Diabetes (diabetes mellitus) is an endocrine disorder characterized by insulin insufficiency (type 1 diabetes) or insulin resistance (type 2 diabetes) and chronically raised blood sugar levels. Vascular diseases (diabetic angiopathies) play a deciding role in the course of the disease. Diabetics are more likely to suffer a heart attack or stroke (macroangiopathy), and almost all sufferers are affected by damage to the small blood vessels (microangiopathy), the eyes (retinopathy), kidneys (nephropathy) or nerves (neuropathy). The metabolic status of diabetes sufferers is characterized by permanent oxidative stress due to impaired carbohydrate and lipid metabolism. Early and sustained sufficient intake of antioxidant micronutrients that regulate carbohydrate metabolism is therefore particularly important in the prevention of diabetes.
Due to the high level of oxidative stress, mitochondrial dysfunction and inflammation of the blood vessels, there may be a greater need for micronutrients where a diabetic disorder exists. A deficient supply of nutrients can exacerbate the condition. Targeted consumption of micronutrients can help improve metabolic control, optimize treatment and reduce the risk of developing diabetic complications. Key to this is an adequate intake of B vitamins, which protect the nerve cells, vitamins C and E, which can help prevent vascular damage, and magnesium, which promotes normal glucose metabolism. Further, the lipid -lowering and antithrombotic properties of omega-3 fatty acids and trace elements that improve insulin sensitivity can all be beneficial in primary and secondary prevention.
As coenzymes the B vitamins play a central role in carbohydrate, protein and lipid metabolism. A diabetic metabolic status is characterized by both higher requirements and increased renal elimination of B vitamins, especially when the diabetes is not well managed. Studies indicate that the majority of type 1 and type 2 diabetics have inadequate supplies of vitamin B1 and impaired thiamine metabolism (1). A tissue-specific vitamin B1 deficiency (e.g., in the kidneys) can increase the risk of vascular complications (e.g., nephropathy) (2), and ensuring sufficient provision should be a focus of therapy. Further, vitamin B1 – as well as vitamins B6 and B12 – supports nervous system functions and helps prevent diabetic neuropathies. The fat-soluble precursor of vitamin B1 (benfotiamine) is used, sometimes in combination with alpha-lipoic acid, to treat diabetic neuropathies (3). In this context an improved energy supply for axonal transport and the increased synthesis of transport proteins are under discussion as potential mechanisms involved in the regeneration of nerve cells. Moreover, benfotiamine and vitamin B6 inhibit the increased glycosylation of proteins associated with elevated blood sugar levels. In studies with patients suffering from a diabetes-related impairment of the peripheral nervous system (polyneuropathy), supplementation with benfotiamine significantly improved symptoms of pain sensation, nerve conduction velocity and vibration sensation compared to placebo (4).
A lack of folic acid and/or vitamin B12 leads to impaired metabolism of the amino acid methionine and is frequently accompanied by elevated plasma homocysteine concentrations. Elevated homocysteine levels are regarded as an independent risk factor for stroke, heart attack, dementia and macular degeneration. Compared to non-diabetics, diabetics are three to five times more likely to suffer a stroke. In addition, patients with type 2 diabetes, elevated homocysteine levels and vitamin B12 deficiency are at substantially greater risk of developing diabetic eye damage (retinopathy). This can range from visual impairment to complete blindness (5). A lack of vitamin B12 can also considerably increase the risk of developing diabetic neuropathies. In older people with elevated homocysteine levels the rate of brain atrophy was clearly slowed by regular intake of vitamins B12, B6 and folic acid (6). Regular administration of vitamin B12 is often indicated for diabetes patients being treated with metformin to prevent a medication-induced deficiency. In one study with type 2 diabetics, treatment with metformin led to a dip in cognitive performance which improved again when treatment was accompanied by supplementation with vitamin B12 and calcium (7).
In high (pharmacological) doses, vitamin B3 has a preventive effect on the manifestation or progression of type 1 diabetes where there is still adequate residual function of insulin -producing islet cells (beta cells). The vitamin inhibits the destruction and enhances regeneration of pancreatic beta cells (8). Hence beta-cell dysfunction can be reduced and insulin sensitivity and glucose utilization improved. Moreover, vitamin B3 appears to reduce the glycosylation of proteins and hemoglobin (HbA1C).
Vitamin C and E
Metabolic disorders that occur with diabetes, such as chronically elevated blood sugar levels (hyperglycemia), a disorder of lipid metabolism (raised fatty acid, triglyceride and LDL concentrations) and insulin resistance, cause increased production of reactive oxygen species (ROS), which trigger structural and functional changes to the lining of the blood vessels through activation of intracellular signaling cascades, and hence lead to the development of atherosclerotic lesions. The developing oxidative stress is inevitably linked to reduced availability of vasodilatory nitrogen monoxide and impaired functioning of the lining of the blood vessels, the endothelium. Parallel to these processes in the vessel linings, blood platelets (thrombocytes) are activated inside or on the surface of the vessels. These encourage the formation of blood clots and increase the risk of thrombosis or even a heart attack or stroke. Oxidative stress, as indicated by elevated levels of cell-damaging products of lipid peroxidation, and a raised rate of protein glycosylation play a central role in the onset of diabetic micro- and macropathies (9).
In diabetics, increased oxidative stress can be demonstrated directly after consumption of a meal (10). Concentrations in plasma of the antioxidant vitamins C and E and the intracellular ratio of ascorbic acid to its oxidized form (dehydroascorbic acid) are significantly lower in diabetics than non-diabetics. In comparison with people who have a healthy metabolism, levels of vitamin C in the plasma and cells of diabetics can be over 30% lower in some cases (11). Cellular uptake of vitamin C is enhanced by insulin and impeded by high blood sugar levels. Increasing the concentration of vitamin C leads to a decrease in the proportion of glycosylated hemoglobin (HbA1C) (12). Increasing plasma levels of vitamin C by 20 micromoles per liter (0.35 mg/dL) reduced the risk of hyperglycemia by almost a third. The antioxidant status of a diabetic can be significantly improved by targeted administration of vitamin C, which reduces protein glycosylation by competitively displacing glucose from the amino groups of proteins. In this way the vitamin prevents endothelial damage induced by glycosylated reaction products and improves endothelium function (13). Vitamin C also reduces aldose reductase and hence slows the intracellular accumulation of the sugar alcohol sorbitol, which can exacerbate damage to nerves, eyes and kidneys (14). In a randomized controlled study with type 2 diabetics, adjunctive administration of 2 x 500 mg vitamin C per day for a period of four months led to a significant decrease in insulin resistance, HbA1C values and plasma levels of total cholesterol, LDL cholesterol and triglyceride, compared with placebo (15). Further, supplementary administration of vitamin C appears to enhance the metabolic regulatory activity of the antidiabetic medication metformin (16) and to have a positive effect on complications like depression (17) and periodontitis (18) in diabetics.
As a highly effective antioxidant, vitamin E protects enzymes and hormones, as well as the polyunsaturated fatty acids of biological membranes and LDL, against oxidation by oxygen radicals. During this process vitamin E is oxidized and must be regenerated by vitamin C or flavonoids. In this way the vitamin combats the oxidative degradation of fatty acids (lipid peroxidation) and in particular the oxidative modifications of LDL that contribute to the incidence of atherosclerosis. Moreover, vitamin E lowers thrombocyte aggregation and hence the risk for thromboses, and reduces the extent of protein glycosylation (HbA1C) (19). In addition, by inhibiting enzymes the vitamin slows inflammatory processes and the proliferation of connective tissue in the blood vessels and therefore reduces the threat or advance of diabetic complications (20).