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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Role of Hepatic Glycogen on Nocturnal EGP in T2D

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: glycogen loading
* Other: No Glycogen Loading


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, hepatic glycogen, endogenous glucose production