The Effect of Ethanol on Overnight Glucose Regulation in Type 2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00566592
Recruitment Status : Completed
First Posted : December 3, 2007
Last Update Posted : September 25, 2014
Information provided by (Responsible Party):
Mark Burge, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes, Insulin Requiring Other: oral ethanol, overnight Other: IV ethanol Other: soda water Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Official Title: The Effect of Ethanol on Overnight Glucose Regulation in Type 2 Diabetes Mellitus
Study Start Date : January 2005
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
Oral ethanol, overnight
Other: oral ethanol, overnight
Oral ethanol before bedtime to achieve approximate BAL of 0.08%
Experimental: 2
IV ethanol, overnight
Other: IV ethanol
IV ethanol before bedtime to achieve approximate BAL of 0.08%
Placebo Comparator: 3
Placebo, overnight
Other: soda water
Oral Placebo before bedtime to achieve approximate BAL of 0.00%
Placebo Comparator: 4
Placebo, daytime
Other: soda water
Oral Placebo to achieve approximate daytime BAL of 0.00%

Primary Outcome Measures :
  1. Rate of glucose recovery from hypoglycemia. [ Time Frame: Hours ]

Secondary Outcome Measures :
  1. Hormone and substrate concentrations [ Time Frame: Hours ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   50 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria: All type 2 diabetes subjects will be aged 50 to 75 years and will have carried the diagnosis of diabetes according to standard criteria and will be receiving insulin therapy alone or in combination with oral diabetes medications for at least 6 months. To exclude subjects with type 1 diabetes, all patients will be anti-GAD antibody negative and will retain the ability to secrete some nominal level of c-peptide in response to stimulation (i.e.- at least 2 ng/ml after ingesting Boost Plus). All subjects will be mentally fit to give informed consent. Nondiabetic control subjects will meet similar inclusion criteria (except for diabetes and hemoglobin A1C criteria). Control subjects will be matched as a group for age, gender and BMI. Finally, control subjects will undergo a standard 75 gram Oral Glucose Tolerance Test to assure the presence of normal glucose tolerance (142).

Exclusion Criteria: Exclusion criteria for all study subjects will include the existence of severe cardiovascular, hepatic or renal disease, or current malignancy as determined by the screening evaluation. Subjects with a past or current history of drug or alcohol abuse will also be excluded from study, as will subjects with a previously diagnosed seizure disorder, subjects with sleep apnea by medical history or as demonstrated during the accommodation sleep study night, subjects with diabetic gastroparesis, or subjects receiving current treatment medications that interfere with glucose homeostasis other than for diabetes therapy (e.g.- glucocorticoids, orlistat). Because of the known adverse effects of ethanol on unborn children, current intrauterine pregnancy will exclude patients from study. A body mass index greater than 36 kg/m2 will also be exclusionary. Additionally, subjects with a score of more than eight points on the Alcohol Use Disorders Identification Test (AUDIT) will be excluded from study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00566592

United States, New Mexico
University of New Mexico Clincal and Translational Science Center
Albuquerque, New Mexico, United States, 87131
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Mark R Burge, MD University of New Mexico

Responsible Party: Mark Burge, Professor of Medicine, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00566592     History of Changes
Other Study ID Numbers: DK61990 (completed)
First Posted: December 3, 2007    Key Record Dates
Last Update Posted: September 25, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs