Influence of Micronutrients on Type 2 Diabetes

Type 2 diabetes (T2D) is a chronic illness caused by impaired insulin secretion or insulin resistance, which leads to impaired glucose and lipid metabolism (1).  Type 2 diabetes accounts for 90-95 percent of all cases of diabetes (2). In 2013, around 8.3 percent of the global population was thought to have T2D (3).

Type 2 diabetes develops much more slowly than Type 1 and is often difficult to spot. It usually only affects adults over the age of 40, except in the case of Afro-Caribbean or South Asian races where the condition is often seen from the age of 25. The incidence of T2D is also considerably higher in these ethnic groups. There is a strong genetic component of T2D, meaning the risk of onset increases 2 to 6 fold if your parents or a sibling already suffer from the condition. Typical symptoms include longer than usual wound healing, tiredness and blurred vision. The higher than normal blood levels of glucose provide a perfect breeding ground for pathogenic micro-organisms.

T2D is associated with other medical disorders such as dyslipidaemia, obesity and hypertension, which are often together termed metabolic syndrome or syndrome X.

Currently, there is no cure for either Type 1 or Type 2 diabetes, but it can be treated by administration of insulin, consuming a healthy diet and through regular exercise.

Vitamin D

A 2011 population study carried out over five years in Australia indicated that people with low serum levels of the bioactive form of vitamin D (25 hydroxy vitamin D) may have an increased risk of T2D (4). Recent studies (5) have also provided evidence that high serum vitamin D levels may protect against diabetes, namely improved insulin sensitivity, improved beta cell function and stabilized HbA1c levels (a risk factor for T2D).

A new study from Australia (6) examined data from 3,393 Australian adults that participated in the 2009 – 2010 Victoria Health Monitor survey. The researchers found a clear, significant association between higher serum 25 hydroxy vitamin D levels and lower plasma fasting glucose (FPG) and Hb1Ac values, even after adjustments for social, dietary and metabolic syndrome factors were taken into account.

Vitamin E

While observational human studies indicate that vitamin E is protective against cardiovascular disease, intervention trials in the general population have not shown any effect. In general, subjects with Type 2 diabetes have lower vitamin E levels compared to controls. The ICARE study (7) gave diabetic patients a daily dose of 400 IU of vitamin E. The study recorded each participants Haptoglobin (Hp) genotype. Haptoglobin performs the important role of scavenging free haemoglobin from the blood.  The study demonstrated that diabetic carriers of the genotype Hp 2-2 had a much higher chance of death due to cardiovascular events than other genotypes, but that the risk could be normalized by a daily intervention of 400 IU of vitamin E. Hp2-2 diabetics usually exhibit increased levels of markers of oxidative stress than other genotypes, so the potent anti-oxidant effect of vitamin E provides a plausible protective mechanism.  The effect was confirmed in post-hoc retrospective subgroup analysis of the HOPE and WHS studies (8)

Coenzyme Q10

Diabetic peripheral neuropathy (DPN) is the most common complication in the more advanced stages of both Type 1 and Type 2 diabetes. DPN initially causes severe pain, which is replaced by loss of sensation as the condition progresses. Recent animal studies have indicated that that early intervention with Coenzyme Q10 may reduce the extent and progression of DPN in diabetics (9).

Marine Omega-3 Fatty Acids

Diabetic retinopathy occurs when excess glucose causes structural changes to blood vessels of the retina at the back of the eye. It is the most common cause of vision loss among older people with Type 1 and Type 2 diabetes, and the leading cause of vision impairment and blindness among working-age adults (10). In the early stages of the condition, there is a narrowing of the retinal arteries associated with reduced retinal blood flow and dysfunction of the neurons of the inner retina, followed in later stages by changes in the function of the outer retina, which causes some initial minor loss of visual acuity. As the condition progresses, the basement membrane of the retinal blood vessels thickens, capillaries degenerate (leading to loss of blood flow), and microscopic balloon-like structures (aneurysms) jut out from the capillary walls causing advanced dysfunction and degeneration of the neurons and glial cells of the retina (11,12). At this stage, there is considerable loss of vision, which can progress to total blindness.

