Type 2 diabetes, formerly known as adult-onset diabetes, is a form of
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
that is characterized by
high blood sugar
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
,
insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
, and relative lack of
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
.
Common symptoms include
increased thirst,
frequent urination
Frequent urination, or urinary frequency (sometimes called pollakiuria), is the need to urinate more often than usual. Diuretics are medications that increase urinary frequency. Nocturia is the need of frequent urination at night. The most common c ...
, and unexplained
weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
.
[ Symptoms may also include increased hunger, feeling tired, and ]sores
Sores is a French surname. Notable people with the surname include:
* Jacques de Sores
Jacques de Sores was a French pirate and corsair who attacked and burnt Havana, Cuba in 1555.
Other than his attack on Havana, little is known of de Sores. ...
that do not heal.[ Often symptoms come on slowly.][ Long-term complications from high blood sugar include ]heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
, stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
s, diabetic retinopathy
Diabetic retinopathy (also known as diabetic eye disease), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries.
Diabetic retinopathy affects up to 80 perc ...
which can result in blindness
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
, kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, and poor blood flow in the limbs which may lead to amputation
Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indi ...
s.[ The sudden onset of ]hyperosmolar hyperglycemic state
Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, leg cramps, vision problems, an ...
may occur; however, ketoacidosis
Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in ...
is uncommon.
Type 2 diabetes primarily occurs as a result of obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
and lack of exercise.[ Some people are ]genetically
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar working in ...
more at risk than others.[
Type 2 diabetes makes up about 90% of cases of ]diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, with the other 10% due primarily to type 1 diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
and gestational diabetes
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
.[ In type 1 diabetes there is a lower total level of insulin to control blood glucose, due to an ]autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
induced loss of insulin-producing beta cells
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
in the pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. Diagnosis of diabetes is by blood tests such as fasting plasma glucose
Many types of glucose tests exist and they can be used to estimate blood sugar levels at a given time or, over a longer period of time, to obtain average levels or to see how fast body is able to normalize changed glucose levels. Eating food for e ...
, oral glucose tolerance test
The glucose tolerance test (GTT, not to be confused with GGT 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, ...
, or glycated hemoglobin
Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymatic ...
(A1C).
Type 2 diabetes is largely preventable by staying a normal weight, exercising
Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness.
It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athleti ...
regularly, and eating a healthy diet (high in fruits and vegetables and low in sugar and saturated fats).[ Treatment involves exercise and dietary changes.][ If blood sugar levels are not adequately lowered, the medication ]metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
is typically recommended. Many people may eventually also require insulin injections. In those on insulin, routinely checking blood sugar levels is advised; however, this may not be needed in those taking pills. Bariatric surgery
Bariatric surgery (or weight loss surgery) includes a variety of procedures performed on people who are obese. Long term weight loss through the standard of care procedures ( Roux en-Y bypass, sleeve gastrectomy, and biliopancreatic diversion ...
often improves diabetes in those who are obese.
Rates of type 2 diabetes have increased markedly since 1960 in parallel with obesity. As of 2015 there were approximately 392 million people diagnosed with the disease compared to around 30 million in 1985. Typically it begins in middle or older age,[ although rates of type 2 diabetes are increasing in young people. Type 2 diabetes is associated with a ten-year-shorter life expectancy.] Diabetes was one of the first diseases ever described, dating back to an Egyptian manuscript from BCE
Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the or ...
. The importance of insulin in the disease was determined in the 1920s.
Signs and symptoms
The classic symptoms of diabetes are frequent urination (polyuria
Polyuria () is excessive or an abnormally large production or passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed diuresis. Polyuria often appears in conjunction with ...
), increased thirst (polydipsia
Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives from the Greek () "very thirsty", which is derived from (, "mu ...
), increased hunger (polyphagia
Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
), and weight loss
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
. Other symptoms that are commonly present at diagnosis include a history of blurred vision
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure. ...
, itchiness
Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
, peripheral neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
, recurrent vaginal infections
Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.
The three main ...
, and fatigue
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
.[ Other symptoms may include loss of taste. Many people, however, have no symptoms during the first few years and are diagnosed on routine testing.][ A small number of people with type 2 diabetes can develop a ]hyperosmolar hyperglycemic state
Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, leg cramps, vision problems, an ...
(a condition of very high blood sugar associated with a decreased level of consciousness
An altered level of consciousness is any measure of arousal other than normal. Level of consciousness (LOC) is a measurement of a person's arousability and responsiveness to stimuli from the environment.
A mildly depressed level of consciousne ...
and low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
).[
]
Complications
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy.[ This is partly due to a number of complications with which it is associated, including: two to four times the risk of ]cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, including ischemic heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
and stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
; a 20-fold increase in lower limb amputations
Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on indivi ...
, and increased rates of hospitalization
A hospital is a health care institution providing patient treatment with specialized Medical Science, health science and auxiliary healthcare staff and medical equipment. The best-known type of hospital is the general hospital, which typically ...
s.[ In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic ]blindness
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
and kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
.[ It has also been associated with an increased risk of ]cognitive dysfunction
Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders in ...
and dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
through disease processes such as Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
and vascular dementia
Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting ...
. Other complications include hyperpigmentation of skin (acanthosis nigricans
Acanthosis nigricans is a medical sign characterised by brown-to-black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the armpits, groin, navel, fore ...
), sexual dysfunction
Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction as ...
, and frequent infections.[ There is also an association between type 2 diabetes and mild hearing loss.
]
Causes
The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors. While some of these factors are under personal control, such as diet
Diet may refer to:
Food
* Diet (nutrition), the sum of the food consumed by an organism or group
* Dieting, the deliberate selection of food to control body weight or nutrient intake
** Diet food, foods that aid in creating a diet for weight loss ...
and obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
, other factors are not, such as increasing age, female sex, and genetics.[ Obesity is more common in women than men in many parts of Africa. The ]nutrition
Nutrition is the biochemical and physiological process by which an organism uses food to support its life. It provides organisms with nutrients, which can be metabolized to create energy and chemical structures. Failure to obtain sufficient n ...
al status of a mother during fetal development may also play a role, with one proposed mechanism being that of DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
. The intestinal bacteria ''Prevotella copri
''Prevotella'' is a genus of Gram-negative bacteria.
''Prevotella'' spp. are members of the oral, List of microbiota species of the lower reproductive tract of women, vaginal, and gut microflora, gut microbiota and are often recovered from ana ...
'' and ''Bacteroides vulgatus
''Bacteroides'' is a genus of Gram-negative, obligate anaerobic bacteria. ''Bacteroides'' species are non endospore-forming bacilli, and may be either motile or nonmotile, depending on the species. The DNA base composition is 40–48% GC. Unus ...
'' have been connected with type 2 diabetes.
Lifestyle
Lifestyle factors are important to the development of type 2 diabetes, including obesity and being overweight
Being overweight or fat is having more body fat than is optimally healthy. Being overweight is especially common where food supplies are plentiful and lifestyles are sedentary.
, excess weight reached epidemic proportions globally, with mo ...
(defined by a body mass index
Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
of greater than 25), lack of physical activity, poor diet, psychological stress
In psychology, stress is a feeling of emotional strain and pressure. Stress is a type of psychological pain. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the environment. Exces ...
, and urbanization
Urbanization (or urbanisation) refers to the population shift from rural to urban areas, the corresponding decrease in the proportion of people living in rural areas, and the ways in which societies adapt to this change. It is predominantly t ...
.[ Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of cases in ]Pima Indians
Pima or PIMA may refer to:
People
* Pima people, the Akimel O'odham, Indigenous peoples in Arizona (U.S.) and Sonora (Mexico)
Places
* Pima, Arizona, a town in Graham County
* Pima County, Arizona
* Pima Canyon, in the Santa Catalina Mountains
...
and Pacific Islander
Pacific Islanders, Pasifika, Pasefika, or rarely Pacificers are the peoples of the list of islands in the Pacific Ocean, Pacific Islands. As an ethnic group, ethnic/race (human categorization), racial term, it is used to describe the original p ...
s.[ Among those who are not obese, a high ]waist–hip ratio
The waist–hip ratio or waist-to-hip ratio (WHR) is the dimensionless ratio of the circumference of the waist to that of the hips.
This is calculated as waist measurement divided by hip measurement (). For example, a person with a 30″ () ...
is often present.[ Smoking appears to increase the risk of type 2 diabetes. A lack of sleep has also been linked to type 2 diabetes.] Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes.[
Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.] The type of fats in the diet are important, with saturated fat
A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched c ...
s and trans fatty acids
Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial p ...
increasing the risk, and polyunsaturated
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple e ...
and monounsaturated fat
Monounsaturated fats are fatty acids that have one double bond in the fatty acid chain with all of the remainder carbon atoms being single-bonded. By contrast, polyunsaturated fats have more than one double bond.
Molecular description
Fatty aci ...
decreasing the risk. Eating a lot of white rice
White rice is milled rice that has had its husk, bran, and germ removed. This alters the flavor, texture and appearance of the rice and helps prevent spoilage, extend its storage life, and makes it easier to digest. After milling (hulling), the ...
appears to play a role in increasing risk. A lack of exercise is believed to cause 7% of cases. Persistent organic pollutant
Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely ...
s may also play a role.
