Complications of diabetes

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Diabetes complication
Specialty Endocrinology

Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. [1] Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications. [2]

Contents

The complications of diabetes can dramatically impair quality of life and cause long-lasting disability. Overall, complications are far less common and less severe in people with well-controlled blood sugar levels. [3] [4] [5] Some non-modifiable risk factors such as age at diabetes onset, type of diabetes, gender, and genetics may influence risk. Other health problems compound the chronic complications of diabetes such as smoking, obesity, high blood pressure, elevated cholesterol levels, and lack of regular exercise. Complications of diabetes are a strong risk factor for severe COVID-19 illness. [6]

Acute complications

Diabetic ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is one of the life-threatening severe complications of diabetes that demands immediate attention and intervention. It is considered a medical emergency and can affect both patients with T1D (type 1 diabetes) and T2D (type 2 diabetes), but it is more common in T1D. [7] DKA results from significantly low insulin levels due to various factors including undiagnosed diabetes (people who did not know they have diabetes), missed or delayed doses, insufficient insulin administration, or undergoing physiological stress (e.g. infection, surgery, Stroke, or trauma). [8] [9]

Due to insulin absence, it simply triggers the release of counter-regulatory hormones resulting in serious health complications. This release prompts excessive free fatty acids (FFAs) production as a result of the adipose tissue exhibiting heightened activity of hormone-sensitive lipase. Subsequently, the liver turns fatty acid to ketone bodies for fuel, a process known as ketosis, which causes Ketonemia (high ketone level in the blood) that decreases the blood's pH, leading to DKA. While periodic ketosis is normal, but can become a serious problem if sustained. These hormones can also induce hyperglycemia (high blood glucose) by stimulating gluconeogenesis thereby increasing the renal glucose output. In addition to the endogenous renal glucose produced by the kidneys. The condition of high circulating concentrations of ketone bodies and hyperglycemia leads to osmotic diuresis, characterized by the excessive presence of glucose and ketones in the urine. Consequently, osmotic diuresis causes dehydration and electrolyte loss. [9] [8] [7] [10] [11] [12]

Symptoms of DKA can be noticed within a few hours, like polyuria (excessive urine production), polydipsia (excessive thirst), Weight loss, weakness, nausea, vomiting, and deep rapid breathing (Kussmaul respiration). Moreover, abdominal pain is common and may be severe. [13] [9] The level of consciousness is typically normal until late in the process, when lethargy may progress to coma. [11] [7] Ketoacidosis can easily become severe enough to cause hypotension, shock, and death. [7] The DKA is diagnosed by the urine analysis which will reveal significant levels of ketone bodies (which have exceeded their renal threshold blood levels to appear in the urine, often before other overt symptoms). And also venous blood investigation for electrolytes, glucose, and acid-base status. [13] [7]

The expected result of the treatment tackles the deeper causes; which are dehydration, acidosis, and hyperglycemia, and initiates a reversal of the ketosis process. [8] While replacing fluid and electrolyte loss, insulin, and acid-placed balance are the aim of this treatment. [7] proper treatment usually results in full recovery, though death can result from inadequate or delayed treatment, or from complications (e.g., brain edema). [11]

Preventing DKA is attainable by following some precautions. While feeling unwell, Start with regular monitoring of blood glucose levels. In addition to measuring blood or urine ketone concentrations twice a day and more. In case there are ketones, insulin doses should be increased. Patients are also advised to focus on dehydration and go to the hospital in case of frequent vomiting. It's essential to emphasize that insulin should never be discontinued, even if there is no intake of food or fluids. Patients' education and awareness of managing a sick day is a key element, as recognizing symptoms, and knowing when to contact a healthcare provider. This education significantly contributes to reducing the occurrence of DKA. [7] [12] [11]

Hyperglycemia hyperosmolar state (HHS)

hyperosmolar non-ketotic state (HONK) or Hyperglycemia hyperosmolar state (HHS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. [13] Oppositely, the prevalence of HHS is common in individuals with T2D. Furthermore, it showcases approximately ten times greater mortality rate than the observed in DKA. [14]

Both DKA and HHS occur when insulin becomes less effective, either due to a shortage of insulin secretion ( as in DKA), or lack of proper insulin action (as in HHS). [7] For a person with very high blood glucose levels(usually considered to be above 30 mmol/L (600 mg/dL), [13] that will result in osmotic diuresis, water is osmotically drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in a loss of water (which contains electrolytes and glucose) that will increase blood osmolarity. [15] [7] If the fluid is not replaced, by mouth or intravenously, will ultimately result in dehydration (which in HHS typically becomes worse than DKA). [15] Also causes electrolyte imbalances which are always dangerous. [7] A decline in consciousness levels is primarily attributed to an increase in plasma osmolality. [9] lethargy may ultimately progress to a coma which is more common in T2D than T1D. [15]

HHS, unlike DKA, does not result in significant ketosis and acidosis, or there may be only a very minimal. This is because the presence of a small quantity of insulin suppresses the release of counterregulatory hormones and limits the production of ketones. [9] Multiple factors can trigger HHS, including infection, myocardial infarction, and trauma, [12] [14] [13] as well as infections in the respiratory, digestive, and urinary systems. [12] [14] Rising obesity rates and the greater consumption of high-carbohydrate beverages have both played a role in the increased incidence of HHS. [15] Moreover, certain medications prescribed for different conditions have the potential to cause HHS. [12] [13] As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. [7] On the whole, HHS is a medical emergency marked with hyperglycemia, hyperosmolarity, dehydration, and mild or no ketosis. [13]

