Effect of Fasting on Hypoglycemic Counterregulation in Type 1 Diabetes

Purpose

Iatrogenic hypoglycemia is still considered to be the number one barrier to effective glycemic control in patients with type 1 diabetes (T1D). In a previous study, it was observed in people without diabetes that fasting can be detrimental to the hormonal and hepatic responses to insulin-induced hypoglycemia. In the experiments described herein, the impact fasting has on hypoglycemic counterregulation in people with T1D will be determined.

Conditions

  • Hypoglycemia
  • Type1diabetes

Eligibility

Eligible Ages
Between 18 Years and 45 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • males and females of any race or ethnicity - non-obese (BMI < or = to 30) - have a diagnosis of type 1 diabetes - C-peptide negative

Exclusion Criteria

  • pregnant women - cigarette smoking - Taking inflammation-targeting steroids (e.g., prednisone). - Taking medications targeting adrenergic signaling (e.g., beta-blockers, bronchodilators). - Hematocrit less than 33%. - Presence of HIV or hepatitis (due to their deleterious effects on the liver). - The presence of cardiovascular or peripheral vascular disease. - The presence of neuropathy, retinopathy or nephropathy. - A detection of the presence of any other disease or condition by one of the study doctors, that would be expected to confound the responses to insulin-induced hypoglycemia or make participation in the study dangerous to the individual.

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Each subject will undergo two metabolic studies, one after having remained fasted and one after having eaten breakfast and lunch.
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Fasting
Subjects will remain fasted prior to insulin-induced hypoglycemia.
  • Other: Fasting
    Subjects remain fasted prior to insulin-induced hypoglycemia.
Experimental
Feeding
Subjects will eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.
  • Other: Feeding
    Subjects eat a normal breakfast and lunch prior to insulin-induced hypoglycemia.

Recruiting Locations

University of Cincinnati
Cincinnati, Ohio 45267-0547
Contact:
Jason Winnick, PhD
513-558-4437
jason.winnick@uc.edu

More Details

Status
Recruiting
Sponsor
University of Cincinnati

Study Contact

Jason Winnick, PhD
513-558-4437
jason.winnick@uc.edu

Detailed Description

Because patients with type 1 diabetes (T1D) are required to estimate and administer their own insulin requirements, they frequently overestimate their needs. This often leads to debilitating insulin-induced hypoglycemia, which is the number one barrier to the safe, effective management of glycemia in this population. In addition to the difficulty estimating one's own insulin requirements after a meal, counterregulatory hormone responses to hypoglycemia are impaired in patients with T1D, thereby reducing hepatic glucose production (HGP) and increasing the depth and duration of the hypoglycemic episode. The discovery of ways by which counterregulatory responses to hypoglycemia can be improved in people with T1D is a priority. In previous experiments, it was observed that fasting reduces counterregulatory hormone secretion in healthy humans during insulin-induced hypoglycemia, thereby reducing hepatic glucose production (HGP). Therefore, the studies proposed herein will determine the effect of fasting on hypoglycemic counterregulation in people with T1D. It is hypothesized that fasting will diminish the hormonal and hepatic responses to insulin-induced hypoglycemia. Each subject will undergo two trials; one where they eat an isocaloric breakfast and lunch prior to an insulin-induced hypoglycemic challenge and a second one during which they remain fasted prior to the hypoglycemic challenge. This study design will allow assessment of the relationship between fasting and the counterregulatory responses to insulin-induced hypoglycemia in a population that is particularly vulnerable to low blood sugar.