Genetics
Most cases of diabetes involve many gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, with each being a small contributor to an increased probability of becoming a type 2 diabetic.[ The proportion of diabetes that is inherited is estimated at 72%.] More than 36 genes and 80 single nucleotide polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...
(SNPs) had been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total heritable component of the disease.[ The ]TCF7L2
Transcription factor 7-like 2 (T-cell specific, HMG-box), also known as TCF7L2 or TCF4, is a protein acting as a transcription factor that, in humans, is encoded by the ''TCF7L2'' gene. The TCF7L2 gene is located on chromosome 10q25.2–q25.3, con ...
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants.[ Most of the genes linked to diabetes are involved in pancreatic ]beta cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
functions.[
There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as monogenic forms of diabetes or "other specific types of diabetes").][ These include ]maturity onset diabetes of the young
Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. MODY is often referred to as monogenic diabetes to disting ...
(MODY), Donohue syndrome
Donohue syndrome (also known as leprechaunism) is an extremely rare and severe genetic disorder. ''Leprechaunism'' derives its name from the hallmark elvish features (small stature, bulging eyes, thick lips, and upturned nostrils) exhibited by the ...
, and Rabson–Mendenhall syndrome
Rabson–Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance. The disorder is caused by mutations in the insulin receptor gene. Symptoms include growth abnormalities of the head, face and nails, ...
, among others.[ Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.
]
Epigenetics
Epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
regulation occurs at multiple levels including (1) direct methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
of cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an am ...
and adenine
Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivati ...
residues in DNA, (2) covalent modification of histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...
proteins in chromatin
Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
, and (3) action of non coding microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s (for other examples, see Wikipedia article “Epigenetics
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
â€). On November 17-19, 2017, the American Diabetes Association held a research symposium entitled “Epigenetics and Epigenomics: Implications for Diabetes and Obesity.†As a result of this symposium, an overview of the state of the field was presented in which it was noted that over 1,000 research articles have been published that address the intersection of diabetes and epigenetics or epigenomics. The current state of knowledge in this field is addressed the Wikipedia article “ Epigenetics of diabetes Type 2.â€
Medical conditions
There are a number of medications and other health problems that can predispose to diabetes. Some of the medications include: glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
s, thiazide
Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The first ...
s, beta blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart ...
s, atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s, and statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low- ...
s. Those who have previously had gestational diabetes
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
are at a higher risk of developing type 2 diabetes.[ Other health problems that are associated include: ]acromegaly
Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other ...
, Cushing's syndrome
Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...
, hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
, pheochromocytoma
Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...
, and certain cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
s such as glucagonoma
Glucagonoma is a very rare tumor of the pancreatic alpha cells that results in the overproduction of the hormone, glucagon. Typically associated with a rash called necrolytic migratory erythema, weight loss, and mild diabetes mellitus, most people ...
s.[ Individuals with cancer may be at a higher risk of mortality if they also have diabetes. ]Testosterone deficiency
Androgen deficiency is a medical condition characterized by insufficient androgenic activity in the body. Androgenic activity is mediated by androgens (a class of steroid hormones with varying affinities for the androgen receptor), and is dependent ...
is also associated with type 2 diabetes. Eating disorder
An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating d ...
s may also interact with type 2 diabetes, with bulimia nervosa
Bulimia nervosa, also known as simply bulimia, is an eating disorder characterized by binge eating followed by purging or fasting, and excessive concern with body shape and weight. The aim of this activity is to expel the body of calories eate ...
increasing the risk and anorexia nervosa
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
decreasing it.
Pathophysiology
Type 2 diabetes is due to insufficient insulin production from beta cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
s in the setting of insulin resistance
Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
.[ Insulin resistance, which is the inability of ]cells
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, and fat tissue. In the liver, insulin normally suppresses glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood.[ The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.][
Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of ]lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
within fat cell
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
s, resistance to and lack of incretin
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-gl ...
, high glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
.[ However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.][
In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity.] But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.
Fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s in the beta cells activate FOXO1
Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the ''FOXO1'' gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glyco ...
, resulting in apoptosis of the beta cells.
The causes of the aging-related insulin resistance seen in obesity and in type 2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance. New evidence also points to a role of a brain region called the hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
in the development of insulin resistance. For one thing, a gene called Dusp8 is linked with an increased risk for diabetes. This gene codes for a protein that regulates neuronal signaling in the hypothalamus. Also, infusions into the hypothalamus of a hormone called leptin normalize blood glucose and diminish insulin resistance in diabetic animals. Activation of hypothalamic cells by leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...
has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
cells of the pancreas AND cells in the hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
may have a role in the etiology of type 2 diabetes.
Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies viscera, internal organs, smooth muscle and glands. The autonomic nervous system is a control ...
. Autonomic innervation of liver and muscle cells stimulates an increased uptake of glucose. In diabetic humans, the control of blood glucose by the autonomic nervous system is abnormal. Leptin-sensitive, glucose regulating neurons become resistant to leptin during aging or during exposure to a high-fat diet. These leptin resistant neurons fail to restrain food intake, obesity, and blood glucose. The reasons for this lowered responsiveness to leptin are uncertain and are part of the puzzle of the causes of type 2 diabetes.
Blood glucose levels can also be normalized in diabetic rodents by a single intrahypothalamic infusion of Fibroblast Growth Factor 1 (FGF1
Fibroblast growth factor 1, (FGF-1) also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the ''FGF1'' gene. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycos ...
), an effect that persists for months even in severely diabetic animals. This remarkable cure of diabetes is accomplished by a stimulation of accessory brain cells called astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
s. Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 (FABP7
Fatty acid binding protein 7, brain (FABP7; also brain lipid binding protein, BLBP), is a human gene.
Function
The protein encoded by this gene is a brain fatty acid binding protein. Fatty acid binding proteins (FABPs) are a family of small, hi ...
) are targets of FGF1; these cells are also in close contact with leptin-sensitive neurons, influence their function, and regulate leptin sensitivity. An abnormal function of FABP7+ astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high-fat diets.
During aging, FABP7+ astrocytes develop cytoplasmic granules derived from degenerating mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
. This mitochondrial degeneration is partly due to the oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria. A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus.
Diagnosis
The World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
definition of diabetes (both type 1 and type 2) 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 test
The glucose tolerance test (GTT, not to be confused with GGT 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, ...
, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/L (200 mg/dL)
A random blood sugar of greater than 11.1 mmol/L (200 mg/dL) in association with typical symptoms[ or a ]glycated hemoglobin
Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymatic ...
(HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes.[ In 2009 an International Expert Committee that included representatives of the ]American Diabetes Association
The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes (including type 1 diabetes, ...
(ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes.[ This recommendation was adopted by the American Diabetes Association in 2010. Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/L (>200 mg/dL).]
Threshold for diagnosis of diabetes is based on the relationship between results of glucose tolerance tests, fasting glucose or HbA1c and complications such as retinal problems.[ A fasting or random blood sugar is preferred over the glucose tolerance test, as they are more convenient for people.][ HbA1c has the advantages that fasting is not required and results are more stable but has the disadvantage that the test is more costly than measurement of blood glucose. It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.][
Type 2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.] This is in contrast to type 1 diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
in which there is an absolute insulin deficiency due to destruction of islet
An islet is a very small, often unnamed island. Most definitions are not precise, but some suggest that an islet has little or no vegetation and cannot support human habitation. It may be made of rock, sand and/or hard coral; may be permanent ...
cells in the pancreas and gestational diabetes
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
that is a new onset of high blood sugars associated with pregnancy. Type 1 and type 2 diabetes can typically be distinguished based on the presenting circumstances.[ If the diagnosis is in doubt ]antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
testing may be useful to confirm type 1 diabetes and C-peptide
The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
levels may be useful to confirm type 2 diabetes, with C-peptide levels normal or high in type 2 diabetes, but low in type 1 diabetes.
Screening
No major organization recommends universal screening
Screening may refer to:
* Screening cultures, a type a medical test that is done to find an infection
* Screening (economics), a strategy of combating adverse selection (includes sorting resumes to select employees)
* Screening (environmental), a ...
for diabetes as there is no evidence that such a program improve outcomes. Screening is recommended by the United States Preventive Services Task Force
The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
(USPSTF) in adults without symptoms whose blood pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
is greater than 135/80 mmHg. For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening.[ There is no evidence that it changes the risk of death in this group of people.][ They also recommend screening among those who are overweight and between the ages of 40 and 70.
The ]World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
recommends testing those groups at high risk[ and in 2014 the USPSTF is considering a similar recommendation. High-risk groups in the United States include: those over 45 years old; those with a ]first degree relative
A first-degree relative (FDR) is a person's parent (father or mother), full sibling (brother or sister) or child. It constitutes a category of family members that largely overlaps with the term nuclear family, but without spouses.
If the persons ...
with diabetes; some ethnic groups, including Hispanics, African-Americans, and Native-Americans; a history of gestational diabetes
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of ...
; polycystic ovary syndrome
Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...
; excess weight; and conditions associated with metabolic syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Metabolic syndrome ...
. The American Diabetes Association
The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes (including type 1 diabetes, ...
recommends screening those who have a BMI over 25 (in people of Asian descent screening is recommended for a BMI over 23).
A Cochrane Cochrane may refer to:
Places Australia
*Cochrane railway station, Sydney, a railway station on the closed Ropes Creek railway line
Canada
* Cochrane, Alberta
* Cochrane Lake, Alberta
* Cochrane District, Ontario
** Cochrane, Ontario, a town wit ...
Systematic Review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
looking at the effects of screening on all-cause and diabetes-related mortality did not show any benefits in these outcomes for either screening or not-screening. This was based on only one included study, so no conclusions can be made on the benefits of screening, or lack thereof. This same review did not assess the effects on other outcomes such as adverse effects, incidence of type 2 diabetes, HbA1c or socioeconomic effects.
In the UK, NICE
Nice ( , ; Niçard: , classical norm, or , nonstandard, ; it, Nizza ; lij, Nissa; grc, Îίκαια; la, Nicaea) is the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative c ...
guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30. For people of Black African
Black is a Racialization, racialized classification of people, usually a Politics, political and Human skin color, skin color-based category for specific populations with a mid to dark brown complexion. Not all people considered "black" have ...
, African-Caribbean
Afro-Caribbean people or African Caribbean are Caribbean people who trace their full or partial ancestry to Sub-Saharan Africa. The majority of the modern African-Caribbeans descend from Africans taken as slaves to colonial Caribbean via the ...
, South Asian
South Asia is the southern Subregion#Asia, subregion of Asia, which is defined in both geography, geographical and culture, ethno-cultural terms. The region consists of the countries of Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, ...
and Chinese
Chinese can refer to:
* Something related to China
* Chinese people, people of Chinese nationality, citizenship, and/or ethnicity
**''Zhonghua minzu'', the supra-ethnic concept of the Chinese nation
** List of ethnic groups in China, people of va ...
descent the recommendation to start prevention starts at the BMI of 27,5. A study based on a large sample of people in England suggest even lower BMIs for certain ethnic groups for the start of prevention, for example 24 in South Asian and 21 in Bangladeshi
Bangladeshis ( bn, বাংলাদেশী ) are the citizens of Bangladesh, a South Asian country centered on the transnational historical region of Bengal along the eponymous bay.
Bangladeshi citizenship was formed in 1971, when the ...
populations.
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. The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss. High levels of physical activity reduce the risk of diabetes by about 28%. Evidence for the benefit of dietary changes alone, however, is limited, with some evidence for a diet high in green leafy vegetables and some for limiting the intake of sugary drinks. There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice. A 2019 review found evidence of benefit from dietary fiber
Dietary fiber (in British English fibre) or roughage is the portion of plant-derived food that cannot be completely broken down by human digestive enzymes. Dietary fibers are diverse in chemical composition, and can be grouped generally by the ...
.
In those with impaired glucose tolerance
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
, a 2019 systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
found moderate-quality evidence that Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
, when compared to diet and exercise or a placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
intervention, appeared to delay or reduce the risk of developing type 2 diabetes. This same review found moderate-quality evidence that when compared to intensive diet and exercise, Metformin did not reduce risk of developing type 2 diabetes, as well as very low-quality evidence that combining Metformin with intensive diet and exercise does not appear to have any effect on risk of developing type 2 diabetes when compared to intensive diet and exercise alone. This systematic review only found one suitable trial comparing Metformin with Sulphonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the bet ...
in reducing risk of type 2 diabetes but it did not report any patient-relevant outcomes.
A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal. While low vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.
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 may be used in combination with education, although the benefit of self-monitoring in those not using multi-dose insulin is questionable.[ In those who do not want to measure blood levels, measuring urine levels may be done.] Managing other cardiovascular risk factors, such as hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, high cholesterol
Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia (high levels of lipids in the blood), hyperlipoproteinemia (high levels of lipoproteins in the blood), ...
, and microalbuminuria
Microalbuminuria is a term to describe a moderate increase in the level of urine albumin. It occurs when the kidney leaks small amounts of albumin into the urine, in other words, when an abnormally high permeability for albumin in the glomerulus o ...
, improves a person's life expectancy.[ Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes. Intensive blood pressure management (less than 130/80 mmHg) as opposed to standard blood pressure management (less than 140-160 mmHg systolic to 85–100 mmHg diastolic) results in a slight decrease in stroke risk but no effect on overall risk of death.
Intensive blood sugar lowering (HbA1c<6%) as opposed to standard blood sugar lowering (HbA1c of 7–7.9%) does not appear to change mortality. The goal of treatment is typically an HbA1c of 7 to 8% or a fasting glucose of less than 7.2 mmol/L (130 mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of ]hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...
and life expectancy.[ Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes. Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long-term benefits, many people – for example people with a life expectancy of less than nine years who will not benefit, are over-treated.
It is recommended that all people with type 2 diabetes get regular ]eye examination
An eye examination is a series of tests performed to assess vision and ability to focus on and discern objects. It also includes other tests and examinations pertaining to the eyes. Eye examinations are primarily performed by an optometrist, op ...
s.[ There is weak evidence suggesting that treating ]gum disease
Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main caus ...
by scaling and root planing
Scaling and root planing, also known as conventional periodontal therapy, non-surgical periodontal therapy or deep cleaning, is a procedure involving removal of dental plaque and calculus (scaling or debridement) and then smoothing, or planing, o ...
may result in a small short-term improvement in blood sugar levels for people with diabetes. There is no evidence to suggest that this improvement in blood sugar levels is maintained longer than four months. There is also not enough evidence to determine if medications to treat gum disease are effective at lowering blood sugar levels.
Lifestyle
Exercise
A proper diet and regular exercise are foundations of diabetic care,[ with one review indicating that a greater amount of exercise improved outcomes. Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.
]
Diet
A diabetic diet
A diabetic diet is a diet that is used by people with diabetes mellitus or high blood sugar to minimize symptoms and dangerous complications of long-term elevations in blood sugar ( i.e.: cardiovascular disease, kidney disease, obesity).
Amon ...
which includes calorie restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
to promote weight loss is generally recommended. Other recommendations include emphasizing intake of fruits, vegetables, reduced saturated fat and low-fat dairy products, and with a macronutrient intake tailored to the individual, to distribute calories and carbohydrates throughout the day. Several diets may be effective such as the Dietary Approaches to Stop Hypertension
The DASH diet (Dietary Approaches to Stop Hypertension) is a dietary pattern promoted by the U.S.-based National Heart, Lung, and Blood Institute (part of the National Institutes of Health (NIH), an agency of the United States Department of Health ...
(DASH), Mediterranean diet
The Mediterranean diet is a diet inspired by the eating habits of people who live near the Mediterranean Sea. When initially formulated in the 1960s, it drew on the cuisines of Greece, Italy, France and Spain. In decades since, it has also incor ...
, low-fat diet
A low-fat diet is one that restricts fat, and often saturated fat and cholesterol as well. Low-fat diets are intended to reduce the occurrence of conditions such as heart disease and obesity. For weight loss, they perform similarly to a low-carb ...
, or monitored carbohydrate diets such as a low carbohydrate diet
Low-carbohydrate diets restrict carbohydrate consumption relative to the average diet. Foods high in carbohydrates (e.g., sugar, bread, pasta) are limited, and replaced with foods containing a higher percentage of fat and protein (e.g., meat ...
. Viscous fiber supplements
Fibre supplements (also spelled fiber supplements) are considered to be a form of a subgroup of functional dietary fibre, and in the United States are defined by the Institute of Medicine (IOM). According to the IOM, functional fibre "consists o ...
may be useful in those with diabetes.
Vegetarian diets
Vegetarianism is the practice of abstaining from the consumption of meat (red meat, poultry, seafood, insects, and the flesh of any other animal). It may also include abstaining from eating all by-products of animal slaughter.
Vegetarianism may ...
in general have been related to lower diabetes risk, but do not offer advantages compared with diets which allow moderate amounts of animal products. There is not enough evidence to suggest that cinnamon improves blood sugar levels in people with type 2 diabetes. A 2021 review showed that consumption of tree nuts (walnut
A walnut is the edible seed of a drupe of any tree of the genus ''Juglans'' (family Juglandaceae), particularly the Persian or English walnut, '' Juglans regia''.
Although culinarily considered a "nut" and used as such, it is not a true ...
s, almond
The almond (''Prunus amygdalus'', syn. ''Prunus dulcis'') is a species of tree native to Iran and surrounding countries, including the Levant. The almond is also the name of the edible and widely cultivated seed of this tree. Within the genus ...
s, and hazelnut
The hazelnut is the fruit of the hazel tree and therefore includes any of the nuts deriving from species of the genus ''Corylus'', especially the nuts of the species ''Corylus avellana''. They are also known as cobnuts or filberts according t ...
s) reduced fasting blood glucose in diabetic people.
Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months. There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes.
, there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake.
An elevated intake of microbiota-accessible carbohydrates Microbiota-accessible carbohydrates (MACs) are carbohydrates that are resistant to digestion by a host's metabolism, and are made available for gut microbes, as prebiotics, to ferment or metabolize into beneficial compounds, such as short chain fa ...
can help reducing the effects of T2D.
