Instruct: Given a question, retrieve relevant passages that answer the question.
Query: What does diabetes cause a resistance to?
Insulin resistance (IR) is considered as a pathological condition in which cells fail to respond normally to the hormone insulin.[1] To prevent hyperglycemia and noticeable organ damage over time,[2] the body produces insulin when glucose starts to be released into the bloodstream, primarily from the digestion of carbohydrates in the diet. Under normal conditions of insulin reactivity, this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy, thereby causing the concentration of glucose in the blood to decrease as a result, staying within the normal range even when a large amount of carbohydrates is consumed. Carbohydrates comprise simple sugars, i.e. monosaccharides, such as glucose and fructose, disaccharides, such as cane sugar, and polysaccharides, e.g. starches. Fructose, which is metabolised into triglycerides in the liver, stimulates insulin production through another mechanism, and can have a more potent effect than other carbohydrates. A habitually high intake of carbohydrates, and particularly fructose, e.g. with sweetened beverages, contributes to insulin resistance and has been linked to weight gain and obesity.[3][4][5] If excess blood sugar is not sufficiently absorbed by cells even in the presence of insulin, the increase in the level of blood sugar can result in the classic hyperglycemic triad of polyphagia (increased appetite), polydipsia (increased thirst), and polyuria (increased urination). Avoiding carbohydrates and sugars, a no-carbohydrate diet or fasting can reverse insulin resistance.[6][7]
It is known that diabetes causes changes to factors associated with coagulation and clotting, however not much is known of the risk of thromboembolism, or clots, in diabetic patients. There are some studies that show that diabetes increases the risk of thromboembolism; other studies show that diabetes does not increase the risk of thromboembolism. A study conducted in the Umea University Hospital, in Sweden, observed patients that were hospitalized due to an thromboembolism from 1997 to 1999. The researchers had access to patient information including age, sex, vein thromboembolism diagnosis, diagnostic methods, diabetes type and medical history. This study concluded that there is, in fact, an increased risk of thromboembolism development in diabetic patients, possibly due to factors associated with diabetes or diabetes itself. Diabetic patients are twice as likely to develop a thromboembolism than are non-diabetic patient. The exact mechanism of how diabetes increases the risk of clot formation remains unclear and could possibly be a future direction for study.
The signs of diabetes mellitus are caused by a persistently high blood glucose concentration, which may be caused by either insufficient insulin, or by a lack of response to insulin. Most cats have a type of diabetes mellitus similar to human diabetes mellitus type 2, with β-cell dysfunction and insulin resistance. Factors which contribute to insulin resistance include obesity and endocrine diseases such as acromegaly. Acromegaly affects 20–30% of diabetic cats; it can be diagnosed by measuring the concentration of insulin-like growth factor-1 (IGF-1) in the blood.
Rare type 2 diabetes cases sometimes use high levels of exogenous insulin. As short-term overdosing of insulin causes short-term insulin resistance, it has been hypothesized that chronic high dosing contributes to more permanent insulin resistance.
Most diabetic foot infections (DFIs) require treatment with systemic antibiotics. The choice of the initial antibiotic treatment depends on several factors such as the severity of the infection, whether the patient has received another antibiotic treatment for it, and whether the infection has been caused by a micro-organism that is known to be resistant to usual antibiotics (e.g. MRSA). The objective of antibiotic therapy is to stop the infection and ensure it does not spread.
Tooth decay and cavities are some of the first oral problems that individuals with diabetes are at risk for. Increased blood sugar levels translate into greater sugars and acids that attack the teeth and lead to gum diseases. Gingivitis can also occur as a result of increased blood sugar levels along with an inappropriate oral hygiene. Periodontitis is an oral disease caused by untreated gingivitis and which destroys the soft tissue and bone that support the teeth. This disease may cause the gums to pull away from the teeth which may eventually loosen and fall out. Diabetic people tend to experience more severe periodontitis because diabetes lowers the ability to resist infection and also slows healing. At the same time, an oral infection such as periodontitis can make diabetes more difficult to control because it causes the blood sugar levels to rise.
It has been suggested that people experiencing short-term sleep restrictions process glucose more slowly than individuals receiving a full 8 hours of sleep, increasing the likelihood of developing type 2 diabetes. In 2005, a study of over 1400 participants showed that participants who habitually slept few hours were more likely to have associations with type 2 diabetes. However, because this study was merely correlational, the direction of cause and effect between little sleep and diabetes is uncertain. The authors point to an earlier study which showed that experimental rather than habitual restriction of sleep resulted in impaired glucose tolerance (IGT). Sleep deprivation can cause insulin resistance in the body, triggering the onset of early diabetes.
It is important to note that those discovered genes do not determine susceptibility to diabetes for all people or cases. As the risk of diabetes is combination of the gene regulations and the interplay between those gene products, certain genes may not pose a threat to increase the susceptibility. TCF7L2 is one of the well-studied genes for diabetes susceptibility in most populations. However, SNPs in TCF7L2 that would normally increase the risk of diabetes does not affect the susceptibility for Pima Indians. However, this gene is associated with regulating the BMI for Pima Indian population.
Insulin resistance in muscle and fat cells reduces glucose uptake (and also local storage of glucose as glycogen and triglycerides, respectively), whereas insulin resistance in liver cells results in reduced glycogen synthesis and storage and also a failure to suppress glucose production and release into the blood. Insulin resistance normally refers to reduced glucose-lowering effects of insulin. However, other functions of insulin can also be affected. For example, insulin resistance in fat cells reduces the normal effects of insulin on lipids and results in reduced uptake of circulating lipids and increased hydrolysis of stored triglycerides. Increased mobilization of stored lipids in these cells elevates free fatty acids in the blood plasma. Elevated blood fatty-acid concentrations (associated with insulin resistance and diabetes mellitus Type 2), reduced muscle glucose uptake, and increased liver glucose production all contribute to elevated blood glucose levels. High plasma levels of insulin and glucose due to insulin resistance are a major component of the metabolic syndrome. If insulin resistance exists, more insulin needs to be secreted by the pancreas. If this compensatory increase does not occur, blood glucose concentrations increase and type 2 diabetes or latent autoimmune diabetes of adults occurs.[55][57]
Diabetes is a chronic metabolic disease characterized by increase blood glucose level. Type 2 diabetes is the most common form of diabetes. It is caused by resistance to insulin or the lack of production of insulin. It is seen most commonly in adults. Type 1 diabetes or juvenile diabetes affects mostly children. This condition is due to little or lack of insulin production from the pancreas.
There are numerous theories as to the exact cause and mechanism in type 2 diabetes. Central obesity is known to predispose individuals for insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines that may possibly impair glucose tolerance. But adiponectin which is found in lower concentration in obese and diabetic individuals has shown to be beneficial and protective in type 2 diabetes mellitus.
Diabetes mellitus is a disease in which the beta cells of the endocrine pancreas either stop producing insulin or can no longer produce it in enough quantity for the body's needs. The condition is commonly divided into two types, depending on the origin of the condition: Type 1 diabetes, sometimes called "juvenile diabetes", is caused by destruction of the beta cells of the pancreas. The condition is also referred to as insulin-dependent diabetes, meaning exogenous insulin injections must replace the insulin the pancreas is no longer capable of producing for the body's needs. Dogs can have insulin-dependent, or Type 1, diabetes; research finds no Type 2 diabetes in dogs. Because of this, there is no possibility the permanently damaged pancreatic beta cells could re-activate to engender a remission as may be possible with some feline diabetes cases, where the primary type of diabetes is Type 2. There is another less common form of diabetes, diabetes insipidus, which is a condition of insufficient antidiuretic hormone or resistance to it.
Diabetes mellitus type 2 is the most common form of diabetes. The causes for high blood sugar in this form of diabetes usually are a combination of insulin resistance and impaired insulin secretion, with both genetic and environmental factors playing an important role in the development of the disease. The management of type 2 diabetes relies on a series of changes in diet and physical activity with the purpose of reducing blood sugar levels to normal ranges and increasing insulin sensitivity. Biguanides such as metformin are also used as part of the treatment along with insulin therapy.
The most common type of insulin resistance is associated with overweight and obesity in a condition known as the metabolic syndrome. Insulin resistance often progresses to full Type 2 diabetes mellitus (T2DM) or latent autoimmune diabetes of adults.[58][59] This often is seen when hyperglycemia develops after a meal, when pancreatic β-cells are unable to produce sufficient insulin to maintain normal blood sugar levels (euglycemia) in the face of insulin resistance. The inability of the β-cells to produce sufficient insulin in a condition of hyperglycemia is what characterizes the transition from insulin resistance to T2DM.[60]
Hepatitis C also makes people three to four times more likely to develop type 2 diabetes and insulin resistance.[15] In addition, "people with Hepatitis C who develop diabetes probably have susceptible insulin-producing cells, and probably would get it anyway, but much later in life.[15] The extra insulin resistance caused by Hepatitis C apparently brings on diabetes at age 35 or 40, instead of 65 or 70."[15]
It happens rarely, but it is possible for a pancreatitis attack to activate the endocrine portion of the organ back into being capable of producing insulin once again in dogs. It is possible for acute pancreatitis to cause a temporary, or transient diabetes, most likely due to damage to the endocrine portion's beta cells. Insulin resistance that can follow a pancreatitis attack may last for some time thereafter. Pancreatitis can damage the endocrine pancreas to the point where the diabetes is permanent.
