Diabetes mellitus type 2
Encyclopedia
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance
and relative insulin
deficiency. Diabetes
is often initially managed by increasing exercise
and dietary modification
. If the condition progresses, medications may be needed. Often affecting the obese
, diabetes requires patients to routinely check their blood sugar
.
Unlike type 1 diabetes
, there is very little tendency toward ketoacidosis
although it is not unheard of. One effect that can occur is nonketonic hyperglycemia
. Long-term complications from high blood sugar can include increased risk of heart attacks, strokes, diabetic retinopathy where eye sight is affected, and kidney failure. For extreme cases, circulation of limbs is affected, potentially requiring amputation. Loss of hearing, eyesight, and cognitive ability has also been linked to this condition.
(frequent urination), polydipsia
(increased thirst), polyphagia
(increased hunger), fatigue and weight loss. Type II diabetes has been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia
. Researchers have shown that reduced glucose tolerance has deleterious effects on memory in the elderly, and concomitant hippocampal atrophy.
, and the pioneering work of Professor Barker.
, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight
was included, the rate was 89% lower. In this study, a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index
. Obesity
has been found to contribute to approximately 55% of cases of type 2 diabetes, and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk. The increased rate of childhood obesity
between the 1960s and 2000s is believed to have led to the increase in type 2 diabetes in children and adolescents. Dietary fat intake is linked to diabetes risk.
A 2010 meta-analysis of eleven studies involving 310,819 participants and 15,043 cases of type 2 diabetes found that "SSBs [sugar-sweetened beverages] may increase the risk of metabolic syndrome and type 2 diabetes not only through obesity but also by increasing dietary glycemic load, leading to insulin resistance, β-cell dysfunction, and inflammation."
Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A weak positive correlation has been found between the concentration in the urine of bisphenol A
, a constituent of some plastics, and the incidence of type 2 diabetes.
, elevated cholesterol
(combined hyperlipidemia
), and with the condition often termed metabolic syndrome
(it is also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include acromegaly
, Cushing's syndrome
, thyrotoxicosis, pheochromocytoma
, chronic pancreatitis
, cancer, and drugs. Additional factors found to increase the risk of type 2 diabetes include aging, high-fat diets and a less active lifestyle.
Subclinical Cushing's syndrome
(cortisol excess) may be associated with type 1 diabetes. The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%. Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas.
Hypogonadism
is often associated with cortisol excess, and testosterone
deficiency is also associated with type 2 diabetes, even if the exact mechanism by which testosterone improves insulin sensitivity is still not known.
connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes substantially. Genetic risk for type 2 diabetes decreased as humans first began migrating around the world, implying a strong environmental component has affected the genetic-basis of type 2 diabetes . In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes.
About 55 percent of type 2 diabetes patients are obese
at diagnosis —chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue
(especially that in the abdomen around internal organs) is a source of several chemical signals, hormones and cytokines, to other tissues. Inflammatory cytokines for example may activate the NF-κB pathway which has been linked to the development of insulin resistance.
Other research shows that type 2 diabetes causes obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.
However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, as compared to lower incidence countries of origins. Such developments can also be found in environments which have had a recent increase in social wealth, increasingly common throughout Asia.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 diabetes have a much higher risk of developing type 2 diabetes, increasing with the number of those relatives. Concordance
among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2
, PPARG, FTO
, KCNJ11, NOTCH2
, WFS1
, CDKAL1, IGF2BP2
, SLC30A8
, JAZF1
, and HHEX
. KCNJ11 (potassium inwardly rectifying channel
, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon
gene expression and thus the production of glucagon-like peptide-1
. Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.
Monogenic
forms, e.g., MODY
, constitute 1–5 % of all cases.
Various hereditary conditions may feature diabetes, for example myotonic dystrophy
and Friedreich's ataxia
. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.
Gene expression promoted by a diet of fat and glucose, as well as high levels of inflammation related cytokines found in the obese, results in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance.
do not respond appropriately when insulin is present.
This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2 diabetes, including renal failure
, erectile dysfunction
, blindness, slow healing wounds (including surgical incisions), and arterial
disease, including coronary artery disease. The onset of type 2 diabetes has been most common in middle age
and later life
, although it is being more frequently seen in adolescents and young adults due to an increase in child obesity and inactivity. A type of diabetes called MODY
is increasingly seen in adolescents, but this is classified as a diabetes due to a specific cause and not as type 2 diabetes.
In the 2008 Banting Lecture of the American Diabetes Association, DeFronzo enumerates eight main pathophysiological factors in the type 2 diabetic organism
Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects
, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long-term steroid
use).
Recent studies of pancreatic beta cells have indicated a molecular connection between diet, obesity that involves the role of fat in activating a pathway to type 2 diabetes. In this mechanism, loss of beta cell glucose sensing contributes substantially to the early manifestation of diabetes, and beta cell dysfunction is responsible for the onset and severity of multiple systemic disease signs including impaired glucose tolerance, hyperglycemia, hepatic steatosis and insulin resistance in muscle and adipose cells. Previous work published in past decades by the laboratories of Roger Unger, Jerrold Olefsky, and Bernard Thorens alluded to the possibility of the importance of beta cell function and glucose sensing in these disease signs. This mechanism of beta cell dysfunction may be contributing substantially to the current epidemic of type 2 diabetes.
A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current diabetes with:
Glycated hemoglobin values that are elevated (over 5%), but not in the diabetic range (not over 7.0%) are predictive of subsequent clinical diabetes in United States female health professionals. In this study, 177 of 1061 patients with glycated hemoglobin value less than 6% became diabetic within 5 years compared to 282 of 26281 patients with a glycated hemoglobin value of 6.0% or more. This equates to a glycated hemoglobin value of 6.0% or more having:
is greater than 135/80 mmHg. For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening. The World Health Organization
recommends only testing those groups at high risk.
Based on a survey conducted in 2011 on 70,000 average persons, the Hungarian Diabetes Society recommends the introduction of a general screening of the adult population for Diabetes Type II.
, diet and exercise and/or metformin
or acarbose
may decrease the risk of developing diabetes. Lifestyle interventions are more effective than metformin.
, high cholesterol, and microalbuminuria
improves a person's life expectancy. Intensive blood sugar lowering as opposed to standard blood sugar lowering does not appear to change mortality.
is beneficial in diabetes with a greater amount of exercise yielding better results. It leads to a decrease in HbA1C, improved insulin sensitivity, and a better V02 max. Resistance training
is also useful and the combination of both types of exercise may be most effective. A diabetic diet
that promotes weight loss is important. While the best diet type to achieve this is controversial a low glycemic index diet has been found to improve blood sugar control. Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels, for up to six months at least.
There are several classes of medications available. Metformin
is generally recommended as a first line treatment as there is good evidence that it decreases mortality. Injections of insulin
may either be added to oral medication or used alone. Other classes of medications used to treat type 2 diabetes are sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and thiazolidinediones.
is used, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are increased to effect.
The initial insulin regimen is often chosen based on the patient's blood glucose profile. Initially, adding nightly insulin to patients failing oral medications may be best. Nightly insulin combines better with metformin
than with sulfonylurea
s.
When nightly insulin is insufficient, choices include:
with no universally accepted algorithm to decide who should have the surgery. In the diabetic patient, certain types result in 99-100% prevention of insulin resistance and 80-90% clinical resolution or remission of type 2 diabetes. In 1991, the NIH (National Institutes of Health) Consensus Development Conference on Gastrointestinal Surgery for Obesity proposed that the body mass index
(BMI) threshold to consider surgery should drop from 40 to 35 in the appropriate patient. More recently, the American Society for Bariatric Surgery
(ASBS) and the ASBS Foundation suggested that the BMI threshold be lowered to 30 in the presence of severe co-morbidities. Debate has flourished about the role of gastric bypass surgery in type 2 diabetics since the publication of The Swedish Obese Subjects Study. The largest prospective series showed a large decrease in the occurrence of type 2 diabetes in the post-gastric bypass patient at both 2 years (odds ratio
was 0.14) and at 10 years (odds ratio was 0.25).
A study of 20-years of Greenville (US) gastric bypass patients found that 80% of those with type 2 diabetes before surgery no longer required insulin or oral agents to maintain normal glucose levels. Weight loss occurred rapidly in many people in the study who had had the surgery. The 20% who did not respond to bypass surgery were, typically, those who were older and had had diabetes for over 20 years.
Research continues and several potential treatments may result in "cures". Examples include resection surgery of the upper small intestine, and very stringent restricted calorie diets. None is, as of 2011, sufficiently well understood, or adequately tested, to be of clinical significance. One or more might, possibly, become clinically significant for some cases, or even all, but this is some years away in the most fortunate instance.
