The Effect of a Nutritional Supplement in Individuals With Type 2 Diabetes Mellitus: a Pilot Study

Study Overview
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Brief Summary
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Diabetes Mellitus (DM) is a major risk factor for cardiovascular disease, with 50% of diabetes-associated deaths being attributed to cardiovascular complications. The characterising features of DM include: the presence of chronic hyperglycaemia, consequent upon decreased secretion or action of insulin; dyslipidaemia; and enhanced levels of oxidative stress and inflammation. Zinc and omega 3 polyunsaturated fatty acids have been shown to influence each of these outcomes via several mechanisms. This pilot study will examine the effect of nutritional supplements containing zinc and omega 3 on these outcomes in a population with type 2 DM.

Detailed Description
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The prevalence of type 2 DM and related-complications continues to increase. Diet is a significant factor in the aetiology of type 2 DM. Intakes of zinc and omega 3 fatty acids may modulate glycaemic control, lipid metabolism, and inflammatory processes in the disease. Zinc is involved in many biological processes that include enzyme action, stabilisation of cell membranes, regulation of gene expression, and cell signalling. Zinc supplementation has been demonstrated to improve glycaemic control in both animals and humans. The normalising effect of zinc on glucose homeostasis may relate to its involvement in insulin metabolism. Zinc functions in the synthesis, storage, secretion, and action of insulin. Omega-3 also enhances glycaemic control and dietary supplementation with omega-3 polyunsaturated fatty acids has been shown to improve insulin sensitivity in subjects with DM. Both zinc and omega-3 function to mediate lipid metabolism. Zinc supplementation has been found to be associated with a beneficial increase in HDL cholesterol concentrations in individuals with type 2 DM. The mechanism may again involve insulin, which has been proposed as an independent predictor of plasma HDL. Omega-3 directly activates transcription factors that regulate lipid metabolism and is known to decrease serum triglyceride levels in DM. Zinc appears to beneficially impact oxidative stress-related parameters in DM via a range of mechanisms, including the regulation of copper,zinc superoxide dismutase, metallothionein, NF-κB and nitric oxide signaling. The purpose of this pilot study is to explore the effect of zinc and omega 3 supplementation on hyperglycaemia, dyslipidaemia, chronic inflammation, and oxidative stress in a population with type 2 DM. This study will recruit 48 postmenopausal women with type 2 DM. Participants will be randomly allocated to one of 4 groups for a period of 12 weeks: placebo, zinc, omega 3, or zinc + omega 3 supplementation. Usual dietary intake will be assessed before and after the trial period using 2-day estimated food records, which will be checked by a research dietitian. Blood samples will be collected from all participants at the start of the intervention (week 0) then at 4 weekly intervals (weeks 4, 8, 12) by qualified phlebotomists. Blood samples will be analysed for plasma zinc, plasma lipids and fatty acids, markers of inflammation and oxidative stress, and indicators of glycaemic control. An aliquot of blood will also be used for the measurement of zinc transporter mRNA levels utilising real-time quantitative PCR techniques.

Official Title
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The Effect of a Nutritional Supplement on Cardiometabolic, Inflammatory, and Oxidative Stress Markers in Individuals With Type 2 Diabetes Mellitus: a Pilot Study

Conditions
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Diabetes Mellitus, Type 2, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Zinc supplements
* Dietary Supplement: Omega 3 supplements
* Dietary Supplement: Placebo supplements


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, postmenopausal Type 2 diabetes (controlled by diet and lifestyle; or oral hypoglycaemic medication (i.e. metformin) for not more than 7 years) Normal Glomerular Filtration Rate (GFR) and normal microalbumin/creatine ratio No nutritional supplements in the 6 weeks prior to the trial & continuing through the trial period Non-smoking Exclusion Criteria: Diagnosed with current major illness (renal disease, significant cardiovascular disease, gastrointestinal disorders, cancer, or other significant disorder likely to interfere with zinc metabolism) Taking medications that are likely to interfere with zinc metabolism

Ages Eligible for Study
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Minimum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zinc supplement<br> | Dietary Supplement: Zinc supplements<br>* Participants will receive 40 mg of zinc each day for 12 weeks.<br>Dietary Supplement: Placebo supplements<br>* Participants will receive placebo supplements each day for 12 weeks.<br>|
| Active Comparator: Omega 3 supplement<br> | Dietary Supplement: Omega 3 supplements<br>* Participants will receive 2 g of omega 3 fatty acids each day for 12 weeks.<br>Dietary Supplement: Placebo supplements<br>* Participants will receive placebo supplements each day for 12 weeks.<br>|
| Active Comparator: Zinc and omega 3 supplements<br> | Dietary Supplement: Zinc supplements<br>* Participants will receive 40 mg of zinc each day for 12 weeks.<br>Dietary Supplement: Omega 3 supplements<br>* Participants will receive 2 g of omega 3 fatty acids each day for 12 weeks.<br>|
| Placebo Comparator: Placebo supplement<br> | Dietary Supplement: Placebo supplements<br>* Participants will receive placebo supplements each day for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) |  | 12 weeks | 
| Glycaemic control (glucose, insulin, HbA1c) |  | 12 weeks | 
| Inflammation & oxidative stress (CRP, TNF-α, IL-1, IL-2, IL-6, IL-10 F2 isoprostanes, NF-κB, MPO, other) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zinc transporter mRNA expression in peripheral blood mononuclear cells |  | 12 weeks | 
| Plasma zinc |  | 12 weeks | 
| Plasma fatty acids |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Dietary supplements, Hyperglycemia, Insulin resistance, Dyslipidemia, Inflammation, Oxidative stress, Zinc, Omega 3