Endocrinology & Diabetology

1. Causes

   Genetics

   • Body composition
   • Muscle fibre composition
   • Hormones
   • Enzymes

   Behaviour

   • Poor diet
   • Lack of exercise
   • Alcohol, smoking
   • Stress

2. Metabolic consequences

   • Abdominal obesity with insulin resistance / hyperinsulinism

3. Metabolic diseases

   • Diabetes mellitus type II
   • Dyslipidaemia
   • Hypertension
   • Impaired fibrinolysis

   Metabolic syndrome

   Chronic silent inflammation

4. Organ damage

   • Coronary heart disease
   • Stroke
   • Peripheral arterial occlusive disease

   Arteriosclerosis

Among indigenous peoples, diabetes and vascular diseases are unknown. However, when they are confronted with the Western lifestyle or even adopt it, serious damage to health appears very quickly. If they find their way back to the original way of life within a foreseeable time, the body can readjust. Turning away from traditional life for decades or for a lifetime, however, leads to diseases of civilisation. This is shown forcefully by migration studies that have compared the state of health of native populations with that of ethnic groups who have emigrated.

The predisposition of Central Europeans and North Americans to diseases of civilisation is correspondingly pronounced. Although the unhealthy way of life only spread in “Western” societies after the Second World War, a hereditary predisposition to adult-onset diabetes appears to have been reached after just 2 generations, with decreasing physical work, increasing prosperity, changed world views and the influence of advertising and the media. Up to 25% of Germans carry the predisposition to diabetes in their genes. As a result, these people react more sensitively to foods that promote diabetes, and differently to insulin.

Before chronic diseases such as diabetes or arteriosclerosis become manifest, the organism has already been damaged by the metabolic syndrome. The symptoms include obesity, raised triglyceride levels, low HDL (“good”) cholesterol, insulin resistance, impaired glucose tolerance and clotting disorders. All of them form the basis for later organ damage. Characteristic of the metabolic syndrome is the combination of an inborn reduced sensitivity to the body's own insulin (which is located in the muscles) and an acquired insulin resistance, which is intensified by obesity and lack of exercise (table). On the one hand, this intensifies macroangiopathy and microangiopathy (narrowing of the blood vessels), which leads to arteriosclerotic damage throughout the vascular system; on the other hand, it promotes the development of type II diabetes (adult-onset diabetes).

Individualised dietary interventions can help to achieve healthy ageing and to reduce the risk of degenerative diseases. A raised body mass index (BMI) and a raised waist-to-hip ratio are significant risk factors for insulin resistance, abnormal blood sugar levels and cardiovascular diseases. They are a genetic expression and a genetic precursor of the signs of wear and tear that are associated with diabetes mellitus (DM) and can thereby lead to conditions such as kidney failure, degeneration of the eyes, non-traumatic amputation and impaired peripheral circulation.

Disorders of glucose metabolism can occur very early in life and show themselves as obesity, unhealthy eating habits and changes in energy production. Adult-onset diabetes can even become manifest in teenagers or in people in their twenties. Many scientific studies indicate that patients with disorders of glucose metabolism in adulthood pass through various stages of insulin resistance before diabetes proper has developed (see table).

Estimates assume that the metabolic disorders precede DM proper by about 15 years. Because adjusting diet and lifestyle, micronutrient supplementation and specific therapies are effective methods of preventing DM, identifying the predisposition in good time is of decisive importance and the key to true prevention.

DM appears to be the end result of a long preceding, insidiously progressing change in metabolism. From normal blood sugar, one first moves through hypoglycaemia (a tendency towards low values because of an overproduction of insulin) to high sugar values and finally to DM type II proper.

How can I prevent this development?

The metabolism is a huge, interconnected chemical factory that the human mind cannot take in as a whole. Nevertheless, we know the most important reactions and their effect on our health when things gradually go off the rails. The most significant assessments are explained below.

Glucose tolerance test

This analysis requires blood and saliva samples before and 2 hours after taking 75 g of sugar. Values that are examined individually or together are insulin, glucose, haemoglobin A1c, fructosamine and IGF-1 somatomedin. In saliva, they are the hormones cortisol and DHEA. Special dietary instructions given beforehand must be followed exactly.

