- Title
- Curcumin and long-chain omega-3 polyunsaturated fatty acids: effects on glycaemic control and blood lipids
- Creator
- Thota, Rohith N.
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2018
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Type 2 diabetes (T2D) is the most common chronic metabolic disorder resulting from either deficit of insulin secretion and/or action. The transition of normal glucose tolerance to T2D is usually accompanied by a cluster of metabolic risk factors such as low-grade inflammation, oxidative stress, insulin resistance (IR) and dyslipidaemia. IR is one of the marked independent predictors among these cluster of metabolic abnormalities that mediates the transition in high risk states such as obesity, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) to overt T2D. IR also is often associated with decreased clearance of lipids and lipoprotein abnormalities, together representing a greater risk of cardiovascular disease (CVD) in both high risk and individuals with T2D. Several studies have employed lipid ratios, homeostatic models, and anthropometric measures as surrogate markers for predicting IR. However, none of these accounted for both insulin and lipid availability in a single model to predict IR or metabolic syndrome (MetS). Therefore, the first aim of my PhD project, presented in the chapter 3, was to develop a novel marker for IR and MetS that accounts for both insulin and lipid availability in a single model. We proposed and evaluated a novel physiologically relevant marker, InsuTAG (product of fasting insulin and fasting triglycerides) as a predictor of IR and MetS. Cross-sectional analysis of data from the Retirement Health and Life-style Study (RHLS, n=618) showed that InsuTAG is a strong predictor of IR over existing lipid based surrogate markers and anthropometric measures. Receiver operating curve analysis indicated InsuTAG (93%) as the favourable marker for IR over other lipid based surrogate markers and anthropometry measures. Prevalence of MetS was significantly higher in individuals with InsuTAG values above the optimal cut-off value of 11.2. InsuTAG exhibited a greater area under than curve than HOMA-IR for identifying MetS. Together these observations indicate the potential of InsuTAG for predicting IR and MetS. Despite effective lifestyle and pharmacological interventions, the prevalence of T2D is growing at an alarming rate in Australia, in line with global prevalence. Failure of long term compliance to these interventions is a major barrier for their effectiveness in halting the transition to T2D in high risk state individuals, indicating a necessity for alternative effective approach. Given the fact that pathogenesis of T2D is chronic, complex and often involving multiple pathological pathways, use of well tolerated dietary bio-active compounds appears to be a potential strategy for delaying the onset of T2D. Several pre-clinical and in-vitro studies have reported the ability of dietary bio-actives to down regulate multiple pathological mechanisms (chronic low-grade inflammation, IR, oxidative stress and β-cell dysfunction) that are involved in the pathogenesis of T2D. We hypothesised that a combination of two lipid-lowering and anti-inflammatory dietary bio-active compounds, curcumin and long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA), could potentially act in multiple pathways to improve the glycaemic control in individuals at high risk of developing T2D. My second aim, presented in chapter 4, was to evaluate the acute effects of curcumin and/or LCn-3PUFA on glycaemic responses. Therefore, in a randomised, cross over trial we investigated the postprandial glucose and insulin response to a single dose of curcumin and/or LCn-3PUFA in healthy individuals. The glucose levels were reduced by curcumin at as early as 30 min, and the maximum effect was observed at 60 min post meal consumption. Curcumin was found to be effective for lowering the insulin demand to control postprandial glucose levels. Similar results were observed following dietary supplementation with curcumin plus LCn-3PUFA. It was apparent that the postprandial effects on glycaemic control were primarily due to curcumin even in the combined treatment group. Thus, providing basis for long-term supplementation study with curcumin for glycaemic control. In chapter 5, a detailed study protocol for 2x2 factorial placebo controlled, double blinded randomised trial with long term (12 weeks) curcumin and LCn-3PUFA supplementation (COP-D trial) was presented. In chapter 6, we examined the effects of curcumin with or without LCn-3PUFA on glycaemic control and blood lipid levels in people at high risk of T2D. 12 weeks of supplementation with curcumin has effectively reduced the fasting insulin levels and IR in individuals with high risk of T2D. Parallel to these results, both curcumin and LCn-3PUFA were able to reduce the fasting triglycerides and atherogenic index of plasma, however the magnitude of reduction was greater with LCn-3PUFA supplementation. InsuTAG levels were also reduced with curcumin and LCn-3PUFA supplementation. However, this study failed to show any complimentary effects with concurrent administration of curcumin and LCn-3PUFA. Though IR and fasting triglycerides, were effectively reduced by these two bio-actives, we did not find any beneficial effects of curcumin and LCn-3PUFA supplementation on fasting glucose and glycosylated haemoglobin levels. In chapter 7, we designed a study to target commonly prevalent dyslipidaemia with curcumin and/or LCn-3PUFA in individuals with T2D (CALFOR-CVD trial). Participants were randomised to either placebo or curcumin or LCn-3PUFA, or curcumin plus LCn-3PUFA for six weeks. This pilot study has demonstrated that supplementation of curcumin can effectively reduce the TG. Contrasting to the results from chapter 6, magnitude of reduction in triglycerides in this study was higher with curcumin than LCn-3PUFA. Preliminary observations also presented a non-significant, but a noteworthy reduction of 0.5 mmol/L in total cholesterol and LDL-Cholesterol with curcumin supplementation. In line with observations from the COP-D trial, curcumin and LCn-3PUFA did not have any complimentary and/or added benefits. In conclusion, the results presented in this thesis demonstrate that InsuTAG has the potential to predict IR and MetS. This provides a basis for further research to validate InsuTAG with gold standard technique for IR and a longitudinal data analysis to determine the ability of InsuTAG to predict T2D in general population. With regards to the intervention trials, our hypothesis of targeting multiple pathways (IR and dyslipidaemia) in high risk and T2D patients with curcumin and LCn-3PUFA supplementation was successful. However, this thesis failed to provide any evidence on beneficial effects of combining curcumin and LCn-3PUFA for better glycaemic control to delay the onset of T2D. This could partly be due to presence of any unknown interactions between the two bio-actives or may be due to uncertainties in co-administration of curcumin and LCn-3PUFA. Thus, paving a way for further research to investigate beneficial effects with single formulation (curcumin and LCn-3PUFA) for achieving glycaemic control. This thesis constitutes a noted contribution to the research area of bio-markers and novel intervention strategies for T2D, and also presents a set of riddles that provides an extensive scope for future research.
- Subject
- curcumin; impaired fasting glucose; impaired glucose tolerance; insulin resistance; insuTAG; omega-3 polyunsaturated fatty acids; postprandial glucose; randomsied controlled trials; type 2 diabetes; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1389618
- Identifier
- uon:32908
- Rights
- Copyright 2018 Rohith N. Thota
- Language
- eng
- Full Text
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