Hypoglycemia

Hypoglycemia, or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, weak, and have many symptoms of sympathetic activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. Consciousness can be altered or even lost in extreme cases, leading to coma, seizures, or even brain damage and death. In patients with diabetes, this may be caused by several factors, such as too much or incorrectly timed insulin, too much or incorrectly timed exercise (exercise decreases insulin requirements) or not enough food (specifically glucose containing carbohydrates). The variety of interactions makes cause identification difficult in many instances.

It is more accurate to note that iatrogenic hypoglycemia is typically the result of the interplay of absolute (or relative) insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine are the primary glucose counterregulatory factors that normally prevent or (more or less rapidly) correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation.

Furthermore, reduced sympathoadrenal responses can cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure (HAAF) or Cryer syndrome [16] in diabetes posits that recent incidents of hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. In many cases (but not all), short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in affected patients, although this is easier in theory than in clinical experience.

In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of glucagon (a hormone with effects largely opposite to those of insulin) or an intravenous infusion of dextrose is used for treatment, but usually only if the person is unconscious. In any given incident, glucagon will only work once as it uses stored liver glycogen as a glucose source; in the absence of such stores, glucagon is largely ineffective. In hospitals, intravenous dextrose is often used.

Diabetic coma

Diabetic coma is a medical emergency [17] in which a person with diabetes mellitus is comatose (unconscious) because of one of the acute complications of diabetes:[ citation needed ]

  1. Severe diabetic hypoglycemia
  2. Diabetic ketoacidosis advanced enough to result in unconsciousness from a combination of severe hyperglycemia, dehydration and shock, and exhaustion
  3. Hyperosmolar nonketotic coma in which extreme hyperglycemia and dehydration alone are sufficient to cause unconsciousness.

Chronic complications

Image of fundus showing scatter laser surgery for diabetic retinopathy Fundus photo showing scatter laser surgery for diabetic retinopathy EDA09.JPG
Image of fundus showing scatter laser surgery for diabetic retinopathy

Microangiopathy

Damage to small blood arteries is the cause of what called microangiopathy, which may lead to any of these:

Macrovascular disease

Macrovascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor:

Cancer

Diabetes can also lead to cancer. Cancers that diabetes can lead to include:

Immune compromise

The immune response is impaired in individuals with diabetes mellitus. Cellular studies have shown that hyperglycemia both reduces the function of immune cells and increases inflammation.

Risk factors

Age

Type 2 diabetes in youth brings a much higher prevalence of complications like diabetic kidney disease, retinopathy and peripheral neuropathy than type 1 diabetes, though no significant difference in the odds of arterial stiffness and hypertension. [39]

Poor glucose control

In the early days of insulin treatment for type 1 diabetes there was much debate as to whether strict control of hyperglycaemia would delay or prevent the long-term complications of diabetes. The work of Pirart [40] suggested that microvascular complications of diabetes were less likely to occur in individuals with better glycaemic control. The issue was finally settled in 1993 with the publication of the Diabetes Control and Complications Trial. [41] In the DCCT, subjects without prior retinopathy who maintained good glycaemic control for a mean of 6.5 years were 76% less likely to develop diabetic retinopathy than subjects with less strict control. Similar results were seen for microalbuminuria and peripheral neuropathy. The benefits of strict control of blood glucose were confirmed in longer-term follow-up by the DCCT EDIC study group. [42] So far as macrovascular disease in type 1 diabetes is concerned, the same group reported improved outcomes for cardiovascular events in the group who had been managed by strict blood glucose control: in this group the incidence of any cardiovascular disease was reduced by 30% (95% CI 7, 48; P = 0.016) compared to the group with less intensive control and the incidence of major cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) was reduced by 32% (95% CI −3, 56; P = 0.07). [43]

The situation regarding glycaemic control and complications in type 2 diabetes is less clear cut than for type 1, though there is evidence from the United Kingdom Prospective Diabetes Study Group that strict blood glucose control is beneficial for both microvascular and macrovascular complications. In the original study [44] a relatively modest difference in glycaemic control between the well-controlled and less well-controlled groups resulted in a 25% lower rate of microvascular complications. In follow-up studies from the same group significant relative risk reductions emerged for myocardial infarction (15%, P=0.014) and all-cause mortality (12%, P=0.007). [45]

Autoimmune processes

Research from 2007 suggested that in type 1 diabetics, the continuing autoimmune disease which initially destroyed the beta cells of the pancreas may also cause neuropathy, [46] and nephropathy. [47] In 2008 it was even suggested to treat retinopathy with drugs to suppress the abnormal immune response rather than by blood sugar control. [48]

Genetic factors

The known familial clustering of the type and degree of diabetic complications indicates that genetics play a role in causing complications:

Some genes appear to provide protection against diabetic complications, as seen in a subset of long-term diabetes type 1 survivors without complications. [54] [55]

Mechanisms

Chronic elevation of blood glucose level leads to damage of blood vessels called angiopathy. The endothelial cells lining the blood vessels take in more glucose than normal, since they do not depend on insulin. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. The resulting problems are grouped under "microvascular disease" due to damage to small blood vessels and "macrovascular disease" due to damage to the arteries. [56]

Studies show that DM1 and DM2 cause a change in balancing of metabolites such as carbohydrates, blood coagulation factors,[ citation needed ] and lipids,[ citation needed ] and subsequently bring about complications like microvascular and cardiovascular complications.

The role of metalloproteases and inhibitors in diabetic renal disease is unclear. [57]

Numerous researches have found inconsistent results about the role of vitamins in diabetic risk and complications. [58] [ clarification needed ]

Thiamine acts as an essential cofactor in glucose metabolism, [59] therefore, it may modulate diabetic complications by controlling glycemic status in diabetic patients. [59] [60] Additionally, deficiency of thiamine was observed to be associated with dysfunction of β-cells and impaired glucose tolerance. [60] Different studies indicated possible role of thiamin supplementation on the prevention or reversal of early stage diabetic nephropathy, [61] [62] as well as significant improvement on lipid profile. [60]

Low serum B12 level is a common finding in diabetics especially those taking Metformin or in advanced age. [63] Vitamin B12 deficiency has been linked to two diabetic complications; atherosclerosis and diabetic neuropathy. [64] [65]

Low plasma concentrations of folic acid were found to be associated with high plasma homocysteine concentrations. [66] In clinical trials, homocysteine concentrations were effectively reduced within 4 to 6 weeks of oral supplementation of folic acid. [67] [68] Moreover, since the activity of endothelial NO synthase enzyme might be potentially elevated by folate, [69] folate supplementation might be capable of restoring the availability of NO in endothelium, [70] therefore, improving endothelial function and reducing the risk for atherosclerosis. van Etten et al., found that a single dose of folic acid might help in reducing the risk of vascular complications and enhancing endothelial function in adults with type 2 diabetes by improving nitric oxide status. [71]

Three vitamins, ascorbic acid; α-tocopherol; and β-carotene, are well recognized for their antioxidant activities in human. Free radical-scavenging ability of antioxidants may reduce the oxidative stress and thus may protect against oxidative damage. [72] Based on observational studies among healthy individuals, antioxidant concentrations were found to be inversely correlated with several biomarkers of insulin resistance or glucose intolerance. [73] [74]

Management

Blood pressure control

Modulating and ameliorating diabetic complications may improve the overall quality of life for diabetic patients. For example, a 2008 study concluded that when elevated blood pressure was tightly controlled, diabetic related deaths were reduced by 32% compared to those with less controlled blood pressure. [2]

Vitamins

Many observational and clinical studies have been conducted to investigate the role of vitamins on diabetic complications, [64]

In the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study, vitamin supplementations were associated with 24% reduction on the risk of diabetes[ clarification needed ], observed during 20 years of follow-up. [75]

Many observational studies and clinical trials have linked several vitamins with the pathological process of diabetes; these vitamins include folate, [67] thiamine, [61] β-carotene, and vitamin E, [73] C, [76] B12, [77] and D. [78]

Vitamin D insufficiency is common in diabetics. [78] Observational studies show that serum vitamin D is inversely associated with biomarkers of diabetes; impaired insulin secretion, insulin resistance, and glucose intolerance. [79] [80] It has been suggested that vitamin D may induce beneficial effects on diabetic complications by modulating differentiation and growth of pancreatic β-cells and protecting these cells from apoptosis, thus improving β-cells functions and survival. [79] Vitamin D has also been suggested to act on immune system and modulate inflammatory responses by influencing proliferation and differentiation of different immune cells. [81] [ clarification needed ], Moreover, deficiency of vitamin D may contribute to diabetic complications by inducing hyperparathyroidism, since elevated parathyroid hormone levels are associated with reduced β-cells function, impaired insulin sensitivity, and glucose intolerance. [78] [79] Finally, vitamin D may reduce the risk of vascular complications by modulating lipid profile. [82]

Vitamin C has been proposed to induce beneficial effects by two other mechanisms. It may replace glucose in many chemical reactions due to its similarity in structure, may prevent the non-enzymatic glycosylation of proteins, [77] and might reduce glycated hemoglobin (HbA1c) levels. [74] Secondly, vitamin C has also been suggested to play a role in lipid regulation as a controlling catabolism of cholesterol to bile acid. [77]

Related Research Articles

The following is a glossary of diabetes which explains terms connected with diabetes.

<span class="mw-page-title-main">Diabetic ketoacidosis</span> Medical condition

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of consciousness. A person's breath may develop a specific "fruity" smell. The onset of symptoms is usually rapid. People without a previous diagnosis of diabetes may develop DKA as the first obvious symptom.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.

<span class="mw-page-title-main">Diabetic coma</span> Medical condition

Diabetic coma is a life-threatening but reversible form of coma found in people with diabetes mellitus.

<span class="mw-page-title-main">Type 2 diabetes</span> Type of diabetes mellitus with high blood sugar and insulin resistance

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">C-peptide</span> Chemical compound

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 be used to distinguish between different conditions with similar clinical features.

Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves. Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.

A complication in medicine, or medical complication, is an unfavorable result of a disease, health condition, or treatment. Complications may adversely affect the prognosis, or outcome, of a disease. Complications generally involve a worsening in the severity of the disease or the development of new signs, symptoms, or pathological changes that may become widespread throughout the body and affect other organ systems. Thus, complications may lead to the development of new diseases resulting from previously existing diseases. Complications may also arise as a result of various treatments.

<span class="mw-page-title-main">Diabetic hypoglycemia</span> Medical condition

Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals. According to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), and based on a sample examined between 2004 and 2005, an estimated 55,819 cases involved insulin, and severe hypoglycemia is likely the single most common event.

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks if not months.

The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.

<span class="mw-page-title-main">Diabetes and pregnancy</span> Effects of pre-existing diabetes upon pregnancy

For pregnant women with diabetes, some particular challenges exist for both mother and fetus. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.

Diabetic angiopathy is a form of angiopathy associated with diabetic complications. While not exclusive, the two most common forms are diabetic retinopathy and diabetic nephropathy, whose pathophysiologies are largely identical. Other forms of diabetic angiopathy include diabetic neuropathy and diabetic cardiomyopathy.

Hyperosmolar hyperglycemic state (HHS), also known as hyperosmolar non-ketotic state (HONK), is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, leg cramps, vision problems, and an altered level of consciousness. Onset is typically over days to weeks. Complications may include seizures, disseminated intravascular coagulopathy, mesenteric artery occlusion, or rhabdomyolysis.

The polyol pathway is a two-step process that converts glucose to fructose. In this pathway glucose is reduced to sorbitol, which is subsequently oxidized to fructose. It is also called the sorbitol-aldose reductase pathway.

<span class="mw-page-title-main">Prediabetes</span> Predisease state of hyperglycemia with high risk for diabetes

Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesity, dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes.

<span class="mw-page-title-main">Diabetic cardiomyopathy</span> Medical condition

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure(HF), with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.

<span class="mw-page-title-main">Diabetes in dogs</span>

Diabetes mellitus is a disease in which the beta cells of the endocrine pancreas either stop producing insulin or can no longer produce it in enough quantity for the body's needs. The disease can affect humans as well as animals such as dogs.

In recent years it has become apparent that the environment and underlying mechanisms affect gene expression and the genome outside of the central dogma of biology. It has been found that many epigenetic mechanisms are involved in the regulation and expression of genes such as DNA methylation and chromatin remodeling. These epigenetic mechanisms are believed to be a contributing factor to pathological diseases such as type 2 diabetes. An understanding of the epigenome of Diabetes patients may help to elucidate otherwise hidden causes of this disease.

<span class="mw-page-title-main">Diabetes</span> Group of endocrine diseases characterized by high blood sugar levels

Diabetes mellitus, often known simply 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 insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, 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. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths every year.

References

  1. ↑ Holleman F (2014-08-18), "Acute and chronic complications of diabetes (revision number 30)", Diapedia, Diapedia.org, doi:10.14496/dia.7104085117.30 , retrieved 2023-09-17
  2. 1 2 Deshpande AD, Harris-Hayes M, Schootman M (November 2008). "Epidemiology of diabetes and diabetes-related complications". Physical Therapy. 88 (11): 1254–1264. doi:10.2522/ptj.20080020. PMC   3870323 . PMID   18801858.
  3. ↑ Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, et al. (December 2005). "Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes". The New England Journal of Medicine. 353 (25): 2643–2653. doi: 10.1056/NEJMoa052187 . PMC   2637991 . PMID   16371630.
  4. ↑ "The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group". Annals of Internal Medicine. 122 (8): 561–568. April 1995. doi:10.7326/0003-4819-122-8-199504150-00001. PMID   7887548. S2CID   24754081.
  5. ↑ "Subject Index", Vascular and Neurologic Complications of Diabetes Mellitus, Frontiers in Diabetes, S. Karger AG, vol. 8, pp. 243–255, 1987, doi:10.1159/000413896, ISBN   978-3-8055-4452-8 , retrieved 2023-09-17
  6. ↑ Kompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY, et al. (July 2021). "Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020-March 2021". Preventing Chronic Disease. 18: E66. doi: 10.5888/pcd18.210123 . PMC   8269743 . PMID   34197283.
  7. 1 2 3 4 5 6 7 8 9 10 11 Gosmanov AR, Gosmanova EO, Kitabchi AE (2000). "Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State". In Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al. (eds.). Endotext. South Dartmouth (MA): MDText.com, Inc. PMID   25905280 . Retrieved 2023-09-17.
  8. 1 2 3 Sood K, Ankita S, Shah AK, Yadav BB (May 2023). "Diabetic Ketoacidosis -Review Article". Journal of Cardiovascular Disease Research.
  9. 1 2 3 4 5 Zammitt N, O'Brien A (28 June 2017). Essentials of Kumar and Clark's Clinical Medicine (6th ed.). Philadelphia: Elsevier. ISBN   978-0-7020-6604-7.
  10. ↑ Perilli G, Saraceni C, Daniels MN, Ahmad A (March 2013). "Diabetic Ketoacidosis: A Review and Update". Current Emergency and Hospital Medicine Reports. 1 (1): 10–17. doi: 10.1007/s40138-012-0001-3 . ISSN   2167-4884.
  11. 1 2 3 4 Dhatariya KK, Glaser NS, Codner E, Umpierrez GE (May 2020). "Diabetic ketoacidosis" (PDF). Nature Reviews. Disease Primers. 6 (1): 40. doi:10.1038/s41572-020-0165-1. PMID   32409703. S2CID   218624258.
  12. 1 2 3 4 5 Umpierrez G, Korytkowski M (April 2016). "Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia". Nature Reviews. Endocrinology. 12 (4): 222–232. doi:10.1038/nrendo.2016.15. PMID   26893262. S2CID   205482047.
  13. 1 2 3 4 5 6 7 Penman ID, Ralston S, Strachan MJ, Hobson RP (2022). Davidson's Principles and Practice of Medicine (24th ed.). Edinburgh: Elsevier. ISBN   978-0-7020-8347-1.
  14. 1 2 3 Pasquel FJ, Umpierrez GE (November 2014). "Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment". Diabetes Care. 37 (11): 3124–3131. doi:10.2337/dc14-0984. PMC   4207202 . PMID   25342831.
  15. 1 2 3 4 Adeyinka A, Kondamudi NP (2023). "Hyperosmolar Hyperglycemic Syndrome". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   29489232 . Retrieved 2023-09-17.
  16. ↑ Dagogo-Jack S (December 2015). "Philip E. Cryer, MD: Seminal Contributions to the Understanding of Hypoglycemia and Glucose Counterregulation and the Discovery of HAAF (Cryer Syndrome)". Diabetes Care. 38 (12): 2193–2199. doi:10.2337/dc15-0533. PMC   4876742 . PMID   26604275.
  17. ↑ "Diabetes Coma". Cleveland Clinic (tertiary source). Retrieved 2019-06-21.
  18. ↑ Aliseda Pérez de Madrid D, Berástegui I (2008). "[Diabetic retinopathy]". Anales del Sistema Sanitario de Navarra. 31 (Suppl 3): 23–34. doi: 10.4321/S1137-66272008000600003 . PMID   19169292.
  19. 1 2 Mailloux L (2007-02-13). "UpToDate Dialysis in diabetic nephropathy". UpToDate. Retrieved 2007-12-07.
  20. ↑ Nagib AM, Elsayed Matter Y, Gheith OA, Refaie AF, Othman NF, Al-Otaibi T (April 2019). "Diabetic Nephropathy Following Posttransplant Diabetes Mellitus". Experimental and Clinical Transplantation. 17 (2): 138–146. doi:10.6002/ect.2018.0157. PMID   30945628. S2CID   93000559.
  21. ↑ Dohrn MF, Winter N, Dafotakis M (August 2020). "[Causes, spectrum, and treatment of the diabetic neuropathy]". Der Nervenarzt (in German). 91 (8): 714–721. doi: 10.1007/s00115-020-00948-3 . PMID   32647958.
  22. ↑ Biessels GJ (2007). "Diabetic Encephalopathy". In Veves A, Malik RA (eds.). Diabetic Neuropathy. Clinical Diabetes. Totowa, NJ: Humana Press. pp. 187–205. doi:10.1007/978-1-59745-311-0_11. ISBN   978-1-58829-626-9 . Retrieved 2023-09-15.
  23. ↑ Gispen WH, Biessels GJ (November 2000). "Cognition and synaptic plasticity in diabetes mellitus". Trends in Neurosciences. 23 (11): 542–549. doi:10.1016/S0166-2236(00)01656-8. PMID   11074263. S2CID   44860763.
  24. ↑ "Diabetes doubles Alzheimer's risk". CNN. 2011-09-19.
  25. ↑ Kobayashi S, Liang Q (February 2015). "Autophagy and mitophagy in diabetic cardiomyopathy". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852 (2): 252–261. doi: 10.1016/j.bbadis.2014.05.020 . PMID   24882754.
  26. ↑ "Erectile Dysfunction by Diabetes". doctor.ac. Archived from the original on 2021-08-18. Retrieved 2 July 2016.
  27. ↑ Defeudis G, Mazzilli R, Tenuta M, Rossini G, Zamponi V, Olana S, et al. (February 2022). "Erectile dysfunction and diabetes: A melting pot of circumstances and treatments". Diabetes/Metabolism Research and Reviews. 38 (2): e3494. doi:10.1002/dmrr.3494. PMC   9286480 . PMID   34514697.
  28. ↑ Mealey BL (October 2006). "Periodontal disease and diabetes. A two-way street". Journal of the American Dental Association. 137 (Suppl): 26S–31S. doi: 10.14219/jada.archive.2006.0404 . PMID   17012733.
  29. 1 2 Preshaw PM, Alba AL, Herrera D, Jepsen S, Konstantinidis A, Makrilakis K, Taylor R (January 2012). "Periodontitis and diabetes: a two-way relationship". Diabetologia. 55 (1): 21–31. doi:10.1007/s00125-011-2342-y. PMC   3228943 . PMID   22057194.
  30. 1 2 Scott G (March–April 2013). "The diabetic foot examination: A positive step in the prevention of diabetic foot ulcers and amputation". Osteopathic Family Physician. 5 (2): 73–78. doi:10.1016/j.osfp.2012.08.002. S2CID   72816348.
  31. ↑ Weiss JS, Sumpio BE (February 2006). "Review of prevalence and outcome of vascular disease in patients with diabetes mellitus". European Journal of Vascular and Endovascular Surgery. 31 (2): 143–150. doi: 10.1016/j.ejvs.2005.08.015 . PMID   16203161.
  32. 1 2 Codner E, Merino PM, Tena-Sempere M (2012). "Female reproduction and type 1 diabetes: from mechanisms to clinical findings". Human Reproduction Update. 18 (5): 568–585. doi: 10.1093/humupd/dms024 . PMID   22709979.
  33. ↑ Shauly-Aharonov M, Shafrir A, Paltiel O, Calderon-Margalit R, Safadi R, Bicher R, et al. (22 July 2021). "Both high and low pre-infection glucose levels associated with increased risk for severe COVID-19: New insights from a population-based study". PLOS ONE. 16 (7): e0254847. Bibcode:2021PLoSO..1654847S. doi: 10.1371/journal.pone.0254847 . PMC   8297851 . PMID   34293038.
  34. ↑ Nobs, Samuel Philip; Kolodziejczyk, Aleksandra A.; Adler, Lital; Horesh, Nir; Botscharnikow, Christine; Herzog, Ella; Mohapatra, Gayatree; Hejndorf, Sophia; Hodgetts, Ryan-James; Spivak, Igor; Schorr, Lena; Fluhr, Leviel; Kviatcovsky, Denise; Zacharia, Anish; Njuki, Suzanne (December 2023). "Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes". Nature. 624 (7992): 645–652. doi: 10.1038/s41586-023-06803-0 . ISSN   1476-4687. PMC   10733144 .
  35. ↑ Ahmed MS, Reid E, Khardori N (June 24, 2008). "Respiratory infections in diabetes: Reviewing the risks and challenges". Journal of Respiratory Diseases. Archived from the original on September 2, 2012. Retrieved December 9, 2009.
  36. ↑ Hsia CC, Raskin P (April 2008). "Lung involvement in diabetes: does it matter?". Diabetes Care. 31 (4): 828–829. doi: 10.2337/dc08-0103 . PMID   18375433.
  37. ↑ Mishra GP, Dhamgaye TM, Tayade BO, Amol BF, Amit S, Jasmin DM (December 2012). "Study of Pulmonary Function Tests in Diabetics with COPD or Asthma" (PDF). Applied Cardiopulmonary Pathophysiology. 16 (4–2012): 299–308. Archived from the original (PDF) on 9 July 2014. Retrieved 13 February 2013.
  38. ↑ Lin EH, Rutter CM, Katon W, Heckbert SR, Ciechanowski P, Oliver MM, et al. (February 2010). "Depression and advanced complications of diabetes: a prospective cohort study". Diabetes Care. 33 (2): 264–269. doi:10.2337/dc09-1068. PMC   2809260 . PMID   19933989.
  39. ↑ Dabelea D, Stafford JM, Mayer-Davis EJ, D'Agostino R, Dolan L, Imperatore G, et al. (February 2017). "Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood". JAMA. 317 (8): 825–835. doi:10.1001/jama.2017.0686. PMC   5483855 . PMID   28245334.
  40. ↑ Pirart J (December 1977). "[Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973 (3rd and last part) (author's transl)]". Diabète & Métabolisme. 3 (4): 245–256. PMID   598565.
  41. ↑ Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, et al. (September 1993). "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus". The New England Journal of Medicine. 329 (14): 977–986. doi: 10.1056/NEJM199309303291401 . PMID   8366922. S2CID   21528496.
  42. ↑ Aiello LP, et al. (DCCT EDIC Research Group) (2014). "Diabetic retinopathy and other ocular findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study". Diabetes Care. 37 (1): 17–23. doi: 10.2337/dc13-2251 . PMC   3867989 . PMID   24356593.
  43. ↑ Gubitosi-Klu R, et al. (The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group) (May 2016). "Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up". Diabetes Care. 39 (5): 686–693. doi: 10.2337/dc15-1990 . PMC   4839174 . PMID   26861924.
  44. ↑ United Kingdom Prospective Diabetes (UKPDS) Study Group (September 1998). "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group". Lancet. 352 (9131): 837–853. doi:10.1016/S0140-6736(98)07019-6. PMID   9742976. S2CID   7019505.
