Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, International Randomized, 2x2 Factorial Design Study to Evaluate the Effects of Lantus (Insulin Glargine) Versus Standard Care, and of Omega-3 Fatty Acids Versus Placebo, in Reducing Cardiovascular Morbidity and Mortality in High Risk People With Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or Early Type 2 Diabetes Mellitus: The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)
Brief Summary: The primary objectives of the ORIGIN study were:

* To determine whether insulin glargine-mediated normoglycemia can reduce cardiovascular morbidity and/or mortality in people at high risk for vascular disease with either Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or early type 2 diabetes;
* To determine whether omega-3 fatty acids can reduce cardiovascular mortality in people with IFG, IGT or early type 2 diabetes.

The secondary objectives of the insulin glargine study were to determine if insulin glargine-mediated normoglycemia can reduce:

* total mortality (all causes);
* the risk of diabetic microvascular outcomes;
* the rate of progression of IGT or IFG to type 2 diabetes.


Options:
A: Inclusion criteria:

I1. Individuals with IFG and/or IGT, or early diabetes, as defined below.

Glucose tolerance status was determined by a 75 g oral glucose tolerance test (OGTT) that was performed fasting (ie, no consumption of food or beverage other than water for at least 8 hours) at the time of screening for all candidates who were not known to have diabetes. The qualifying OGTT could be obtained up to 4 weeks prior to screening provided that anti-diabetic therapy (if any) remained unchanged between the qualifying OGTT and the screening visit. Two plasma glucose values were drawn during the OGTT - a fasting value (FPG) and a value drawn two hours after the 75 g oral glucose load was administered (postprandial plasma glucose \[PPG\]).

- Impaired glucose tolerance (IGT), defined as a PPG value ≥140 and \<200 mg/dL (ie, ≥7.8 and \<11.1 mmol/L), with a FPG \<126 mg/dL (7.0 mmol/L).

OR

- Impaired fasting glucose (IFG), defined as an FPG ≥110 and \<126 mg/dL (≥6.1 and \<7 mmol/L), without diabetes mellitus (PPG must be \<200 mg/dL \[11.1 mmol/L\]).

OR

- Early type 2 diabetes, defined as a FPG ≥126 mg/dL (7.0 mmol/L) or a PPG of ≥200 mg/dL (11.1 mmol/L), or a previous diagnosis of diabetes, and either:

* on no pharmacological treatment (while ambulatory) for at least 10 weeks prior to screening, with screening glycated hemoglobin \<150% of the upper limit of normal (ULN) for the laboratory (eg, \<9% if the ULN is 6%)
* or taking one oral antidiabetic drug (OAD) from among sulfonylureas (SU), biguanides, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), and meglitinides (MGTs) at a stable dose while ambulatory for at least 10 weeks at the time of screening (or for the 10 weeks prior to hospitalization if identified while hospitalized for a CV event), with screening glycated hemoglobin \<133% of the ULN for the laboratory (eg, \<8% if the ULN is 6%) if taking this medication at half-maximum dose or greater, and glycated hemoglobin \<142% of the ULN for the laboratory (eg, \<8.5% if the ULN is 6%) if taking this medication at less than half-maximum dose. Individuals taking combination products containing two or more OADs were not eligible.

I2. Men or women aged 50 years and older

I3. At least one of the following CV risk factors:

* previous myocardial infarction (MI) (≥ 5 days prior to randomization)
* previous stroke (≥ 5 days prior to randomization)
* previous coronary, carotid or peripheral arterial revascularization
* angina with documented ischemic changes (at least 2 mm ST segment depression on electrocardiogram during a Graded Exercise Test \[GXT\]; or with a cardiac imaging study positive for ischemia); or unstable angina with documented ischemic changes (either ST segment depression of at least 1 mm or an increase in troponin above the normal range but below the range diagnostic for acute myocardial infarction)
* microalbuminuria or clinical albuminuria (an albumin: creatinine ratio ≥ 30 μg/mg in at least one or timed collection of urine with albumin excretion ≥20 μg/min or ≥30 mg/24 hours or total protein excretion ≥500 mg/24 hours)
* left ventricular hypertrophy by electrocardiogram or echocardiogram
* significant stenosis on angiography of coronary, carotid, or lower extremity arteries (ie, 50% or more stenosis)
* ankle-brachial index \< 0.9.

I4. Provision of signed and dated informed consent prior to any study procedures.

I5. Ability and willingness to complete study diaries and questionnaires.

I6. Demonstrated ability to use the self-glucose-monitoring device, and to self-inject insulin prior to randomization.

