Diabetes mellitus

Diabetes mellitus (DM), also colloquially known as "sugar", is a chronic, non-communicable disease manifested by impaired utilisation of the carbohydrate glucose. The resulting hyperglycaemias are the characteristic feature of DM and originate from either deficient insulin secretion or impaired body cell response to insulin (insulin resistance). With a prevalence of 422 million people affected, DM is one of the leading causes of death worldwide and represents a health challenge as a growing burden. Four different types of DM can be distinguished, with type 1 diabetes (T1D) and especially type 2 diabetes (T2D) among the most important representatives. T1D is an autoimmune disease caused by the destruction of the insulin-producing β-cells in the pancreas, which is why the therapy is based on compensating for the absolute insulin deficiency with specific insulin doses and the corresponding nutritional therapy. The cause of T2D, on the other hand, lies in an interplay of a strong genetic component, nutrition, environmental influences and other risk factors such as obesity and lack of exercise, which is why lifestyle recommendations play an essential role in this type in addition to controlling blood glucose levels.
 

DM can be divided into 4 forms, including type 1 diabetes, type 2 diabetes, other specific types (type 3 diabetes) and gestational diabetes (type 4 diabetes). 

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is also called autoimmune or insulin-dependent diabetes and occurs mostly in children and young adults. T1D is characterised by certain factors that characterise the autoimmune process leading to the destruction of pancreatic β-cells, including markers of immune destruction such as autoantibodies to insulin and glutamic acid decarboxylase (GAD) and islet cell autoantibodies, which can be found in 85-90% of affected individuals. Destruction of pancreatic ß-islet cells results in a severe deficiency or absence of insulin secretion, which causes blood glucose levels to rise, necessitating treatment with insulin injections. 

Type 2 diabetes (T2D), also colloquially known as 'adult-onset diabetes', is a progressive defect in insulin secretion based on insulin resistance. Affected individuals are often affected by resistance to the effects of insulin with long-term complications to the eyes, kidneys, nerves and blood vessels, which is also the major cause of both morbidity and death from diabetes. Various factors are cited as the cause of T2D, such as sedentary lifestyle, obesity, advancing age and genetic factors. Because of its gradual development, type 2 diabetes mellitus is often discovered rather accidentally during routine examinations. In addition, there are other specific types of diabetes mellitus, which are also referred to as T3D. The most common form of these DM types results from mutations on chromosome 12 in the so-called hepatocyte nuclear factor (HNF)-1a and are also referred to as genetic defects of β-cell function (MODY "maturity onset diabetes of the young") or genetic defects of insulin action. T3D also includes individuals with exocrine pancreatic disorders (e.g. cystic fibrosis, chronic pancreatitis), endocrinopathies (e.g. acromegaly and Cushing's syndrome) and individuals with drug-induced or infection-attributable pancreatic dysfunction. 

Another form is gestational diabetes mellitus (GDM), also known colloquially as "gestational diabetes" or Type 4 diabetes (T4D). This form of DM is glucose intolerance that occurs for the first time during pregnancy or is diagnosed during pregnancy. Accordingly, women who develop T1D during pregnancy and women with undiagnosed asymptomatic T2D discovered during pregnancy are diagnosed with GDM. GDM is also the term used for diabetes that is diagnosed during pregnancy, disappears after delivery and cannot be clearly identified as diabetes. 
 

The cause of DM is said to be disorders or abnormalities in the glucose receptors of the ß-cells or a relative ß-cell deficiency, which in both cases leads to impaired insulin secretions and ß-cell failure. The hormones insulin and glucagon are secreted by the pancreas and play an essential role as antagonists in carbohydrate metabolism and the pathogenesis of DM. Insulin is secreted by ß-cells and glucagon by α-cells, both of which are located in the pancreatic islets of Langerhans. Due to this rise in blood glucose, insulin is secreted and subsequently blood glucose levels are lowered, transporting glucose to the liver, muscles and adipose tissue where it is used for energy production. While erythrocytes and neural tissue do not require insulin for glucose utilisation, the α-cells play an essential role in controlling blood glucose by producing glucagon and thereby raising blood glucose levels (by accelerating glycogenolysis). In the presence of DM, the lack of insulin leads to a decrease in the supply of cells of the fat and muscle tissue, which is why they starve, so to speak. Furthermore, hyperglycaemia is promoted by the absence of insulin's inhibitory effect on gluconeogenesis and glycogenolysis in the liver. The common symptoms of DM are sometimes persistent thirst (polydipsia), frequent urination (polyuria), feelings of weakness, weight loss, disturbances in visual acuity and frequent infections.  If DM is long term, it can cause effects of the kidneys such as nephropathy with possible renal failure, the eyes such as retinopathy with potential blindness, sexual dysfunction and neuropathy with the risk of ulcers on the foot, features of autonomic dysfunction and Charcot foot. 
 

According to the Austrian Diabetes Association (ÖDG), DM is diagnosed on the basis of 3 parameters:

1. fasting glucose (normal value < 100 mg/dl in venous plasma)
2. oral glucose tolerance test (oGTT) or
3. haemoglobin A1c (HbA1c)

 Standard diagnosis of diabetes mellitus and increased risk of diabetes according to the ÖDG

^a An increased risk of diabetes can also exist without evidence of glycaemic disorders and can be determined by means of defined risk tests.
^b If 2 different tests are positive, the diagnosis of diabetes is given, so that the test repetition can be dispensed with. If different tests give different results, then the test with the increased result must be repeated.
^c If hyperglycaemia and classic symptoms are present, the diagnosis is given without repeating the test, because, for example, the HbA1c may be normal in the case of the first manifestation of T1D.
^d Further diagnosis by fasting glucose or oGTT is required.

However, the ÖDG points out that all tests are subject to different time courses and therefore a certain variability due to disturbances of fasting and postprandial glycaemia. For this reason, repeat testing is recommended unless classic clinical symptoms are present. 
 

The therapy of DM depends primarily on the type of diabetes and can sometimes be complex. While regular administration of insulin (insulin therapy) is necessary for T1D, lifestyle recommendations such as weight reduction and diet, regular blood glucose measurements and, if necessary, drug therapy with antidiabetic drugs and insulin therapy are in the foreground for T2D. The aim of the therapy recommendations is primarily an individualised treatment, the avoidance of complications, as well as the preservation or restoration of the quality of life of those affected. Proper nutrition is a decisive factor in the success of treatment for DM and therefore plays an important role. The primary goal is to consume foods that keep blood glucose within the normal range and at the same time reduce or avoid obesity. Accordingly, a balanced proportion of protein, carbohydrates and fats should be consumed and, if necessary, the calorie intake should be reduced if weight gain occurs. The emphasis of the diet should be on a low-fat, high-fibre and varied mixed diet with the main focus on carbohydrate intake, especially avoiding foods high in sugar and salt, red meat and excessive alcohol consumption. Carbohydrate intake should generally be reduced due to the direct effect on blood glucose levels in DM and, if consumed, should be in the form of whole foods. On a different note, numerous studies show that people who are overweight and obese not only often suffer from DM, but also have an increased risk of developing the disease in the first place. Weight reduction is therefore an essential factor in the prevention as well as treatment of DM. A recent study found that people who achieve a weight loss of 10% or more 5 years after diagnosis of T2D have the greatest chance of remission of the disease.Regular exercise is recommended in patients with T1D because physical activity improves glycaemic control, reduces the risk of cardiovascular disease and mortality. Even activities that do not involve significant physical exertion, such as walking, gardening and housework, can be helpful in keeping the body fit. A study has also shown that walking for at least 30 minutes a day reduces the risk of type 2 diabetes by about 50%. Evidence also suggests that nicotine exposure is also associated with T2D, or influences factors associated with the disease, including body composition, insulin sensitivity and β-cell function.
 

In addition, the use of a variety of antioxidants, including vitamins and herbal agents, also plays an important role in counteracting the oxidative stress caused by T2DM. Antioxidants play a central role in its prevention, but also in its complications.

Chromium is primarily used therapeutically in diabetes mellitus, because diabetics excrete more chromium (chromuria), which manifests itself in lower plasma levels. Chromium is an active component of the glucose tolerance factor, which controls the binding of insulin to the specific receptors of the cell membranes. Chromium supplementation of 200-1000 µg per day can improve insulin receptor binding, cellular glucose utilisation and blood lipid levels in diabetics. Chromium and selenium have proven insulin mimetic properties. Their activities include stimulation of glucose uptake, regulation of glycolysis and fatty acid synthesis.

Plant extracts also show a positive influence on blood glucose levels in studies. Green tea, for example, shows strong antioxidant effects as well as antidiabetic effects by positively influencing glucose and lipid metabolism and increasing glucose tolerance. In addition, blueberry extract, extracts of the gurmar (Gymnema sylvestre), bitter melon (Momordica charantia) and ginseng also show antidiabetic and blood sugar-lowering effects. 

In cases of impaired glucose tolerance, optimising vitamin D levels improves insulin sensitivity. The pancreatic islet cells require vitamin D for normal insulin secretion. Deficiency can be associated with impaired glucose tolerance, impaired insulin secretion and reduced insulin sensitivity. Increasing serum vitamin D levels through supplementation results in up to 34% improvement in insulin secretion in type 2 diabetics.

L-carnitine is involved in the oxidative breakdown of long-chain fatty acids and the resulting release of energy. In diabetes mellitus, therapeutic doses of L-carnitine can compensate for the increased excretion, which contributes to a reduction in blood lipid levels that are often elevated in diabetes. L-carnitine prevents the accumulation of triglycerides in the serum, which seem to play a role in the development of insulin resistance. In addition, L-carnitine can significantly improve the regeneration of nerves and nerve sensations in diabetic neuropathic disorders.

Numerous studies demonstrate the positive effects of zinc in patients with diabetes mellitus. According to these, zinc supplementation reduces fasting blood glucose levels in patients with type 2 diabetes and also leads to a decrease in blood glucose after a meal. Furthermore, zinc also reduces lipid parameters in patients with type 2 diabetes, including total cholesterol and lipoprotein cholesterol. Significant reductions in systolic and diastolic blood pressure may also induce supplementation with zinc. Zinc supplementation can normalise frequently decreased zinc levels in diabetics, lead to improved glycaemic control and protect against diabetes-induced cardiomyopathies.

Ginkgo biloba promotes local microcirculation. In diabetic polyneuropathies, an increase in nerve conduction velocity could be achieved in studies through supplementation with ginkgo. Oxidative stress plays a not insignificant role in the development of microangiopathic changes. The prevention of oxidative tissue damage with antioxidant agents such as coenzyme Q10, vitamin E, vitamin D and vitamin C is therefore recommended.

Elevated homocysteine levels are considered an independent risk factor for cardiovascular disease and further exacerbate diabetes. Vitamin B6, vitamin B12 and folic acid contribute to the normalisation of homocysteine metabolism, reduce the progression of secondary disease and play an important role in the repair and function of the nervous system as well as in neurotransmitter synthesis.

Recently, it has been established that oxidative stress is the main cause for the development of diabetic polyneuropathy. This is supported by the fact that the occurrence of free radicals in diabetics correlates with the severity of neuropathy. Alpha lipoic acid (ALA) inhibits these processes and can prevent the development of complications or improve existing symptoms. In controlled clinical studies, oral administration of 800 mg/day of ALA over 4 months significantly alleviated neuropathic disorders. Nerve conduction velocity was increased and cardiac autonomic myocardial ischemia was improved by an increase in heart rate variability. Peripheral insulin sensitivity and glucose uptake are also enhanced by alpha lipoic acid.