While obesity is an independent risk factor for type 2 diabetes that may be linked to lifestyle, obesity is also a trait that may be strongly inherited. Other research also shows that type 2 diabetes can cause obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.
The nerve damage associated with the disease was first thought to be caused by metabolic changes such as endoneurial microvessel disease, which is the degeneration of pericytes due to hyperglycemia, and the reproduction of basement membranes when the pericytes are no longer regulating their cell cycle. The decreased size of the lumen plus the absence of the pericyte, which regulate capillary blood flow and phagocytosis of cellular debris, leads to ischemia. Nerve biopsies have shifted the view toward an immune mechanism that causes Micro Vasculitis, which could eventually lead to ischemia. Experimental treatments using immunosuppressive proteins have provided further corroborative evidence to the immune mechanism theory. Although this disease does occur in patients without diabetes the prevalence is much greater in the diabetic indicating that although hyperglycemia does not directly cause the nerve damage it may play a role.
Research on the two types of HAIR-AN demonstrated that patients with both forms of HAIR-AN had very high levels of insulin and, critically, that it was the high insulin that caused the elevation in androgen. The patient affected by HAIR-AN syndrome has insulin resistance inside their body. Insulin resistance is a condition in which the body produces insulin but does not use it properly. This causes the pancreas to produce more insulin in the body. High levels of insulin stimulate the ovaries to make excess of androgen, leading to excessive hair growth, acne and irregular periods in the female body. Insulin resistance can also lead to diabetes, heart disease and excessive growth and darkening of the skin (acanthosis nigricans)
Alloxan is a toxic glucose analogue, which selectively destroys insulin-producing cells in the pancreas (that is beta cells) when administered to rodents and many other animal species. This causes an insulin-dependent diabetes mellitus (called "alloxan diabetes") in these animals, with characteristics similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially accumulates in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, generates reactive oxygen species (ROS) in a cyclic reaction with its reduction product, dialuric acid. The beta cell toxic action of alloxan is initiated by free radicals formed in this redox reaction. Studies suggests that alloxan does not cause diabetes in humans. Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1.
Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) 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 (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, "malnutrition-related diabetes mellitus" (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
Diabetes mellitus type 2 is a common disease that causes reduced insulin secretion and increased insulin resistance in the periphery. It results in increased blood glucose levels, or hyperglycemia, which can be fatal if untreated. Since Wnt signaling is involved in insulin sensitivity, malfunctioning of its pathway could be involved. Overexpression of Wnt5b, for instance, may increase susceptibility due to its role in adipogenesis, since obesity and type II diabetes have high comorbidity. Wnt signaling is a strong activator of mitochondrial biogenesis. This leads to increased production of reactive oxygen species (ROS) known to cause DNA and cellular damage. This ROS-induced damage is significant because it can cause acute hepatic insulin resistance, or injury-induced insulin resistance. Mutations in Wnt signaling-associated transcription factors, such as TCF7L2, are linked to increased susceptibility.
CFRD shares features of both type 1 and type 2 diabetes. CFRD patients are typically young and are not obese, and lack metabolic syndrome features. On the other hand, the cause is not autoimmune, some insulin resistance is present, and ketosis is rare.
The degree of blood sugar elevation does not worsen rapidly with age, and long-term diabetic complications are rare. In healthy children and adults, a high blood sugar level can be avoided by a healthy diet and exercise, primarily avoiding large amounts of carbohydrates. However, as people who have MODY2 enter their 50's and 60's, even though they continue to eat a healthy diet and exercise, they sometimes are unable to control a high blood sugar level with these measures. In these cases, many medicines for type II diabetes mellitus are not effective, because MODY2 does not cause insulin resistance. Repaglinide (Prandin) can help the body regulate the amount of glucose in the blood by stimulating the pancreas to release insulin before meals. In some cases, the baseline glucose levels are too high as well and insulin is required.
The concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by Professor Wilhelm Falta and published in Vienna in 1931,[91] and confirmed as contributory by Sir Harold Percival Himsworth of the University College Hospital Medical Centre in London in 1936,[92] however, type 2 diabetes does not occur unless there is concurrent failure of compensatory insulin secretion.[93]