  45. ↑ UKPDS
  46. ↑ Granberg V, Ejskjaer N, Peakman M, Sundkvist G (August 2005). "Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy". Diabetes Care. 28 (8): 1959–1964. doi: 10.2337/diacare.28.8.1959 . PMID   16043739.
  47. ↑ Ichinose K, Kawasaki E, Eguchi K (2007). "Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy". American Journal of Nephrology. 27 (6): 554–564. doi: 10.1159/000107758 . PMID   17823503.
  48. ↑ Adams DD (June 2008). "Autoimmune destruction of pericytes as the cause of diabetic retinopathy". Clinical Ophthalmology. 2 (2): 295–298. doi: 10.2147/OPTH.S2629 . PMC   2693966 . PMID   19668719.
  49. ↑ Foss CH, Vestbo E, Frøland A, Gjessing HJ, Mogensen CE, Damsgaard EM (March 2001). "Autonomic neuropathy in nondiabetic offspring of type 2 diabetic subjects is associated with urinary albumin excretion rate and 24-h ambulatory blood pressure: the Fredericia Study". Diabetes. 50 (3): 630–636. doi: 10.2337/diabetes.50.3.630 . PMID   11246884.
  50. ↑ Ban CR, Twigg SM (2008). "Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers". Vascular Health and Risk Management. 4 (3): 575–596. doi: 10.2147/VHRM.S1991 . PMC   2515418 . PMID   18827908.
  51. ↑ Tarnow L, Groop PH, Hadjadj S, Kazeem G, Cambien F, Marre M, et al. (January 2008). "European rational approach for the genetics of diabetic complications--EURAGEDIC: patient populations and strategy". Nephrology, Dialysis, Transplantation. 23 (1): 161–168. doi: 10.1093/ndt/gfm501 . PMID   17704113.
  52. ↑ Monti MC, Lonsdale JT, Montomoli C, Montross R, Schlag E, Greenberg DA (December 2007). "Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes". The Journal of Clinical Endocrinology and Metabolism. 92 (12): 4650–4655. doi: 10.1210/jc.2007-1185 . PMID   17878250.
  53. ↑ Liew G, Klein R, Wong TY (2009). "The role of genetics in susceptibility to diabetic retinopathy". International Ophthalmology Clinics. 49 (2): 35–52. doi:10.1097/IIO.0b013e31819fd5d7. PMC   2746819 . PMID   19349785.
  54. ↑ Sun JK, Keenan HA, Cavallerano JD, Asztalos BF, Schaefer EJ, Sell DR, et al. (April 2011). "Protection from retinopathy and other complications in patients with type 1 diabetes of extreme duration: the joslin 50-year medalist study". Diabetes Care. 34 (4): 968–974. doi:10.2337/dc10-1675. PMC   3064059 . PMID   21447665.
  55. ↑ Porta M, Toppila I, Sandholm N, Hosseini SM, Forsblom C, Hietala K, et al. (April 2016). "Variation in SLC19A3 and Protection From Microvascular Damage in Type 1 Diabetes". Diabetes. 65 (4): 1022–1030. doi:10.2337/db15-1247. PMC   4806664 . PMID   26718501.
  56. ↑ Viberti GC (November 1983). "Increased capillary permeability in diabetes mellitus and its relationship to microvascular angiopathy". The American Journal of Medicine. 75 (5B): 81–84. doi:10.1016/0002-9343(83)90257-7. PMID   6673594.
  57. ↑ P. Zaoui, et al, (2000) "Role of Metalloproteases and Inhibitors in the Occurrence and Prognosis of Diabetic Renal Lesions," Diabetes and Metabolism, vol. 26 (Supplement 4), p. 25
  58. ↑ Bonnefont-Rousselot D (2004). "The role of antioxidant micronutrients in the prevention of diabetic complications". Treatments in Endocrinology. 3 (1): 41–52. doi:10.2165/00024677-200403010-00005. PMID   15743112. S2CID   35818398.
  59. 1 2 Arora S, Lidor A, Abularrage CJ, Weiswasser JM, Nylen E, Kellicut D, Sidawy AN (September 2006). "Thiamine (vitamin B1) improves endothelium-dependent vasodilatation in the presence of hyperglycemia". Annals of Vascular Surgery. 20 (5): 653–658. doi:10.1007/s10016-006-9055-6. PMID   16741654. S2CID   9028358.
  60. 1 2 3 Thornalley PJ (August 2005). "The potential role of thiamine (vitamin B1) in diabetic complications". Current Diabetes Reviews. 1 (3): 287–298. doi:10.2174/157339905774574383. PMID   18220605.
  61. 1 2 Karachalias N, Babaei-Jadidi R, Rabbani N, Thornalley PJ (July 2010). "Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes". Diabetologia. 53 (7): 1506–1516. doi: 10.1007/s00125-010-1722-z . PMID   20369223.
  62. ↑ Rabbani N, Thornalley PJ (July 2011). "Emerging role of thiamine therapy for prevention and treatment of early-stage diabetic nephropathy". Diabetes, Obesity & Metabolism. 13 (7): 577–583. doi:10.1111/j.1463-1326.2011.01384.x. PMID   21342411. S2CID   11763040.
  63. ↑ Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R (2009). "The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study". Journal of the American Board of Family Medicine. 22 (5): 528–534. doi: 10.3122/jabfm.2009.05.090044 . PMID   19734399.
  64. 1 2 Al-Maskari MY, Waly MI, Ali A, Al-Shuaibi YS, Ouhtit A (July 2012). "Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes". Nutrition. 28 (7–8): e23–e26. doi:10.1016/j.nut.2012.01.005. PMID   22595450.
