Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word crystallography is derived from the Ancient Greek word κρύσταλλος (krústallos; "clear ice, rock-crystal"), and γράφειν (gráphein; "to write"). In July 2012, the United Nations recognised the importance of the science of crystallography by proclaiming 2014 the International Year of Crystallography.
Crystallography is a broad topic, and many of its subareas, such as X-ray crystallography, are themselves important scientific topics. Crystallography ranges from the fundamentals of crystal structure to the mathematics of crystal geometry, including those that are not periodic or quasicrystals. At the atomic scale it can involve the use of X-ray diffraction to produce experimental data that the tools of X-ray crystallography
can convert into detailed positions of atoms, and sometimes electron
density. At larger scales it includes experimental tools such as orientational imaging to examine the relative orientations at the grain boundary
in materials. Crystallography plays a key role in many areas of
biology, chemistry, and physics, as well new developments in these
fields.
Before the 20th century, the study of crystals was based on physical measurements of their geometry using a goniometer. This involved measuring the angles of crystal faces relative to each
other and to theoretical reference axes (crystallographic axes), and
establishing the symmetry of the crystal in question. The position in 3D space of each crystal face is plotted on a stereographic net such as a Wulff net or Lambert net. The pole to each face is plotted on the net. Each point is labelled with its Miller index. The final plot allows the symmetry of the crystal to be established.
The discovery of X-rays and electrons
in the last decade of the 19th century enabled the determination of
crystal structures on the atomic scale, which brought about the modern
era of crystallography. The first X-ray diffraction experiment was
conducted in 1912 by Max von Laue, while electron diffraction was first realized in 1927 in the Davisson–Germer experiment and parallel work by George Paget Thomson and Alexander Reid. These developed into the two main branches of crystallography, X-ray crystallography and electron
diffraction. The quality and throughput of solving crystal structures
greatly improved in the second half of the 20th century, with the
developments of customized instruments and phasing algorithms. Nowadays, crystallography is an interdisciplinary field, supporting theoretical and experimental discoveries in various domains. Modern-day scientific instruments for crystallography vary from laboratory-sized equipment, such as diffractometers and electron microscopes, to dedicated large facilities, such as photoinjectors, synchrotron light sources and free-electron lasers.
Crystallographic methods depend mainly on analysis of the diffraction patterns of a sample targeted by a beam of some type. X-rays are most commonly used; other beams used include electrons or neutrons. Crystallographers often explicitly state the type of beam used, as in the terms X-ray diffraction, neutron diffraction and electron diffraction. These three types of radiation interact with the specimen in different ways.
Neutrons are scattered by the atomic nuclei through the strong nuclear forces, but in addition the magnetic moment of neutrons is non-zero, so they are also scattered by magnetic fields. When neutrons are scattered from hydrogen-containing
materials, they produce diffraction patterns with high noise levels,
which can sometimes be resolved by substituting deuterium for hydrogen.
Crystallography
is used by materials scientists to characterize different materials. In
single crystals, the effects of the crystalline arrangement of atoms is
often easy to see macroscopically because the natural shapes of
crystals reflect the atomic structure. In addition, physical properties
are often controlled by crystalline defects. The understanding of
crystal structures is an important prerequisite for understanding crystallographic defects.
Most materials do not occur as a single crystal, but are
poly-crystalline in nature (they exist as an aggregate of small crystals
with different orientations). As such, powder diffraction
techniques, which take diffraction patterns of samples with a large
number of crystals, play an important role in structural determination.
Other physical properties are also linked to crystallography. For example, the minerals in clay
form small, flat, platelike structures. Clay can be easily deformed
because the platelike particles can slip along each other in the plane
of the plates, yet remain strongly connected in the direction
perpendicular to the plates. Such mechanisms can be studied by
crystallographic texture
measurements. Crystallographic studies help elucidate the relationship
between a material's structure and its properties, aiding in developing
new materials with tailored characteristics. This understanding is
crucial in various fields, including metallurgy, geology, and materials
science. Advancements in crystallographic techniques, such as electron
diffraction and X-ray crystallography, continue to expand our
understanding of material behavior at the atomic level.
In another example, iron transforms from a body-centered cubic (bcc) structure called ferrite to a face-centered cubic (fcc) structure called austenite when it is heated. The fcc structure is a close-packed structure unlike the bcc structure;
thus the volume of the iron decreases when this transformation occurs.
Crystallography is useful in phase identification. When
manufacturing or using a material, it is generally desirable to know
what compounds and what phases are present in the material, as their
composition, structure and proportions will influence the material's
properties. Each phase has a characteristic arrangement of atoms. X-ray
or neutron diffraction can be used to identify which structures are
present in the material, and thus which compounds are present.
Crystallography covers the enumeration of the symmetry patterns which
can be formed by atoms in a crystal and for this reason is related to group theory.
X-ray crystallography is the primary method for determining the molecular conformations of biological macromolecules, particularly protein and nucleic acids such as DNA and RNA.
The first crystal structure of a macromolecule was solved in 1958, a
three-dimensional model of the myoglobin molecule obtained by X-ray
analysis. Neutron crystallography
is often used to help refine structures obtained by X-ray methods or to
solve a specific bond; the methods are often viewed as complementary,
as X-rays are sensitive to electron positions and scatter most strongly
off heavy atoms, while neutrons are sensitive to nucleus positions and
scatter strongly even off many light isotopes, including hydrogen and
deuterium. Electron diffraction has been used to determine some protein structures, most notably membrane proteins and viral capsids.
Macromolecular structures determined through X-ray crystallography (and other techniques) are housed in the Protein Data Bank (PDB)–a freely accessible repository for the structures of proteins and other biological macromolecules. There are many molecular graphics codes available for visualising these structures.
Neutron diffraction or elastic neutron scattering is the application of neutron scattering to the determination of the atomic and/or magnetic structure of a material. A sample to be examined is placed in a beam of thermal or coldneutrons to obtain a diffraction pattern that provides information of the structure of the material. The technique is similar to X-ray diffraction but due to their different scattering properties, neutrons and X-rays provide complementary information: X-Rays are suited for superficial analysis, strong x-rays from synchrotron radiation are suited for shallow depths or thin specimens, while neutrons having high penetration depth are suited for bulk samples.[1]
In 1921, American chemist and physicist William D. Harkins introduced the term "neutron" while studying atomic structure and nuclear reactions. He proposed the existence of a neutral particle within the atomic nucleus, though there was no experimental evidence for it at the time. In 1932, British physicist James Chadwick provided experimental proof of the neutron's existence. His discovery confirmed the presence of this neutral subatomic particle, earning him the Nobel Prize in Physics in 1935. Chadwick's research was influenced by earlier work from Irène and Frédéric Joliot-Curie, who had detected unexplained neutral radiation but had not recognized it as a distinct particle. Neutrons are subatomic particles that exist in the nucleus of the atom,
it has higher mass than protons but no electrical charge.
In the 1930s Enrico Fermi and colleagues gave theoretical contributions establishing the foundation of neutron scattering. Fermi developed a framework to understand how neutrons interact with atomic nuclei.
Early diffraction work
Diffraction was first observed in 1936 by two groups, von Halban and Preiswerk and by Mitchell and Powers. In 1944, Ernest O. Wollan, with a background in X-ray scattering from his PhD work under Arthur Compton, recognized the potential for applying thermal neutrons from the newly operational X-10 nuclear reactor to crystallography. Joined by Clifford G. Shull they developed neutron diffraction throughout the 1940s.
Neutron diffraction experiments were carried out in 1945 by Ernest O. Wollan using the Graphite Reactor at Oak Ridge. He was joined shortly thereafter (June 1946) by Clifford Shull,
and together they established the basic principles of the technique,
and applied it successfully to many different materials, addressing
problems like the structure of ice and the microscopic arrangements of
magnetic moments in materials. For this achievement, Shull was awarded
one half of the 1994 Nobel Prize in Physics. (Wollan died in 1984). (The other half of the 1994 Nobel Prize for Physics went to Bert Brockhouse for development of the inelastic scattering technique at the Chalk River facility of AECL. This also involved the invention of the triple axis spectrometer).
1950–60s
The development of neutron sources such as reactors and spallation sources emerged. This allowed high-intensity neutron beams, enabling advanced scattering experiments. Notably, the high flux isotope reactor
(HFIR) at Oak Ridge and Institut Laue Langevin (ILL) in Grenoble,
France, emerged as key institutions for neutron scattering studies.
1970–1980s
This
period saw major advancements in neutron scattering techniques by
developing techniques to explore different aspects of material science,
structure and behaviour.
Small angle neutron scattering (SANS):
Used to investigate large-scale structural features in materials. The
works of Glatter and Kratky also helped in the advancements of this
method, though it was primarily developed for X-rays.
Inelastic neutron scattering (INS): Provides insights into the dynamic process at the microscopic level. Majorly used to examine atomic and molecular motions.
In 1949, Ernest Wollan and Clifford Shull conducted experiments using a double-crystal neutron spectrometer positioned on the southern side of the ORNL graphite reactor to collect data.
1990-present
Recent
advancements focus on improved sources, using sophisticated detectors
and enhanced computational techniques. Spallation sources have been
developed at SNS (Spallation Neutron Source) in the U.S. and ISIS Neutron and Muon Source in the U.K., which can generate pulsed neutron beams for time-of-flight experiments. Neutron imaging and reflectometry
were also developed, which are powerful tools to analyse surfaces,
interfaces and thin film structures, thus providing valuable insights
into the material properties.
Comparison of neutron scattering, XRD and electron scattering
Neutrons are produced through three major processes, fission, spallation, and Low energy nuclear reactions.
Fission
In research reactors, fission takes place when a fissile nucleus, such as uranium-235 (235U),
absorbs a neutron and subsequently splits into two smaller fragments.
This process releases energy along with additional neutrons. On average,
each fission event produces about 2.5 neutrons. While one neutron is required to maintain the chain reaction, the surplus neutrons can be utilized for various experimental applications.
Spallation
In spallation sources, high-energy protons (on the order of 1 GeV) bombard a heavy metal target (e.g., uranium (U), tungsten (W), tantalum (Ta), lead (Pb), or mercury
(Hg)). This interaction causes the nuclei to spit out neutrons. Proton
interactions result in around ten to thirty neutrons per event, of which
the bulk are known as "evaporation neutrons"(~2 MeV), while a minority
are identified as "cascade neutrons" with energies reaching up to the
GeV range. Although spallation is a very efficient technique of neutron
production, the technique generates high energy particles, therefore
requiring shielding for safety.
Illustration
of three major fundamental processes generating neutrons for scattering
experiments: Nuclear fission (Top), Spallation (middle), Low energy
reaction (bottom).
Low energy nuclear reactions
Low-energy
nuclear reactions are the basis of neutron production in
accelerator-driven sources. The selected target materials are based on
the energy levels; lighter metals such as lithium (Li) and beryllium (Be) can be used toachieve their maximum possible reaction rate under 30 MeV, while heavier elements such as tungsten (W) and carbon
(C) provide better performance above 312 MeV. These Compact
Accelerator-driven Neutron Sources (CANS) have matured and are now
approaching the performance of fission and spallation sources.
De-Broglie relation
Neutron scattering relies on the wave-particle dual nature of neutrons. The De-Broglie relation links the wavelength (λ) of a neutron to its energy (E)
where h is the Planck constant, p is the momentum of the neutron, m is the mass of the neutron, v is the velocity of the neutron.
Scattering
Neutron
scattering is used to detect the distance between atoms and study the
dynamics of materials. It involves two major principles: elastic scattering and inelastic scattering.
Elastic scattering provides insight into the structural
properties of materials by looking at the angles at which neutrons are
scattered. The resulting pattern of the scattering provides information
regarding the atomic structure of crystals, liquids and amorphous
materials.
Inelastic scattering focuses on material dynamics through the
study of neutron energy and momentum changes during interactions. It is
key to study phonons, magnons, and other excitations of solid materials.[22]
Neutron matter interaction
X-
rays interact with matter through electrostatic interaction by
interacting with the electron cloud of atoms, this limits their
application as they can be scattered strongly from electrons. While
being neutral, neutrons primarily interact with matter through the
short-range strong force with atomic nuclei. Nuclei are far smaller than
the electron cloud, meaning most materials are transparent to neutrons
and allow deeper penetration. The interaction between neutrons and
nuclei is described by the Fermi pseudopotential, that is, neutrons are well above their meson mass threshold, and thus can be treated effectively as point-like scatterers. While most elements have a low tendency to absorb neutrons, certain ones such as cadmium (Cd), gadolinium (Gd), helium (3He), lithium (6Li), and boron (10B)
exhibit strong neutron absorption due to nuclear resonance effects. The
likelihood of absorption increases with neutron wavelength (σa ∝ λ), meaning slower neutrons are absorbed more readily than faster ones.
Instrumental and sample requirements
The technique requires a source of neutrons. Neutrons are usually produced in a nuclear reactor or spallation source. At a research reactor, other components are needed, including a crystal monochromator
(in the case of thermal neutrons), as well as filters to select the
desired neutron wavelength. Some parts of the setup may also be movable.
For the long-wavelength neutrons, crystals cannot be used and gratings
are used instead as diffractive optical components. At a spallation source, the time of flight technique is used to sort
the energies of the incident neutrons (higher energy neutrons are
faster), so no monochromator is needed, but rather a series of aperture
elements synchronized to filter neutron pulses with the desired
wavelength.
The technique is most commonly performed as powder diffraction,
which only requires a polycrystalline powder. Single crystal work is
also possible, but the crystals must be much larger than those that are
used in single-crystal X-ray crystallography. It is common to use crystals that are about 1 mm3.
The technique also requires a device that can detect the neutrons after they have been scattered.
Summarizing, the main disadvantage to neutron diffraction is the
requirement for a nuclear reactor. For single crystal work, the
technique requires relatively large crystals, which are usually
challenging to grow. The advantages to the technique are many -
sensitivity to light atoms, ability to distinguish isotopes, absence of
radiation damage, as well as a penetration depth of several cm.
Nuclear scattering
Like all quantumparticles, neutrons can exhibit wave phenomena typically associated with light or sound. Diffraction is one of these phenomena; it occurs when waves encounter obstacles whose size is comparable with the wavelength.
If the wavelength of a quantum particle is short enough, atoms or their
nuclei can serve as diffraction obstacles. When a beam of neutrons
emanating from a reactor is slowed and selected properly by their speed,
their wavelength lies near one angstrom (0.1 nm),
the typical separation between atoms in a solid material. Such a beam
can then be used to perform a diffraction experiment. Impinging on a
crystalline sample, it will scatter under a limited number of
well-defined angles, according to the same Bragg law that describes X-ray diffraction.
Neutrons and X-rays interact with matter differently. X-rays interact primarily with the electron cloud surrounding each atom. The contribution to the diffracted x-ray intensity is therefore larger for atoms with larger atomic number (Z). On the other hand, neutrons interact directly with the nucleus of the atom, and the contribution to the diffracted intensity depends on each isotope;
for example, regular hydrogen and deuterium contribute differently. It
is also often the case that light (low Z) atoms contribute strongly to
the diffracted intensity, even in the presence of large-Z atoms. The scattering length varies from isotope to isotope rather than linearly with the atomic number. An element like vanadium
strongly scatters X-rays, but its nuclei hardly scatters neutrons,
which is why it is often used as a container material. Non-magnetic
neutron diffraction is directly sensitive to the positions of the nuclei
of the atoms.
The nuclei of atoms, from which neutrons scatter, are tiny. Furthermore, there is no need for an atomic form factor
to describe the shape of the electron cloud of the atom and the
scattering power of an atom does not fall off with the scattering angle
as it does for X-rays. Diffractograms
therefore can show strong, well-defined diffraction peaks even at high
angles, particularly if the experiment is done at low temperatures. Many
neutron sources are equipped with liquid helium cooling systems that
allow data collection at temperatures down to 4.2 K. The superb high
angle (i.e. high resolution) information means that the atomic positions in the structure can be determined with high precision. On the other hand, Fourier maps (and to a lesser extent difference Fourier maps) derived from neutron data suffer from series termination errors, sometimes so much that the results are meaningless.
Magnetic scattering
Although neutrons are uncharged, they carry a magnetic moment,
and therefore interact with magnetic moments, including those arising
from the electron cloud around an atom. Neutron diffraction can
therefore reveal the microscopic magnetic structure of a material.
Magnetic scattering does require an atomic form factor
as it is caused by the much larger electron cloud around the tiny
nucleus. The intensity of the magnetic contribution to the diffraction
peaks will therefore decrease towards higher angles.
Neutron diffraction is closely related to X-ray powder diffraction. In fact, the single crystal version of the technique is less commonly
used because currently available neutron sources require relatively
large samples and large single crystals are hard or impossible to come
by for most materials. Future developments, however, may well change
this picture. Because the data is typically a 1D powder diffractogram
they are usually processed using Rietveld refinement.
In fact the latter found its origin in neutron diffraction (at Petten
in the Netherlands) and was later extended for use in X-ray diffraction.
One practical application of elastic neutron scattering/diffraction is that the lattice constant of metals
and other crystalline materials can be very accurately measured.
Together with an accurately aligned micropositioner a map of the lattice
constant through the metal can be derived. This can easily be converted
to the stress field experienced by the material. This has been used to analyse stresses in aerospace and automotive
components to give just two examples. The high penetration depth
permits measuring residual stresses in bulk components as crankshafts,
pistons, rails, gears. This technique has led to the development of
dedicated stress diffractometers, such as the ENGIN-X instrument at the ISIS neutron source.
Neutron diffraction can also be employed to give insight into the 3D structure any material that diffracts.
Another use is for the determination of the solvation number of ion pairs in electrolytes solutions.
The magnetic scattering effect has been used since the
establishment of the neutron diffraction technique to quantify magnetic
moments in materials, and study the magnetic dipole orientation and
structure. One of the earliest applications of neutron diffraction was
in the study of magnetic dipole orientations in antiferromagnetic
transition metal oxides such as manganese, iron, nickel, and cobalt
oxides. These experiments, first performed by Clifford Shull, were the
first to show the existence of the antiferromagnetic arrangement of
magnetic dipoles in a material structure. Now, neutron diffraction continues to be used to characterize newly developed magnetic materials.
Hydrogen, null-scattering and contrast variation
Neutron
diffraction can be used to establish the structure of low atomic number
materials like proteins and surfactants much more easily with lower
flux than at a synchrotron radiation source. This is because some low
atomic number materials have a higher cross section for neutron
interaction than higher atomic weight materials.
One major advantage of neutron diffraction over X-ray diffraction is that the latter is rather insensitive to the presence of hydrogen (H) in a structure, whereas the nuclei 1H and 2H (i.e. Deuterium,
D) are strong scatterers for neutrons. The greater scattering power of
protons and deuterons means that the position of hydrogen in a crystal
and its thermal motions can be determined with greater precision by
neutron diffraction. The structures of metal hydride complexes, e.g., Mg2FeH6 have been assessed by neutron diffraction.
The neutron scattering lengths bH = −3.7406(11) fm and bD = 6.671(4) fm, for H and D respectively, have opposite sign, which allows the technique to distinguish them. In fact there is a particular isotope ratio for which the contribution of the element would cancel, this is called null-scattering.
It is undesirable to work with the relatively high concentration
of H in a sample. The scattering intensity by H-nuclei has a large
inelastic component, which creates a large continuous background that
is more or less independent of scattering angle. The elastic pattern
typically consists of sharp Bragg reflections
if the sample is crystalline. They tend to drown in the inelastic
background. This is even more serious when the technique is used for the
study of liquid structure. Nevertheless, by preparing samples with
different isotope ratios, it is possible to vary the scattering contrast
enough to highlight one element in an otherwise complicated structure.
The variation of other elements is possible but usually rather
expensive. Hydrogen is inexpensive and particularly interesting, because
it plays an exceptionally large role in biochemical structures and is
difficult to study structurally in other ways.
Applications
Study of hydrogen storage materials
Since neutron diffraction is particularly sensitive to lighter elements like hydrogen, it can be used for its detection. It can play a role in determining the crystal structure and hydrogen binding sites within metal hydrides, a class of materials of interest for hydrogen storage applications. The order of hydrogen atoms in the lattice reflects the storage capacity and kinetics of the material.
Magnetic structure determination
Neutron
diffraction is also a useful technique for determining magnetic
structures in materials, as neutrons can interact with magnetic moments.
It can be used to determine the antiferromagnetic structure of manganese oxide (MnO) using neutron diffraction. Neutron Diffraction Studies can be used to measure the magnetic moment.
Orientation study demonstrates how neutron diffraction can detect the
precise alignment of the magnetic moment in materials, something that is
much more challenging with X-rays.
Phase transition in ferroelectrics
Neutron diffraction has been widely employed to understand phase transitions in materials including ferroelectrics, which show the transition of crystal structure with temperature or pressure. It can be utilised to study the ferroelectric phase transition in lead titanate (PbTiO3). It can be used to analyse atomic displacements and corresponding lattice distortions.
Residual stress analysis in engineering materials
Neutron
diffraction can be used as a technique for the nondestructive
assessment of residual stresses in engineering materials, including metals and alloys. Also used for measuring residual stresses in engineering materials.
Lithium-ion batteries
Neutron diffraction is especially useful for the investigation of lithium-ion battery materials, because lithium atoms are almost opaque
to X-ray radiation. It can further be used to investigate the
structural evolution of lithium-ion battery cathode materials during
charge and discharge cycles.
High temperature superconductors
Neutron diffraction has played an important role in revealing the crystal and magnetic structures in high-temperature superconductors. A neutron diffraction study of magnetic order in the high-temperature superconductor YBa2Cu3O6+x
was done. The work of each of these scientific teams together with
others across the globe has revealed the origins of the relationship
between magnetic ordering and superconductivity, delivering crucial insights into the mechanism of high-temperature superconductivity.
Mechanical behaviour of alloys
Advancements in neutron diffraction have facilitated in situ
investigations into the mechanical deformation of alloys under load,
permitting observations on the mechanisms of deformation. The deformation behavior of titanium alloys
under mechanical loads can be investigated using in situ neutron
diffraction. This technique allows real-time monitoring of lattice
strains and phase transformations throughout deformation.
Neutron
diffraction, used along with molecular simulations, revealed that an
ion channel's voltage sensing domain (red, yellow and blue molecule at
center) perturbs the two-layered cell membrane that surrounds it (yellow
surfaces), causing the membrane to thin slightly.
Neutron diffraction for ion channels
Neutron
diffraction can be used to study ion channels, highlighting how
neutrons interact with biological structures to reveal atomic details.
Neutron diffraction is particularly sensitive to light elements like
hydrogen, making it ideal for mapping water molecules, ion positions,
and hydrogen bonds within the channel. By analysing neutron scattering
patterns, researchers can determine ion binding sites, hydration
structures, and conformational changes essential for ion transport and
selectivity.
Current developments in neutron diffraction
Advancements in Neutron Diffraction Research
Neutron
diffraction has made significant progress, particularly at Oak Ridge
National Laboratory (ORNL), which operates a suite of 12
diffractometers—seven at the Spallation Neutron Source (SNS) and five at the High Flux Isotope Reactor (HFIR). These instruments are designed for different applications and are grouped into three categories: powder diffraction, single crystal diffraction, and advanced diffraction techniques.
To further enhance neutron diffraction research, ORNL is undertaking several key projects:
Expansion of the SNS First Target Station: New beamlines
equipped with state-of-the-art instruments are being installed to
broaden the scope of scientific investigations.
Proton Power Upgrade: This initiative aims to double the proton
power used for neutron production, which will enhance research
efficiency, allow for the study of smaller and more complex samples, and
support the eventual development of a next-generation neutron source at
SNS.
Development of the SNS Second Target Station: A new facility is
being constructed to house 22 beamlines, making it a leading source for
cold neutron research, crucial for studying soft matter, biological
systems, and quantum materials.
Enhancements at HFIR: Planned upgrades include optimizing the cold
neutron guide hall to improve experimental capabilities, expanding isotope production (including plutonium-238 for space exploration), and enhancing the performance of existing instruments.
These advancements are set to significantly improve neutron
diffraction techniques, allowing for more precise and detailed analysis
of material structures. By expanding research capabilities and
increasing neutron production efficiency, these developments will
support a wide range of scientific fields, from materials science to energy research and quantum physics.
Modern trends in neutron scattering information technology
Neutron
diffraction technology is evolving rapidly, with a focus on improving
beam intensity and instrument efficiency. Modern instruments are
designed to produce smaller, more intense beams, enabling high-precision
studies of smaller samples, which is particularly beneficial for new
material research. Advanced detectors, such as boron-based alternatives to helium-3,
are being developed to address material shortages, while improved
neutron spin manipulation enhances the study of magnetic and structural
properties. Computational advancements, including simulations and virtual instruments, are optimizing neutron sources, streamlining experimental design, and integrating machine learning
for data analysis. Multiplexing and event-based acquisition systems are
enhancing data collection by capturing multiple datasets
simultaneously. Additionally,next-generation spallation sources like the
European Spallation Source (ESS) and Oak Ridge's Second Target Station
(STS) are increasing neutron production efficiency. Lastly, the rise of
remote-controlled experiments and automation is improving accessibility
and precision in neutron diffraction research.
Current trends in structural biology
Modern
advancements in neutron diffraction are enhancing data precision,
broadening structural research applications, and refining experimental
methodologies. A key focus is the improved visualization of hydrogen
atoms in biological macromolecules, crucial for studying enzymatic activity and hydrogen bonding. The expansion of specialized diffractometers has increased accessibility in structural biology, with techniques like monochromatic,
quasi-Laue, and time-of-flight methods being optimized for efficiency.
Innovations in sample preparation, particularly protein deuteration, are
minimizing background noise and reducing the need for large crystals. Additionally, computational tools,
including quantum chemical modeling, are aiding in the interpretation
of complex molecular interactions. Improved neutron sources, such as
spallation facilities, along with advanced detectors, are further
boosting measurement accuracy and structural resolution. These
developments are solidifying neutron diffraction as a critical technique
for exploring the molecular architecture of biological systems.
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of the body becoming unresponsive to insulin's effects. Classic symptoms include the three Ps: polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes.
The major types of diabetes are type 1 and type 2. The most common treatment for type 1 is insulin replacement therapy (insulin injections), while anti-diabetic medications (such as metformin and semaglutide) and lifestyle modifications can be used to manage type 2. Gestational diabetes, a form that sometimes arises during pregnancy,
normally resolves shortly after delivery. Type 1 diabetes is an
autoimmune condition where the body's immune system attacks the beta cells
in the pancreas, preventing the production of insulin. This condition
is typically present from birth or develops early in life. Type 2
diabetes occurs when the body becomes resistant to insulin, meaning the
cells do not respond effectively to it, and thus, glucose remains in the
bloodstream instead of being absorbed by the cells. Additionally, diabetes can also result from other specific causes, such
as genetic conditions (monogenic diabetes syndromes like neonatal diabetes and maturity-onset diabetes of the young), diseases affecting the pancreas (such as pancreatitis), or the use of certain medications and chemicals (such as glucocorticoids, other specific drugs and after organ transplantation).
The number of people diagnosed as living with diabetes has
increased sharply in recent decades, from 200 million in 1990 to 830
million by 2022. It affects one in seven of the adult population, with type 2 diabetes
accounting for more than 95% of cases. These numbers have already risen
beyond earlier projections of 783 million adults by 2045. The prevalence of the disease continues to increase, most dramatically in low- and middle-income nations. Rates are similar in women and men, with diabetes being the seventh leading cause of death globally.The global expenditure on diabetes-related healthcare is an estimated US$760 billion a year.
Signs and symptoms
Overview of the most significant symptoms of diabetesRetinopathy, nephropathy, and neuropathy are potential complications of diabetes
Common symptoms of diabetes include increased thirst, frequent urination, extreme hunger, and unintended weight loss. Several other non-specific signs and symptoms may also occur, including
fatigue, blurred vision, sweet smelling urine/semen and genital
itchiness due to Candida infection. About half of affected individuals may also be asymptomatic. Type 1 presents abruptly following a pre-clinical phase, while type 2
has a more insidious onset; patients may remain asymptomatic for many
years.
Diabetic ketoacidosis
is a medical emergency that occurs most commonly in type 1, but may
also occur in type 2 if it has been longstanding or if the individual
has significant β-cell dysfunction. Excessive production of ketone bodies leads to signs and symptoms including nausea, vomiting, abdominal pain, the smell of acetone in the breath, deep breathing known as Kussmaul breathing, and in severe cases decreased level of consciousness. Hyperosmolar hyperglycemic state is another emergency characterized by dehydration secondary to severe hyperglycemia, with resultant hypernatremia leading to an altered mental state and possibly coma.
Hypoglycemia is a recognized complication of insulin treatment used in diabetes. An acute presentation can include mild symptoms such as sweating, trembling, and palpitations, to more serious effects including impaired cognition, confusion, seizures, coma, and rarely death. Recurrent hypoglycemic episodes may lower the glycemic threshold at
which symptoms occur, meaning mild symptoms may not appear before
cognitive deterioration begins to occur.
Microvascular disease affects the eyes, kidneys, and nerves. Damage to the retina, known as diabetic retinopathy, is the most common cause of blindness in people of working age. The eyes can also be affected in other ways, including development of cataract and glaucoma. It is recommended that people with diabetes visit an optometrist or ophthalmologist once a year.
Hearing loss is another long-term complication associated with diabetes.
Based on extensive data and numerous cases of gallstone disease,
it appears that a causal link might exist between type 2 diabetes and
gallstones. People with diabetes are at a higher risk of developing
gallstones compared to those without diabetes.
There is a link between cognitive deficit
and diabetes; studies have shown that diabetic individuals are at a
greater risk of cognitive decline, and have a greater rate of decline
compared to those without the disease. Diabetes increases the risk of dementia, and the earlier that one is diagnosed with diabetes, the higher the risk becomes. The condition also predisposes to falls in the elderly, especially those treated with insulin.
Type 1 accounts for 5 to 10% of diabetes cases and is the most common type of diabetes diagnosed in patients under 20 years; however, the older term "juvenile-onset diabetes" is no longer used as onset in adulthood is possible. The disease is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to severe insulin deficiency, and can be further classified as immune-mediated or idiopathic (without known cause). The majority of cases are immune-mediated, in which a T cell-mediated autoimmune attack causes loss of beta cells and thus insulin deficiency. Patients often have irregular and unpredictable blood sugar levels due
to very low insulin and an impaired counter-response to hypoglycemia.
Autoimmune attack in type 1 diabetes.
Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes,
known to influence the risk of diabetes. In genetically susceptible
people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.
Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults
(LADA) is the diagnostic term applied when type 1 diabetes develops in
adults; it has a slower onset than the same condition in children. Given
this difference, some use the unofficial term "type 1.5 diabetes" for
this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause. LADA leaves adults with higher levels of insulin production than type 1
diabetes, but not enough insulin production for healthy blood sugar
levels.
Reduced insulin secretion or weaker effect of insulin on its receptor leads to high glucose content in the blood.
Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases
due to a known defect are classified separately. Type 2 diabetes is the
most common type of diabetes mellitus accounting for 95% of diabetes. Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.
Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet such as Western Pattern Diet, and stress. Excess body fat is associated with 30% of cases in people of Chinese
and Japanese descent, 60–80% of cases in those of European and African
descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.
Dietary factors such as sugar-sweetened drinks are associated with an increased risk. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people.
Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.
Gestational diabetes resembles type 2 diabetes in several respects,
involving a combination of relatively inadequate insulin secretion and
responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of
the increase in insulin-antagonist hormone levels that occurs at this
time. However, after pregnancy approximately 5–10% of women with gestational
diabetes are found to have another form of diabetes, most commonly type
2. Gestational diabetes is fully treatable, but requires careful medical
supervision throughout the pregnancy. Management may include dietary
changes, blood glucose monitoring, and in some cases, insulin may be
required.
As the risk of developing type 2 diabetes is about 10 times
higher in women with a history of gestational diabetes, postpartum
screening may involve dietary, lifestyle, and drug interventions to
prevent or delay its progression.
Maturity-onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting
1–2% of all cases. The name of this disease refers to early hypotheses
as to its nature. Being due to a defective gene, this disease varies in
age at presentation and in severity according to the specific gene
defect; thus, there are at least 14 subtypes of MODY. People with MODY often can control it without using insulin.
Malnutrition-related
Malnutrition-related
diabetes, also termed Type 5 diabetes, involves decreased insulin
production, similar to Type 1 diabetes, but is primarily related to
malnutrition rather than autoimmune damage of pancreas beta cells.
Unlike in Type 1 diabetes, patients with Type 5 diabetes do not develop
ketonuria or ketosis. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (ICD-10 code E12), was previously deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
Other types
Some
cases of diabetes are caused by the body's tissue receptors not
responding to insulin (even when insulin levels are normal, which is
what separates it from type 2 diabetes); this form is very uncommon.
Genetic mutations (autosomal or mitochondrial)
can lead to defects in beta cell function. Abnormal insulin action may
also have been genetically determined in some cases. Any disease that
causes extensive damage to the pancreas may lead to diabetes (for
example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). Yet another form of diabetes that people may develop is double diabetes.
This is when a type 1 diabetic becomes insulin resistant, the hallmark
for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.
The following is a list of disorders that may increase the risk of diabetes:
The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted.Mechanism of insulin release in normal pancreatic beta cells.
Insulin production is more or less constant within the beta cells. Its
release is triggered by food, chiefly food containing absorbable
glucose.
Insulin is the principal hormone that regulates the uptake of glucose
from the blood into most cells of the body, especially liver, adipose
tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.
The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body.
Insulin can inhibit the breakdown of glycogen or the process of
gluconeogenesis, it can stimulate the transport of glucose into fat and
muscle cells, and it can stimulate the storage of glucose in the form of
glycogen.
Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans
in the pancreas, in response to rising levels of blood glucose,
typically after eating. Insulin is used by about two-thirds of the
body's cells to absorb glucose from the blood for use as fuel, for
conversion to other needed molecules, or for storage. Lower glucose
levels result in decreased insulin release from the beta cells and in
the breakdown of glycogen to glucose. This process is mainly controlled
by the hormone glucagon, which acts in the opposite manner to insulin.
If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance),
or if the insulin itself is defective, then glucose is not absorbed
properly by the body cells that require it, and is not stored
appropriately in the liver and muscles. The net effect is persistently
high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.
When there is too much glucose in the blood for a long time, the kidneys cannot absorb it all (reach a threshold of reabsorption) and the extra glucose gets passed out of the body through urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria)
and increased fluid loss. Lost blood volume is replaced osmotically
from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).
Diabetes mellitus is diagnosed with a test for the glucose content in
the blood, and is diagnosed by demonstrating any one of the following:
Fasting plasma glucose level
≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period
of fasting, i.e. in the morning before breakfast, after the patient had
sufficient time to fast overnight or at least 8 hours before the test.
A positive result, in the absence of unequivocal high blood sugar,
should be confirmed by a repeat of any of the above methods on a
different day. It is preferable to measure a fasting glucose level
because of the ease of measurement and the considerable time commitment
of formal glucose tolerance testing, which takes two hours to complete
and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements
at or above 7.0 mmol/L (126 mg/dL) is considered diagnostic for diabetes
mellitus.
Per the WHO, people with fasting glucose levels from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) are considered to have impaired fasting glucose. People with plasma glucose at or above 7.8 mmol/L (140 mg/dL), but not
over 11.1 mmol/L (200 mg/dL), two hours after a 75 gram oral glucose
load are considered to have impaired glucose tolerance.
Of these two prediabetic states, the latter in particular is a major
risk factor for progression to full-blown diabetes mellitus, as well as
cardiovascular disease. The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/L (100 to 125 mg/dL).
There is no known preventive measure for type 1 diabetes. However, islet autoimmunity and multiple antibodies can be a strong predictor of the onset of type 1 diabetes. Type 2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.
The relationship between type 2 diabetes and the main modifiable
risk factors (excess weight, unhealthy diet, physical inactivity and
tobacco use) is similar in all regions of the world. There is growing
evidence that the underlying determinants of diabetes are a reflection
of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.
Comorbidity
Diabetes
patients' comorbidities have a significant impact on medical expenses
and related costs. It has been demonstrated that patients with diabetes
are more likely to experience respiratory, urinary tract, and skin
infections, develop atherosclerosis, hypertension, and chronic kidney
disease, putting them at increased risk of infection and complications
that require medical attention. Patients with diabetes mellitus are more likely to experience certain
infections, such as COVID-19, with prevalence rates ranging from 5.3 to
35.5%. Maintaining adequate glycemic control is the primary goal of diabetes
management since it is critical to managing diabetes and preventing or
postponing such complications.
People with type 1 diabetes have higher rates of autoimmune disorders
than the general population. An analysis of a type 1 diabetes registry
found that 27% of the 25,000 participants had other autoimmune
disorders. Between 2% and 16% of people with type 1 diabetes also have celiac disease.
Diabetes management concentrates on keeping blood sugar levels close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).
Learning about the disease and actively participating in the
treatment is important, since complications are far less common and less
severe in people who have well-managed blood sugar levels. The goal of treatment is an A1C level below 7%. Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndromeobesity, and lack of regular exercise.Specialized footwear is widely used to reduce the risk of diabetic foot ulcers by relieving the pressure on the foot. Foot examination for patients living with diabetes should be done annually which includes sensation testing, foot biomechanics, vascular integrity and foot structure.
Concerning those with severe mental illness, the efficacy of type 2 diabetes
self-management interventions is still poorly explored, with
insufficient scientific evidence to show whether these interventions
have similar results to those observed in the general population.
People with diabetes can benefit from education about the disease and
treatment, dietary changes, and exercise, with the goal of keeping both
short-term and long-term blood glucose levels within acceptable bounds.
In addition, given the associated higher risks of cardiovascular
disease, lifestyle modifications are recommended to control blood
pressure.
Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes. No single dietary pattern is best for all people with diabetes. Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others. According to the ADA, "reducing overall carbohydrate intake for
individuals with diabetes has demonstrated the most evidence for
improving glycemia", and for individuals with type 2 diabetes who cannot
meet the glycemic targets or where reducing anti-glycemic medications
is a priority, low or very-low carbohydrate diets are a viable approach. For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.
A 2020 Cochrane systematic review compared several non-nutritive
sweeteners to sugar, placebo and a nutritive low-calorie sweetener (tagatose), but the results were unclear for effects on HbA1c, body weight and adverse events. The studies included were mainly of very low-certainty and did not
report on health-related quality of life, diabetes complications,
all-cause mortality or socioeconomic effects.
In children
While
type 1 diabetes is more prevalent in pediatric diabetes, type 2
diabetes has increasing prevalence, accounting for some 33% of new
diagnoses. Risk factors for type 2 diabetes include ethnicity, family history,
sedentary lifestyle, unhealthy diet, a mother with gestational diabetes,
female gender, and obesity. Children with type 2 diabetes have increased risk of developing
complications, which include insulin resistance, hyperglycemia,
polyuria, ketosis, and dehydration. Early recognition, screening, treatment, and education of diabetic
children are needed to prevent long-term disease complications.
Screening for type 2 diabetes typically starts at 10 years old for obese children and those who have at least two risk factors. Diagnostic criteria include plasma blood glucose of more than 200 mg per deciliter
(dl) or a fasting blood glucose above 126 mg per dl in children with
overt symptoms. Differentiating type 1 from type 2 diabetes may include
assessment of fasting blood insulin or C-peptide, or determination of autoantibodies for type 1 diabetes.
Treatment and management
Adoption of healthy lifestyle practices and metformin medication are recommended as initial treatments. Lifestyle changes include daily exercise for at least 60 minutes, reduced screen time, and dietary education.
Metformin at 500 mg per day is used upon diagnosis. Insulin is used for children with a blood glucose of more than 250 mg per dl and a hemoglobin A1c greater than 8.5%.
Education
Diabetes
management for children requires the integration of the family and
health care team to be committed and continuous for promotion of
self-management. A health care team may include a pediatric endocrinologist or physician trained in pediatric diabetes, a diabetes specialist nurse, a registered dietitian, a psychologist, a social worker, and child life specialist.
The goal of the health care team and child's family is to empower
the child to make informed decisions for health‐promoting lifestyle
choices.
Most medications used to treat diabetes act by lowering blood sugar levels
through different mechanisms. There is broad consensus that when people
with diabetes maintain tight glucose control – keeping the glucose
levels in their blood within normal ranges – they experience fewer
complications, such as kidney problems or eye problems. There is, however, debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.
There are a number of different classes of anti-diabetic medications. Type 1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals. Type 2 diabetes is generally treated with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.
Metformin is generally recommended as a first-line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the liver's production of glucose, and increasing the amount of glucose stored in peripheral tissue. Several other groups of drugs, mainly oral medication, may also
decrease blood sugar in type 2 diabetes. These include agents that
increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors). When insulin is used in type 2 diabetes, a long-acting formulation is
usually added initially, while continuing oral medications.
Some severe cases of type 2 diabetes may also be treated with
insulin, which is increased gradually until glucose targets are reached.
Blood pressure lowering
Cardiovascular disease
is a serious complication associated with diabetes, and 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 systematic 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.
Aspirin
The use of aspirin to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended by some 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%). National guidelines for England and Wales by the National Institute for Health and Care Excellence
(NICE) recommend against the use of aspirin in people with type 1 or
type 2 diabetes who do not have confirmed cardiovascular disease.
Surgery
Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased. There is, however, a 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.
Diabetic peripheral neuropathy (DPN) affects 30% of all diabetes patients. When DPN is superimposed with nerve compression, DPN may be treatable with multiple nerve decompressions. The theory is that DPN predisposes peripheral nerves
to compression at anatomical sites of narrowing, and that the majority
of DPN symptoms are actually attributable to nerve compression, a
treatable condition, rather than DPN itself. The surgery is associated with lower pain scores, higher two-point discrimination (a measure of sensory improvement), lower rate of ulcerations, fewer falls (in the case of lower extremity decompression), and fewer amputations.
Self-management and support
In countries using a general practitioner
system, such as the United Kingdom, care may take place mainly outside
hospitals, with hospital-based specialist care used only in case of
complications, difficult blood sugar control, or research projects. In
other circumstances, general practitioners and specialists share care in
a team approach. Evidence has shown that social prescribing led to
slight improvements in blood sugar control for people with type 2
diabetes. Home telehealth support can be an effective management technique.
The use of technology
to deliver educational programs for adults with type 2 diabetes
includes computer-based self-management interventions to collect for
tailored responses to facilitate self-management. There is no adequate evidence to support effects on cholesterol, blood pressure, behavioral change (such as physical activity levels and dietary), depression, weight and health-related quality of life, nor in other biological, cognitive or emotional outcomes.
Rates of diabetes worldwide in 2014. The worldwide prevalence was 9.2%.Mortality rate of diabetes worldwide in 2012 per million inhabitants
28–91
92–114
115–141
142–163
164–184
185–209
210–247
248–309
310–404
405–1879
An estimated 382 million people worldwide had diabetes in 2013 up from 108 million in 1980. Accounting for the shifting age structure of the global population, the
prevalence of diabetes is 8.8% among adults, nearly double the rate of
4.7% in 1980. Type 2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with
higher type 2 incidence, possibly due to sex-related differences in
insulin sensitivity, consequences of obesity and regional body fat
deposition, and other contributing factors such as high blood pressure,
tobacco smoking, and alcohol intake.
The WHO estimates that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death. However, another 2.2 million deaths worldwide were attributable to high
blood glucose and the increased risks of cardiovascular disease and
other associated complications (e.g. kidney failure), which often lead
to premature death and are often listed as the underlying cause on death
certificates rather than diabetes. For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0 million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.
Diabetes occurs throughout the world but is more common
(especially type 2) in more developed countries. The greatest increase
in rates has, however, been seen in low- and middle-income countries, where more than 80% of diabetic deaths occur. The fastest prevalence increase is expected to occur in Asia and
Africa, where most people with diabetes will probably live in 2030. The increase in rates in developing countries follows the trend of
urbanization and lifestyle changes, including increasingly sedentary
lifestyles, less physically demanding work and the global nutrition
transition, marked by increased intake of foods that are high
energy-dense but nutrient-poor (often high in sugar and saturated fats,
sometimes referred to as the "Western-style" diet). The global number of diabetes cases might increase by 48% between 2017 and 2045.
As of 2020, 38% of all US adults had prediabetes. Prediabetes is an early stage of diabetes.
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine." The Ebers papyrus includes a recommendation for a drink to take in such cases. The first described cases are believed to have been type 1 diabetes.
The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis. The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career. This is possibly due to the diet and lifestyle of the ancients, or
because the clinical symptoms were observed during the advanced stage of
the disease. Galen named the disease "diarrhea of the urine" (diarrhea
urinosa). Indian physicians around the sixth century CE identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.
The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rdcentury
CE). He described the symptoms and the course of the disease, which he
attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School".
He hypothesized a correlation between diabetes and other diseases, and
he discussed differential diagnosis from the snakebite, which also
provokes excessive thirst. His work remained unknown in the West until
1552, when the first Latin edition was published in Venice.
Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500 CE with one type being associated with youth and another type with being overweight. Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Best isolated and purified insulin in 1921 and 1922. This was followed by the development of the long-acting insulin NPH in the 1940s.
Etymology
The word diabetes (/ˌdaɪ.əˈbiːtiːz/ or /ˌdaɪ.əˈbiːtɪs/) comes from Latindiabētēs, which in turn comes from Ancient Greekδιαβήτης (diabētēs), which literally means "a passer through; a siphon". Ancient Greek physician Aretaeus of Cappadocia (fl. 2nd century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease. Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through", which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go". The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus (/məˈlaɪtəs/ or /ˈmɛlɪtəs/) comes from the classical Latin word mellītus, meaning "mellite" (i.e. sweetened with honey; honey-sweet). The Latin word comes from mell-, which comes from mel, meaning "honey"; sweetness; pleasant thing, and the suffix -ītus, whose meaning is the same as that of the English suffix "-ite". It was Thomas Willis
who in 1675 added "mellitus" to the word "diabetes" as a designation
for the disease, when he noticed the urine of a person with diabetes had
a sweet taste (glycosuria). This sweet taste had been noticed in urine
by the ancient Greeks, Chinese, Egyptians, and Indians.
The 1989 "St. Vincent Declaration" was the result of international efforts to improve the care accorded to
those with diabetes. Doing so is important not only in terms of quality
of life and life expectancy but also economically – expenses due to
diabetes have been shown to be a major drain on health – and
productivity-related resources for healthcare systems and governments.
Several countries established more and less successful national diabetes programmes to improve treatment of the disease.
Diabetes stigma
Diabetes
stigma describes the negative attitudes, judgment, discrimination, or
prejudice against people with diabetes. Often, the stigma stems from the
idea that diabetes (particularly Type 2 diabetes) resulted from poor
lifestyle and unhealthy food choices rather than other causal factors
such as genetics and social determinants of health. Manifestation of stigma can be seen throughout different cultures and
contexts. Scenarios include diabetes statuses affecting marriage
proposals, workplace-employment, and social standing in communities.
Stigma is also seen internally, as people with diabetes can also
have negative beliefs about themselves. Often these cases of self-stigma
are associated with higher diabetes-specific distress, lower
self-efficacy, higher rates of depression, and poorer provider-patient
interactions during diabetes care.
Racial and economic inequalities
Racial and ethnic minorities are disproportionately affected with
higher prevalence of diabetes compared to non-minority individuals. While US adults overall have a 40% chance of developing type 2 diabetes, Hispanic/Latino adults chance is more than 50%. African Americans also are much more likely to be diagnosed with
diabetes compared to White Americans. Asians have increased risk of
diabetes as diabetes can develop at lower BMI due to differences in
visceral fat compared to other races. For Asians, diabetes can develop
at a younger age and lower body fat compared to other groups.
Additionally, diabetes is highly underreported in Asian American people,
as 1 in 3 cases are undiagnosed compared to the average 1 in 5 for the
nation.
People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.
In 2010, diabetes-related emergency room (ER) visit rates in the
United States were higher among people from the lowest income
communities (526 per 10,000 population) than from the highest income
communities (236 per 10,000 population). Approximately 9.4% of
diabetes-related ER visits were for the uninsured.
Naming
The
term "type 1 diabetes" has replaced several former terms, including
childhood-onset diabetes, juvenile diabetes, and insulin-dependent
diabetes mellitus. Likewise, the term "type 2 diabetes" has replaced
several former terms, including adult-onset diabetes, obesity-related
diabetes, and noninsulin-dependent diabetes mellitus. Beyond these two
types, there is no agreed-upon standard nomenclature.
Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus. Diabetes insipidus is an unrelated disease with symptoms that can mimic diabetes mellitus.
Diabetes can occur in mammals or reptiles. Birds do not develop diabetes because of their unusually high tolerance for elevated blood glucose levels. There is some indication that amphibians have the ability to develop diabetes.
In animals, diabetes is most commonly encountered in dogs and
cats. Middle-aged animals are most commonly affected. Female dogs are
twice as likely to be affected as males, while according to some
sources, male cats are more prone than females. In both species, all
breeds may be affected, but some small dog breeds are particularly
likely to develop diabetes, such as Miniature Poodles.
Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.
The symptoms may relate to fluid loss and polyuria, but the
course may also be insidious. Diabetic animals are more prone to
infections. The long-term complications recognized in humans are much
rarer in animals. The principles of treatment (weight loss, oral
antidiabetics, subcutaneous insulin) and management of emergencies (e.g.
ketoacidosis) are similar to those in humans.
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