What is insulin resistance?
Under the insulin resistance (IR) is defined as a reduced response of body cells to the hormone insulin. In particular, the muscles, the liver and the adipose tissue less sensitive to insulin. This reduced sensitivity interferes with the action of both endogenous and of injected insulin.
Insulin resistance definition
The concept of insulin resistance has been around since the 1960s. It was felt that the pancreas can distribute up to 200 International Units (IU) of insulin per day and defined as "severe insulin resistance" an insulin requirement of more than 200 IU several days, in order to achieve normal glucose levels. Although it was now clear that a normal physiological insulin production between 20 and 40 units is, this old definition is further considered useful in order to distinguish patients with severe, unusual insulin resistance problems.
Since 1985, the term was more generally known and a reduced response of cells of the human or animal body to insulin.
Daily results
Early morning insulin resistance is highest by the nocturnal secretion of insulin antagonists (see dawn phenomenon). Often there is also a late afternoon second, less high increase in insulin resistance.
What causes insulin resistance?
Insulin resistance occurs as a phenomenon in type 2 diabetes and its precursors, as a disorder of metabolism in glucose and insulin balance of the cells, and as a consequence of disturbances in the function of the affected organ tissue. The exact mechanisms that lead to insulin resistance, are still in intensive research.
Insulin resistance affects both lean and obese type 2 diabetics, but obesity is a major risk factor. The combination of family planning (both for obesity, diabetes mellitus type 2 as well as the decreased insulin sensitivity), to abundant calories and too little physical activity leads to an imbalance of energy supply and consumption and increases the concentration of free fatty acids in the blood, which in turn interferes with glucose utilization in muscle and adipose tissue. This recovery of the disorder of glucose characteristic of the insulin resistance. In response, there is an increased release of insulin (hyperinsulinism). This leads to a down-regulation of insulin receptors on the cells, the resistance is increasing. The insulin as adipogenic factor increases fat storage, the man continues to increase in weight.
Other causes of insulin resistance
-Drugs, for example. Cortisol can be one of the antagonist of insulin weaken its effectiveness
-Serious infectious diseases among others on the distribution kontrainsulinärer hormones
-Metabolic disorders such as hypertriglyceridemia
-Disease with overproduction kontrainsulinärer hormones, eg. As acromegaly with the increased release of somatotropin
-In polycystic ovary syndrome (PCOS) is present overproduction kontrainsulinärer hormones, it comes to insulin resistance and subsequent hyperinsulinemia, which applies in addition to other hormone disorders as an important factor in the formation and maintenance of PCOS.
-Significant ongoing poor nutrition (malnutrition)
-Congenital generalized lipodystrophy
Insulin resistance mechanism
Insulin resistance is increased by:
-Abnormal insulin receptors (such. as when Donahue's syndrome, a rare genetically determined short stature syndrome with early mortality)
-Reduction in the number of receptors, eg. As in permanently elevated insulin levels
-IgG antibodies which inhibit the biological activity of the insulin
-Increased enzymatic cleavage of insulin
-Reduced binding of insulin to its receptors
-Insulin resistance-promoting proteins such as tumor necrosis factor alpha (TNF-alpha), plasminogen activator inhibitor type I (PAI-1) and resistin
Insulin resistance
A first indication of insulin resistance can be increased body weight. For all type 2 diabetics a genetic insulin resistance is present, but is particularly useful for morbid obesity revealed. Today it is assumed that especially the fat in the abdominal area multiplied hormonally active substances distributes that promote and enhance insulin resistance.
As a measure of the belly fat of waist circumference can be measured and the body mass index (BMI), the / m² together with familial predisposition is an indication of insulin resistance from values of 27 kg.
Furthermore, the levels of triglycerides may be an indication of insulin resistance. In (triglyceride levels above 2.44 mmol / l or 215 mg / dl) may be insulin resistance, especially when simultaneously high fetuin-A levels are measured.
Adiponectin
The adipose tissue adiponectin is produced by adipose tissue decreased the insulin-resistant people. Decreased adiponectin indicate insulin resistance.
Proinsulin
In the manufacture of insulin in the pancreas, a first precursor molecule - so-called proinsulin - synthesized. The actual hormone insulin is produced only by elimination of the so-called C-peptide. In the context of insulin resistance is more and more insulin, thus also disproportionately made much proinsulin. The latter is not sufficiently split into insulin and can be detected as elevated proinsulin in the blood.
More resistance tests
-Glucose tolerance test (oral glucose tolerance test, OGTT short)
-Fasting insulin levels: in diabetic patients with insulin resistance is increased at least in the early years of type 2 diabetes the insulin levels, see hyperinsulinism.
-Glucose "clamp" technique: Determination of the glucose infusion rate, which is a slightly elevated (e.g., 125 mg / dl or 6.9 mmol / l.), However, constant blood sugar value required.
-Determining the HOMA index (Homeostasis Model Assessment) = insulin (uU / ml) × glucose (mmol / l) / 22.5
Values> = 2 Note on IR,> 2.5 = IR likely> = 5.0 average in type 2 diabetics
Therapy
Insulin resistance in obese type can 2 diabetes in the short term by a significant reduction in caloric intake (eg for a few days less than 1000 kcal / day) reduced the long term through increased physical activity or.
Even a short-term increase in insulin intake to very high doses, z. B. intravenously over a drug pump or subcutaneous administration (injections into the subcutaneous adipose tissue) of normal or analog insulin (see Insulin preparations) in short intervals of a few hours "breaks" after a few days, the insulin resistance. After achieving normal blood sugar levels significantly lower insulin dose is then necessary to further therapy.
The influence of diets (eg low-fat, low-carb) on the origin and treatment for insulin resistance is controversial.
Effective and clinically common active ingredients to reduce insulin resistance are:
-Acarbose
-Metformin
-Insulin sensitizers (glitazones), such as pioglitazone