J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Review

Volume 7, Number 1, January 2015, pages 8-12

Effects of Intake of Fish or Fish Oils on the Development of Diabetes

**Table 1.** Clinical Trials and Prospective Cohort Studies to Show Effects of Intake of Fish or Fish Oils on the Development of Diabetes
Authors	Study design	Subjects studied	Results/conclusions
ALA: α-linolenic acid; CI: confidence interval; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FA: fatty acids; PUFA: polyunsaturated fatty acids; RR: relative risk.
Giacco et al [14]	Healthy individuals were randomly assigned to monounsaturated fats and the other rich in saturated fats for 3 months. Within each group there was a second randomization to fish oil (n-3 fatty acids 3.6 g/day) or placebo.	162 healthy individuals. Performed in Sweden.	A moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance.
Griffin et al [15]	In a randomized, parallel design, four diets providing 6% of energy as PUFA with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1 for 6 months were compared. The diets were enriched in ALA, EPA and DHA, or both.	258 subjects aged 45 - 70 years old. Performed in UK.	Decreasing the n-6:n-3 does not influence insulin sensitivity.
Brostow et al [16]	To examine the association between total omega-3 FA, marine omega-3 (EPA, DHA), nonmarine omega-3 (ALA), and omega-6 FA and omega-6:omega-3 ratio and risk of type 2 diabetes.	43,176 Chinese men and women free of chronic disease, aged 45 - 74 years old, in the Singapore Chinese Health Study.	Omega-3 FA from marine sources were not associated with diabetes risk.
Villegas et al [17]	A prospective population-based cohort study. A Cox regression model was used to evaluate the association of fish, shellfish, and long-chain n-3 FA with risk of type 2 diabetes.	51,963 Chinese men and 64,193 Chinese women free of type 2 diabetes, cardiovascular diseases, and cancer.	An inverse association between fish and shellfish intake and type 2 diabetes in women was found.
Djousse et al [18]	A prospective study. Incident type 2 diabetes was self-reported and validated primarily through the collection of supplementary information from participants. Information on omega-3 and fish intakes was obtained by using a validated food-frequency questionnaire. Cox proportional hazard models were used to estimate adjusted RR.	36,328 women (mean age: 54.6 years old) who participated in the Women’s Health Study and who were followed from 1992 to 2008. Performed in USA.	An increased risk of type 2 diabetes with the intake of long-chain omega-3 FA, especially with higher intakes (≥ 0.20 g omega-3/day or ≥ 2 servings of fish/day).
Van Woudenbergh et al [19]	A population-based cohort. Hazard ratios (RR) with 95% CIs were used to examine risk associations adjusted for age, sex, lifestyle, and nutritional factors.	4,472 Dutch participants aged ≥ 55 years old without diabetes.	A beneficial effect of total fish, type of fish, or EPA and DHA intake on the risk of type 2 diabetes was not observed.
Djousse et al [20]	Plasma phospholipid n-3 FA were measured by using gas chromatography, and incident diabetes was ascertained by using information on hypoglycemic agents and serum glucose. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks.	3,088 older men and women (mean age: 75 years old) from the Cardiovascular Health Study (1992 - 2007). Performed in USA.	Long-chain n-3 FA were not associated with a higher incidence of diabetes.

Table 1. Clinical Trials and Prospective Cohort Studies to Show Effects of Intake of Fish or Fish Oils on the Development of Diabetes

Authors

Study design

Subjects studied

Results/conclusions

ALA: α-linolenic acid; CI: confidence interval; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FA: fatty acids; PUFA: polyunsaturated fatty acids; RR: relative risk.

Giacco et al [14]

Healthy individuals were randomly assigned to monounsaturated fats and the other rich in saturated fats for 3 months. Within each group there was a second randomization to fish oil (n-3 fatty acids 3.6 g/day) or placebo.

162 healthy individuals. Performed in Sweden.

A moderate supplementation of fish oil does not affect insulin sensitivity, insulin secretion, beta-cell function or glucose tolerance.

Griffin et al [15]

In a randomized, parallel design, four diets providing 6% of energy as PUFA with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1 for 6 months were compared. The diets were enriched in ALA, EPA and DHA, or both.

258 subjects aged 45 - 70 years old. Performed in UK.

Decreasing the n-6:n-3 does not influence insulin sensitivity.

Brostow et al [16]

To examine the association between total omega-3 FA, marine omega-3 (EPA, DHA), nonmarine omega-3 (ALA), and omega-6 FA and omega-6:omega-3 ratio and risk of type 2 diabetes.

43,176 Chinese men and women free of chronic disease, aged 45 - 74 years old, in the Singapore Chinese Health Study.

Omega-3 FA from marine sources were not associated with diabetes risk.

