Metabolic Syndrome, Pre-Diabetes
Conditions
Keywords
Time Restricted Eating, Circadian Rhythm, Glucose Homeostasis, Mitochondrial Function, Fasting
Brief summary
In a randomized controlled trial, the investigators intend to measure the health impact of TRE in patients with metabolic syndrome (with three or more of the following criteria: increased waist circumference, abnormal cholesterol levels, elevated blood pressure, or elevated blood sugar), who habitually eat for more than 14 hours every day. Patients will be randomly assigned to a control group of behavioral nutrition counseling (standard of care) or the intervention group of behavioral nutrition counseling with the addition of adopting a 8-10 hour eating window for 12 weeks (TRE).
Detailed description
Circadian rhythms optimize nutrient homeostasis by orchestrating catabolic and anabolic metabolism to appropriate times of the 24 hour day. Chronic circadian rhythm disruption predisposes individuals to metabolic diseases including obesity and type 2 diabetes. Conversely, maintaining a daily rhythm of feeding and fasting cycles sustains a robust circadian rhythm which improves cellular bioenergetics and results in improved metabolism. Time-restricted eating (TRE) is a specific feeding-fasting pattern in which feeding is restricted to 8-12 hours a day. At the beginning and end of the study (which will be three months in duration), the following parameters will be measured: height, weight, body mass index, percent body fat, waist/hip circumference and blood pressure. Blood sugar levels will be monitored continuously for 2 weeks at a time at the beginning and end of the study using a continuous glucose monitor. Additionally, a dual energy X-ray absorptiometry (DXA) scan will be used to collect information about body composition. Information will be collected about the mitochondria with a muscle biopsy. Participants will use a smartphone application (called myCircadianClock (mCC), developed by the Salk Institute) to keep track of food/beverage intake and will wear a wrist-worn actigraphy device to monitor physical activity levels and sleep.
Interventions
Participants in this arm will adhere to a daily, consistent 8-10-hr eating window for the course of the study as well as receive nutritional counseling from the study dietitian.
BEHAVIORALStandard of Care
Participants in this arm will receive nutritional counseling from the study dietician, but will not be required to adopt a 8-10-hr eating window.
Sponsors
University of California, San Diego
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Salk Institute for Biological Studies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years 2. 41 ≥ BMI ≥ 25 AND 3. Metabolic syndrome, as defined as presence of 3 or more of the following criteria: Elevated fasting plasma glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% \< 7.1% Elevated waist circumference: In Asians: ≥ 90 cm in men, ≥ 80 cm in women, all other races: ≥ 102 cm in men, ≥ 88 cm in women Fasting plasma triglycerides ≥ 150 mg/dL, or on drug treatment for elevated triglycerides Reduced High-density lipoprotein (HDL)-cholesterol \< 40 mg/dL in males or \< 50 mg/dL in females, or drug treatment for reduced HDL-cholesterol Elevated blood pressure, Systolic blood pressure ≥ 135 mm Hg and/or diastolic blood pressure ≥ 85 mm Hg or drug treatment for hypertension 4. Own a smartphone (Apple iOS or Android OS) 5. Baseline eating period ≥ 12 hour window 6. If patients are on cardiovascular medications (HMG CoA reductase inhibitors (statins), other lipid modifying drugs (including over the counter drugs such as red yeast rice and fish oil), anti-hypertensive, anti-diabetes drugs), no dose adjustments will be allowed during the study period.
