The Effect of Ethanol on Overnight Glucose Regulation in Type 2
Condition: Type 2 Diabetes, Insulin Requiring
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      Hypoglycemia is the principal barrier to the achievement of target glycemic goals in type 2
      diabetes. Alcohol consumption is very prevalent in our society and a proven cause of
      hypoglycemia. Population studies suggest that elderly, insulin requiring type 2 diabetes
      patients are particularly vulnerable to severe hypoglycemia and that this problem accounts
      for an estimated $50 million or more in healthcare costs in the USA each year. We hypothesize
      that low dose ethanol significantly increases the vulnerability to overnight hypoglycemia and
      impairs the recovery of plasma glucose in elderly, insulin requiring patients with type 2
      diabetes. Our preliminary studies suggest that low dose ethanol impairs recovery from day
      time insulin-induced hypoglycemia in type 2 diabetes patients but not in age matched healthy
      control subjects. The proposed studies will examine the effects of low dose ethanol on
      overnight glucose regulation in elderly, insulin requiring type 2 diabetes patients and will
      establish the mechanism of these impairments through a series of systematic evaluations.
      Specifically, these studies will document suppression of the dawn phenomenon by ethanol,
      and/or exacerbation of a deficient counterregulatory response to hypoglycemia during sleep,
      especially growth hormone. Specific mechanisms for the suppression of growth hormone to be
      examined include that evening ethanol (3) inhibits peak overnight ghrelin secretion and/or
      (4) reduces pituitary sensitivity to GHRH. Additionally, these studies will characterize (5)
      the dose response characteristics of ethanol on overnight glucose homeostasis and will (6)
      carefully evaluate the effect of the timing of ethanol administration in relation to meal
      ingestion on overnight hypoglycemic vulnerability. To address these aims, we will assess the
      effect of moderate doses of orally administered ethanol or placebo on overnight growth
      hormone release, ghrelin, total IGF-1, free IGF-1, insulin-like growth factor binding protein
      1 (IGFBP-1) concentrations, glucose production and other parameters of glucose homeostasis
      among elderly control subjects versus elderly, insulin requiring subjects with type 2
      diabetes. These important studies will provide a scientific basis for the prevention of
      overnight hypoglycemia (and the attendant cost savings) by providing mechanistic insights
      into the causes of nocturnal hypoglycemia.
    


Intervention name(s): oral ethanol, overnight; IV ethanol; soda water; soda water
Intervention type(s): Other; Other; Other; Other
Intervention description(s): Oral ethanol before bedtime to achieve approximate BAL of 0.08%; IV ethanol before bedtime to achieve approximate BAL of 0.08%; Oral Placebo before bedtime to achieve approximate BAL of 0.00%; Oral Placebo to achieve approximate daytime BAL of 0.00%
Intervention MeSH terms: Ethanol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)