Restoring 24-hour Substrate Rhythmicity to Improve Glycemic Control by Timing of Lifestyle Factors (TIMED)

This is an interventional prevention trial for Prediabetic State focused on measuring Postprandial metabolism, High-intensity interval training Read More

Inclusion Criteria:

• Pre-diabetes:

  • Fasting plasma glucose: 6.1 to 6.9 mmol/L or
  • 2-hour plasma glucose post 75g OGTT: 7.8 to 11.0 mmol/L and
  • HbA1c: 6.0 to 6.4%
  • or Insulin resistant: glucose clearance rate ≤ 360 ml/kg/min as determined using the Oral Glucose Insulin Sensitivity Index at Time 120 min.
• BMI > 25 kg/m2
• To be willing and able to adhere to the specifications of the protocol;
• To have signed an informed consent document indicating that they understood the purpose of and procedures required for the study and were willing to participate in the study.

Exclusion Criteria:

• overt cardiovascular disease as assessed by medical history, physical exam, and abnormal ECG
• Treatment with any drug known to affect lipid or carbohydrate metabolism, except statins (to be stopped 3 weeks prior to study A), metformin or anti-hypertensive drugs (to be stopped 7 days prior to the studies);
• presence of liver or renal disease other than uncomplicated NASH or mild isolated proteinuria; uncontrolled thyroid disorder;
• Uncontrolled severe hypertension, systolic pressure ≥ 180 mm Hg or diastolic pressure ≥ 110 mm Hg;
• History of ischemic heart disease, tachyarrhythmia, QT interval prolongation, risk factors for torsade de pointes (eg hypokalemia), or taking any medication known to prolong the QT interval;
• History of serious gastrointestinal disorders (malabsorption, peptic ulcer, gastroesophageal reflux requiring surgery, etc.);
• Presence of a pacemaker;
• Having undergone a PET study or CT scan in the past year;
• Any contraindication to stopping statins for 3 months and stopping an anti-hypertensive medication and metformin for 7 days;
• smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day;
• No blood donation two month prior the study;
• prior history or current fasting plasma cholesterol level > 7 mmol/l or fasting TG > 6 mmol/l.