I7. A negative pregnancy test for all women of childbearing potential (ie, ovulating, pre- menopausal, and not surgically sterile) and the agreement of these women to use a reliable method of birth control to prevent pregnancy during the duration of the study .

I8. Willingness to discontinue prior omega-3 PUFA supplements for the duration of the study.

Exclusion criteria

E1. Type 1 diabetes.

E2. Requiring ambulatory insulin treatment or uncontrolled or symptomatic hyperglycemia that is likely to require the addition of ambulatory insulin therapy or a new antidiabetic agent either before or within 2 weeks after randomization.

E3. Known anti-glutamic acid decarboxylase antibody (anti-GAD Ab) positivity in the past.

E4. Screening glycated hemoglobin ≥150% of the ULN for the laboratory (eg, ≥9% if the ULN is 6%).

E5. Unwillingness to inject insulin or perform self-monitoring of blood glucose.

E6. Nonadherence to the run-in requirement to inject placebo insulin and do capillary glucose monitoring for at least 4 days prior to randomization.

E7. Coronary artery bypass grafting (CABG) either planned at the time of screening, or CABG within the 4 years prior to screening - however, participants with angina, MI, or stroke since a previous CABG will be eligible for randomization, even if the last CABG was within 4 years.

E8. Serum creatinine \>2.0 mg/dL (176 μmol/L) at screening.

E9. Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times ULN at screening.

E10. Chronic or recurrent treatment with systemic corticosteroids, or niacin treatment for hyperlipidemia.

E11. Heart failure of New York Heart Association (NYHA) Functional Class III or IV.

E12. Expected survival of \<3 years for non-CV causes such as cancer.

E13. Any other factor likely to limit protocol compliance or reporting of adverse events (AEs).

E14. Unwilling or unable to discontinue TZDs.

E15. Simultaneous participation in any other clinical trial of an active pharmacologic agent.

E16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data and treatment assignment.

E17. History of hypersensitivity to the investigational products.

E18. Previous randomization in this study.

E19. A prior heart transplant, or awaiting a heart transplant.

E20. Known infection with human immunodeficiency virus (HIV).
B: Inclusion Criteria:

* Persistent atrial fibrillation

Exclusion Criteria:

* Contraindications or known hypersensitivity to n-3 PUFA
* Current treatment with n-3 PUFA for any reason
* Heart failure NYHA class IV
* Coronary artery bypass surgery or valve replacement within the past 3 months
* Planned cardiac procedures
* Known sick-sinus syndrome
* Diagnosis of Wolff-Parkinson-White
* Clinical significant valvular etiologies
* Presence of arrhythmia associated with an acute reversible condition
* Advanced chronic lung disease
* Contraindications for anticoagulation therapy
* Pregnancy or lactation
* Any non cardiac illness associated with a life expectancy of \< 2 years
* Treatment with any investigational agent within 3 month before randomization
* Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol
C: Inclusion Criteria:

* 65-79 years old.
* Free of clinically diagnosed overt disease for at least 2 years.
* Free-living, independent.

Exclusion Criteria:

* \<65 or \> 79 years old.
* Overt disease such as aggressive cancer or dementia.
* Unstable organ failure or organ failure necessitating a special diet.
* Heart failure.
* Renal failure.
* Respiratory failure.
* Liver failure.
* Type 1 diabetes mellitus.
* Chronic use of corticosteroids.
* Recent (previous 2 months) use of antibiotics.
* Recent (previous 3 months) change to habitual medication (e.g statins and thyroxine) use
* Presence of food allergy/intolerance or disease necessitating a special diet.
* Malnutrition, as diagnosed by body mass index \< 18.5 kg/m2.
* Body weight loss of \>10% BW within 6 months.
* Presence of frailty (as assessed by the presence of at least three out of five criteria according to Fried et al., 2001: unintentional weight loss, self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity).
* Individual unable to give informed consent.
* Volunteers showing previously unrecognized illness will also be excluded.
D: To be eligible for the study, respondents had to, at study entry,:

1. be men aged 50 or older or women aged 55 or older;
2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, coronary-artery bypass grafting, or percutaneous coronary intervention;
3. have none of the following safety exclusions: history of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or granulomatosis with polyangiitis (Wegener's);
4. have no allergy to fish or soy;
5. have no other serious illness that would preclude participation;
6. be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D \[e.g., Fosamax Plus D\], and multivitamins), or, if taking, willing to decrease or forego such use during the trial;
7. be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial;
8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial

Answer: A