Effects of Colchicine in Non-Diabetic Adults With Metabolic Syndrome

* INCLUSION CRITERIA FOR SUBJECTS RANDOMIZED TO COLCHICINE or PLACEBO:: Subjects will qualify for randomization to colchicine or placebo if they meet the following criteria: * Good general health. In general subjects should take no medications. However, individuals taking medications for obesity-related co-morbid conditions, who have not had changes in dosage for more than 3 months, may be included, at the discretion of the principal investigator. * Obesity, defined as a body mass index (BMI) greater than or equal to 30 kg/m\^2, but weight less than 450 lbs in order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning. * Age 18 to 100 years. * Metabolic Syndrome defined as any 3 of the following 5: * FPG greater than or equal to 100 mg/dl, or Impaired Glucose Tolerance (Glucose greater than or equal to 140 mg/dl at 2 hours of OGTT) * Triglycerides greater than or equal to 150 mg/dl, or on treatment * Waist Circumference: Men greater than or equal to 40 in (greater than or equal to 102 cm); Women greater than or equal to 35 in (greater than or equal to 88 cm) * Reduced HDL-C: Men \< 40 mg/dl; Women \< 50 mg/dl, or on treatment * Hypertension: greater than or equal to 130 mmHg systolic, or greater than or equal to 85 mmHg diastolic, or on treatment * HOMA-IR greater than or equal to 2.6. Our goal is to enroll participants who have pre-existing insulin resistance. * high sensitivity C-reactive protein (hs-CRP) greater than or equal to 2.0 mg/L. We aim to recruit participants with increased baseline level of inflammation. Individuals with hsCRP above 2.0 mg/L have been shown to have an increased risk for cardiovascular events. EXCLUSION CRITERIA FOR SUBJECTS RANDOMIZED TO COLCHICINE OR PLACEBO: * Type 2 diabetes mellitus, as determined by either having: * Clear clinical diagnosis of diabetes, such as a patient in a hyperglycemic crisis or classic symptoms of hyperglycemia and a random plasma glucose greater than or equal to 200 mg/dL * Two of the following three: * Fasting plasma glucose greater than or equal to 126 mg/dL * Hemoglobin A1c greater than or equal to 6.5% * An oral glucose tolerance test glucose concentration of greater than or equal to 200 mg/dL at 2 hours. * One of the above three criteria (bi.-biii.) meeting the T2DM cutoff on two different days. If only one of the above three criteria (bi.-biii.) meet the T2DM threshold during the Screening Visit, that test will be repeated on another day to determine if the subject has T2DM or not. As per ADA guidelines, The diagnosis \[of T2DM\] is made on the basis of the confirmed test.Moreover, because HbA1c has been shown to be higher in African Americans (AA) as compared to other races for the same glycemia, non-diabetic AA may be unfairly excluded by their HbA1c alone. Therefore, for AA subjects, if their 2 hour OGTT and fasting glucoses are in the non-diabetic range, and the HbA1c is \< 7.0%, we will consider them non-diabetic. * Presence of a significant active or chronic illness likely to limit life span and/or increase risk of intervention, including renal (GFR less than or equal to 60 ml/min/1.73m2), cardiovascular, hepatic (other than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing syndrome), pulmonary (other than either asthma not requiring continuous medication or sleep apnea-related disorders), or other disorders at the discretion of the investigators. * Recent use of colchicine or anorexiant medications in the last 3 months. * Known allergy to colchicine. * Previous history of agranulocytosis, gout, or significant myositis. * Females who are pregnant, planning to become pregnant, currently nursing an infant, or have irregular menses, defined as cycles less than 21 days or greater than 45 days. * Individuals who have current substance abuse or a psychiatric disorder or any other condition that in the opinion of the investigators would impede competence, compliance, or participation in the study. * Subjects who regularly use prescription medications unrelated to the complications of obesity, especially those known to affect enzymes involved in colchicine metabolism, such as CYP3A4 or P-glycoprotein (P-gp) . Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication or have stopped taking an exclusionary medication for at least 3 months prior to study entry may be eligible . * Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight change of more than 3% of body weight in the past two months. * Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 7 days prior to fat biopsy. * History of keloid formation. * Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes). INCLUSION CRITERIA FOR SUBJECTS WHO ARE EVALUATED BUT NOT ELIGIBLE FOR RANDOMIZATION: Subjects will qualify for the Evaluation-only arm if they meet the following criteria: * Good general health. In general subjects should take no medications. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication or have stopped taking an exclusionary medication for at least 3 months prior to study entry may be eligible. * Weight less than 450 lbs in order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning. * Age 18 years to 100 years. EXCLUSION CRITERIA FOR SUBJECTS WHO ARE EVALUATED BUT NOT ELIGIBLE FOR RANDOMIZATION:\<TAB\> * Type 2 diabetes mellitus that is not well controlled with diet alone: subjects taking an antidiabetic medication (e.g. metformin, insulin, sulfonylureas, etc.) or having a Hemoglobin A1c \> 9.0% * Presence of a significant active or chronic illness likely to limit life span and/or increase risk of intervention, including renal (GFR less than or equal to 60 ml/min/1.73m2), cardiovascular, hepatic (other than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing syndrome), pulmonary (other than either asthma not requiring continuous medication or sleep apnea-related disorders), or other disorders at the discretion of the investigators. * Recent use of colchicine or anorexiant medications in the last 3 months. * Females who are pregnant, planning to become pregnant, or are currently nursing an infant. * Individuals who have current substance abuse or a psychiatric disorder or any other condition that in the opinion of the investigators would impede competence, compliance, or participation in the study. * Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight change of more than 3% of body weight in the past two months. * Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 7 days prior to fat biopsy. * History of keloid formation. * Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes). INCLUSION CRITERIA FOR SUBJECTS WITH DIET-CONTROLLED T2DM Subjects will qualify for the Open Label arm if they meet the following criteria: * A diagnosis of T2DM. * Not on any diabetic/hypoglycemic agents * Not having an alternate cause of hyperglycemia (e.g. T1DM, glucocorticoidinduced, lipodystrophy, acromegaly, etc.) * Hemoglobin A1c less than or equal to 9.0% * Good general health. In general subjects should take no medications. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication or have stopped taking an exclusionary medication for at least 3 months prior to study entry may be eligible * Age greater than or equal to 18 to 100 years. * Obesity, defined as a body mass index (BMI) greater than or equal to 30 kg/m2, but weight less than 450 lbs in order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning. * Metabolic Syndrome (Any 3 of the following 5): * FPG greater than or equal to100 mg/dl or Impaired Glucose Tolerance (Glucose greater than or equal to 140 mg/dl at 2 hours of OGTT) * Triglycerides greater than or equal to 150 mg/dl, or on treatment * Waist Circumference: Men greater than or equal to 40 in (greater than or equal to 102 cm); Women greater than or equal to 35 in (greater than or equal to 88 cm) * Reduced HDL-C: Men \< 40 mg/dl; Women \< 50 mg/dl, or on treatment * Hypertension: greater than or equal to 130 mmHg systolic, or greater than or equal to 85 mmHg diastolic, or on treatment * HOMA-IR greater than or equal to 2.6. Our goal is to enroll participants who have pre-existing insulinresistance. * hsCRP greater than or equal to 2.0 mg/L. We aim to recruit participants with increased baseline level of inflammation. Individuals with hsCRP above 2.0 mg/L have been shown to have an increased risk for cardiovascular events. EXCLUSION CRITERIA FOR SUBJECTS WITH DIET-CONTROLLED T2DM * T2DM that is not well controlled with diet alone: subjects will not be eligible if they take an anti-diabetic medication (e.g. metformin, insulin, sulfonylurea, etc.), or have HbA1c \>9%. * Presence of a significant active or chronic illness likely to limit life span and/or increase risk of intervention, including renal (GFR less than or equal to 30 ml/min/1.73m2), cardiovascular, hepatic (other than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing syndrome), pulmonary (other than either asthma not requiring continuous medication or sleep apnea-related disorders), or other disorders at the discretion of the investigators. * Recent use of colchicine or anorexiant medications in the last 3 months. * Known allergy to colchicine. * Previous history of agranulocytosis, gout, or significant myositis. * Females who are pregnant, planning to become pregnant, currently nursing an infant, or have irregular menses, defined as cycles less than 21 days or greater than 45 days. * Individuals who have current substance abuse or a psychiatric disorder or any other condition that in the opinion of the investigators would impede competence, compliance, or participation in the study. * Subjects who regularly use prescription medications unrelated to the complications of obesity, especially those known to affect enzymes involved in colchicine metabolism, such as CYP3A4 or P-glycoprotein (P-gp). Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication or have stopped taking an exclusionary medication for at least 3 months prior to study entry may be eligible. * Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight change of more than 3% of body weight in the past two months. * Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 7 days prior to fat biopsy. * History of keloid formation. * Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes).