Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and triacylglycerol in humans

Although the reduction of serum triacylglycerol concentrations by dietary fish oil is a well-known effect, the exact mechanism of this effect has not been previously studied in human subjects. Therefore, the aim of this study was (i) to examine the effect of short-term fish oil supplementation on blood concentrations of ketone bodies, free fatty acids and triacylglycerol in healthy humans and (ii) to verify whether the observed relationships between these variables would be consistent with reduced lipolysis and/or enhanced hepatic fatty acid oxidation after fish oil supplementation. Twenty subjects (21-23 years, normal liver function tests) were randomly divided into two groups to supplement their usual diet with either 30 g/d of fish oil (n=11) or olive oil (n=9). Venous blood samples were drawn after an overnight fast, before and after 1, 3 and 7 d of fish oil/olive oil supplementation. Blood concentrations of triacylglycerol and free fatty acids decreased consistently after fish oil supplementation; the reduction was already significant after one day of fish oil (P0.10). No significant changes in glucose, insulin or ketone body levels were observed in either group after supplementation. After fish oil, but not after olive oil supplementation, the ratio of blood ketone body levels to free fatty acid levels increased significantly (P<0.05). Furthermore, after fish oil supplementation only, free fatty acid levels were significantly correlated with levels of ketone bodies (day 7 of supplementation: r=0.90, P<0.001) and triacylglycerol (maximum value on day 3: r=0.77, P<0.01). These findings suggest that reduced lipolysis and increased hepatic β-oxidation/ketogenesis may contribute to reduced triacylglycerol levels after ω3 fatty acid supplementation in humans. Turnover studies are needed in order to further quantitate these processes

Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices

The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), SI (Cau r = −0.51, P < 0.01; SA r = −0.41, P < 0.01), Φdynamic (Cau r = −0.41, P < 0.01; SA r = −0.57, P < 0.01), and Φoral (Cau r = −0.61, P < 0.01; SA r = −0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10–10.5 mmol L−1 in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0–2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83–0.98; SA 0.75–0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state

Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial

OBJECTIVE: To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery. SUMMARY BACKGROUND DATA: Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results. METHODS: Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources. RESULTS: Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects. CONCLUSIONS: In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise

Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

Transcription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk allele of the rs7903146 in the TCF7L2 gene increases the risk of type 2 dia

Failing beta-cell adaptation in South Asian families with a high risk of type 2 diabetes

We performed an extended oral glucose tolerance test (OGTT) to investigate the relationship between early and late beta-cell response and type 2 diabetes (T2D) in families of South Asian origin and indigenous Dutch, burdened by T2D. Based on the OGTT, 22 individuals were normoglycemic, 12 glucose intolerant and 23 had T2D in the South Asian families; these numbers were 34, 12 and 18 in the Caucasian families, respectively. The OGTT had 11 blood samplings in 3.5 h for glucose, insulin and C-peptide measurements. Through early and late insulin secretion rate (ISR), the above basal glucose area-under-the-curve after glucose load (glucose disposal) and insulin sensitivity index (ISI), we obtained early and late disposition indices (DI). South Asians on average had lower ISI than Caucasians (3.8 ± 2.9 vs. 6.5 ± 4.7, respectively, P < 0.001), with rapid decline of their early and late DI between normal glucose tolerance versus impaired fasting glucose/impaired glucose tolerance (late DI; P < 0.0001). Adjusted for ISI, age, gender and waist-to-hip ratio, early ISR was significantly associated with glucose disposal in South Asians (β = 0.55[0.186; 0.920]), but not in Caucasians (β = 0.09[-0.257; 0.441]). Similarly, early ISR was strongly associated with late ISR (β = 0.71[0.291; 1.123]; R2 = 45.5 %) in South Asians, but not in Caucasians (β = 0.27[-0.035; 0.576]; R2 = 17.4 %), with significant interaction between ethnicity and early ISR (β = 0.341[0.018; 0.664]). Ordinal regression analyses confirmed that all South Asian OGTT subgroups were homogenously resistant to insulin and solely predicted by early ISR (β = -0.782[-1.922; 0.359], β = -0.020[-0.037; -0.002], respectively), while in Caucasian families both ISI and early ISR were related to glucose tolerance state (β = -0.603[-1.105; -0.101], β = -0.066[-0.105; -0.027], respectively). In South Asian individuals, rapid beta-cell deterioration might occur under insulin resistant conditions. As their early insulin response correlates strongly with both glucose disposal and late insulin response, alterations in beta-cell dynamics may give an explanation to their extreme early onset of T2D, although larger prospective studies are required

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

Whole-body protein turnover in peritoneal dialysis patients: A comparison of the [15N]glycine end product and the [13C]leucine precursor methods

Background. Two well-described methods for measuring whole-body protein turnover (WBPT) are the precursor method using a primed continuous infusion of [1-13C]leucine and the end-product method with a single oral dose of [15N]glycine. We previously measured the effects of amino acid (AA)-containing dialysate on protein anabolism in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using the [1-13C]leucine technique. Here, we examine whether the less invasive [15N]glycine method could also be appropriate for studying nutritional interventions. Methods. We compared the results of WBPT measurements using a single oral dose of [15N]glycine with those obtained with the primed continuous infusion of [1-13C]leucine during AA and glucose (G) dialysis and G-only dialysis in 12 CAPD patients in the fed state. Results. The end-product method showed a wide variation for protein synthesis and breakdown measurements. It did not detect a small but significant increase in protein synthesis with AA-containing dialysate as shown by the precursor method. However, a significant relation was found between both methods for net protein synthesis (i.e. protein synthesis minus breakdown) during AA and G (r = 0.75, P = 0.005) or during G-only dialysis (r = 0.86, P < 0.001). The agreement between the two methods for the net protein balance was good [intra-class correlation coefficient (ICC) = 0.88] with G-only dialysate and moderate (ICC = 0.70) with AA and G dialysate. Conclusion. While the precursor method shows less variation, the more convenient end-product method may be useful in larger groups of selected patients including those on PD