Villegas et al [17]

A prospective population-based cohort study. A Cox regression model was used to evaluate the association of fish, shellfish, and long-chain n-3 FA with risk of type 2 diabetes.

51,963 Chinese men and 64,193 Chinese women free of type 2 diabetes, cardiovascular diseases, and cancer.

An inverse association between fish and shellfish intake and type 2 diabetes in women was found.

Djousse et al [18]

A prospective study. Incident type 2 diabetes was self-reported and validated primarily through the collection of supplementary information from participants. Information on omega-3 and fish intakes was obtained by using a validated food-frequency questionnaire. Cox proportional hazard models were used to estimate adjusted RR.

36,328 women (mean age: 54.6 years old) who participated in the Women’s Health Study and who were followed from 1992 to 2008. Performed in USA.

An increased risk of type 2 diabetes with the intake of long-chain omega-3 FA, especially with higher intakes (≥ 0.20 g omega-3/day or ≥ 2 servings of fish/day).

Van Woudenbergh et al [19]

A population-based cohort. Hazard ratios (RR) with 95% CIs were used to examine risk associations adjusted for age, sex, lifestyle, and nutritional factors.

4,472 Dutch participants aged ≥ 55 years old without diabetes.

A beneficial effect of total fish, type of fish, or EPA and DHA intake on the risk of type 2 diabetes was not observed.

Djousse et al [20]

Plasma phospholipid n-3 FA were measured by using gas chromatography, and incident diabetes was ascertained by using information on hypoglycemic agents and serum glucose. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks.

3,088 older men and women (mean age: 75 years old) from the Cardiovascular Health Study (1992 - 2007). Performed in USA.

Long-chain n-3 FA were not associated with a higher incidence of diabetes.

**Table 2.** Meta-Analyses to Show Effects of Intake of Fish or Fish Oils on the Development of Diabetes
Authors	Study design	Subjects studied	Results/Conclusions
CI: confidence interval; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FA: fatty acids; PUFA: polyunsaturated fatty acids; RCT: randomized controlled trial.
Akinkuolie et al [21]	To systematically review the effect of n-3 PUFA on insulin sensitivity by conducting a meta-analysis of available RCTs. MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov from the beginning of each database until October 2010 were used.	Eleven RCTs (n = 618) were eligible for inclusion in the analysis.	This meta-analysis is consistent with a lack of n-3 PUFA effects on insulin sensitivity.
Wallin et al [22]	To find the evidence on the association between fish consumption, dietary long-chain n-3 FA, and risk of type 2 diabetes, studies were identified by searching the PubMed and EMBASE databases through December 15, 2011 and by reviewing the reference lists of retrieved articles.	Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included.	For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02 - 1.09), 1.03 (0.96 - 1.11), and 0.98 (0.97 - 1.00) combining US, European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 FA, the corresponding summary estimates were 1.17 (1.09 - 1.26), 0.98 (0.70 - 1.37), and 0.90 (0.82 - 0.98), respectively.
Zheng et al [23]	A systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with type 2 diabetes risk.	PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 were used to identify relevant studies.	Marine n-3 PUFA have beneficial effects on the prevention of type 2 diabetes in Asian populations.
Wu et al [24]	Systematically search for multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of diabetes.	Sixteen studies including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident diabetes.	The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA + DHA on development of diabetes.

Table 2. Meta-Analyses to Show Effects of Intake of Fish or Fish Oils on the Development of Diabetes

Authors

Study design

Subjects studied

Results/Conclusions

CI: confidence interval; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; FA: fatty acids; PUFA: polyunsaturated fatty acids; RCT: randomized controlled trial.

Akinkuolie et al [21]

To systematically review the effect of n-3 PUFA on insulin sensitivity by conducting a meta-analysis of available RCTs. MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov from the beginning of each database until October 2010 were used.

Eleven RCTs (n = 618) were eligible for inclusion in the analysis.

This meta-analysis is consistent with a lack of n-3 PUFA effects on insulin sensitivity.

Wallin et al [22]

To find the evidence on the association between fish consumption, dietary long-chain n-3 FA, and risk of type 2 diabetes, studies were identified by searching the PubMed and EMBASE databases through December 15, 2011 and by reviewing the reference lists of retrieved articles.

Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included.

For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02 - 1.09), 1.03 (0.96 - 1.11), and 0.98 (0.97 - 1.00) combining US, European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 FA, the corresponding summary estimates were 1.17 (1.09 - 1.26), 0.98 (0.70 - 1.37), and 0.90 (0.82 - 0.98), respectively.

Zheng et al [23]

A systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with type 2 diabetes risk.

PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 were used to identify relevant studies.

Marine n-3 PUFA have beneficial effects on the prevention of type 2 diabetes in Asian populations.

Wu et al [24]

Systematically search for multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of diabetes.

Sixteen studies including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident diabetes.

The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA + DHA on development of diabetes.