Effect of High Carbohydrate vs. Low Carbohydrate Diet in Type 2 Diabetes

Role of Hepatic Glycogen on Nocturnal EGP in T2D

The experimental approach in this study intends to investigate the role of hepatic glycogen content on nocturnal regulation of endogenous glucose production including the relative contributions of glycogenolysis and gluconeogenesis and the extent to which this differs between subjects with type 2 diabetes and subjects without diabetes. Both participants with type 2 diabetes and participants without diabetes will be studied after consuming either a low carbohydrate (no glycogen loading) or high carbohydrate (glycogen loading) diet.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus
• Intervention / Treatment: Other: glycogen loading; Other: No Glycogen Loading

Detailed Description

Physiology study for looking at glycogen loading vs non loading in improving nightime glucose tolerance by increasing glycogen in liver and resulting higher glycogenolysis at night.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 30-75
• BMI 20-35kg/m^2

• Participants with type 2 diabetes:

  • HbA1c less than or equal to 8.5% on lifestyle therapy or monotherapy with metformin or sulphonylureas (SU); or less than or equal to 7.5% on two oral hypoglycemic agents (Metformin and SU)

Exclusion Criteria:

• Pregnancy or breast feeding
• Morbidities precluding participation

• Participants with type 2 diabetes:

  • Therapy with insulin
  • SGLT2 inhibitors
  • GLP-1 based approaches
  • TZDs
  • Unstable diabetic retinopathy
  • Microalbuminuria
  • Macrovascular disease
  • Medications affecting GI motility (eg., erythromycin, pramlintide)
  • Upper GI disorder/surgery

• Participants without diabetes:

  • Medications (except stable thyroid hormone or hormone replacement therapy) that could influence glucose tolerance
  • History of diabetes mellitus in first degree family members or prior history of diabetes mellitus or gestational diabetes, or pre-diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Type 2 diabetes; Participants with Type 2 Diabetes received Glycogen loading (GL) and Non-Glycogen loading (NGL) meal in a randomized manner.	Other: glycogen loading; Subjects will consume an isocaloric diet [60% carbs, 20% protein, 20% fat (33 kcal/kg/day)] for 3 days prior to the overnight study.; Other: No Glycogen Loading; Subjects will consume an isocaloric diet [40% carbs, 20% protein, 40% fat (33 kcal/kg/day)] for 3 days prior to the overnight study.
Experimental: Participants without diabetes; Participants with no Diabetes received Glycogen loading (GL) and Non-Glycogen loading (NGL) meal in a randomized manner.	Other: glycogen loading; Subjects will consume an isocaloric diet [60% carbs, 20% protein, 20% fat (33 kcal/kg/day)] for 3 days prior to the overnight study.; Other: No Glycogen Loading; Subjects will consume an isocaloric diet [40% carbs, 20% protein, 40% fat (33 kcal/kg/day)] for 3 days prior to the overnight study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes	We measured the rates and contribution of Gluconeogenesis (GNG) to nocturnal Endogenous Glucose Production (EGP) using the deuterated water technique after either glycogen loading or no glycogen loading in subjects with type 2 diabetes.	Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Glycogenolysis in Subjects With Type 2 Diabetes	Rates and contribution of glycogenolysis (GLY) to nocturnal EGP will be measured using the deuterated water technique after glycogen loading and no glycogen loading in subjects with type 2 diabetes.	Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks
Rates of Gluconeogenesis in Healthy Subjects	Rates of GNG will be measured through the night using the deuterated water technique after either glycogen loading or no glycogen loading in healthy subjects.	Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Mayo Clinic; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2020
• Primary Completion (Actual): August 15, 2022
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 1, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; hepatic glycogen; endogenous glucose production
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 22074; R01DK029953 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No