  65. ↑ Selhub, J., Jacques, P., Dallal, G., Choumenkovitch, S., & Rogers, G. (2008). The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food and Nutrition Bulletin, 29(s), 67–73
  66. ↑ Mangoni AA, Sherwood RA, Asonganyi B, Swift CG, Thomas S, Jackson SH (February 2005). "Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes". American Journal of Hypertension. 18 (2 Pt 1): 220–226. doi: 10.1016/j.amjhyper.2004.08.036 . PMID   15752950.
  67. 1 2 Mangoni AA, Sherwood RA, Swift CG, Jackson SH (December 2002). "Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial". Journal of Internal Medicine. 252 (6): 497–503. doi: 10.1046/j.1365-2796.2002.01059.x . PMID   12472909. S2CID   9353868.
  68. ↑ Mangoni AA, Jackson SH (May 2002). "Homocysteine and cardiovascular disease: current evidence and future prospects". The American Journal of Medicine. 112 (7): 556–565. doi:10.1016/s0002-9343(02)01021-5. PMID   12015248.
  69. ↑ Title LM, Ur E, Giddens K, McQueen MJ, Nassar BA (May 2006). "Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering". Vascular Medicine. 11 (2): 101–109. doi:10.1191/1358863x06vm664oa. PMID   16886840. S2CID   8771566.
  70. ↑ Montezano, A. C., & Touyz, R. M. (2012). Reactive oxygen species and endothelial function - role of nitric oxide synthase uncoupling and nox family nicotinamide adenine dinucleotide phosphate oxidases. Basic & Clinical Pharmacology & Toxicology, 110(1), 87–94
  71. ↑ van Etten RW, de Koning EJ, Verhaar MC, Gaillard CA, Rabelink TJ (July 2002). "Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate". Diabetologia. 45 (7): 1004–1010. doi: 10.1007/s00125-002-0862-1 . PMID   12136399.
  72. ↑ Rahimi R, Nikfar S, Larijani B, Abdollahi M (August 2005). "A review on the role of antioxidants in the management of diabetes and its complications". Biomedicine & Pharmacotherapy. 59 (7): 365–373. doi:10.1016/j.biopha.2005.07.002. PMID   16081237.
  73. 1 2 3 Song Y, Cook NR, Albert CM, Van Denburgh M, Manson JE (August 2009). "Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial". The American Journal of Clinical Nutrition. 90 (2): 429–437. doi:10.3945/ajcn.2009.27491. PMC   2848361 . PMID   19491386.
  74. 1 2 Sargeant LA, Wareham NJ, Bingham S, Day NE, Luben RN, Oakes S, et al. (June 2000). "Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study". Diabetes Care. 23 (6): 726–732. doi: 10.2337/diacare.23.6.726 . PMID   10840986.
  75. ↑ Kataja-Tuomola M, Sundell JR, Männistö S, Virtanen MJ, Kontto J, Albanes D, Virtamo J (January 2008). "Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes". Diabetologia. 51 (1): 47–53. doi: 10.1007/s00125-007-0864-0 . PMID   17994292.
  76. ↑ Ceriello A, Novials A, Ortega E, Canivell S, Pujadas G, La Sala L, et al. (June 2013). "Vitamin C further improves the protective effect of GLP-1 on the ischemia-reperfusion-like effect induced by hyperglycemia post-hypoglycemia in type 1 diabetes". Cardiovascular Diabetology. 12: 97. doi: 10.1186/1475-2840-12-97 . PMC   3699412 . PMID   23806096.
  77. 1 2 3 Afkhami-Ardekani M, Shojaoddiny-Ardekani A (November 2007). "Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients". The Indian Journal of Medical Research. 126 (5): 471–474. PMID   18160753.
  78. 1 2 3 Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD (March 2008). "Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels". Diabetic Medicine. 25 (3): 320–325. doi: 10.1111/j.1464-5491.2007.02360.x . PMID   18279409.
  79. 1 2 3 Takiishi T, Gysemans C, Bouillon R, Mathieu C (June 2010). "Vitamin D and diabetes". Endocrinology and Metabolism Clinics of North America. 39 (2): 419–46, table of contents. doi:10.1016/j.ecl.2010.02.013. PMID   20511061.
  80. ↑ Talaei A, Mohamadi M, Adgi Z (February 2013). "The effect of vitamin D on insulin resistance in patients with type 2 diabetes". Diabetology & Metabolic Syndrome. 5 (1): 8. doi: 10.1186/1758-5996-5-8 . PMC   3586569 . PMID   23443033.
  81. ↑ Muthian G, Raikwar HP, Rajasingh J, Bright JJ (May 2006). "1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic encephalomyelitis". Journal of Neuroscience Research. 83 (7): 1299–1309. doi:10.1002/jnr.20826. PMID   16547967. S2CID   71926561.
  82. ↑ Gannagé-Yared MH, Azoury M, Mansour I, Baddoura R, Halaby G, Naaman R (August 2003). "Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women". Journal of Endocrinological Investigation. 26 (8): 748–753. doi:10.1007/bf03347358. PMID   14669830. S2CID   30463402.
  83. ↑ Mullan BA, Young IS, Fee H, McCance DR (December 2002). "Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes". Hypertension. 40 (6): 804–809. CiteSeerX   10.1.1.538.5875 . doi:10.1161/01.hyp.0000039961.13718.00. PMID   12468561. S2CID   8103446.
  84. ↑ Regensteiner JG, Popylisen S, Bauer TA, Lindenfeld J, Gill E, Smith S, et al. (2003). "Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes". Vascular Medicine. 8 (3): 169–175. doi: 10.1191/1358863x03vm489oa . PMID   14989557.
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