The Effect of Ethanol on Overnight Glucose Regulation in Type 2

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00566592
First received: November 29, 2007
Last updated: February 3, 2011
Last verified: December 2009
  Purpose

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 Intervention
Type 2 Diabetes, Insulin Requiring
Other: oral ethanol, overnight
Other: IV ethanol
Other: soda water

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Official Title: The Effect of Ethanol on Overnight Glucose Regulation in Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Rate of glucose recovery from hypoglycemia. [ Time Frame: Hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hormone and substrate concentrations [ Time Frame: Hours ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2005
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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%

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00566592

Locations
United States, New Mexico
University of New Mexico Clincal and Translational Science Center
Albuquerque, New Mexico, United States, 87131
Sponsors and Collaborators
Investigators
Principal Investigator: Mark R Burge, MD University of New Mexico
  More Information

No publications provided

Responsible Party: Mark R. Burge, MD, University of New Mexico
ClinicalTrials.gov Identifier: NCT00566592     History of Changes
Other Study ID Numbers: DK61990 (completed), DK061990
Study First Received: November 29, 2007
Last Updated: February 3, 2011
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on August 28, 2014