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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 ...
that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, and unexplained weight loss. Symptoms may also include increased hunger, feeling tired, and sores that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease,
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
s, diabetic retinopathy 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 amputations. The sudden onset of hyperosmolar hyperglycemic state 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 ...
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 ...
and lack of exercise. Some people are genetically 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 ...
, 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 f ...
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 ...
. In type 1 diabetes there is a lower total level of insulin to control blood glucose, due to an autoimmune induced loss of insulin-producing beta cells 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 ...
. Diagnosis of diabetes is by blood tests such as fasting plasma glucose, oral glucose tolerance test, 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-enzymat ...
(A1C). Type 2 diabetes is largely preventable by staying a normal weight, exercising 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 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 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. 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 wi ...
), 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 (, " ...
), 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 t ...
), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, 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 mai ...
, and fatigue. 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 (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).


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, including ischemic heart disease and
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations. 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 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 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), sexual dysfunction, 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 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 ...
, 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 ...
al status of a mother during fetal development may also play a role, with one proposed mechanism being that of DNA methylation. The intestinal bacteria '' Prevotella copri'' and '' Bacteroides vulgatus'' have been connected with type 2 diabetes.


Lifestyle

Lifestyle factors are important to the development of type 2 diabetes, including obesity and being overweight (defined by a body mass index of greater than 25), lack of physical activity, poor diet, psychological stress, 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 th ...
. 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 and
Pacific Islander 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 O ...
s. Among those who are not obese, a high waist–hip ratio 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 fats and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk. Eating a lot of white rice appears to play a role in increasing risk. A lack of exercise is believed to cause 7% of cases. Persistent organic pollutants 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 b ...
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 (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
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 chrom ...
, 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 di ...
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, 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, al ...
, among others. Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.


Epigenetics

Epigenetic regulation occurs at multiple levels including (1) direct methylation 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 ( ...
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 deriv ...
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 a ...
proteins in
chromatin Chromatin is a complex of DNA and protein found in eukaryote, 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 ...
, and (3) action of non coding microRNAs (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 ...
”). 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.”


Medical conditions

There are a number of medications and other health problems that can predispose to diabetes. Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics, and statins. 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 ...
are at a higher risk of developing type 2 diabetes. Other health problems that are associated include: acromegaly, Cushing's syndrome,
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 hyperthyroidis ...
,
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 glucagonomas. Individuals with cancer may be at a higher risk of mortality if they also have diabetes. Testosterone deficiency is also associated with type 2 diabetes. Eating disorders 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 eaten ...
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 Gre ...
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 di ...
s in the setting of insulin resistance. 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 only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, 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, u ...
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 in ...
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, high glucagon 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 p ...
. 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, f ...
s in the beta cells activate FOXO1, 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 hypothalamus ...
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 has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine 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 hypothalamus ...
may have a role in the etiology of type 2 diabetes. Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system. 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- glyco ...
), 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 astrocytes. Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 ( FABP7) 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. This mitochondrial degeneration is partly due to the oxidative stress 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 o ...
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, 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-enzymat ...
(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 (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 f ...
in which there is an absolute insulin deficiency due to destruction of islet 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 ...
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 t ...
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'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 levels can ...
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), ...
for diabetes as there is no evidence that such a program improve outcomes. Screening is recommended by the United States Preventive Services Task Force (USPSTF) in adults without symptoms whose blood pressure 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 o ...
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 ...
;
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. The American Diabetes Association 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 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 published studies on t ...
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, Νίκαια; la, Nicaea) is the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative ...
guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30. For people of Black African,
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 and Chinese 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 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. In those with impaired glucose tolerance, a 2019
systematic review A systematic review is a 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 published studies on t ...
found moderate-quality evidence that Metformin, 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 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 Lipophilicity, 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 ar ...
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, high cholesterol, and microalbuminuria, 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 bel ...
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 examinations. There is weak evidence suggesting that treating gum disease by scaling and root planing 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 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 b ...
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 (DASH), Mediterranean diet, low-fat diet, 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., me ...
. Viscous fiber supplements may be useful in those with diabetes. Vegetarian diets 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 ( walnuts, almonds, and hazelnuts) 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 A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A ...
concluded that, red and white meat consumption is associated with an increased risk contrary to dairy products which have a diminished risk.


Medications


Blood sugar control

There are several classes of anti-diabetic medications available. Metformin 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: sulfonylureas, thiazolidinediones,
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 – si ...
s, SGLT2 inhibitors, and glucagon-like peptide-1 analogs. 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, 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 Can ...
, and repaglinide, 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 and detemir 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, 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 (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs), or aliskiren 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 Lipophilicity, 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 ar ...
supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c. Sharing their electronic health records 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 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 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 headqu ...
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. 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, Pacific Islanders, Latinos, and Native Americans. This may be due to enhanced sensitivity to a Western lifestyle 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 ...
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 Greek ἐπί ''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 of infectious ...
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 o ...
.


History

Diabetes is one of the first diseases described with an Egyptian manuscript from BCE 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, Basileía tôn Rhōmaíōn) was the post-Roman Republic, Republican period of ancient Rome. As a polity, it included large territorial holdings aro ...
with
Galen Aelius Galenus or Claudius Galenus ( el, Κλαύδιος 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 o ...
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 ''Suśruta'' (Sanskrit: सुश्रुत, 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 o ...
and Charaka 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 Joh ...
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