Innovative or Simply Post-Modern?

Innovative or Simply Post-Modern?

New Paradigms in the Study of "Diabetes 

Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus: The cause of this autoimmune response is unknown.

Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to insulin properly. This form was previously referred to as "non insulin-dependent diabetes mellitus" or "adult-onset diabetes". The most common cause is a combination of excessive body weight and insufficient exercise.

Type 1 diabetes must be managed with insulin injections. Control of blood pressure and maintaining proper foot and eye care are important for people with the disease. Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes. Gestational diabetes usually resolves after the birth of the baby.

an estimated 463 million people had diabetes worldwide, with type 2 diabetes making up about 90% of the cases. Rates are similar in women and men. The global economic cost of diabetes-related health expenditure in 2017 was estimated at billion. Average medical expenditures among people with diabetes are about 2.3 times higher.

Signs and symptoms 

The classic symptoms of untreated diabetes are unintended weight loss, polyuria, polydipsia, and polyphagia. Symptoms may develop rapidly in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Diabetic emergencies 

People with diabetes may also experience diabetic ketoacidosis, a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital. A rarer but more dangerous condition is hyperosmolar hyperglycemic state, which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars. Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

Complications 

All forms of diabetes increase the risk of long-term complications. These typically develop after many years but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease and about 75% of deaths in people with diabetes are due to coronary artery disease. Other macrovascular diseases include stroke, and peripheral artery disease. These complications are also a strong risk factor for severe COVID-19 illness.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation. Having diabetes, especially when on insulin, increases the risk of falls in older people.

Causes 

Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types". "Hybrid forms of diabetes" include slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. "Hyperglycemia first detected during pregnancy" includes gestational diabetes mellitus and diabetes mellitus in pregnancy. The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.

Type 1 

Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults.

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis, and endocrinopathies.

Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans. Among dietary factors, data suggest that gliadin may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.

Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.

Type 2 

Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.

Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity, lack of physical activity, poor diet, stress, and urbanization. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Lack of physical activity may increase the risk of diabetes in some people.

Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.

Antipsychotic medication side effects and unhealthy lifestyles, are potential risk factors.

Gestational diabetes 

Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time.

Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia, congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetus's blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.

Other types 

Maturity onset diabetes of the young is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.

Some cases of diabetes are caused by the body's tissue receptors not responding to insulin ; this form is very uncommon. Genetic mutations can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes. Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes. Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance. The ICD-10 diagnostic entity, malnutrition-related diabetes mellitus, was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.

Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.

The following is a list of disorders that may increase the risk of diabetes:

Genetic defects of β-cell function

Maturity onset diabetes of the young

Mitochondrial DNA mutations

Genetic defects in insulin processing or insulin action

Defects in proinsulin conversion

Insulin gene mutations

Insulin receptor mutations

Exocrine pancreatic defects 

Chronic pancreatitis

Pancreatectomy

Pancreatic neoplasia

Cystic fibrosis

Hemochromatosis

Fibrocalculous pancreatopathy

Endocrinopathies

Growth hormone excess 

Cushing syndrome

Hyperthyroidism

Hypothyroidism

Pheochromocytoma

Glucagonoma

Infections

Cytomegalovirus infection

Coxsackievirus B

Drugs

Glucocorticoids

Thyroid hormone

β-adrenergic agonists

Statins

Pathophysiology 

Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.

The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen, the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.

If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin, or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency. This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst.

Diagnosis 

Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 7.0 mmol/L is considered diagnostic for diabetes mellitus.

Per the WHO, people with fasting glucose levels from 6.1 to 6.9 mmol/L are considered to have impaired fasting glucose. People with plasma glucose at or above 7.8 mmol/L, but not over 11.1 mmol/L, two hours after a 75 gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The American Diabetes Association since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/L.

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.

Prevention 

There is no known preventive measure for type 1 diabetes. by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet.