Diabetes mellitus type 2In diabetes mellitus type 2, the organism loses the ability to regulate glucose metabolism. The ability of somatic cells to take up glucose from the blood and the function of pancreatic beta cells to produce and release insulin decreases over time. The result is chronically elevated blood glucose levels with damage to blood vessels and nerves.
Diabetes mellitus type 2: Overview
Diabetes, adult-onset diabetes, type 2 diabetes
Diabetes mellitus refers to a group of metabolic diseases that are all characterized by hyperglycemia as a result of disturbances in insulin secretion and/or insulin action. Depending on the etiology, different forms are distinguished. Among adults, type 2 diabetes dominates, a chronic, highly heterogeneous, multifactorial, progressive disease that u. a. Characterized by inherited and acquired insulin resistance and by qualitative and quantitative insulin secretion disorders.
The disease is one of the most common metabolic disorders. Data from the Robert Koch Institute show that a total of 7.2% of adults (4.6 million) aged 18 to 79 have ever been diagnosed with diabetes (2008-2011). Since the last evaluation (1997-1999), the prevalence increased by 1.6% (from 5.6 to 7.2%). However, the risk of disease has not changed, but the increase is mainly based on the larger number of older people. At the age of about 80 years the prevalence of type 2 diabetes is highest.
There are regional differences throughout Germany. The prevalence of diabetes ranges from 8.9% to 11.6%. These regional differences are caused, among other things, by structural deprivation (z.B. high unemployment rate, lower tax revenues in a defined region) and influenced by living conditions (health-promoting environment such as green spaces and pedestrian-friendliness). About 16% of all deaths are associated with type 2 diabetes.
According to current knowledge, type 2 diabetes mellitus is based on a multifactorial predisposition to the disease. The development of the clinical picture of the disease occurs under the influence of so-called manifestation or risk factors. In addition to a genetic predisposition, factors that promote manifestation could include a high-fat diet, obesity and lack of exercise, and are often present in the form of a metabolic syndrome. Often, in the early stages, the disease can be relegated to latency if the modifiable manifesting factors are successfully treated.
In type 2 diabetes, insulin resistance of peripheral ties results in increased insulin requirements. This in turn initially leads to an increase in the insulin-producing beta cell mass and to hyperinsulinemia. However, the stock of beta cells is gradually depleted and dysfunction (defects in insulin secretion) sets in. Eventually the mass of beta cells is lost by apoptosis. Leads to chronic hyperglycemia.
At the beginning, diabetes mellitus often progresses without symptoms. Only later do typical symptoms such as:
– strong thirst – dullness, exhaustion – increased urination – itching – ravenous appetite – visual disturbances – susceptibility to infections.
Chronic hyperglycemia in diabetes is associated with a significantly increased risk of severe concomitant and secondary diseases of various organs, especially the eyes, kidneys, nerves and cardiovascular system.
If left untreated, hyperglycemia can lead to diabetic coma.
The German Diabetes Society has published an algorithm for the diagnosis of glucose metabolism disorders. The diagnosis of diabetes is made at
– HbA1c ≥6.5% (≥48mmol/mol Hb) and – Fasting plasma glucose of ≥126mg/dl (≥7.0mmol/l) and/or – OGTT-2-h value in venous plasma ≥200mg/dl (≥11.1mmol/l).
Since accompanying or. secondary diseases are already present to a large extent at the time of diagnosis of type 2 diabetes, the guidelines provide for an investigation of diabetes-associated complications in people with type 2 diabetes already at the time of diagnosis, especially:
– Diabetic neuropathy – Foot lesions – Nephropathy – Retinal complications – Macrovascular and microvascular overall risk – Depressive disorder.
The therapeutic goal is to adjust blood glucose levels to:
– 80 to 120 mg/dl (4.4 and 6.7 mmol/l) during the day – 100 to 140 mg/dl (5.6 and 7.8 mmol/l) before bedtime – HbA1c levels< 7%.
Physicians choose which medications to use for each patient, taking into account the presence of co-morbidities, dietary and exercise habits, body weight, and other factors. If blood glucose levels are not too high at diagnosis, physicians initially recommend non-drug measures. In the case of blood glucose values >200 mg/dl (11.1 mmol/l) or if it is not possible to reduce the blood glucose values through lifestyle changes over a period of several months, medication is used.
Non-drug basic therapy
Lifestyle change counseling should include the following areas:
– Switching to a healthy and balanced diet – Physical activity – Weight loss in overweight and obese people – If necessary. Smoking cessation – If applicable. Stress Management.
The guidelines call for a stepwise approach, starting with metformin or other monotherapy if metformin is intolerant. If the individual HbA1c target is not reached after 3 – 6 months, a second and possibly a third therapy can be started. third preparation can be combined. A combination of two agents with different mechanisms of action is recommended. If blood glucose control remains inadequate, insulin can be used in addition to oral antidiabetics or as monotherapy.
There are a number of antidiabetic medications available:
– Metformin (first choice) and thiazolidinediones (glitazones) and glinides – DPP-4 inhibitors – GLP-1 analogues – alpha-glucosidase inhibitors (AGI) .
A dual combination is necessary for many patients for metabolic reasons and is more favorable with regard to side effects of the individual substances, since lower doses can often be used in the combination.
Typical combination partners include metformin and sulfonylureas or metformin and GLP-1 analogues or. DPP-4 inhibitors, but also combinations of the above-mentioned diabetes drugs with an SGLT-2 inhibitor (Gliflozine) are increasingly used. These are also good combination partners for metformin and DPP-4 inhibitors due to the novel therapeutic principle (excretion of the elevated blood glucose via the kidney).
Nowadays, not only a double but also a triple combination is possible without increasing the risk of hypoglycemia. Triple therapy is also an option when patients decide against early insulin therapy.
Conventional insulin therapy, also combined with oral antidiabetics
The form of insulin therapy chosen depends on the patient's individual conditions and needs and the blood glucose profiles in everyday life. In addition to controlling blood glucose levels, the avoidance of severe hypoglycemia. Significant weight gain is an important therapy goal.
Intensified insulin therapy
Intensified insulin therapy – now standard in type 1 diabetes – is defined as the administration of at least three insulin injections per day. Above all, however, it is characterized by a substitution of basal insulin requirements with long-acting "basal insulin". Prandial insulin requirement with short-acting "bolus insulin" at meals (basal-bolus principle). If the insulin dosage is to be adjusted and varied particularly precisely, there is the option of using an insulin pump.
When conservative therapy options for weight loss have been exhausted, patients with extreme obesity (BMI>40) or with BMI>35 and secondary diseases may be considered for gastric reduction surgery. Reduction in stomach volume and/or distance of gastrointestinal passage alters food intake, absorption and metabolic processes.
Diabetes therapy during pregnancy and lactation
In ca. In 85% of cases, a change in diet with restriction of fat or insulin intake is sufficient. Carbohydrate and calorie intake, an increase in fiber intake and a distribution of carbohydrates over six meals are sufficient to lower blood glucose levels into the target range. If target values are exceeded in more than half of the measurements despite diet, insulin therapy is necessary. Insulin dose is continuously adjusted to meet changing needs until birth. Further information can be found in the section on gestational diabetes. Both hypoglycemia and hyperglycemia are acute emergencies. Must be treated as quickly as possible.
Hypoglycemia is when the blood glucose level drops below 50 mg/dl. Hypoglycemia can have various causes such as z.B. Overdose of blood glucose-lowering drugs or too low an energy intake (z.B. Skipping a meal) or severe physical exertion while insulin or tablet doses remain constant. Typical symptoms of hypoglycemia are sweating, trembling, palpitations, feelings of hunger and anxiety, and at blood glucose levels below 30 mg/dl also convulsions and unconsciousness.
Acute therapy for hypoglycemia consists of carbohydrate ingestion, injection of glucagon, or infusion of glucose solution.
Hyperglycemia is a rise in blood glucose levels to levels above 250 mg/dl.
Diabetic ketoacidosis usually occurs in type 1 diabetes, but can also occur in a mild form in patients with type 2 diabetes. It is defined as the simultaneous occurrence of
– Hyperglycemia (blood glucose usually well above 250 mg/dl), – Metabolic acidosis (arterial pH< 7.35 or venous pH< 7,3), – Ketonemia / ketonuria.
The most frequent cause of ketoacidosis in diabetics are infections, especially pneumonia, urinary tract infections and abscesses, as well as forgotten or underdosed insulin doses and technical problems with insulin pump therapy.
Clinical symptoms in ketoacidosis are not always clear-cut. Frequently clinically leading are nausea, vomiting and abdominal pain. In case of severe derailment, there is a strong deepening of breathing with acetone odor in the breathing air.
The basis of the therapy is fluid replacement and insulin administration under close monitoring.
Hyperosmolar hyperglycemic syndrome (HHS) mostly affects older people with type 2 diabetes. Defined HHS as the simultaneous occurrence of:
– extreme hyperglycemia (600 mg/dl to over 1000 mg/dl) – hyperosmolality (water deficit due to an excess of dissolved glucose) – severe dehydration (dehydration).
As with ketoacidosis, the most frequent causes are infections and application or technical errors in insulin therapy.
Symptoms often begin with uncharacteristic complaints such as fatigue and sleepiness. Other possible symptoms include dehydration from polyuria, hypotension, muscle reflex weakening, apathy to coma.
The basis of therapy is the slow compensation of fluid loss. After a normal metabolism has been achieved, the diabetes mellitus is readjusted.
A number of high-quality, international studies have shown that lifestyle changes such as weight reduction, physical activity, and a high-fiber, low-fat diet reduce the relative risk of developing diabetes from impaired glucose tolerance (prediabetes) by up to 70%. In addition to lifestyle modifications, certain medications can also be helpful in supporting the primary prevention of type 2 diabetes.
Despite modern drug therapies, it is not possible to completely normalize blood glucose levels in all cases, so that up to 50% of patients suffer chronic sequelae and serious complications such as macroangiopathies (coronary heart disease, stroke, arterial occlusive disease), microangiopathies (retinopathy, nephropathy), neuropathies, and diabetic foot syndrome (neuropathy and angiopathy) with the risk of amputation.
Other forms of diabetes
Type 1 diabetes
In type 1 diabetes mellitus, an autoimmune reaction destroys the insulin-producing beta cells in the islets of Langerhans in the pancreas, resulting in insulin deficiency.
type 3 diabetes
Experts of the Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association summarized further, rare forms of diabetes mellitus, which are not classified as type 1 or type 2, under the term type 3 diabetes:
– Type 3a diabetes: genetic defects in beta cells (MODY) – Type 3b diabetes: genetic defects in insulin action – Type 3c diabetes: pancreatic disorders – Type 3d diabetes: impaired hormone production – Type 3e diabetes: chemicals and drugs – Type 3f diabetes: viruses – Type 3g diabetes: autoimmune disorders – Type 3h diabetes: genetic syndromes.
Glucose tolerance disorder occurring for the first time during pregnancy is called gestational or gestational diabetes. The increased steroid hormones present in the body inhibit the action of insulin, so blood glucose levels rise sharply when the pancreas cannot compensate for the increased insulin demand. Usually, this form of diabetes disappears after pregnancy ends. The risk of later development of type 2 diabetes is greatly increased in mothers and children.
Curative treatment options under development
To date, there is no curative treatment for diabetes mellitus. Researchers hope to achieve enhancement of endogenous mechanisms of beta cell regeneration in type 2 diabetes, leading to improved blood glucose control. The most promising approaches of current research programs are (a) increasing beta cell self-replication or neogenesis from pancreatic facultative stem cells and (b) converting pancreatic alpha cells into beta cells.