The Services Diamedica Siena, Strada Massetana Romana 65/15, Siena - tel. 0577051849 - email
diamedicasiena@gmail.com
Diabetologist Dr. Cadirni Alice
Specialist Surgeon Doctor in Endocrinology
Diabetology visit for Type 1 and 2 Diabetes; Training for the use of advanced technologies for the treatment and monitoring of Diabetes; Endocrinology visit for thyroid diseases, dyslipidemia, obesity, and overweight
For appointments: Diamedica Siena 0577051849 diamedicasiena@gmail.com
Diabetes
Diabetology
Diabetology studies diabetes mellitus which is a form of diabetes that is, a group of metabolic disorders characterized by persistent instability of the blood glucose level, ranging from more frequent conditions of hyperglycemia to conditions of hypoglycemia.
Although the term diabetes commonly refers only to the condition of diabetes mellitus, that is, sweet (so called by the ancient Greeks because of the presence of urine with that taste), there is another pathological condition called diabetes insipidus. These diseases are linked only by the fact that they present large quantities of urine, as they do not in fact share causes or other symptoms.
The percentage of the world population affected is estimated to be around 5%. About 90% of the diabetic population is affected by type 2 DM. In Italy, the percentage of individuals affected by this condition is on average 3%.
In 2002, more than 18 million people in the USA alone were affected by this condition, and it is estimated that one in every five elderly people over the age of 65 is affected by it.
The WHO estimates that there will be a very strong increase in the prevalence of DM in the USA, in the Middle East and in Southeast Asia while in Europe the increase will be more modest. In 2030, more than 360 million people are expected to be affected.
A higher prevalence has been found in females - (m:f = 1:1.25). A study on young people aged 15-29 with type 1 diabetes recorded a higher incidence in males compared to females, possibly due to factors such as sex hormones or different exposure to environmental toxins.[13] However, this difference has not been confirmed by subsequent studies.
It is estimated that in 2005 it affected more than 180,000 people under the age of 20, while in those over 60 years of age more than 12 million cases were recorded.[16] In Italy alone, in age groups under 35 it is 0.5%, while above 65 it exceeds 10%.
Type 1 DM begins in about half of cases at an age younger than 20 years (for this reason, in the past it was called "juvenile diabetes") and more frequently during puberty.
diabetes mellitus can be caused by a number of factors
.
Some may be derived from defects in insulin action, such as type A insulin resistance, leprechaunism, Rabson-Mendenhall syndrome and lipodystrophic syndromes; some diseases of the pancreas may cause diabetes, as in the case of pancreatitis, cystic fibrosis, hemochromatosis and pancreatic tumor.
Among the drugs that can cause diabetic forms are Vacor used as rat poison, pentamidine, nicotinic acid, glucocorticoids, thyroid hormones, diazoxide, β-agonists, thiazides, phenytoin, interferon a, protease inhibitors, clozapine, β-blockers).
Some infections can lead to the onset of diabetes, such as congenital rubella, cytomegalovirus and coxackievirus.
Among the numerous genetic disorders responsible for the development of diabetes are Down syndrome, Turner syndrome, Klinefelter syndrome, Huntington's chorea, Laurence-Moon-Biedl syndrome, porphyria. The existence of a genetic predisposition is suggested by the fact that, in the case of twins, Type 2 diabetes is present in both in a very high percentage, much higher than what occurs with Type 1 diabetes. It is likely that defects affecting multiple genes (polygenic disease) involved in insulin production and glucose metabolism are at play; the type of deficiency would vary from patient to patient, since up to now it has not been possible to identify genetic anomalies common to all Type 2 patients.
Diseases such as acromegaly, Cushing's syndrome, hypogonadism, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma may be other causes.
Among the risk factors are:
· Obesity (BMI greater than or equal to 25 kg/m² for DM2)
· Physical inactivity
· Hypertension (Systolic blood pressure (maximum) greater than or equal to 140 mmHg and/or Diastolic blood pressure (minimum) greater than or equal to 90 mmHg)
· Cholesterol HDL (less than or equal to 35 mg/dl)
· Triglycerides (greater than or equal to 250 mg/dl)
· Hypogonadism: in hypogonadal men, testosterone intake decreases insulin resistance and improves glycemic profile
· Sleep disorders, which favor the onset of type 2.
Age also favors the onset of diabetes, as it is accompanied by a physiological reduction of testosterone and IGF-I and therefore to a decreased sensitivity of peripheral tissues to insulin.
Type 1 diabetes
Type 1 form has an etiology that develops over time:
· Genetic predisposition, among the various responsible genes, the one located in the HLA region of chromosome 6
· Immune stimulation
This phase, known as the honeymoon phase, lasts for several months, after which the symptoms reappear and persist steadily, definitively leading to the diabetic state. The explanation for this phenomenon lies in the compensatory overproduction of insulin by the β cells of the pancreas.
Type 2 diabetes
Type 2 diabetes has a multifactorial etiology, as it is caused by the combination of several factors, both genetic and environmental.
The detection of type 2 DM is very often incidental during laboratory tests that the patient undergoes for other reasons, because the disease develops very slowly and it takes a long time before the symptoms can become clinically evident; on the other hand, in many patients, symptoms of hyperglycemia and glycosuria never appear.
The causal (etiological) factors responsible for the disease act through the combination of two main mechanisms (pathogenesis): the alteration of insulin secretion and the reduced sensitivity of target tissues (muscle, liver, and adipose tissue) to its action (insulin resistance).
Defects in insulin secretion are present not only in patients with Type 2 diabetes, but very often also in healthy twins and first-degree relatives; in the latter, insulin resistance has also been frequently detected. It is therefore thought that Type 2 diabetes is preceded by a prediabetic phase, in which the resistance of peripheral tissues to the action of insulin is compensated by an increase in pancreatic insulin secretion (hyperinsulinemia). Only when both insulin secretion defects and insulin resistance worsen (as a result of aging, obesity, physical inactivity, or pregnancy), does postprandial hyperglycemia first become apparent, followed by fasting hyperglycemia.
Visceral (or central) obesity plays a leading role in the development of insulin resistance. Adipose tissue is, in fact, capable of producing a series of substances (leptin, TNF-α, free fatty acids, resistin, adiponectin) that contribute to the development of insulin resistance. Furthermore, in obesity, adipose tissue is the site of a state of low-grade chronic inflammation, which represents a source of chemical mediators that worsen insulin resistance. As a result, inflammation markers, such as interleukin 6 and C-reactive protein, are often elevated in this type of diabetes.
Pathogenesis
Glucose metabolism
Glucose represents the most important source of energy for the cells of our body and for this reason, in addition to being used immediately, it is also stored in glycogen reserves. Glucose, therefore, from the blood (in which it is dissolved after the process of digestion of food) must be transported inside the cells to be used and stored.
Insulin is the main hormone that regulates the entry of glucose from the blood into the cells (mainly muscle cells and fat cells; not in the cells of the nervous system), the deficit of insulin secretion or insensitivity to its action are precisely the two main mechanisms through which DM occurs. Most carbohydrates in food are converted into glucose within a couple of hours. Insulin is produced by the β cells of the pancreas as an exact response to the rise in blood glucose levels blood (for example after a meal), the β cells of the pancreas are in fact stimulated by high blood sugar values and inhibited by low values.
If the availability of insulin is insufficient (insulin deficiency) or if the cells respond inadequately to it (insulin resistance) or if the insulin produced is defective, glucose cannot be effectively used by our body: the consequence of this is a state of glucose deficiency in the tissues with high levels in the bloodstream.
When fasting blood glucose exceeds 126 mg/dl, it is referred to as DM, while for values between 110 and 125 mg/dl it is called "impaired fasting blood glucose" (a risk factor for the future onset of DM). Glucose appears in the urine (glycosuria) for blood glucose values greater than 180/200 mg/dl.
Insulin resistance
The reduced ability of insulin to act effectively on target tissues (muscles and liver) is the main characteristic of type 2 DM and is called insulin resistance. This is a "relative" resistance since supraphysiological levels of insulinemia cause normalization of blood glucose. It is believed that this type of resistance is due to post-receptor defects, specifically the IRS-1 gene appears to be involved, which is essential for the synthesis of IRS proteins involved in a series of metabolic pathways that ultimately promote the entry of glucose into cells, thus decreasing blood glucose.
Chronic insulin resistance is defined as a daily insulin requirement greater than 200 IU for several days in the absence of infection or ketoacidosis.
The most common causes are obesity and IgG-type anti-insulin antibodies. The most important consequence is the lack of glycemic control.
In almost all diabetic patients, within 60 days from the start of insulin therapy, antibodies develop. It is thought that their binding to insulin is the most important cause of severe resistance, but the correlation between the antibody titer and resistance is not always close.
Recent studies have found that early insulin therapy can prevent the progression of both forms of diabetes, which is why the intake of sugars must be reduced.
Alterations of insulin secretion
When insulin resistance develops, there is initially a compensatory increase in insulin secretion (hyperinsulinemia) by the pancreatic β cells, however, the disease has a progressive course that leads to a true insufficiency of compensatory mechanisms. In the pathogenesis of the progressive deficit of insulin secretion, necrosis and apoptosis of beta cells play a decisive role, to which dyslipidemia (lipotoxicity) and chronic hyperglycemia (glucotoxicity) contribute, through complex biochemical mechanisms, which, among other things, cause an increase in the production of free radicals (oxidative stress), an uncoupling of mitochondrial oxidative phosphorylation, and alterations of the endoplasmic reticulum (reticular stress).
