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

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance
• Interventions: Dietary Supplement: Zinc supplements; Dietary Supplement: Omega 3 supplements; Dietary Supplement: Placebo supplements

• Registration Number: NCT01505803
• Lead Sponsor: University of Sydney

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2011-10-25
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2012-01
• Study First Submitted QC: 2012-01-05
• Last Update Submitted: 2012-01-05
• Study First Posted: 2012-01-09
• Last Update Posted: 2012-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 48

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zinc supplement	Zinc supplements	-
Zinc supplement	Placebo supplements	-
Omega 3 supplement	Omega 3 supplements	-
Omega 3 supplement	Placebo supplements	-
Zinc and omega 3 supplements	Zinc supplements	-
Zinc and omega 3 supplements	Omega 3 supplements	-
Placebo supplement	Placebo supplements	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Zinc transporter mRNA expression in peripheral blood mononuclear cells	12 weeks
Plasma zinc	12 weeks
Plasma fatty acids	12 weeks

Trial Locations

Locations (1)

University of Sydney; 🇦🇺 Sydney, New South Wales, Australia