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Hypothesis: Intensive insulin therapy-induced mortality is due to excessive serotonin autoinhibition and autonomic

Undurti N Das1

  • 1Undurti N Das, Jawaharlal Nehru Technological University, Kakiada 533 003, Andhra Pradesh, India.

World Journal of Diabetes
|May 4, 2011
PubMed

Insights

Intensive blood glucose control in type 2 diabetes trials, including ACCORD and NICE-SUGAR, failed to show benefits and increased mortality. Proposed reasons include altered brain serotonin and autonomic dysregulation.

Area of Science:

  • Endocrinology
  • Cardiology
  • Metabolic Disorders

Background:

  • Major clinical trials like ACCORD, ADVANCE, and VADT aimed to reduce cardiovascular risk in type 2 diabetes by intensifying glucose control.
  • These studies, along with the NICE-SUGAR study, unexpectedly revealed increased mortality with intensive glycemic management.

Purpose of the Study:

  • To investigate the reasons behind the failure of intensive glucose control to provide cardiovascular benefits in type 2 diabetes.
  • To explore potential pathophysiological mechanisms contributing to increased mortality observed in intensive therapy arms.

Main Methods:

  • Analysis of data from large-scale clinical trials (ACCORD, ADVANCE, VADT, NICE-SUGAR) evaluating intensive versus standard glucose control.
  • Review of proposed biological mechanisms potentially affected by intensive glycemic management.

Main Results:

  • Intensive glucose control did not reduce cardiovascular events or mortality in patients with type 2 diabetes.
  • The NICE-SUGAR study confirmed increased mortality in intensive care unit patients with intensive glycemic control.
  • The ACCORD trial showed increased cardiovascular deaths in the intensive therapy arm.

Conclusions:

  • The failure of intensive glucose control to benefit patients with type 2 diabetes is multifactorial.
  • Proposed contributing factors include altered brain serotonin, autonomic dysregulation, systemic inflammation, reduced nitric oxide, increased free radicals, and impaired antioxidant defenses.
Keywords:
Anti-oxidantsCardiovascular eventsCoronary heart diseaseDyslipidemiaEssential fatty acidsFree radicalsInsulinNitric oxideStrokeType 2 diabetes mellitus

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