Please select the eligibility criteria that correspond to the clinical trial below.
Title: The Impact of Liraglutide on Glucose Tolerance and the Risk of Type 2 Diabetes in Women With Previous Gestational Diabetes Mellitus
Brief Summary: It is well-known that women with previous gestational diabetes mellitus are in risk of developing type 2 diabetes later in life; approximately half of the women develop overt type 2 diabetes within the first 10 years after pregnancy. Knowing this, we want to examine the effect of the type 2 diabetes medicine, liraglutide (Victoza), in women with previous gestational diabetes with the aim of reducing the risk of developing type 2 diabetes.


Options:
A: Inclusion Criteria:

* Greater than or equal to 18 years old
* Impaired glucose tolerance: 2-hr oral glucose tolerance test (OGTT) plasma glucose \>140 mg/dL OR impaired fasting glucose: fasting glucose \> or = 100 mg/dL OR elevated glycosylated hemoglobin: Hemoglobin A1c \> or = 5.7%
* Abdominal obesity: waist circumference \>102 cm (men) and \>88 cm (women)
* Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study

Exclusion Criteria:

* Type 2 diabetes
* Current use of glycemic control medications within one month of randomization
* Fasting glucose \>126 mg/dL
* Current use of weight loss medication
* Previous weight loss surgery
* History of severe gastrointestinal disease
* Standard clinical contraindications to exenatide or metformin therapy
* Unstable angina
* Heart failure
* Stroke or coronary artery bypass graft within 3 months of screening
* Women who are currently pregnant or planning to become pregnant
* Breastfeeding women
* Clinically significant liver disease
* Creatinine \> 1.5 mg/dL
* Hepatic function greater than 3 times upper limit of normal
* Patients who are mentally incompetent and cannot sign a Patient Informed Consent
B: Inclusion Criteria:

1. Males age 18-65 years old
2. Patients must have Body Mass Index (BMI) between 25 and 40 kg/m2
3. 2-hour glucose concentration above 140mg/dl after 75g glucose load, ie, having impaired glucose tolerance or newly diagnosed type 2 diabetes.
4. Patients must have BMI of 25-40 kg/m2
5. Patients must have no known severe liver or kidney disease, cancer, neurologic, psychiatric or systemic disease, ability to understand the study.
6. Only patients whose body weight has been stable (±3-4 pounds) over the three months prior to study will be included.
7. Patients must have the following laboratory values:

   * Hematocrit ≥ 34 vol%
   * Serum creatinine\* ≤ 1.5 mg/dl in males and
   * Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT): ≤ 2.5 times upper limit of normal
   * Alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT): ≤ 2.5 times upper limit of normal
   * Alkaline phosphatase ≤ 2.5 times upper limit of normal
   * If serum creatinine is ≤ 1.5 mg/dl in males, the PI can grant an exception and not exclude the patient if the Glomerular filtration rate (GFR) is \>70 ml/min

Exclusion Criteria:

Patients are excluded from participation in the study if they meet any of the following criteria:

1. Patients with major chronic illness (cancer, liver, kidney, cardiovascular disease)
2. Patients with BMI over 40 and under 25
3. Patient with age below 18 yrs and over 65 yrs
4. Female subjects
5. Patients with type 1 diabetes
6. Patients treated for type 2 diabetes
7. Subjects with normal glucose tolerance (NGT)
C: Inclusion Criteria for women with previous GDM:

* Informed oral and written consent
* Previous diagnosis of GDM according to current Danish guidelines (mainly PG concentrationa t 120 min after 75 g OGTT ≥ 9.0 mM) during pregnancy within the last 5 years
* Age \>18 years
* 25 kg/m2 \< BMI \< 45 kg/m2
* NGT, IFG and or IGT
* Safe contraception and negative pregnancy test

Exclusion Criteria for women with previous GDM:

* Patients with diabetes
* HbA1c ≥6.5%
* Patients with previous pancreatitis or previous neoplasia
* Pregnant or breast feeding women
* Anaemia (haemoglobin \<7 mM)
* Women planning to become pregnant within the next 5 years
* Women using other contraception than intrauterine device (IUD) or oral contraceptives. Women who do not use safe contraception will be offered application of an IUD.
* Women treated with statins, corticosteroids or other hormone therapy (except estrogens and gestagens)
* Ongoing abuse of alcohol or narcotics
* Impaired hepatic function (liver transaminases \>3 times upper normal limit)
* Impaired renal function (se-creatinine \>120 μM and/or albuminuria)
* Uncontrolled hypertension (systolic blood pressure \>180 mmHg, diastolic blood pressure \>100 mmHg)
* Any condition that the investigator feels would interfere with trial participation
* Receiving any investigational drug within the last 3 months

Inclusion criteria for women without previous GDM:

* Informed oral and written consent
* Age \>18 years
* 25 kg/m2 \< BMI \< 45 kg/m2
* NGT
* Safe contraception and negative pregnancy test
* Pregnancy within the last ten years without GDM

Exclusion Criteria for women without previous GDM :

* Pregnant or breast feeding women
* Anaemia (haemoglobin \<7 mM)

Inclusion Criteria for women without previous GDM and without NAFLD:

* Informed oral and written consent
* Age \>18 years
* 25 kg/m2 \< BMI \< 45 kg/m2
* NGT
* At least one pregnancy witin the last ten years without GDM

Exclusion Criteria for women without previous GDM and without NAFLD:

* Pregnant or breast feeding women
* Anaemia (haemoglobin \<7 mM)
* Steatosis as assessed by ultrasound scanning
* Recieving any investigational drug within the last 3 months
* Any condition that the investigator feels would interfere with the trial participation

Inclusion Criteria for women with biopsi-verified NAFLD:

* Informed oral and written consent
* Women with known NAFLD or NASH
* Age \>18 years
* 25 kg/m2 \< BMI \< 45 kg/m2
* NGT
* At least one prior pregnancy

Exclusion Criteria for women with biopsi-verified NAFLD:

* women with established cirrhosis
* Pregnant or breast feedning women
* Anaemia (haemoglobin \<7 mM)
* Women treated with statins, corticosteroids or other hormone therapy ( except oestrogens and gestagens)
* Ongoing abuse of alcohol or narcotics
* Impaired renal function (se-creatinine \> 120 μM and/or albuminuria)
* Uncontrolled hypertension (systolic blood pressure \> 180 mmHg, diastolic blood presure \> 100 mmHg)
* Any condition that the investigator feels would interfere with trial participation
D: Inclusion Criteria:

* 18-65 yr old HIV infected men and women.
* Stable (at least the past 6 months) on combined antiretroviral therapy (cART).
* Stable immune (\> 300 CD4+ T-cells/µL) and virologic (\< 50 copies HIV RNA/mL) status.
* Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).
* Waist circumference \> 102 cm (men), \> 88 cm (women).
* BMI \> 20 kg/m2.
* Fasting hypertriglyceridemia \> 150 mg/dL.
* Low HDL-cholesterol (\< 40 mg/dL in men or \< 50 mg/dL in women).
* Platelet count \> 30,000/mm3.
* Absolute neutrophil count \> 750/mm3.
* Transaminases \< 2.5x the upper limit of normal.
* Long-term non-progressors (not taking anti-HIV medications) are not eligible.

Exclusion Criteria:

* Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea).
* Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.
* History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension \> 160/95 mmHg), irregular heart rhythm, resting ST-segment depression \> 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.
* Moderate to severe renal insufficiency. Serum creatinine \> 1.7 mg/dL (men) \> 1.5 mg/dL (women).
* Plan or anticipate a change in anti-HIV medications during the study.
* Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 6 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
* Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable Hep C RNA).
* Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Active substance abuse that the MD-scientist believes may compromise safety, compliance, interfere with study drug or data interpretation.
* Hematocrit \< 34% in men or \< 25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin \< 10 gm/dL with symptoms.
* Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If using birth control pills-must be stable on this medication for at least 6 months prior to enrollment.
* Active malignancy or treatment with chemotherapeutic agents or radiation therapy or any cytokine or anti-cytokine therapy during 6 months prior to enrollment.
* History of pancreatitis
* \> 10% unintentional weight loss during the 6 months prior to enrollment.
* Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
* Blinded investigational drugs for 3 months prior to enrollment that will not be unblinded before enrollment.
* Nausea, vomiting, diarrhea (\> 4 loose stools/day) that are unresponsive to treatment.

Answer: C