In the United States
there are 23.6 million people (7.8% of the population) with diabetes with 17.9 million being diagnosed, 90% of whom are type 2. With prevalence rates doubling between 1990 and 2005, CDC
has characterized the increase as an epidemic
.
Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates due to alterations in dietary patterns as well as in life styles during childhood.
Type-2 diabetes mellitus is known to affect ethnic subgroups differently due to unique risk factors. For example, African Americans have a 12-fold greater prevalence than black natives of Africa. Cross-sectional epidemiological data suggests that the population with the highest type-two diabetes prevalence, however is the American Pima Indians. Their prevalence rates of 38% are substantially higher than those of Pima Indians in Mexico (prevalence of 6.9%). It appears that both insulin resistance and beta-cell dysfunction were common, leading to inherent genetic predisposition to type-2 diabetes across all Pima Indians. It is therefore concluded that the disproportionately high prevalence of diabetes in American Pima Indians is likely due to changes in westernization and urbanization of lifestyle/ environmental conditions in conjunction with underlying physiological predisposition.
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
and relative insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
deficiency. Diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
is often initially managed by increasing exercise
Physical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...
and dietary modification
Dieting
Dieting is the practice of eating food in a regulated fashion to achieve or maintain a controlled weight. In most cases dieting is used in combination with physical exercise to lose weight in those who are overweight or obese. Some athletes, however, follow a diet to gain weight...
. If the condition progresses, medications may be needed. Often affecting the obese
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, diabetes requires patients to routinely check their blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
.
Unlike type 1 diabetes
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
, there is very little tendency toward ketoacidosis
Diabetic ketoacidosis
Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
although it is not unheard of. One effect that can occur is nonketonic hyperglycemia
Non Ketonic Hyperglycemic coma
- Overview :Non-ketotic hyperglycemic coma is a metabolic derangement in which there is an abnormally high serum glucose level without ketoacidosis. It can occur as a complication of diabetes mellitus type 2 . In 30–40% of cases, it is the patient's initial presentation of diabetes...
. Long-term complications from high blood sugar can include increased risk of heart attacks, strokes, diabetic retinopathy where eye sight is affected, and kidney failure. For extreme cases, circulation of limbs is affected, potentially requiring amputation. Loss of hearing, eyesight, and cognitive ability has also been linked to this condition.
Signs and symptoms
The classic symptoms of diabetes are polyuriaPolyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
(frequent urination), polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
(increased thirst), polyphagia
Polyphagia
Polyphagia means "eating too much". It derives from the Greek words πολύς which means "very much", and φαγῶ , verb for "I eat"....
(increased hunger), fatigue and weight loss. Type II diabetes has been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia
Multi-infarct dementia
Multi-infarct dementia is one type of vascular dementia. Vascular dementia is the second most common form of dementia after Alzheimer's disease in older adults. Multi-infarct dementia is thought to be an irreversible form of dementia, and its onset is caused by a number of small strokes or...
. Researchers have shown that reduced glucose tolerance has deleterious effects on memory in the elderly, and concomitant hippocampal atrophy.
Cause
Type 2 diabetes is due to a combination of lifestyle and genetic factors. Recently, intrauterine growth restriction (IUGR) or prenatal undernutrition (macro- and micronutrient) was identified as another probable factor A clue for this concept was the Dutch Hunger Winter (1944-1945) during World War IIWorld War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, and the pioneering work of Professor Barker.
Lifestyle
A number of lifestyle factors are known to be important to the development of type 2 diabetes. In one study, those who had high levels of physical activity, a healthy dietHealthy diet
A healthy diet is one that helps maintain or improve general health. It is important for lowering many chronic health risks, such as obesity, heart disease, diabetes, hypertension and cancer. A healthy diet involves consuming appropriate amounts of all essential nutrients and an adequate amount of...
, did not smoke, and consumed alcohol in moderation had an 82% lower rate of diabetes. When a normal weight
Classification of obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health. Relative weight and body mass index are nearly identical and are reasonable estimates of body fatness as measured by percentage body fat...
was included, the rate was 89% lower. In this study, a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index
Glycemic index
The glycemic index, glycaemic index, or GI is a measure of the effects of carbohydrates on blood sugar levels. Carbohydrates that break down quickly during digestion and release glucose rapidly into the bloodstream have a high GI; carbohydrates that break down more slowly, releasing glucose more...
. Obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
has been found to contribute to approximately 55% of cases of type 2 diabetes, and decreasing consumption of saturated fats and trans fatty acids while replacing them with unsaturated fats may decrease the risk. The increased rate of childhood obesity
Childhood obesity
Childhood obesity is a condition where excess body fat negatively affects a child's health or wellbeing. As methods to determine body fat directly are difficult, the diagnosis of obesity is often based on BMI. Due to the rising prevalence of obesity in children and its many adverse health effects...
between the 1960s and 2000s is believed to have led to the increase in type 2 diabetes in children and adolescents. Dietary fat intake is linked to diabetes risk.
A 2010 meta-analysis of eleven studies involving 310,819 participants and 15,043 cases of type 2 diabetes found that "SSBs [sugar-sweetened beverages] may increase the risk of metabolic syndrome and type 2 diabetes not only through obesity but also by increasing dietary glycemic load, leading to insulin resistance, β-cell dysfunction, and inflammation."
Environmental toxins may contribute to recent increases in the rate of type 2 diabetes. A weak positive correlation has been found between the concentration in the urine of bisphenol A
Bisphenol A
Bisphenol A is an organic compound with two phenol functional groups. It is used to make polycarbonate plastic and epoxy resins, along with other applications....
, a constituent of some plastics, and the incidence of type 2 diabetes.
Medical conditions
There are many factors which can potentially give rise to, or exacerbate, type 2 diabetes. These include obesity, hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, elevated cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
(combined hyperlipidemia
Combined hyperlipidemia
In medicine, combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL...
), and with the condition often termed metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
(it is also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
, Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
, thyrotoxicosis, pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...
, chronic pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
, cancer, and drugs. Additional factors found to increase the risk of type 2 diabetes include aging, high-fat diets and a less active lifestyle.
Subclinical Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
(cortisol excess) may be associated with type 1 diabetes. The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%. Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas.
Hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
is often associated with cortisol excess, and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
deficiency is also associated with type 2 diabetes, even if the exact mechanism by which testosterone improves insulin sensitivity is still not known.
Genetics
There is also a strong inheritable geneticGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes substantially. Genetic risk for type 2 diabetes decreased as humans first began migrating around the world, implying a strong environmental component has affected the genetic-basis of type 2 diabetes . In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes.
About 55 percent of type 2 diabetes patients are obese
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
at diagnosis —chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
(especially that in the abdomen around internal organs) is a source of several chemical signals, hormones and cytokines, to other tissues. Inflammatory cytokines for example may activate the NF-κB pathway which has been linked to the development of insulin resistance.
Other research shows that type 2 diabetes causes obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance.
However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment as compared to the same genetic pool who have not. Immigrants to Western developed countries, for instance, as compared to lower incidence countries of origins. Such developments can also be found in environments which have had a recent increase in social wealth, increasingly common throughout Asia.
There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree relatives with type 2 diabetes have a much higher risk of developing type 2 diabetes, increasing with the number of those relatives. Concordance
Concordance (genetics)
Concordance as used in genetics usually means the presence of the same trait in both members of a pair of twins. However, the strict definition is the probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic. For example,...
among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type 2 diabetes, include TCF7L2
TCF7L2
Transcription factor 7-like 2 also known as TCF7L2 or TCF4 is a protein acting as a transcription factor. In humans this protein is encoded by the TCF7L2 gene...
, PPARG, FTO
FTO gene
Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16...
, KCNJ11, NOTCH2
NOTCH2
Neurogenic locus notch homolog protein 2 also known as notch 2 is a protein that in humans is encoded by the NOTCH2 gene.NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome.- Function :Notch 2 a member of the notch family...
, WFS1
WFS1
Wolframin is a protein that in humans is encoded by the WFS1 gene.-Function:Wolframin is a transmembrane protein. Wolframin appears to function as a cation-selective ion channel.-Clinical significance:...
, CDKAL1, IGF2BP2
IGF2BP2
Insulin-like growth factor 2 mRNA-binding protein 2 is a protein that in humans is encoded by the IGF2BP2 gene.-Further reading:...
, SLC30A8
SLC30A8
Solute carrier family 30 , member 8, also known as SLC30A8, is a human gene that codes for a zinc transporter related to insulin secretion in humans. Certain alleles of this gene may increase the risk for developing type 2 diabetes....
