Targeted Precision Nutrition Strategy To Prevent Chronic Metabolic Diseases

Matsuda Index

The primary objective of this study is to evaluate the effect of a 12-month Metabotype-targeted diet (PN) versus a non-targeted diet (CN) on whole-body insulin sensitivity (Matsuda Index; marker of whole-body fasting and postprandial insulin sensitivity). This will include within group post-hoc testing. The primary outcome measure will be assessed by means of a 7-point oral glucose tolerance test (OGTT), and calculated as follows: \[10,000 / square root of \[fasting plasma glucose (mg/dL) × fasting insulin (mU/L)\] × \[mean glucose (mg/dL) x mean insulin (mU/L)\]\].

Glucose tolerance

Optimal (PN) versus sub-optimal (CN) diet, including within group post-hoc testing. Determined by 2-hour plasma glucose values (mmol/L) during an oral glucose tolerance test (OGTT).

Disposition Index (DI)

Optimal (PN) versus sub-optimal (CN) diet, including within group post-hoc testing. The Disposition Index is a composite marker of first phase insulin secretion and insulin sensitivity during a 2-hour 7-point oral glucose tolerance test (OGTT). Disposition index will be calculated as follows: \[Insulin sensitivity index (ISI) \* (AUC30 min insulin / AUC30 min glucose)\], where AUC30 min is the area under the curve between 0 and 30 minutes of the OGTT for insulin (pmol/l) and glucose (mmol/l), respectively, and ISI is defined as: \[10,000 ÷ square root of (fasting plasma glucose (mmol/l) x fasting insulin (pmol/l)) x (mean glucose (mmol/l) x mean insulin (pmol/l))\]. Higher values represent a higher insulin sensitivity.

HOMA-IR

Optimal (PN) versus sub-optimal (CN) diet, including within group post-hoc testing. HOMA-IR is a fasting measure for insulin resistance, which can be calculated as follows: HOMA-IR = (Fasting plasma glucose (mmol/L) \* Fasting Insulin (mU/L)) / 22.5. Higher values represent a higher degree of insulin resistance. Determined in plasma during a 2-hour, 7-points oral glucose tolerance test (OGTT).

Muscle insulin sensitivity (MISI)

Optimal (PN) versus sub-optimal (CN) diet, including within group post-hoc testing. Determined during a 2-hour, 7-point oral glucose tolerance test (OGTT). The muscle insulin sensitivity index (MISI) will be calculated as follows: MISI (mmol/l/min/pmol/l) = (dG/dt) / mean plasma insulin concentration (pmol/l) during OGTT. Here, dG/dt is the rate of decay of plasma glucose concentration (mmol/L) during the OGTT, calculated as the slope of the least square fit to the decline in plasma glucose concentration from peak to nadir. Higher values represent higher muscle insulin sensitivity.

Baseline characteristics

Baseline characteristics (age, sex, ethnicity, lifestyle, socioeconomic status, medical history, medication use, family composition and history of T2DM, and menopausal state) will also be recorded, for the purpose of screening, metabolic classification and potential post-hoc analysis.

Metabotype cluster

The Metabotype cluster (one of three possible groups for each sex) will be assessed at three time points. Namely, baseline, at 6 months and at 12 months. To determine the Metabotype, several outcome measures derived from the OGTT and anthropometrics will be aggregated by the described classification algorithm (see study description).

Capillary Blood Samples (CBS)

Capillary Blood Samples (CBS) samples will be obtained via fingerpick parallel to the venous fasting blood sample collected during the oral glucose tolerance test (OGTT). These samples will be analyzed to explore the feasibility of developing a simplified classification algorithm for determining Metabotype, providing a potentially more accessible and less invasive diagnostic approach. CBS will only be obtained in a sub-group of participants at the MUMC+, none will be obtained from participants at WUR.