Please select the eligibility criteria that correspond to the clinical trial below.
Title: Rapid Effects of the DPP-4 Inhibitor Linagliptin on Monocyte Polarization and Endothelial Progenitor Cells in Type 2 Diabetic Patients With and Without Chronic Renal Failure. A Randomized Cross-over Trial Versus Placebo
Brief Summary: Diabetes mellitus is characterized by chronic low grade inflammation, which is worsened by the co-existence of renal failure.

One key aspect of chronic inflammatory diseases is the alteration in the polarization profile of circulating monocyte-macrophage cells.

Namely, monocytes-macrophages can exist in a pro-inflammatory (M1) polarized form or an anti-inflammatory (M2) polarized state. Alterations in the M1/M2 balance is thought to contribute to inflammation within atherosclerotic lesions and visceral adipose tissue which, in turn, can worsen cardiovascular disease and metabolic features in type 2 diabetic patients.

M1 and M2 are regulated by a complex interplay of soluble signaling molecules, many of which are substrate of the enzyme DPP-4 (dipeptidyl peptidase-4). Therefore, inhibition of DPP-4 can affect the M1/M2 polarization balance.

In this clinical trial, the investigators will test whether the DPP-4 inhibitor Linagliptin, compared to placebo, modifies the M1/M2 balance in type 2 diabetic patients with and without chronic renal failure.

In addition, we will test whether DPP-4 inhibition with Linagliptin acutely affects endothelial progenitor cells (EPCs), which are vasculoprotective cells implicated in the pathobiology of diabetic complications.


Options:
A: Inclusion Criteria:

* Has T2DM
* Has HbA1c between 6.5% (48 mmol/mol) and 8.0% (64 mmol/mol) on stable dose(s) of antihyperglycemic agent(s), including insulin
* Has pre-existing cardiovascular disease

Exclusion Criteria:

* Has a history of type 1 diabetes mellitus or ketoacidosis.
* Is not able to take sitagliptin
B: Inclusion criteria:

1. Dated written informed consent that is in accordance with GCP and local legislation.
2. Male and female Black / African American patients
3. Diagnosis of type 2 diabetes at least 3 months prior to the informed consent.
4. HbA1c more than or equal to 7.5% and less than or equal to 11% at Visit 1.
5. Patients are currently treatment-naive or being treated with up to one oral antidiabetic medication. Antidiabetic medication is to be unchanged for at least 10 weeks prior to the informed consent.
6. Age more than 18 and less than 80 years at Visit 1 (Screening).
7. BMI (Body Mass Index) less than 45 kg/m2 at Visit 1.

Exclusion criteria:

1. Myocardial infarction (MI), stroke or transient ischemic attack (TIA) within 3 months of informed consent.
2. Type 1 diabetes.
3. Impaired hepatic function, defined by serum levels of either alanine aminotransferase (ALT, SGPT), aspartate aminotransferase (AST, SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN) as determined at Visit 1.
4. Known prior hypersensitivity or allergy to the investigational product or its excipients.
5. Treatment with insulin within 3 months prior to informed consent.
6. Treatment with anti-obesity drugs (e.g., sibutramine, orlistat, rimonabant) within three months prior to informed consent or initiating therapy during the study.
7. Any prior use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
8. Glucagon-like peptide-1 (GLP-1) agonists are excluded 3 months prior to informed consent.
9. History of alcohol or drug abuse within 3 months prior to informed consent that would interfere with trial participation as assessed by the Investigator.
10. Participation in another trial with an investigational drug within 3 months prior to informed consent or during the study.
11. Pre-menopausal women (last menstruation less than 1 year prior to informed consent) who:

    * are nursing or pregnant
    * are not surgically sterile
    * or are of child-bearing potential and are not practicing an acceptable method of birth control or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include transdermal patch, intrauterine devices/systems (IUDs / IUSs), oral, implantable or injectable contraceptives, and vasectomised partners. No exceptions will be made.

    Hormonal birth control should have been in use for at least three months prior to signing informed consent and continue at least until the next menstrual period after completing the study.
12. Current treatment with chronic use of systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent.
13. History of bariatric surgery.
14. Patients who have demonstrated an inability to be compliant (80-120%) with the dosing regimen during the placebo run-in period.
C: Inclusion Criteria:

* Type 2 diabetes mellitus
* Drug naive
* Hemoglobin (Hb) A1c \>= 7.0% and \<= 10.0% (\>10% and \<= 12% for open label arm)
* Fasting C-peptide \>= 1 ng/mL
* Body mass index \<= 40 kg/m2

Exclusion Criteria:

* Symptomatic poorly controlled diabetes
* Recent cardiac or cerebrovascular event
* Serum creatinine \>= 1.5 mg/dL for males and \>= 1.4 mg/dL for Women of Child Bearing Potential
D: Inclusion Criteria:

* Type 2 diabetes
* eGFR \> 60 mL/min/1.73 mq (for the patients without renal failure)
* eGFR 10-60 mL/min/1.73 mq (for the patients with renal failure)

Exclusion Criteria:

* Type 1 diabetes
* Hypersensitivity to Linagliptin or excipients
* Intolerance to other DPP-4 inhibitors
* Terminal renal failure (eGFR \< 10 mL/min/1.73 mq)
* Use of GLP-1 analogs or other DPP-4 inhibitors
* Recent (within 1 month) trauma or surgery or acute diseases
* Any acute or chronic inflammatory condition
* Immunosuppression or organ transplantation
* Pregnancy or lactation
* Inability to provide informed consent.

Answer: D