A recent article (13) provides some initial evidence that regular intake of marine omega-3 fatty acids can help delay the onset of diabetic retinopathy in older Type 2 diabetics. The observational study features a subset of data from the PREDIMED randomized controlled trial in Spain (14) where the participants were assessed for a series of clinical end points after following various forms of the Mediterranean diet. The use of a detailed validated dietary questionnaire enabled a realistic assessment of the intake of marine omega fatty acids. The subset cohort consisted of 3,482 older persons with Type 2 diabetes and an average age of 67.5 years. At the follow-up period of an average of 6 years, 0.17 percent of the group consumed more than 500 mg per day of marine omega-3 fatty acids developed diabetic retinopathy compared with 0.49 percent for the group that consumed less than 500 mg per day. The European Food Safety Authority (EFSA) permits a health claim of “maintenance of normal vision” to be used on foodstuffs that contribute to intakes of 250 mg/day or more of the marine omega-3 fatty acid docosahexaenoic acid (DHA) (15).

Diabetic dyslipidaemia is characterized by hypertriglyceridaemia and is considered to be a major predisposing factor for various macrovascular complications. A study (16) comprised of 105 recently diagnosed diabetics demonstrated that a twice daily intervention of 500 mg metformin and 1 g EPA and DHA for 12 weeks was able to dramatically reduce blood triglyceride levels and restore the blood lipid balance.

A very recent meta-analysis (17) has revealed a complex relationship between marine omega-3 intake and Type 2 diabetes. It found a general reduction in risk of T2D in adult Asian populations but an increased risk for adult Western populations with an intake of 430 mg per day of EPA, DPAn-3 and DHA. However, higher doses of 1 g per day or more were found to be protective.

There is an increasing body of evidence that supports the role micronutrient status can have on symptoms of this distressing disease.

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REFERENCES

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2. American Diabetes Association; “Diagnosis and Classification of Diabetes mellitus”; Diabetes Care 2014; 37 (suppl 1): S81-90.
3. Guariguarta L; “Contribute data to the 6^th edition of the IDF Diabetes Atlas”; Diabetes Res Clin Prac 2013; 100; 280-1.
4. Gagnon C, Lu ZX, Dunstan DW et al.; “Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study)”; Diabetes Care 2011; 34(5): 11133-1135.
5. Nagpal J, Pande JN & Bhartia A; “A double-blind, randomized, placebo-controlled trial of the short-term effect of Vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men”; Diabet Med 2009: 26(1): 19-27.
6. Pannu PK, Piers LS, Soares MJ et al.; “Vitamin D status is inversely associated with markers of risk for type 2 diabetes: A population based study in Victoria, Australia”; PLoS ONE 2017, 12(6), 1-14.
7. Blum S, Vardi M, Brown JB et al., “Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype”; Pharmacogenomics. 2010; 11(5): 675–684.
8. Vardi M, Blum S and Levy AP; “Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus — natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature”; Eur J Intern Med. 2012; 23(7): 628–632.
9. Shi T-J S, Zhang M-D, Hugo Zeberg H et al.; “Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db−/db− mouse, a type 2 diabetes model”; PNAS 2013; 110(2): 690–695.
10. National Eye Institute; “Facts About Diabetic Eye Disease”;  https://nei.nih.gov/health/diabetic/retinopathy .
11. Xu H, Curtis T & Stit A; "Pathophysiology and Pathogenesis of Diabetic Retinopathy": Diapedia 13 August 2013. 7104343513 (14). doi:10.14496/dia.7104343513.14..
12. Pardianto G; et al. (2005). "Understanding diabetic retinopathy". Mimbar Ilmiah Oftalmologi Indonesia. 2: 65–6
13. Chew EY, “Dietary Intake of Omega-3 Fatty Acids from fish and risk of diabetic retinopathy”; JAMA June 6, 2017; 317 (21):2226-7.
14. Sala-Vila A,  Díaz-López A,  Valls-Pedret C  et al.; “Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes Prospective Investigation From the PREDIMED Trial”:  JAMA Ophthalmol 2016; 134(10); 1142-1149.
15. Official Journal of the European Union 25.2.12, Commission regulation (EU) 432/2012 of 16th May 2012.
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17. Chen C, Yang Y, Yu X et al.; “Association between omega‐3 fatty acids consumption and the risk of type 2 diabetes: A meta‐analysis of cohort studies”;  J Diabetes Investig. 2017 Jul; 8(4): 480–488.