patients with type 1 diabetes.

 

 

 

Type 2 diabetes may have been present for several years before diagnosis and microvascular complications can be present at diagnosis.  Macro-vascular complications are not as strongly related to duration of diabetes.

 

 

 

The pathophysiology of the complications of diabetes is complex.  Macrovascular complications are mediated through a process of accelerated atheroma which tends to occur at a younger age than in the general population and in more distal vessels in heart, brain and the peripheral circulation. The atheroma is histologically identical to that found in patients without diabetes.

 

 

 

Electron microscopy shows changes in capillary architecture in most tissues of the body but this does not seem to cause clinical problems except in the eye and kidney where the characteristic retinal and glomerular lesions occur.

 

 

 

It is not clear whether diabetic neuropathy is due to a ‘microvascular’ problem of the nerves or to a possible toxic metabolic effect of high glucose levels on nerve structure or function.

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Predisposing Factors:
 
 

Causes of various micro & macrovascular complications are complex but following factors play significant role its pathogenesis  

 

 

 

 

Exposure to chronic hyperglycaemia: direct effect on tissues may be mediated through excessive glycosylation of tissue proteins.

 

Higher prevalence (clustering) of traditional cardiovascular risk factors in diabetes.

The linkage between glycaemic control and the incidence and progression of complications was established by two landmark studies.

In Type 1 diabetes the Diabetes Control and Complications Study (DCCT) showed a marked reduction in microvascular complications in an intensively controlled group compared to conventional levels of control.  A follow up of the DCCT patients (EDIC) demonstrated a benefit for macrovascular disease as well.

The United Kingdom Prospective Diabetes Study (UKPDS) showed similar findings in a large group of patients with newly diagnosed Type 2 diabetes.  This study also looked at the effect of blood pressure control on outcome and showed that control of hypertension was also associated with improved outcomes.

The UKPDS did not show statistically significant effects of tight glycaemic control on macrovascular outcome except in a sub-group of overweight patients treated with metformin. Post study monitoring results, however, showed that good glycaemic control during the study period was associated with significantly lower risks of myocardial infarction and reduced all cause mortality for 10 years after the study had ended.  The observed benefits of good blood pressure control at the end of the study were lost over time.

Other studies designed to show whether tight glycaemic control would reduce macrovascular complications have not been positive. The ACCORD Study suggested that tight control was associated with increased mortality and was stopped early.  The study did not show the increased mortality but also failed to show an effect on cardiovascular endpoints. It is thought that the increased mortality seen in ACCORD may have been related to increased hypoglycaemia in the tightly controlled arm of the study.

One major difference between the two later studies and the UKPDS is that they looked at patients with established diabetes rather than the newly diagnosed subjects of the UKPDS. 

It is possible that good control early in Type 2 diabetes is crucial in reducing cardiovascular problems later on (“metabolic memory”)This would suggest there could be particular benefits in obtaining and maintaining good control early on and that losing control for a period of time and then regaining it may not have the same effect.

The benefits of good control of blood glucose and blood pressure would seem to be synergistic and there is now a considerable evidence base to support the benefits of controlling both of them.

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Further Complication Guidelines

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Microvascular & Macrovascular Complications

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Screening & Management of Eye Complications

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Screening & Management of Foot Complications

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Screening & Management of Renal Complications

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Diabetic Neuropathy

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Useful External Resources / Links

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Diabetes Control and Complications Study

The Diabetes Control and Complications Trial (DCCT) was a major clinical study conducted from 1983 to 1993 and funded by the National Institute of Diabetes and Digestive and Kidney Diseases. The study showed that keeping blood glucose levels as close to normal as possible slows the onset and progression of the eye, kidney, and nerve damage caused by diabetes.

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United Kingdom Prospective Diabetes Study (UKPDS)

The UK Prospective Diabetes Study (UKPDS) was a landmark randomised, multicentre trial of glycaemic therapies in 5,102 patients with newly diagnosed type 2 diabetes. It ran for twenty years (1977 to 1997) in 23 UK clinical centres and showed conclusively that the complications of type 2 diabetes, previously often regarded as inevitable, could be reduced by improving blood glucose and/or blood pressure control.

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UKPDS - Post Study Monitoring

When the intervention trial finished in September 1997, all surviving UKPDS patients were entered into a ten-year, post-trial monitoring programme. This was completed in December 2007 with the results presented at the September 2008 EASD meeting.

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ACCORD Study

The New England Journal of Medicine - Effects of Intensive Glucose Lowering in Type 2 Diabetes - 12 June 2008.

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