Insulin

The main stimulus for insulin production is blood sugar. Besides diet, constant exposure to growth hormones, oestrogens, cortisol and progesterone also promotes the formation of insulin. Chromium, vanadium, magnesium and zinc are also involved in the synthesis and availability of insulin in its active form. Low blood sugar concentrations stimulate the adrenal medulla, which results in increased production of adrenaline, which activates the sugar reserves in the form of glycogen from the liver.

Insulin is broken down mainly in the liver and in skeletal muscle. Two pathways are known: one via a protease enzyme that has a sulphydryl group, the second via the formation of glutathione-insulin, which is then metabolised further. Adequate supplementation with the sulphur-containing amino acids methionine and cysteine can therefore be important for this metabolism.

The effect of insulin

Membrane transport: Insulin speeds up the transport of glucose and other sugars (galactose, arabinose) into the peripheral cells and into the fat cells, where they are phosphorylated for the purpose of energy production. The inflow of amino acids into the muscle cells is likewise supported, as is the transport of potassium, calcium and phosphorus.

Glucose utilisation: In the presence of sufficient insulin, glucose is converted as follows: 50% to ATP (the energy of the cell), 30 to 40% to fat and 10% to glycogen (storage sugar). In the fat cells, insulin provides the starting substances for fatty acid synthesis and supports enzyme activity in the direction of fat deposition.

Fat and protein metabolism: Insulin inhibits lipolysis (the breakdown of fat) in the liver and in fatty tissue by inhibiting lipase activity and reducing circulating adenosine monophosphate (cAMP). This results in a lowered level of free fatty acids in the blood. Insulin stimulates protein synthesis and the uptake of neutral amino acids and inhibits the breakdown of protein, which ultimately results in an anabolic effect.

Cell proliferation and genetic expression: Insulin influences cell division and takes part in the control of growth. Insulin regulates more than 100 messenger ribonucleic acids, which has a significant effect on enzyme synthesis and gene functions. The genes that are addressed could also be human “obesity” genes and could favour the interactions of metabolic genes with environmental, nutritional, behavioural and other life factors. Genes are activated differently in the course of life. Many diseases also only become manifest at an advanced age, possibly through the influence on the corresponding genes over time. There are indications that hyperinsulinaemia also speeds up cell division and can thereby bring the ageing process forward. In this way, improper insulin therapy can also produce peripheral hyperinsulinism. Hyperinsulinaemia is an independent factor for arteriosclerosis, DM type II, certain forms of dementia and other diseases. Obesity (apple shape) is always associated with hyperinsulinism. It is conceivable that the life-prolonging effect of a low calorie intake comes about through the reduction of insulin and thus a slowing of the rate of cell division. This connection has been confirmed in animal experiments.

HbA1c

HbA1c is glycated haemoglobin. Excess sugar binds to protein molecules, in this case to haemoglobin, the blood pigment in the red blood cells. As the red blood cells have a lifespan of about 2 to 3 months, the measurement of HbA1c reflects sugar metabolism over this period. The more persistently high the sugar values in the blood are, the more sugar will bind to the haemoglobin. It is not only diabetics who can benefit from this test result. In the context of the health check-up and weight control, the rule is that the lower the value, the lower the risk of suffering in the longer term from complications of diabetes or from glycation of the connective tissue.

Control of HbA1c is decisive for the formation of advanced glycation end products (AGEs), which initiate cytokine-mediated processes that can lead to tissue remodelling, inflammation and thick blood (a decrease in thrombomodulin).

Fructosamine

Fructosamine is also a glycated protein molecule. Fructosamine values change more quickly than HbA1c and reflect sugar control over the last 2 to 3 weeks. By normalising this parameter, the likelihood of protein glycation is reduced to a minimum.

DHEA, cortisol, IGF-1

These hormones can point to changes in metabolism. Insensitivity to insulin and hyperinsulinism are involved in the emptying of the DHEA stores in the adrenal glands. When insulin is overproduced, cortisol production is favoured, or rather activated. As DHEA and cortisol have the same precursors, DHEA goes short. For this reason too, normalising cortisol has a considerable effect in controlling weight metabolism and in lowering the risk of cardiovascular diseases, cancer, kidney failure, blindness or vascular occlusion. IGF-1 stands for “insulin-like growth factor”, that is, an insulin-like growth factor. This molecule, a peptide, is able to raise the level of free magnesium in the cell, above all by potentiating the effect of insulin. Low cellular Mg levels are characteristic of patients with DM. It remains unclear, however, whether low Mg is cause or effect in the context of the diabetic metabolic state. The higher the cell concentration of Mg, the more sensitively the cell reacts to insulin.

Clinical treatment strategies

• Slowing the absorption of glucose from the intestinal tract
• Lowering glucose production in the liver
• Improving the response to insulin
• Improving the breakdown of sugar

Regrettably, stress is a fixed part of our modern society. It can come from the environment, from thoughts and feelings or from the body itself. The adrenal hormones cortisol and DHEA are of central importance for how the body adapts to stress. If cortisol and DHEA are not in balance, resilience falls to the same degree. Abnormal levels of the two hormones are also found in various important diseases.

This overview explains what the adrenal glands do, what cortisol and DHEA bring about, how we measure their function and which measures come into consideration depending on the findings.

The adrenal glands

The adrenal glands are cap-like glands that sit on top of the kidneys. Each gland consists of an inner and an outer layer of tissue. The outer layer, the adrenal cortex, is the source of the cortisones, of which there are various kinds, such as the mineralocorticoids and the glucocorticoids. The inner layer produces adrenaline.

Although DHEA and cortisol both come from the adrenal glands, in many respects they have opposite effects.

Cortisol, the stress hormone

The cortisol level shows the activity of the adrenal cortex. It is highest in the morning and falls markedly over the course of the day and night. There is a reason for this: cortisol is an activity hormone (flight and fight). In the morning, cortisol is needed to make sugar available, which is necessary for energy production and muscle work. The night, with its low cortisol level, is the phase of rest and regeneration, but also of inflammation and healing (fever usually rises towards evening).

Many of the tasks of cortisol are thus aimed at mobilising the body's reserves. Cortisol is the most important “stress hormone” and is released in large quantities above all during physical, physiological and emotional stress. If the stressors persist, the increased activity of the adrenal cortex can tip over into exhaustion. The natural reserves of the adrenal glands fall, and a certain degree of underactivity can even set in.

Possible consequences of excess cortisol:

• Muscle breakdown
• Excess weight, mainly on the trunk, chest, neck and face
• Immune deficiency
• Reduced bone density, increased risk of osteoporosis

Possible consequences of cortisol deficiency:

• Loss of vitality, general tiredness, exhaustion
• Depression

DHEA

Dehydroepiandrosterone (DHEA) is an intermediate stage in the formation of the male hormone testosterone and the female hormone oestrogen. DHEA reaches its maximum between the ages of 25 and 30 and falls again with increasing age. In parallel, the immune defence declines (infections in old age are more dangerous!), and the diseases of old age increase.

DHEA influences fat metabolism, energy production in the mitochondria, protein synthesis and thyroid function. DHEA also follows a day-night rhythm.

Effects on metabolism:

• Fat breakdown
• Muscle growth
• Lowering of blood pressure
• Immune support
• Coping with tiredness and stress
• Improvement of memory and sleep

For this reason, DHEA is one of the anti-ageing hormones.

Possible consequences of DHEA deficiency:

• Osteoporosis
• Cardiovascular diseases
• Immune disorders, autoimmune diseases
• Thyroid diseases
• Diabetes
• Raised blood pressure
• Excess weight

Possible consequences of excess DHEA:

• Male-pattern hair growth in women
• Blood pressure that is too low

The ratio of cortisol to DHEA

More cortisol means less DHEA, depending on how metabolism in the adrenal glands is regulated. The ratio of the two hormones is therefore a good indication of how the organism is coping with stress.

Measuring adrenal function

The analysis essentially measures:

• Cortisol (daily cortisol profile)
• Cortisol and DHEA (adrenal stress index)

In conventional medicine, cortisol is measured in a blood sample. It is important that the blood is always taken in the morning between 7 and 9 a.m. However, the result says nothing about how the adrenal glands behave over the course of the day. For that, cortisol is examined in several saliva samples: in the morning, at midday and in the evening. This gives us the daily rhythm, which is important for assessing healthy hormone function.

Test result

This example shows a normal daily course with a high level in the morning and low values at midday and in the evening. The green lines are the upper and lower limits of the normal range, the blue line is the patient's result.

Treatment

Which measures come into consideration depends on the findings. A healthy diet, stress reduction and fitness are always part of it.

When cortisol is low

Suspected: weakness or exhaustion of the adrenal glands.

• Lifestyle
  • Stress reduction: chronic stress exhausts the adrenal glands
  • Rest
  • Moderate exercise
  • Prayer and contemplation
  • Meditation
  • Relaxation exercises
• Change of diet
  • Balancing blood sugar
  • Fewer calories
  • More protein
  • More complex carbohydrates and fibre
• Food supplements
  • High-quality multivitamins and minerals
  • Vitamin C
  • Vitamin B5, B6
  • Zinc, as required
• Medicinal plants
  • American or Korean ginseng (Panax spp.)
  • Siberian ginseng (Eleutherococcus senticosus)
  • Withania (Withania somnifera)
  • Liquorice (Glycyrrhiza glabra): prolongs the half-life of cortisol
  • Sarsaparilla (Smilax spp.): precursor of cortisol
• Support of the hormone glands with organ preparations *
  • Adrenal gland
  • Pituitary gland and others
• Hormone replacement therapy *
  • Cortisol
  • DHEA
  • Pregnenolone

* It is important to take the circadian rhythm into account: taken in the morning and at midday; taking it later is not recommended.

When cortisol is raised

Suspected: a certain hyperactivity or overactivity of the adrenal glands in response to stress coming from the environment, the body or the psyche.

• Lifestyle
  • Stress reduction
  • Rest
  • Moderate exercise
  • Prayer and contemplation
  • Meditation
  • Relaxation exercises
  • Monitoring and stabilising blood sugar
  • Sufficient sleep
  • Elimination of food intolerances
  • Restoring normal bowel function
• Food supplements
  • High-quality multivitamins and minerals
  • Vitamin C
  • Vitamin B5, B6
  • Zinc, as required
  • Phosphatidylserine: it can make the HP axis sensitive again to negative feedback from cortisol.
• Medicinal plants
  • St John's wort (Hypericum perforatum)
  • Passion flower (Passiflora)
  • Valeriana
  • Scutellaria
  • Hops (Humulus lupulus)
  • Siberian ginseng (Eleutherococcus senticosus)
  • Withania (Withania somnifera)

When cortisol is high, DHEA is low or the DHEA/cortisol ratio is low, the medicinal plants are given spread over the whole day.

When DHEA is low or the DHEA/cortisol ratio is low

Suspected: a physiological response to stress in which steroid synthesis shifts towards cortisol, at the expense of DHEA.

• Lifestyle, change of diet and medicinal plants as for raised cortisol
• Replacement of DHEA or pregnenolone can be considered.
• If appropriate, analyses of testosterone and oestrogen
• When the DHEA/cortisol ratio is low: immunological support as required

DHEA should only be given under medical supervision and at the lowest possible dose (women about 10 mg per day, men about 25 mg per day). In women, a high dose can lead to menstrual disorders and male-pattern hair growth. A natural, plant source of DHEA is yam root.

When DHEA is raised or the DHEA/cortisol ratio is raised

Suspected: an unphysiological response to stress in which steroid synthesis shifts towards DHEA, at the expense of cortisol. When DHEA is raised, intake from outside and polycystic ovaries should also be considered.

• Lifestyle, change of diet and medicinal plants as for low cortisol
• If appropriate, analyses of testosterone and oestrogen