The Relationship of Metabolic Syndrome Traits with Beta-Cell Function and Insulin Sensitivity by Oral Minimal Model Assessment in South Asian and European Families Residing in the Netherlands.

Background. There are different metabolic syndrome traits among patients with different ethnicities. Methods. We investigated this by studying 44 South Asians and 54 Europeans and classified them in three groups according to the occurrence of metabolic syndrome (MetS) and Type 2 Diabetes (T2D). Insulin sensitivity index (ISI), static, dynamic, and total beta-cell responsivity indices (Φ), and disposition indices (DIs) were calculated with the use of oral minimal model (OMM). Results. In both ethnicities, ISI was lower in the subgroup with MetS and T2D as compared to the subgroup without MetS nor T2D (P < 0.004). South Asians without MetS were more insulin resistant than Europeans without MetS (P = 0.033). In the South Asians, ISI, dynamic DI, and static DI were associated significantly (P < 0.006) with high-density lipoprotein cholesterol and triglycerides. In the Europeans, ISI was associated with waist-to-hip ratio (P = 0.005) and systolic and diastolic blood pressure (P < 0.005), while static DI was related to the systolic blood pressure (P = 0.005). Conclusions. MetS was linked with insulin resistance and reduced capacity to handle glucose regardless of ethnicity. ISI and DIs were associated with lipid traits in South Asians and with blood pressure in Europeans suggesting that insulin resistance enhances different metabolic syndrome traits among different ethnicities.

A stable isotope method for in vivo assessment of human insulin synthesis and secretion.

AIMS: In vitro, beta cells immediately secrete stored but readily releasable insulin in response to a rise of glucose. During a prolonged insulin response, this is followed by newly synthesized insulin. Our aim was to develop an in vivo test to determine the ratio between readily available and newly synthesized insulin after a stimulus in humans by labelling newly synthesized insulin. METHODS: A stable isotope tracer of 1.0 g 13C leucine with C-peptide as target peptide was administered 45 min prior to 75 g glucose load of a frequently blood sampled 210-min oral glucose tolerance test (OGTT). Our OGTT also encompassed collection of urine, which has a high content of C-peptide. Prior, the optimal conditions under which the tracer 13C leucine was administered for enrichment of (pre) proinsulin were established. Also, techniques to obtain urinary C-peptide under highly purified circumstances were set up. Our main outcome measure was the stable isotope enrichment of de novo C-peptide, which we related to early plasma insulin and glucose AUC. Twelve healthy Caucasian individuals (M4F8, age 41.8 ± 2.3, BMI 28.3 ± 1.7) with normal glucose tolerance underwent our OGTT. RESULTS: We found that during a 75-g OGTT, newly synthesized insulin contributed approximately 20 % of total insulin secretion. The pattern of isotope enrichment obtained by collecting multiple urine voids was suggestive that the newly synthesized insulin contributes to the late phase of insulin secretion. De novo C-peptide correlated negatively with both early plasma insulin AUC (r = -0.629, P = 0.028) and early plasma glucose AUC (r = -0.605, P = 0.037). CONCLUSIONS: With stable isotope technique added to OGTT, we were able to measure newly synthesized insulin in healthy individuals. This new technique holds the promise that it is feasible to develop a direct in vivo beta cell function test.