Nutritional Supplementation and Insulin Sensitivity

Type 2 diabetes mellitus (T2DM) is a progressive disease and early intervention and prevention strategies are therefore very important. An important early hallmark in the development of T2DM is insulin resistance. Since the majority of postprandial glucose disposal occurs in skeletal muscle, improving muscle insulin sensitivity will thus have a major impact on disease prevention. Abdominally obese men and women have an increased risk to develop T2DM, and are also characterized by an impaired vascular function. This may hamper proper delivery of insulin, glucose and oxygen to muscles, thereby contributing to - and possibly causing - muscle insulin resistance. Earlier it has been shown that supplementation with L- arginine improves vascular function by improving nitric oxide (NO) bioavailability. These NO- mediated beneficial effects on vascular function may improve delivery of insulin, glucose and oxygen to the muscle tissue, thereby improving muscle insulin sensitivity and mitochondrial function. However, the doses needed of this amino acid cannot be provided by regular diets or supplements, also due to the bitter taste of L-arginine. Alternatively, smaller amounts of L- arginine with a specific combination of other nutritional components (i.e. nitrate and nitrite), which are already part of the regular diet and support alternative pathways to improve NO- mediated vascular function, may also induce beneficial effects. The investigators now hypothesize that in abdominally obese adults with impaired fasting glucose concentrations L-arginine combined with nitrate/nitrite increases muscle insulin sensitivity.


Eligibility Criteria:
Inclusion Criteria:

* Aged between 50-70 years
* Men and postmenopausal (two or more years after last menstruation) women
* Waist circumference for men 3 102 cm and for women 3 88 cm (abdominally obese)
* Impaired fasting glucose concentrations (between 5.6 - 7.0 mmol/L in accordance with the American Diabetes Association guidelines for prediabetes) at two screening visits
* Fasting serum total cholesterol \< 8.0 mmol/L
* Stable body weight (weight gain or loss \< 3 kg in the past three months)
* Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
* No difficult venipuncture as evidenced during the screening visit
* Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue-scraping during the study

Exclusion Criteria:

* Current smoker, or smoking cessation \< 12 months
* Diabetic patients
* Familial hypercholesterolemia
* Abuse of drugs
* More than 3 alcoholic consumptions per day
* Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators
* Use of anticoagulant drugs or drugs to treat blood pressure, lipid/glucose metabolism
* Use of an investigational product within another biomedical intervention trial within the previous 1-month
* Intolerance or allergy to the ingredients of the intervention products
* Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
* Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident