Diabetes mellitus diabetes 2

Diabetes mellitus
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Definition

Diabetes mellitus describes a heterogeneous group of metabolic diseases whose basic characteristic is the Chronic hyperglycemia with consequently increased sugar content in the urine is. This is why the term diabetes mellitus is derived from the historical term "honey-sweet flow.

Epidemiology

80% of people in Germany suffer from diabetes mellitus, 90% of whom have type 2 diabetes. Women and men are affected about equally often.

In Germany today approx. every 13. suffering from diabetes. (Diabetes Center Germany DZD)

Formerly a disease of old age ("adult-onset diabetes"), type 2 diabetes is also occurring more and more frequently in younger people and children. As the incidence increases by 3-4% per year, the number of people with diabetes worldwide is expected to double in 2030.

Etiology and pathogenesis

At the center of this metabolic disorder is the insulin. This hormone is produced in the beta cells of the pancreas and ensures the uptake (and also storage) of glucose in various cells of the body. The insulin receptor involved, a transmembrane protein with tyrosine kinase activity, causes translocation of the glucose carrier protein GLUT4 to the cell surface, so that glucose is increasingly transported from the capillary bed into the intracellular space. The glucose level in the blood decreases. In people with diabetes mellitus, this mechanism is disturbed at different levels.

We distinguish between different forms of diabetes mellitus on the basis of their etiology:

Diabetes mellitus type 1

Destruction of the beta cells results in an absolute insulin deficiency. Such destruction occurs either idiopathically (rather rarely, type 1A) or by autoimmunological processes (ca. 5 % of all diabetics in Germany, type 1B).

Genetic factors play a predisposing role. As a special form of this immunological form of diabetes, the LADA (= Late Autoimmune Diabetes in Adults), in which a diabetogenic metabolic state does not develop until adulthood (> 25 years) occurs. To a pathological hyperglycemia there is usually a beta cell loss of approx. 80 %. In the autoimmuneIn the diagnosis of MODY2, antibodies against cytoplasmic islet cells, anti-GAD antibodies, insulin auto-antibodies and anti-tyrosine phosphatase-2 antibodies are frequently found.

Diabetes mellitus type 2

In 90 % of diabetes cases, there is a different pronounced triad consisting of insulin resistance of the target tie, a secretory defect or a progressive apoptosis of the beta cells. This constellation often develops in combination with a metabolic syndrome, which is very common in our affluent society.

Overeating with simultaneous lack of exercise and obesity leads to permanently high insulin levels, which reduce the sensitivity of the insulin receptor and lead to downregulation. This increases in the sense of a vicious circle (vicious circle) the insulin level continues to rise. At the same time Dyslipoporteinemia in combination with diabetes mellitus type 2 a combined progressive atherosclerosis with corresponding multiple late complications.

Notice: With regard to the hereditary tendency of diabetes mellitus types 1 and 2, first-degree relatives are more frequently affected in diabetes mellitus type 2 than in diabetes mellitus type 1. A child with a parent with diabetes mellitus type 2 has a 50% chance of suffering from the same disease in the course of life, whereas only ca. 10% of those with type 1 diabetes mellitus have a positive family history of the disease.

Diabetes type III: Other causes

Genetic defects of beta cells: MODY

There are a number of genetic defects that lead to hereditary diabetes mellitus. This affects about 1 % of all diabetics, and these people are mostly affected by the disease at a very young age. This form of diabetes is called Maturity Onset Diabetes of the Young (= MODY) and knows different genetic causes. To score well on an exam, remember the most common MODY forms:

MODY2: 15% of cases, affected gene is glucokinase, mild course usually without late complications MODY3: 65% of cases, affected gene is the HNF-1-alpha

What are the rare causes of diabetes mellitus?

Rarer causes of diabetes mellitus are:

– Diseases of the exocrine pancreas – Endocrinopathies – Medications (glucocorticoids, oral contraceptives, u.a.) – infections – cystic fibrosis – hemochromatosis

Diabetic metabolism can also occur postoperatively after pancreatic surgery.

If diabetes mellitus occurs due to destruction of the general pancreatic tie, it is called a pancreopriven diabetes.Such a form of diabetes is extremely difficult to treat, because not "only" the beta cells are destroyed, but also the glucagon and somatostatin production is inhibited.

Type IV diabetes: gestational diabetes

As Gestational diabetes applies to any disorder of carbohydrate metabolism detected during pregnancy. In most cases, the diabetic metabolic tendency disappears after the end of pregnancy, but a later manifest diabetes mellitus can develop with increased risk. If it comes during a pregnancy to a Gestational diabetes increases the risk for preeclampsia, hydramnios and urinary tract infections.

Certain peripartum health risks also arise for the child via the mother's pathological metabolic state. Thus, a respiratory distress syndrome could be clustered. A postpartum (reactive) hypoglycemia is observed.

Symptoms and clinic

Initially, diabetes mellitus is manifested by nonspecific general symptoms such as fatigue, exhaustion, or weakness.

Hyperglycemia classically leads to a polyuria with polydipsia and a weight loss. This also upsets electrolyte balance, so many sufferers report calf cramps or vision problems.

Often diabetes can also be recognized by the skin. Typical are a facial flushing (rubeosis diabetica) or skin infections due to a weakened immunological barrier.

Men also report potency disorders.

Note: Type 1 diabetes mellitus tends to become symptomatic rapidly, whereas type 2 diabetes mellitus may remain undiagnosed for a long time. Acute symptoms of diabetes mellitus include hyperglycemia or hypoglycemia, which will be discussed in detail later.

Figure: "Overview of the most significant possible symptoms of diabetes.". License: Public Domain

Complications of diabetes mellitus

The full extent of the disease of diabetes mellitus becomes clear only when one approaches the late effects caused by the Chronic hyperglycemia develop.

The elevated blood glucose levels are present in the entire organism, thus diabetes mellitus resembles a systemic disease with a correspondingly pronounced spectrum of complications. Especially the walls of large. Small vessels suffer certain damage over time.

One divides thereby macroangiopathic damage with arteriosclerosis and microangiopathic damage by glycosylation of proteins of the basement membrane.

Macroangiopathic damage as a consequence of diabetes mellitus

The distribution pattern of the damage is non-specific. About half of all diabetics die of heart attack. In addition to coronary arteries, peripheral arterial occlusive disease is common. To arteriosclerosis of the cerebral arteries with following cerebral infarctions.

Tip for the clinic: In diabetic coronary artery disease, there is often microangiopathic damage (s.u.) a silent angina pectoris symptomatology with painless infarctions, so that one cannot rely on the diabetic history for a suspected myocardial infarction!

Microangiopathic damage as a result of diabetes mellitus

The disturbances at the capillary level mainly affect the kidney, the retina, the nervous system and the intramural, smaller coronary arteries.

diabetic nephropathy

While type 1 diabetes leads to Glomerulosclerosis (= M. Kimmelstiel Wilson), type 2 diabetes has a nonspecific pattern of damage to the kidney. Diabetes mellitus is the most frequent reason for the need of dialysis in Germany. Hyperglycemia leads to an activation of growth factors, which causes renal hypertrophy with thickening of the basement membrane and thus increased glomerular permeability cause. Via fibrotic remodeling processes this then leads to renal failure.

diabetic retinopathy

In this case, a microangiopathy with mircoaneurysms, venous caliber fluctuations, intraretinal hemorrhages. If angiogenic growth factors are then produced, a proliferative retinopathy with vascular neoplasms at the optic disc may occur in addition to a non-proliferative form.

Diabetic neuropathy

Image: "Diabetic retinopathy after focal laser treatment" License: Public domain

One suspects a microcirculastion disturbance of the vasa nervorum in connection with glycosylation of various neuronal proteins. This classically results in a peripheral sensorimotor neuropathy with distally accentuated, symmetrical expression. In the neurological examination, besides a trophic disturbance of the lower legs and feet, a Areflexia and Pallhypesthesia at. Patients often report paresthesias ("burning feet syndrome") and may suffer from paresis.

In addition to this form of distribution, diabetic focal polyneuropathy, peripheral facial nerve palsy or diabetic radiocarcinopathy also occur. In addition, neuropathy of the vegetative system is often present. Both sympathetic and parasympathetic nervous system can be damaged. The symptoms are as varied as the autonomic nervous system. We distinguish cardiovascular forms from autonomic diabetic neuropathies of the gastrointestinal tract, genitourinary system, neuroendocrine system or thermoregulation. Diabetics often have warm. Dry feet! Of course, this does not apply if pAVK is present at the same time!

The diabetic foot syndrome

Picture: "Diabetic foot syndrome" by PhilippN. License: CC BY-SA 3.0

As a combined macro- and mircoangiopathic late complication, many diabetics complain of injuries to the foot. The diabetic foot syndrome is the most frequent complication. Different forms of diabetic foot syndrome are distinguished:

The neuropathic diabetic foot is typically warm and dry. There is impaired sensitivity with good perfusion. Affected persons often wear the wrong footwear or do not notice small injuries, so that ulcerating, painless ulcers arise.

The ischemic foot in the presence of peripheral occlusive disease, on the other hand, is cool and pale due to lack of perfusion. Necrosis or gangrene can be very painful.

Particularly unfavorable are combined forms, which unfortunately is present in 35% of diabetic feet. In this case, surgical amputation is also more common than in the other forms.

Other complications of diabetes mellitus

In addition to microangiopathic and marcoangiopathic damage, diabetic patients may continue to have diabetic cardiomyopathy an immunological reduction in resistance leads to an increased tendency to infection and lipid metabolism disorders ultimately cause a Steatosis hepatis.

Diagnosis

The clinical symptoms of manifest diabetes mellitus in conjunction with a spontaneous blood glucose level of > 200 mg/dl are sufficient to make the diagnosis. Also multiple measured spontaneous blood glucose values of> 200 mg/dl without further symptoms are sufficient for a diagnosis.

Furthermore, the fasting blood glucose or a oral glucose load test (oGTT) glucose tolerance and a diabetes mellitus are diagnosed. Accordingly, pregnant women should have their blood glucose levels tested closely. If there is reason to believe that there is a high risk of diabetes, an oral glucose tolerance test is recommended.

Due to the high prevalence and the serious (also economic) late complications, diabetes screening is recommended for all individuals> 45 years recommended. If risk factors exist, this screening should be carried out at an earlier stage.

Once the diagnosis has been made, further clinical examinations can be performed according to the late complications, especially since many of them can be performed easily and without complicated instrumental measures. By taking a detailed history, additional (cardio-) vascular risk factors must be inquired about in order to assess and treat angiopathic damage in a timely manner.

At least once a year a test for Microalbuminuria necessary.

Therapy

Diet in diabetes mellitus

In principle, a distribution of smaller meals throughout the day is advantageous in order not to provoke too great a fluctuation in insulin requirements. Alcohol inhibits gluconeogenesis and therefore increases the risk of hypoglycemia during insulin therapy. If alcohol is drunk, carbohydrates should always be taken at the same time.

It is a common opinion that diabetics should eat a particularly "low-sugar" diet, but this is not advantageous. Glucose requirements are not reduced by the disease.

It is much more important to aim for a balanced diet with slowly absorbable saccharides be observed. In conjunction with adequate dietary fiber, a more leisurely rate of sugar resorption can be achieved, attenuating blood sugar spikes. Fructose is processed independently of insulin, but is more likely to lead to dyslipoproteinemia and obesity than other sugars.

Optimal composition of the diet:

– 30% fat – 55% carbohydrates – 15% proteins

With regard to dietary recommendations, it is also important to distinguish between types of diabetes. The following principles can be remembered:

– Weight normalization has the highest priority for type 2 diabetics. This can lead to a breakthrough of the above described Circulus vitiosus be achieved and the insulin resistance tendency be normalized again. – Type 1 diabetics are usually normal or underweight. In this case, an optimal balance between glucose intake and insulin administration must be sought through diet in order to avoid dangerous hypo- or hyperglycemia.

Pharmacological therapy of diabetes mellitus

Type 1 diabetes mellitus is essentially dependent on the administration of insulin due to its absolute insulin deficiency. In type 2 diabetes mellitus, a phase-specific stepwise therapy consisting of weight normalization, oral antidiabetics and insulin is used.

The oral antidiabetic drugs (OAD)

Because of the high prevalence of diabetes, a wide range of oral antidiabetic agents is available. A distinction is made between insulinotropic. Non-insulinotropic medication. Effect on target tie of insulin. Improve its efficiency. The risk of hypoglycemia is significantly lower in this case. Used especially at the beginning of the disease. Cell increased insulin secretion. Can still be used in later stages of the disease. However, there is an increased risk of relevant hypoglycemia.

Non-insulinotropic antidiabetics include Biguanides (metformin), alpha glucosidase inhibitors (acarbose, miglitol) and Glitazones (pioglitazone, rosiglitazone).

Insulinotropic agents include the group of sulfonylureas (glibenclamide, glimepiride), the glinides (Repaglinide, nateglinide) and GLP1-oriented therapy using DPP4 inhibitors (sitagliptin, vildagliptin, saxaglitpin) or incretin mimetics (Exenatide, liraglutide).

The GLP1 (= GLucagon like Peptide 1) is a small intestinal hormone that is released in a meal-dependent manner, promotes insulin secretion and inhibits glucagon release and gastric emptying. GLP1 thus stimulates insulin secretion primarily in a glucose-dependent manner and under hyperglycemic conditions, so there is little effect of GLP1 under normoglycemic blood glucose levels.

Notice: At the time of diagnosis, there is often a relatively high insulin level due to the metabolic syndrome. Insulinotropic substances improve blood glucose via further increased insulin secretion, but at the same time increase metabolic syndrome!

Therapy with insulins

Image: "Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6). It works at other sizes, but sometimes truncates the text on the far right." by Magnus Manske. License: Public Domain

Insulin is a polypeptide which causes glucose uptake in muscle and fat cells and also supports an anabolic metabolic state. Insulin also causes a transport of potassium to the intracellular level. We humans normally experience permanent basal insulin secretion. A food-dependent increase in insulin secretion to cope with the sudden sugar oversupply. If there is an absolute deficiency or a relative deficit that can no longer be compensated for by oral antidiabetic drugs, a therapy option using insulin must be found that is as close as possible to "natural" insulin production.

To achieve this, a number of different insulins with special pharmacokinetic properties are available:

Therapeutic regimens for individual insulin therapy

In order to optimally serve the individual insulin needs, there are various strategies that take into account the risks and possibilities of the patient:

1. Basal-assisted oral therapy (BOT): In this case, oral antidiabetic therapy is supplemented by the administration of long-acting insulins.

2. BOT plus therapy: In addition to BOT, blood glucose peaks caused by intensive meals are compensated with a short-acting insulin preparation

3. Conventional insulin therapy: In patients with regular daily routines and comparable daily meals, twice-daily administration of a mixed insulin may be considered.

A fixed amount of insulin is administered at breakfast and dinner to cover the entire daily requirement. This concept is very easy to implement if the meal size remains constant. Changes in the structure of daily life can become problematic (sports, alcohol, excursions, etc).). Either dangerous hyper- or hypoglycemia can occur.

4. Intensified conventional insulin therapy: A long-acting insulin is given as a fixed basal insulin dose. The remaining daily insulin requirement should cover the blood glucose peaks in the form of meal-dependent doses. The amount of insulin required in this case must be determined independently. Includes not only the calculated meal size but also the present fasting glucose value. This allows insulin to be administered as needed.

In addition to detailed diabetes training, the essential prerequisites for this therapy are cooperative patients who are capable of therapeutic self-care with daily blood glucose self-monitoring and also care by physicians with diabetes experience.

Notice: This concept replaces physiological insulin production most successfully! However, this insulin concept is not suitable for everyone.

Image: "Insulin pump and single malts" by Alden Chadwick . License: CC BY 2.0

5. Therapy with the insulin pump: A normal insulin or rapid-acting analog insulin can be administered via a pump attached externally to the belt s.c. can be administered. The pump continuously delivers a programmed amount of insulin every hour. At mealtimes, users determine a calculated insulin bolus according to intensified conventional insulin therapy, which is then "communicated" to the pump so that it gives the bolus additionally. The insulin pump is used, for example, in pregnant women or a pronounced dawn phenomenon.

How to treat acutely derailed blood glucose?

Acute hyperglycemic derailments are part of everyday medical life. Especially for situations in the emergency room, a few useful basic ideas should be remembered for the future:

– Administration of short-acting or long-acting insulin alone is not sufficient! – An individual baseline bolus therapy should be calculated. – For this, a basic insulin requirement of 0.5 E/kg body weight can be amed without the hypoglycemic risk becoming too great. – Depending on the level of the current blood glucose status, this basal requirement is initially extended according to a fixed correction scheme. – After this start of therapy, the blood glucose situation should be checked daily with appropriate dose titration.

A practical example to determine the starting dose: An 80 kg patient requires 80 kg x 0.5 E/kg body weight = 40 E insulin per day. These are distributed as 40 % basal insulin and 60 % to the prandial blood glucose peaks in the amed ratio 2 : 1 : 1 i.e. 12 E : 6 E : 6 E. Depending on the current blood glucose, this ratio is initially supplemented evenly, but the basal insulin amount remains the same!

The following supplementary table may be helpful and can be used in everyday clinical practice:

Hyperglycemia vs. Hypoglycemia – symptoms and emergency medication

Acute derailments of the blood glucose can, under certain circumstances, also ame life-threatening proportions. Hyper- and also hypoglycemic states can be somnolent or even comatose. These metabolic states must be quickly. Proper care.

The hyperglycemic derailment

Hyperglycemia causes hyperosmolarity with intracellular dehydration via insulin deficiency.

Typical symptoms are:

– Loss of appetite – Vomiting – Thirst – Polyuria – Weakness – Tachypnea – Exsiccosis

At the same time (especially in type 1 diabetics) there is an increased Lipolysis which can be achieved via the accumulation of ketone bodies to the metabolic acidosis (Ketoacidosis) with Pseudoperitonitis or acidotic breathing (with acetone odor).

Therapy is carried out under intensive medical measures. Rehydration should be provided as needed with compensation of the Hyperosmolarity occur. Via intravenous normal insulin in low dosage. Regular laboratory chemistry control results in a mild decrease in hyperglycemia. Acidosis is seen only with severe pH change (< 7,1) balanced with careful administration of bicarbonate.

The hypoglycemic derailment

Various factors can cause hypoglycemia in diabetics: Too much insulin, alcohol and sport or too few carbohydrates in the diet are the most common causes.

Conscious people can be treated with dextrose or sugary drinks (no sweeteners. ) intercept their blood glucose drop. unconscious patients receive intravenous high percentage (20% – 60%) glucose under regular blood glucose control. This should be followed by a minute clear up. If this does not succeed, the administration must be repeated (and other causes of unconsciousness considered).