A 2022 umbrella review In medical research, an umbrella review is a review of systematic reviews or meta-analyses. They may also be called overviews of reviews, reviews of reviews, summaries of systematic reviews, or syntheses of reviews. Umbrella reviews are among the hi ...
concluded that, red and white meat consumption is associated with an increased risk contrary to dairy product
Dairy products or milk products, also known as lacticinia, are food products made from (or containing) milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food items in th ...
s which have a diminished risk.
Medications
Blood sugar control
There are several classes of anti-diabetic medications
Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists (liraglutide, exenatide, and others), and pramlintide, all are administered orally and are thu ...
available. Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems.
A second oral agent of another class or insulin may be added if metformin is not sufficient after three months. Other classes of medications include: sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s, thiazolidinedione
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in ...
s, dipeptidyl peptidase-4 inhibitor
Inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.
The first agent of the class – sita ...
s, SGLT2 inhibitor
SGLT2 inhibitors, also called gliflozins or flozins, are a class of medications that modulate sodium-glucose transport proteins in the nephron (the functional units of the kidney), unlike SLC5A1, SGLT1 inhibitors that perform a similar function in ...
s, and glucagon-like peptide-1 analog
Glucagon-like peptide-1 receptor agonists, also known as GLP-1 receptor agonists (GLP-1-RA) or incretin mimetics, are agonists of the GLP-1 receptor. This class of medications is used for the treatment of type 2 diabetes Some drugs are also approve ...
s.[ As of 2015 there was no significant difference between these agents.][ A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment.
]Rosiglitazone
Rosiglitazone (trade name Avandia) is an antidiabetic drug in the thiazolidinedione class. It works as an insulin sensitizer, by binding to the PPAR in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutica ...
, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. Additionally it is associated with increased rates of heart disease and death.
The effects of Plioglitazone have been compared in a Cochrane systematic review to that of other blood sugar lowering-medicine, including metformin, acarbose
Acarbose (INN) is an anti-diabetic drug used to treat diabetes mellitus type 2 and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay (Bayer AG), in North America as Precose (Bayer Pharmaceuticals), and in Cana ...
, and repaglinide
Repaglinide is an antidiabetic drug in the class of medications known as meglitinides, and was invented in 1983. Repaglinide is an oral medication used in addition to diet and exercise for blood sugar control in type 2 diabetes mellitus. The mech ...
, not showing any benefit in reducing the chance of developing type 2 diabetes in people at risk. It did, however, show reduction of risk of developing type 2 diabetes when compared to a placebo or to no treatment. These results should be interpreted considering that most of the data of the studies included in this review were of low or very-low certainty.
Injections of insulin may either be added to oral medication or used alone.[ Most people do not initially need insulin.][ When it is used, a long-acting formulation is typically added at night, with oral medications being continued.][ Doses are then increased to effect (blood sugar levels being well controlled).][ When nightly insulin is insufficient, twice daily insulin may achieve better control.][ The long acting insulins ]glargine
Insulin glargine, sold under the brand name Lantus among others, is a long-acting modified form of medical insulin, used in the management of type I and type II diabetes. It is typically the recommended long acting insulin in the United King ...
and detemir
Insulin detemir, sold under the brand name Levemir among others, is a long-acting modified form of medical insulin used to treat both type 1 and type 2 diabetes. It is used by injection under the skin. It is effective for up to 24 hours.
...
are equally safe and effective, and do not appear much better than neutral protamine Hagedorn (NPH) insulin, but as they are significantly more expensive, they are not cost effective as of 2010. In those who are pregnant
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
, insulin is generally the treatment of choice.[
]
Blood pressure lowering
Many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130–140mmHg, although there was an increased risk of adverse events.
2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that angiotensin converting enzyme inhibitors
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...
(ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers
Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...
(ARBs), or aliskiren
Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically reco ...
in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.
Other
The use of aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%).
Vitamin D
Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c.
Sharing their electronic health records
An electronic health record (EHR) is the systematized collection of patient and population electronically stored health information in a digital format. These records can be shared across different health care settings. Records are shared throu ...
with people who have type 2 diabetes helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.
Surgery
Weight loss surgery
Bariatric surgery (or weight loss surgery) includes a variety of procedures performed on people who are obese. Long term weight loss through the standard of care procedures ( Roux en-Y bypass, sleeve gastrectomy, and biliopancreatic diversion ...
in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medication following surgery and long-term mortality is decreased.[ There however is some short-term mortality risk of less than 1% from the surgery. The ]body mass index
Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.
Epidemiology
The International Diabetes Federation
The International Diabetes Federation (IDF) is an umbrella organization of over 230 national diabetes associations in more than 160 countries and territories. The Federation has been leading the global diabetes community since 1950. It is headqua ...
estimates nearly 537 million people lived with diabetes worldwide in 2021, 90–95% of whom have type 2 diabetes. Diabetes is common both in the developed and the developing world
A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
.[ It remains uncommon, however, in the least developed countries.][
Women seem to be at a greater risk as do certain ethnic groups,][ such as ]South Asians
South Asian ethnic groups are an ethnolinguistic grouping of the diverse populations of South Asia, including the nations of India, Pakistan, Bangladesh, Nepal, Bhutan, the Maldives, and Sri Lanka. While Afghanistan is variously considered to b ...
, Pacific Islanders
Pacific Islanders, Pasifika, Pasefika, or rarely Pacificers are the peoples of the Pacific Islands. As an ethnic/racial term, it is used to describe the original peoples—inhabitants and diasporas—of any of the three major subregions of Ocea ...
, Latinos
Hispanic and Latino Americans ( es, Estadounidenses hispanos y latinos; pt, Estadunidenses hispânicos e latinos) are Americans of Spanish and/or Latin American ancestry. More broadly, these demographics include all Americans who identify as ...
, and Native Americans.[ This may be due to enhanced sensitivity to a ]Western lifestyle
Western lifestyle or cowboy culture is the lifestyle, or behaviorisms, of, and resulting from the influence of, the (often romanticized) attitudes, ethics and history of the American Western cowboy. In the present day these influences affect this s ...
in certain ethnic groups. Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel with rising obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
rates.[ Type 2 diabetes is now diagnosed as frequently as type 1 diabetes in teenagers in the United States.][
Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005.][ This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity.][ The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7 million, China 20.8 million, the United States 17.7 million, Indonesia 8.4 million, and Japan 6.8 million.] It is recognized as a global epidemic
An epidemic (from Ancient Greek, Greek á¼Ï€Î¯ ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time.
Epidemics ...
by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
.
History
Diabetes is one of the first diseases described[ with an Egyptian manuscript from ]BCE
Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the or ...
mentioning "too great emptying of the urine."[ The first described cases are believed to be of type 1 diabetes.] Indian physicians around the same time identified the disease and classified it as ''madhumeha'' or ''honey urine'' noting that the urine would attract ants.[ The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius Memphites.][ The disease was rare during the time of the ]Roman empire
The Roman Empire ( la, Imperium Romanum ; grc-gre, Βασιλεία τῶν Ῥωμαίων, BasileÃa tôn RhÅmaÃÅn) was the post-Republican period of ancient Rome. As a polity, it included large territorial holdings around the Mediterr ...
with Galen
Aelius Galenus or Claudius Galenus ( el, ΚλαÏδιος Γαληνός; September 129 – c. AD 216), often Anglicized as Galen () or Galen of Pergamon, was a Greek physician, surgeon and philosopher in the Roman Empire. Considered to be one of ...
commenting that he had only seen two cases during his career.[
Type 1 and type 2 diabetes were identified as separate conditions for the first time by the Indian physicians ]Sushruta
Sushruta, or ''SuÅ›ruta'' (Sanskrit: सà¥à¤¶à¥à¤°à¥à¤¤, IAST: , ) was an ancient Indian physician. The ''Sushruta Samhita'' (''Sushruta's Compendium''), a treatise ascribed to him, is one of the most important surviving ancient treatises on ...
and Charaka
Charaka was one of the principal contributors to Ayurveda, a system of medicine and lifestyle developed in Ancient India. He is known as an editor of the medical treatise entitled ''Charaka Samhita'', one of the foundational texts of classical ...
in 400–500 AD with type 1 associated with youth and type 2 with being overweight.[ Effective treatment was not developed until the early part of the 20th century when the Canadians ]Frederick Banting
Sir Frederick Grant Banting (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, physician, painter, and Nobel laureate noted as the co-discoverer of insulin and its therapeutic potential.
In 1923, Banting and J ...
and Charles Best discovered insulin in 1921 and 1922.[ This was followed by the development of the long acting NPH insulin in the 1940s.][
In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful.] Subsequent research has supported this, and weight loss is a first line treatment in type 2 diabetes.
Research
Researchers developed the Diabetes Severity Score (DISSCO), a tool that might better than the standard blood test at identify if a person's condition is declining. It uses a computer algorithm to analyse data from anonymised electronic patient records and produces a score based on 34 indicators.
References
Works cited
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*
External links
IDF Diabetes Atlas 2015
National Diabetes Information Clearinghouse
ADA's Standards of Medical Care in Diabetes 2019
{{DEFAULTSORT:Diabetes Mellitus Type 2
Aging-associated diseases
Diabetes
Medical conditions related to obesity