Exclusion criteria
1. Taking insulin within the last 6 months. 2. Manifest diabetes, defined as HbA1c \> 7.0% given a 0.3% margin of error in lab readings, or diagnosis of diabetes. 3. Known inflammatory and/or rheumatologic disease. 4. Active tobacco abuse or illicit drug use or history of treatment for alcohol abuse. 5. Pregnant or breast-feeding women. 6. Shift workers with variable (e.g. nocturnal) hours. 7. Caregivers for dependent requiring frequent nocturnal care/sleep interruptions. 8. Planned travel to a time zone with greater than a 3-hour difference during study period. 9. History of major adverse cardiovascular event within the past 1 year (acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack (TIA)). 10. Uncontrolled arrhythmia (i.e. rate-controlled atrial fibrillation/atrial flutter are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glucose Levels Assessed Via HbA1c | Baseline and 14 weeks | HbA1c (%) |
| Change in Glycemic Parameters Assessed Via Fasting Glucose | Baseline and 14 weeks | Glycemic parameters assessed via fasting glucose (mg/dL) |
| Change in Glycemic Parameters Assessed Via HOMA-IR | Baseline and 14 weeks | Glycemic parameters assessed via HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) - a calculated index estimating insulin resistance from fasting blood glucose and insulin levels, using the formula (fasting glucose × fasting insulin) ÷ 405. Lower scores indicate healthier insulin sensitivity, while higher scores indicate greater insulin resistance. |
| Glycemic Parameters Assessed Via Fasting Insulin | Baseline and 14 weeks | Glycemic parameters assessed via fasting insulin (μIU/mL) |
| Glycemic Parameters Assessed Via CGM Mean Glucose | Baseline and 14 weeks | Glycemic parameters assessed via CGM mean glucose (mg/dL). |
| Glycemic Parameters Assessed Via CGM CONGA | Baseline and 14 weeks | Glycemic parameters assessed via CGM CONGA (Continuous Overall Net Glycemic Action) |
| Glycemic Parameters Assessed Via CGM MODD | Baseline and 14 weeks | Glycemic parameters assessed via CGM MODD (mg/dL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in LDL Particle Number | Baseline and 14 weeks | LDL particle number (nmol/L) via NMR lipoprofile |
| Change in LDL Cholesterol | Baseline and 14 weeks | LDL cholesterol (mg/dl) |
| Change in HDL Cholesterol | Baseline and 14 weeks | HDL cholesterol (mg/dl) |
| Change in Triglycerides | Baseline and 14 weeks | Triglycerides (mg/dl) |
| Change in Body Composition by DXA | Baseline and 14 weeks | Lower abdominal fat mass as assessed by dual-energy X-ray absorptiometry (DXA). |
| Change in Hs-CRP | Baseline and 14 weeks | High sensitivity C-reactive protein (mg/L) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPam Taub, MD
Associate Professor of Medicine
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.74 years STANDARD_DEVIATION 10.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Medications for treatment of metabolic syndrome 1 or more medication listed | 84 participants |
| Medications for treatment of metabolic syndrome Antihypertensives and diuretics | 31 participants |
| Medications for treatment of metabolic syndrome Metformin | 3 participants |
| Medications for treatment of metabolic syndrome Nonstatin lipid-lowering drugs | 2 participants |
| Medications for treatment of metabolic syndrome Statins | 31 participants |
| Metabolic syndrome classification HbA1c≥5.7 %, fasting glucose ≥5.55 mmol/L (100 mg/dL), or drug treatment | 61 participants |
| Metabolic syndrome classification HDL cholesterol: M <40 mg/dL or F < 50 mg/dL (F), or drug treatment of reduced HDL cholesterol | 44 participants |
| Metabolic syndrome classification SBP ≥130 mm Hg and/or DBP ≥85 mm Hg, or drug treatment of hypertension | 48 participants |
| Metabolic syndrome classification Triglycerides ≥1.69 mmol/L (150 mg/dL), or drug treatment of elevated triglycerides | 25 participants |
| Metabolic syndrome classification Waist circumference: Asian: ≥90 cm (M) or ≥80 cm (F); all other races: ≥102 cm (M) or ≥88 cm (F) | 107 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment United States | 61 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 61 |
| other Total, other adverse events | 0 / 61 | 1 / 61 |
| serious Total, serious adverse events | 0 / 61 | 0 / 61 |
Outcome results
None listed