Now showing 1 - 3 of 3
  • Publication
    Uncovering Factors Related to Pancreatic Beta-Cell Function
    Aim: The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Methods: Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. Results: Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. Conclusions: Waist-to-hip ratio and RA index were identified as significant modulators of beta-cell function. The ability of the RA index to modulate insulin secretion was confirmed in mechanistic studies. Future work should identify strategies to alter the RA index.
    Scopus© Citations 4  399
  • Publication
    Sexual dimorphism, age, and fat mass are key phenotypic drivers of proteomic signatures
    Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.
    Scopus© Citations 13  405
  • Publication
    Variable glycemic responses to intact and hydrolysed milk proteins in overweight and obese adults reveal the need for precision nutrition
    Background: Dietary modifications can contribute to improved pancreatic beta cell function and enhance glycemic control. Objective: The objectives of this study were to 1) investigate the potential of milk protein hydrolysates to modulate postprandial glucose response, 2) assess individual responses, 3) explore the inter and intra-individual reproducibility of the response. Methods: A 14-day randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B (CH-A and CH-B) consumed in random order with a 2-day washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 male/ 9 female) aged 50 ± 8 y with a body mass index of 30.2 ± 3.1 kg/m2 were recruited. Primary outcome was glucose levels assessed at 15 min intervals using glucose monitors. Results: Repeated measures-ANOVA revealed that for breakfast there was a significant difference across the three treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to CH-B in comparison to intact caseinate (P = 0.039). However, despite this significant difference further examination revealed that only three out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients (ICCs) were obtained for glucose response to study meals (ICC: 0.892 for breakfast with intact caseinate). The inter-individual coefficient of variations (CVs) were higher than intra-individual CVs. Mean inter- and intra-individual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion: Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response, however at an individual level only three participants were classified as responders, highlighting the need for precision nutrition. Exploration of high inter-individual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach.
    Scopus© Citations 9  165