The Effects of Anti-Inflammatory Treatment on Insulin Resistance in Healthy Volunteers
Condition: Type 2 Diabetes; Diabetes
MeSH terms: Diabetes Mellitus; Insulin Resistance
Intervention: Salsalate; Placebo
Intervention description: The intervention was salsalate (3g/day) for 7 days.; Identical placebo for 7 days.
Intervention MeSH terms: Salicylsalicylic acid
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Salsalate; Insulin Resistance; Diabetes Mellitus; Inflammation; Diabetes; HCV

Summary:

      This study, conducted at the Phoenix Indian Medical Center, Phoenix, Arizona, will determine
      whether reducing subclinical inflammation lessens insulin resistance in healthy, obese
      volunteers. The study findings may lead to new strategies for preventing type 2 diabetes. In
      diabetes, blood sugar is higher than normal and can result in serious medical problems, such
      as blindness and kidney failure. People with subclinical inflammation-inflammation that does
      not produce symptoms, such as fever, pain, or skin redness-are at increased risk for
      diabetes. Although the reasons for this are not completely understood, it is known that
      subclinical inflammation exacerbates insulin resistance, which is a cause of diabetes.
      Insulin is a hormone that helps control blood sugar, and when it does not work properly, the
      condition is known as insulin resistance.

      Normal, healthy volunteers between 18 and 45 years old with a body mass index of at least 30
      kg/m2 and who have subclinical inflammation (determined by blood tests) may be eligible for
      this study. Candidates must be non-smokers and must not have an alcohol or drug problem.
      Candidates will be screened with a medical history and physical examination,
      electrocardiogram, and blood and urine tests. Participants will maintain a standard diet and
      undergo tests and procedures during a 14-day inpatient stay at the Phoenix Indian Medical
      Center.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Age: Greater than 18 and less than 45 years.

        Number: 44 completed studies (22 placebo, 22 Salsalate).

        Sex: 22 Males and 22 Females.

        BMI: Greater than or equal to 30 kg.m(2)

        EXCLUSION CRITERIA:

          -  Age below 18 or above 45 years to minimize the risk of glucose clamp.

          -  Diabetes mellitus (as per 75 g OGTT, WHO 1999 criteria)

          -  Cardiovascular disease including: abnormal EKG, personal history of coronary heart
             disease;symptomatic angina pectoris or cardiac insufficiency as defined by NYHA;
             classification as functional class III or IV.

          -  Systolic blood pressure greater than 160mmHG and/or diastolic blood pressure greater
             than 100 mmHg and/or on antihypertensive therapy or resting heart rate greater than 90
             bpm.

          -  Hematological disorder, including prolonged prothrombin time (normal range 10.9-12.9
             sec) and partial thromboplastin time (24-36 sec) and thrombocytopenia (less than
             150,000 mm(3)).

          -  Respiratory disease (including influenza, asthma)

          -  Allergies (including hay fever)

          -  Gastrointestinal (including peptic ulcer), hepatic or renal disease (ALT and AST
             greater than 3-fold above upper limit of normal range, creatinine greater than 1.3
             mg/dl).

          -  Alcoholism, alcohol-induced autonomic neuropathy.

          -  Any endocrinological disorder, including hypopituitarism/pituitary dysfunctions or
             lesions, hypo/hyperthyroidism, insulinoma.

          -  CNS disease

          -  Psychosis or personal history of any psychiatric disorder.

          -  Taking medications within one month prior to beginning the study, including
             medications known to have pharmacological interactions with salicylates or that may
             affect insulin sensitivity and secretion (including salicylates, COX 1 and COX 2
             inhibitors, warfarin, Beta-Blockers, phenothiazines, antidepressants, antiarrhythmic
             drugs, antimuscarinic drugs).

          -  Acute inflammation as assessed by history, physical and laboratory examination
             (subjects with C-reactive protein 2 standard deviations above the population mean will
             not be admitted). The population mean was calculated from subjects admitted at our
             research unit.

          -  Pregnant or lactating females or females on hormonal contraceptives.

          -  History of metabolic acidosis.

          -  Allergy to aspirin, other salicylates, or bleeding diathesis or currently on oral
             anticoagulants.

          -  Any current viral illness.

          -  Active cancer within 5 years prior to screening for the study.

          -  Positive urine drug screening test.

          -  Inability to provide informed consent.

          -  Smokers