The concept of insulin resistance has been around since the 1960’s.  It was felt that the pancreas could distribute up to 200 units of insulin and was defined as “severe insulin resistance,” an insulin requirement of more than 200 IU over several days to reach normal blood glucose levels.  Although it is now clear that a normal physiological insulin production is from 20 to 40 units, this old definition is further considered appropriate to differentiate so that patients with severe, unusual insulin have no resistance problems.  Since 1985, the term has a broader scope and refers to a reduced response of cells of the human or animal body to insulin.

Insulin resistance during the day is highest in the early morning.  There is often late in the afternoon a second, less high increase in insulin resistance.

Causes

Insulin resistance is the main cause of type 2 diabetes. The exact mechanisms that lead to insulin resistance in humans are currently poorly understood, but are under intense research.  In this context, and in addition to polygenic predisposition, a number of secondary environmental factors are discussed. These include obesity, metabolic factors, age and lack of physical activity.

Not all scientists see the influence of carbohydrate-rich foods with a high glycemic index as a factor.  The insulin resistance of type 2 diabetic patients is caused primarily by obesity and physical inactivity.  Genetic factors are also a cause.  In people the same age, same sex, same body weight and size, with the same caloric intake and physical activity, they can still have a different effect of insulin on the target cells. These differences are probably due to hereditary factors. Insulin resistance may also be increased by drugs.  Infectious diseases may increase insulin resistance.

Mechanisms of insulin resistance

Insulin resistancy is increased by reducing the number of receptors with permanently elevated levels of insulin by IgG antibodies, which inhibit the biological activity of the insulin increased by enzymatic cleavage of insulin and decreased binding of insulin to its receptors.  There are proteins:  Tumour necrosis factor alpha (TNF-alpha); Plasminogen activator inhibitor I (PAI-1) and Resistin.

Determine the insulin resistance

A first indication of the presence of insulin resistance is the body weight.  In all obese diabetics insulin resistance is assumed.  It is now thought that especially the fat in the abdominal area distributes more substances which promote and strengthen resistance to insulin.

Waist circumference is a measure of supposedly dangerous abdominal fat, and body mass index (BMI), which has starting values of 27 kg/m2, together with an indication of familial predisposition to insulin tolerance.  Furthermore, the blood lipid level (triglyceride levels above 2.44 mmol / l or can 215 mg / dL can be an indication of insulin resistance.

Proinsulin

In the production of insulin, the pancreas is first a precursor molecule – the so-called proinsulin and is synthesized. This is again split.  It then creates the actual hormone insulin, and an ineffective waste product, the C-peptide.  In the context of insulin resistance there is more and more insulin, while disproportionately makes a lot of proinsulin. The latter is split into insufficient insulin and can be higher than that which is detected in the blood.

Therapy

The insulin resistance in type 2 diabetics is best broken up by a strong reduction in caloric intake and by increasing physical activity.  Even a short-term increase in insulin delivery to very high doses is needed in order to force a normnahe glycemic control, breaking through after a few days and insulin resistance, as seen by the much lower dose of insulin is necessary after the treatment. Insulin resistance may also be reduced by drugs: Acarbose; Metformin; Insulin sensitizers such as pioglitazone; Omega-3 fatty acids; ACE inhibitors and Rimonabant.

Insulin resistance and other diseases

Metabolic syndrome is closely associated with insulin resistance, because both diseases have the same origin.  Furthermore, Type-2 diabetes, which develops from insulin resistance, is a risk factor for the emergence of the metabolic syndrome.  Coming to obesity, when two other risk factors – diabetes, lipid disorders and hypertension are added, it is called metabolic syndrome. The metabolic syndrome is the main cause of heart attacks and strokes – the number 1 cause of death in The UK.

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Oral insulin has been ineffective, because the protein chains are degraded in the gastrointestinal tract of the body’s own enzymes before they can be effective, but there are developments that include changing insulin molecules into nanoparticles and then the undigested insulin is injected into the bloodstream.

In the past there have been attempts to use insulin in the context of so-called insulin shock treatments for people with mental illnesses. This procedure is no longer practiced today, however.

Insulin is on the list of banned doping substances because it is abused in several areas.  Since insulin counteracts the decreased glucose uptake of somatotropin in the muscle cells, it is often used to compensate for this unwanted side effect, see also anabolic.  Other applications are to promote the filling of glycogen stores in endurance athletes and support the building of muscle mass.

In March 2008, the nurse Colin Norris in Newcastle was sentenced to a prison term of 30 years because he killed four of his patients by injecting them with high doses of insulin.

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Each year diabetes type 1 affects hundreds of children. With the child obesity rate increasing in the UK ,diabetes is increasing as well. Nutritionists are very concerned with the number of children that are obese. Children are becoming fascinated with junk food which has large amounts of fat. Obesity can cause a number of disorders that are life threatening such as diabetes, blood pressure, cardiovascular disorders and strokes.

There are a number of factors that are responsible for developing diabetes in young children. The main cause in children is still not clear, but the most probable reason it the mutation of genes and other environmental symptoms.

According to a recent survey, most of those who suffer type 1 diabetes have no family history of diabetes. Symptoms for diabetes include excessive thirst, weakness and tiredness, a sudden large loss of weight, urination on a frequent basis, an increase of appetite on an ‘all of a sudden’ basis, irritation and a sudden increase of weight.

There are some children that have had symptoms like cramps/pains in the stomach, severe headaches and behavioural patterns that are disturbed. Awareness of diabetes should be initiated in high school. If your young child has even the smallest of changes in their system it is important you contact your physician.

Many children are unable to communicate with anyone about the changes taking place in their body. Therefore parents need to be aware of their children’s health. There is not cure for diabetes but it is manageable and controllable.

If a child gets diagnosed with diabetes, treatment should start immediately so any further complications can be prevented. Usually kids are at least bothered by something that does not seem right in them. Parents need to express to their kids how important it is they communicate any problems they have or any time they feel out of the ordinary.

You should also consult an experienced dietitian to help customize a diet for your child to help come up with the best and healthiest diet possible. The diet should become a daily routine and should be changed as infrequently as possible.

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This was part of a collaboration that was multinational with the Wellcome Trust financing the MuTHER study and scientists from University of Oxford, Wellcome Trust, the University of Geneva and King’s College London collaborating with help from DeCode Genetics as well.

The role that KLF14 played up until now has been unknown, even though researchers knew previously that the gene was linked to diabetes type 2 and cholesterol levels. Subcutaneous fat (fat samples taken from below the skin) biopsies were taken by the team of 776 twins (female) in Great Britain and then over 20,000 genes were analyzed in the fat cells.

Their findings were that KLF14 acts as a controller and influences the behaviour, in the fat tissue, of distant cells. Another 600 fat samples were taken from a group in Iceland and confirmed their original findings. Fat is a key factor in our susceptibility to metabolic diseases such as diabetes, heart disease and obesity.

The mother passes along the KLF14 gene and as is always the case we receive genes from both parents, but the KLF14 gene received from the father is turned off making the mother’s the active gene with this being known as imprinting. If there were medications to directly target the KLF14, the treatment of many metabolic diseases could become much more effective.

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The prototype for the gadget which is used for treating Type 1 diabetes has been tested on 17 children in Cambridge and electronically monitors blood sugar levels so that the perfect amount of insulin can be injected into the blood.

At the moment the new gadget requires a nurse in order for the insulin device to be programmed, but it does raise the question of if an automated device can be used in the future to control diabetes.

Type 1 diabetes is one of the most common childhood diseases that carries with it long term problems and the number of children that will be affected by the disease is expected to continue to rise, after doubling over the last ten years.

Those that are affected by Type 1 diabetes have an immune system that attacks the cells in the pancreas responsible for making insulin.  When the body does not have insulin it cannot regulate sugar levels within the blood which leads to serious health problems.

Type 1 diabetes brings with a lifetime of insulin injections and at the moment the only alternative to taking injections is an insulin pump which releases insulin into the body slowly and continuously throughout the day.

They are about the size of a mobile phone and can be used with approval from the NHS on people that have problems controlling diabetes with regular injections.

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