The Effects of Hypoglycaemia in People With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemia
Study type: Interventional

Summary: 
      Strict glycaemic control has been associated with increased hypoglycaemia and mortality rate,
      the cause of which was unclear, in subjects with type 2 diabetes. In this study, we
      hypothesised that acute hypoglycaemia will result in platelet activation in people with type
      2 diabetes to a higher degree than controls.
    

Detailed description: 
      Type 2 diabetes is associated with increased risk of cardiovascular disease. Although the
      United Kingdom Prospective Diabetes Study (UKPDS) follow-up data suggested reduced
      macrovascular complications with tight glycaemic control, recent studies in people with type
      2 diabetes failed to replicate these findings. Furthermore, all-cause mortality was found to
      be increased with strict glycaemic control in the Action to Control Cardiovascular Risk in
      Diabetes (ACCORD) study. The cause of the increased deaths remains unclear.

      Strict glycaemic control is associated with increased risk of hypoglycaemia. Although,
      hypoglycaemia has traditionally been considered a complication of the treatment for type 1
      diabetes, it has recently been recognised as a problem in people with type 2 diabetes
      particularly those on insulin therapy. In the ACCORD study, the risk of death was
      significantly increased in those with one or more episode of severe hypoglycaemia in both the
      strict and standard study treatment arms. As plasma glucose falls to below 4.0 mmol/L, a
      series of defence mechanisms occur, at an individualised glycaemic thresholds, to reverse
      hypoglycaemia including a rise in catecholamine levels. This may lead to hypokalaemia,
      prolonged QT interval, and cardiac arrhythmias. It may also lead to impaired cardiovascular
      autonomic function for up to 16 hours afterwards; increased inflammatory markers; platelet
      activation and promote vascular damage. As the majority of studies assessing the effects of
      hypoglycaemia on cardiovascular risk markers are conducted in people with type 1 diabetes and
      healthy controls, their findings may not necessarily be applicable to people with type 2
      diabetes. In particular, the effects of hypoglycaemia on platelet function and thrombotic
      risk in people with type 2 diabetes require further clarification. In this study, we
      hypothesised that acute hypoglycaemia will result in platelet activation in people with type
      2 diabetes to a higher degree than controls.
    

Intervention name(s): Insulin (Humulin S); Euglycaemic Hypoglycaemic Insulin clamp
Intervention type(s): Drug; Device
Intervention description(s): Using insulin and glucose infusions (hyperinsulinaemic clamps), blood glucose levels were stabilised over 1 hour to reach 5 mmol/L and maintained at that level for 1 hour, then gradually reduced over 1 hour to 2.8 mmol/L and maintained at that level for 1 hour. Blood samples were collected at times 0 (baseline), 2 hours (euglycaemia), 4 hours (hypoglycaemia) and at 24 hours after the clamp studies.
Other intervention name(s): Glucose (20% Dextrose).
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Hypoglycemic Agents
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Type 2 diabetes; Hypoglycaemia; Platelets; Inflammation