, JAZF1
JAZF1
Juxtaposed with another zinc finger protein 1 also known as TAK1-interacting protein 27 or zinc finger protein 802 is a protein that in humans is encoded by the JAZF1 gene...
, and HHEX
HHEX
Hematopoietically-expressed homeobox protein HHEX is a protein that in humans is encoded by the HHEX gene.-Interactions:HHEX has been shown to interact with Promyelocytic leukemia protein.-Further reading:...
. KCNJ11 (potassium inwardly rectifying channel
Inward-rectifier potassium ion channel
Inwardly rectifying potassium channels are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types...
, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates proglucagon
Proglucagon
Proglucagon is a protein that in humans is encoded by the GCG gene.Proglucagon is a precursor of glucagon, and several other components. It is generated in the alpha cells of the pancreas and in the intestinal L cells in the distal ileum and colon...
gene expression and thus the production of glucagon-like peptide-1
Glucagon-like peptide-1
Glucagon-like peptide-1 is derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. The biologically active forms of GLP-1 are: GLP-1- and GLP-1-NH2...
. Moreover, obesity (which is an independent risk factor for type 2 diabetes) is strongly inherited.
Monogenic
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
forms, e.g., MODY
Maturity onset diabetes of the young
Maturity onset diabetes of the young refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene disrupting insulin production...
, constitute 1–5 % of all cases.
Various hereditary conditions may feature diabetes, for example myotonic dystrophy
Myotonic dystrophy
Myotonic dystrophy is a chronic, slowly progressing, highly variable inherited multisystemic disease. It is characterized by wasting of the muscles , cataracts, heart conduction defects, endocrine changes, and myotonia. Myotonic dystrophy can occur in patients of any age...
and Friedreich's ataxia
Friedreich's ataxia
Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system, resulting in symptoms ranging from gait disturbance to speech problems; it can also lead to heart disease and diabetes....
. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder that first becomes evident in childhood. It consists of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.
Gene expression promoted by a diet of fat and glucose, as well as high levels of inflammation related cytokines found in the obese, results in cells that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance.
Pathophysiology
Insulin resistance means that body cellsCell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
do not respond appropriately when insulin is present.
This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2 diabetes, including renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, erectile dysfunction
Erectile dysfunction
Erectile dysfunction is sexual dysfunction characterized by the inability to develop or maintain an erection of the penis during sexual performance....
, blindness, slow healing wounds (including surgical incisions), and arterial
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
disease, including coronary artery disease. The onset of type 2 diabetes has been most common in middle age
Middle age
Middle age is the period of age beyond young adulthood but before the onset of old age. Various attempts have been made to define this age, which is around the third quarter of the average life span of human beings....
and later life
Old age
Old age consists of ages nearing or surpassing the average life span of human beings, and thus the end of the human life cycle...
, although it is being more frequently seen in adolescents and young adults due to an increase in child obesity and inactivity. A type of diabetes called MODY
Mody
Mody may refer to:* Maturity onset diabetes of the young * Hormusjee Naorojee Mody...
is increasingly seen in adolescents, but this is classified as a diabetes due to a specific cause and not as type 2 diabetes.
In the 2008 Banting Lecture of the American Diabetes Association, DeFronzo enumerates eight main pathophysiological factors in the type 2 diabetic organism
Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long-term steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
use).
Recent studies of pancreatic beta cells have indicated a molecular connection between diet, obesity that involves the role of fat in activating a pathway to type 2 diabetes. In this mechanism, loss of beta cell glucose sensing contributes substantially to the early manifestation of diabetes, and beta cell dysfunction is responsible for the onset and severity of multiple systemic disease signs including impaired glucose tolerance, hyperglycemia, hepatic steatosis and insulin resistance in muscle and adipose cells. Previous work published in past decades by the laboratories of Roger Unger, Jerrold Olefsky, and Bernard Thorens alluded to the possibility of the importance of beta cell function and glucose sensing in these disease signs. This mechanism of beta cell dysfunction may be contributing substantially to the current epidemic of type 2 diabetes.
Diagnosis
The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:- fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)
- or
- With a glucose tolerance testGlucose tolerance testA glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...
, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
- With a glucose tolerance test
Early detection
If a 2-hour postload glucose level of at least 11.1 mmol/L (≥ 200 mg/dL) is used as the reference standard, the fasting plasma glucose > 7.0 mmol/L (126 mg/dL) diagnoses current diabetes with:- sensitivity about 50%
- specificity greater than 95%
A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current diabetes with:
- sensitivity = 75%
- specificity = 88%
Glycated hemoglobin values that are elevated (over 5%), but not in the diabetic range (not over 7.0%) are predictive of subsequent clinical diabetes in United States female health professionals. In this study, 177 of 1061 patients with glycated hemoglobin value less than 6% became diabetic within 5 years compared to 282 of 26281 patients with a glycated hemoglobin value of 6.0% or more. This equates to a glycated hemoglobin value of 6.0% or more having:
- sensitivity = 16.7%
- specificity = 98.9%
Screening
No major organization recommends universal screening for diabetes as there is no evidence that such a program would improve outcomes. Screening is recommended by the United States Preventive Services Task Force in adults without symptoms whose blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
is greater than 135/80 mmHg. For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
recommends only testing those groups at high risk.
Based on a survey conducted in 2011 on 70,000 average persons, the Hungarian Diabetes Society recommends the introduction of a general screening of the adult population for Diabetes Type II.
Prevention
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise. Intensive lifestyle measures may reduce the risk by over half. Evidence for the benefit of dietary changes alone however is limited. In those with impaired glucose toleranceImpaired glucose tolerance
Impaired glucose tolerance is a pre-diabetic state of dysglycemia that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years...
, diet and exercise and/or metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
or acarbose
Acarbose
Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay , in North America as Precose , and in Canada as Prandase...
may decrease the risk of developing diabetes. Lifestyle interventions are more effective than metformin.
Management
Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes was recommended by the National Health Services in 2008 however the benefit of self monitoring in those not using multi-dose insulin is questionable. Managing other cardiovascular risk factors including hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, high cholesterol, and microalbuminuria
Microalbuminuria
Microalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus.-Diagnosis:...
improves a person's life expectancy. Intensive blood sugar lowering as opposed to standard blood sugar lowering does not appear to change mortality.
Lifestyle
Aerobic exerciseAerobic exercise
Aerobic exercise is physical exercise of relatively low intensity that depends primarily on the aerobic energy-generating process. Aerobic literally means "living in air", and refers to the use of oxygen to adequately meet energy demands during exercise via aerobic metabolism...
is beneficial in diabetes with a greater amount of exercise yielding better results. It leads to a decrease in HbA1C, improved insulin sensitivity, and a better V02 max. Resistance training
Resistance training
Resistance training has two different meanings. A broader meaning that refers to any training that uses a resistance to the force of muscular contraction , and elastic or hydraulic resistance, which refers to a specific type of strength training that uses elastic or hydraulic tension to provide...
is also useful and the combination of both types of exercise may be most effective. A diabetic diet
Diabetic diet
There is much controversy regarding what diet to recommend to sufferers of diabetes mellitus. The diet most often recommended is high in dietary fiber, especially soluble fiber, but low in fat . Recommendations of the fraction of total calories to be obtained from carbohydrate intake range from 1/6...
that promotes weight loss is important. While the best diet type to achieve this is controversial a low glycemic index diet has been found to improve blood sugar control. Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels, for up to six months at least.
Medications
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
is generally recommended as a first line treatment as there is good evidence that it decreases mortality. Injections of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
may either be added to oral medication or used alone. Other classes of medications used to treat type 2 diabetes are sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and thiazolidinediones.
Insulin
When insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
is used, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are increased to effect.
The initial insulin regimen is often chosen based on the patient's blood glucose profile. Initially, adding nightly insulin to patients failing oral medications may be best. Nightly insulin combines better with metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
than with sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
s.
When nightly insulin is insufficient, choices include:
- Premixed insulin with a fixed ratio of short and intermediate acting insulin; this tends to be more effective than long acting insulin, but is associated with increased hypoglycemia. Initial total daily dosage of biphasic insulin can be 10 units if the fasting plasma glucose values are less than 180 mg/dl or 12 units when the fasting plasma glucose is above 180 mg/dl". A guide to titrating fixed ratio insulin is available.
- Long acting insulins include insulin glargineInsulin glargineInsulin glargine, marketed by Sanofi-Aventis under the name Lantus, is a long-acting basal insulin analogue, given once daily to help control the blood sugar level of those with diabetes. It consists of microcrystals that slowly release insulin, giving a long duration of action of 18 to 26 hours,...
and insulin detemirInsulin detemirInsulin detemir is a long-acting human insulin analogue for maintaining the basal level of insulin. Novo Nordisk markets it under the trade name Levemir. It is an insulin analogue in which a fatty acid is bound to the lysine amino acid at position B29. It is quickly absorbed after which it binds...
. A meta-analysisMeta-analysisIn statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomized controlled trials by the Cochrane CollaborationCochrane CollaborationThe Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2". More recently, a randomized controlled trial found that although long acting insulins were less effective, they were associated with reduced hypoglycemic episodes.
Surgery
Gastric Bypass procedures are currently considered an elective procedureElective surgery
Elective surgery is surgery that is scheduled in advance because it does not involve a medical emergency...
with no universally accepted algorithm to decide who should have the surgery. In the diabetic patient, certain types result in 99-100% prevention of insulin resistance and 80-90% clinical resolution or remission of type 2 diabetes. In 1991, the NIH (National Institutes of Health) Consensus Development Conference on Gastrointestinal Surgery for Obesity proposed that the body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(BMI) threshold to consider surgery should drop from 40 to 35 in the appropriate patient. More recently, the American Society for Bariatric Surgery
American Society for Bariatric Surgery
The American Society for Metabolic and Bariatric Surgery ----American Society for Metabolic and Bariatric Surgery is a United States medical organization founded in 1983 to advance bariatic surgery....
(ASBS) and the ASBS Foundation suggested that the BMI threshold be lowered to 30 in the presence of severe co-morbidities. Debate has flourished about the role of gastric bypass surgery in type 2 diabetics since the publication of The Swedish Obese Subjects Study. The largest prospective series showed a large decrease in the occurrence of type 2 diabetes in the post-gastric bypass patient at both 2 years (odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...
was 0.14) and at 10 years (odds ratio was 0.25).
A study of 20-years of Greenville (US) gastric bypass patients found that 80% of those with type 2 diabetes before surgery no longer required insulin or oral agents to maintain normal glucose levels. Weight loss occurred rapidly in many people in the study who had had the surgery. The 20% who did not respond to bypass surgery were, typically, those who were older and had had diabetes for over 20 years.
Progression
The way type 2 diabetes is managed may change with age. Insulin production decreases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissue and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population. Age-related glucose intolerance is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people. Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.Prognosis
Even if properly and carefully managed, type 2 diabetes is currently a chronic disease, which is, in most cases, compatible with an otherwise full life. Some cases, for reasons obscure, cannot be reasonably managed and lead to damage or even death sooner rather than later. Non-compliance with management is a contributor in some cases (unwillingness to monitor blood glucose, take prescribed medication, or reliance on unusual or exotic treatment regimes without credible track record), but not all. Much of the damage is due to the complications of diabetes, not directly to diabetes' acute effects. For example, in the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of non-traumatic blindness and kidney failure.Research continues and several potential treatments may result in "cures". Examples include resection surgery of the upper small intestine, and very stringent restricted calorie diets. None is, as of 2011, sufficiently well understood, or adequately tested, to be of clinical significance. One or more might, possibly, become clinically significant for some cases, or even all, but this is some years away in the most fortunate instance.
Epidemiology
Globally in 2003 it was estimated that there were 150 million people with type 2 diabetes. The incidence varies substantially in different parts of the world, almost certainly because of environmental and lifestyle factors, though these are not known in detail.In the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
there are 23.6 million people (7.8% of the population) with diabetes with 17.9 million being diagnosed, 90% of whom are type 2. With prevalence rates doubling between 1990 and 2005, CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
has characterized the increase as an epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
.
Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates due to alterations in dietary patterns as well as in life styles during childhood.
Type-2 diabetes mellitus is known to affect ethnic subgroups differently due to unique risk factors. For example, African Americans have a 12-fold greater prevalence than black natives of Africa. Cross-sectional epidemiological data suggests that the population with the highest type-two diabetes prevalence, however is the American Pima Indians. Their prevalence rates of 38% are substantially higher than those of Pima Indians in Mexico (prevalence of 6.9%). It appears that both insulin resistance and beta-cell dysfunction were common, leading to inherent genetic predisposition to type-2 diabetes across all Pima Indians. It is therefore concluded that the disproportionately high prevalence of diabetes in American Pima Indians is likely due to changes in westernization and urbanization of lifestyle/ environmental conditions in conjunction with underlying physiological predisposition.