Diabetes Mellitus, Diabetes Mellitus, Type 2
Conditions
Keywords
Diabetes Mellitus, hepatic glycogen, endogenous glucose production
Brief summary
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
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.
Interventions
OTHERglycogen 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.
OTHERNo 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.
Sponsors
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
A total of 34 subjects participated.
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes | Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Glycogenolysis in Subjects With Type 2 Diabetes | Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks | 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. |
| Rates of Gluconeogenesis in Healthy Subjects | Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
17 Type 2 Diabetes subjects were screened, 1 subject did not meet eligibility criteria, 2 subjects withdrew from the study. 17 subjects without Diabetes were screened, 2 subjects withdrew from the study.
Pre-assignment details
Subject enrolled after consent were screened to meet inclusion criteria. If not met subjects were excluded. 14 Type 2 Diabetes and 15 without Diabetes subjects were randomized to receive, either Glycogen loading or Non-Glycogen loading meal during visit 1. All subjects were tested for Glycogen loading and Non-Glycogen loading meal in a randomized order. 1Type 2 Diabetes and 2 without Diabetes subjects did not participate in visit 2.
Participants by arm
| Arm | Count |
|---|---|
| Type 2 Diabetes High Carbohydrate (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.
Low carbohydrate (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.
Baseline characteristics of all subjects with Type 2 Diabetes reported. | 14 |
| Participants Without Diabetes High Carbohydrate (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.
Low carbohydrate (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.
Baseline characteristics of all subjects without Diabetes reported. | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Washout (3-6 Weeks) | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Participants Without Diabetes | Total | Type 2 Diabetes |
|---|---|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 14 | 58.7 years STANDARD_DEVIATION 12.1 | 63.2 years STANDARD_DEVIATION 7.7 |
| BMI (Kg/m^2) | 28.5 Kg/m^2 STANDARD_DEVIATION 2.9 | 28.2 Kg/m^2 STANDARD_DEVIATION 2.8 | 28.0 Kg/m^2 STANDARD_DEVIATION 2.8 |
| Body Weight (Kg) | 82.5 Kg STANDARD_DEVIATION 12.5 | 82.4 Kg STANDARD_DEVIATION 11.6 | 82.4 Kg STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 29 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fasting Plasma Glucose (mmol/L) | 4.7 mmol/L STANDARD_DEVIATION 0.4 | 6.3 mmol/L STANDARD_DEVIATION 2.9 | 8.0 mmol/L STANDARD_DEVIATION 3.5 |
| HbA1C | 5.3 % of Glycosylated Haemoglobin STANDARD_DEVIATION 0.4 | 6.2 % of Glycosylated Haemoglobin STANDARD_DEVIATION 1.3 | 7.1 % of Glycosylated Haemoglobin STANDARD_DEVIATION 1.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 27 Participants | 12 Participants |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 8 |
| other Total, other adverse events | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 8 |
Outcome results
Primary
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.
Time frame: Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks
Population: Gluconeogenesis (GNG) and Endogenous Glucose Production (EGP) measured after glycogen loading (GL) or no glycogen loading (NGL) in subjects with type 2 diabetes.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Type 2 Diabetes - Glycogen Loading | Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes | GNG (umol/kgFFM/min) | 8.2 umol/kgFFM/min |
| Type 2 Diabetes - Glycogen Loading | Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes | EGP (umol/kgFFM/min) | 17.4 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes | EGP (umol/kgFFM/min) | 15.6 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Hepatic Glycogen Content and Rates of Gluconeogenesis in Subjects With Type 2 Diabetes | GNG (umol/kgFFM/min) | 9.4 umol/kgFFM/min |
Secondary
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.
Time frame: Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks
Population: Gluconeogenesis (GNG) and Endogenous Glucose Production (EGP) measured after glycogen loading (GL) or no glycogen loading (NGL) in subjects without diabetes.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Type 2 Diabetes - Glycogen Loading | Rates of Gluconeogenesis in Healthy Subjects | GNG (umol/kgFFM/min) | 7.7 umol/kgFFM/min |
| Type 2 Diabetes - Glycogen Loading | Rates of Gluconeogenesis in Healthy Subjects | EGP(umol/kgFFM/min) | 15.9 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Rates of Gluconeogenesis in Healthy Subjects | GNG (umol/kgFFM/min) | 8.5 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Rates of Gluconeogenesis in Healthy Subjects | EGP(umol/kgFFM/min) | 13.5 umol/kgFFM/min |
Secondary
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.
Time frame: Subjects will complete both glycogen loading and no glycogen loading visits within approximately 6 weeks
Population: Glycogenolysis (GGL) and Endogenous Glucose Production (EGP) measured after glycogen loading (GL) or no glycogen loading (NGL) in subjects with type 2 diabetes.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Type 2 Diabetes - Glycogen Loading | Rates of Glycogenolysis in Subjects With Type 2 Diabetes | GGL (umol/kgFFM/min) | 9.2 umol/kgFFM/min |
| Type 2 Diabetes - Glycogen Loading | Rates of Glycogenolysis in Subjects With Type 2 Diabetes | EGP (umol/kgFFM/min) | 17.4 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Rates of Glycogenolysis in Subjects With Type 2 Diabetes | GGL (umol/kgFFM/min) | 6.3 umol/kgFFM/min |
| Type 2 Diabetes - Non-Glycogen Loading | Rates of Glycogenolysis in Subjects With Type 2 Diabetes | EGP (umol/kgFFM/min) | 15.6 umol/kgFFM/min |