Increased hepatic glucose production
As will be seen later, DM causes an increase in ketone bodies in circulation, which metabolically is equivalent to the development of a deceptive condition of "chronic fasting" (even if the patient eats normally): under fasting conditions, there is an increase in glycogenolysis (release of carbohydrate reserves) and gluconeogenesis (de novo synthesis of glucose). All this causes a further worsening of the state of hyperglycemia.
Complications
Examination of the fundus oculi in a patient with diabetic retinopathy
Acute metabolic complications[edit | edit wikitext]
Among the most important acute complications of diabetes are ketoacidosis and hyperosmolar hyperglycemia.
Ketoacidosis
The excessive concentration of ketone bodies in the blood is due to a lack of insulin and the consequent excess of glucagon; it is typical of type 1 DM and triggered by severe stress (infections, trauma, surgical interventions).
Under normal conditions, triglycerides are stored in VLDL (particular lipoproteins with a transport function); in conditions of fasting and excess glucagon accompanied by a deficit of insulin, the pathway for the formation of ketone bodies is activated: the passage of these into the blood is the basis of metabolic acidosis (up to pH values close to 7.0) that can develop in patients with DM.[
Present: very high levels of hyperglycemia (between 500 and 700 mg/dl) and glycosuria with significant dehydration, abdominal pain, anorexia, vomiting, nausea. At this stage, a very common mistake must not be made: thinking you are dealing with a gastroenteric disease and consequently suspending the administration of insulin. This could lead the patient to a potentially fatal condition of diabetic ketoacidosis coma.[
Furthermore, even an excess of cortisol, or growth hormone or similar, can lead to this complication.[22]
Hyperglycemic hyperosmolar syndrome (or HHS)
Characteristic of type 2 DM, it is observed mostly in elderly patients, in whom the diabetic condition is aggravated by recurrent events (e.g. infections or stroke cerebral) and with an impaired ability to drink, making it impossible to compensate for osmotic diuresis.
Symptoms: confusional state up to coma and, if untreated, death (which still occurs in half of patients who are treated promptly). Always present is abnormal glycosuria (above 1000 mg/dl).
Ketoacidosis is absent, perhaps because the concentration of insulin in the portal vein is sufficiently high to prevent the full activation of hepatic ketogenesis.
Serum levels of free fatty acids are generally lower than in DM I ketosis.
In the treatment of this form of coma, several liters of isotonic saline solutions are required, followed by hypotonic solutions and then 5% glucose solutions, when blood glucose reaches normal levels. Insulin is also necessary, but at lower doses compared to the diabetic ketoacidosis coma of type 1 DM.
Long-term complications
Microscopic appearance of a glomerulus in diabetic glomerulosclerosis
· Diabetic macroangiopathy: tendency to develop atherosclerosis phenomena earlier and more intensely, the excess of glucose in the blood promotes glycation (which, unlike glycosylation, is a non-enzymatic process) of low-density lipoproteins (LDL) which is the basis of atherosclerosis;
· Diabetic ulcer: frequent development of sores near the lower limbs due to friction (e.g. shoes that are too tight), for this reason diabetics must take great care of their hygiene.
· Glaucoma
· Cardiac complications: diabetic patients can, due to high blood sugar and insulin levels, show atherosclerosis, with very dangerous manifestations ranging from angina pectoris to myocardial infarction. To reduce the risk, it is not enough to control triglycerides.
· infections
· dermatological infections
· oral infections
· cataract
Microangiopathies
There are 3 most famous and important forms of complication:
· diabetic nephropathy, affects the kidney. It often causes kidney failure, and the underlying disease does not appear until either failure or nephrotic syndrome is detected.
· diabetic retinopathy, affects the retina. A very dangerous visual complication, it leads to total loss of vision in adults; the fundus examination is the only test to understand its onset, which can be slow or rapid.[23]
· diabetic neuropathy, affects the peripheral nervous system in various forms.
Signs and symptoms
Main clinical manifestations of diabetes
Among the symptoms and signs are:
· Polyuria
· Polydipsia (secondary to polyuria),
· Paradoxical polyphagia (the patient eats a lot but loses weight), often the onset symptom is diabetic ketoacidosis, present especially in type 1;[25]
· Weight loss
· Nausea
· Vomiting
· Feeling of fatigue, irritability.
· Asthenia
· Headache
· Skin ulcers
· Necrobiosis lipoidica diabeticorum
· Itching
· Xanthelasmas and Xanthomas
Classification
The first classification provided a distinction based on age, distinguishing juvenile diabetes from mature-onset diabetes. Then in 1977 Irvine proposed a classification concerning the presence of anti-insulin-pancreatic antibodies detected or not during the diagnosis of the disease, a hypothesis that was soon discarded for various reasons.[
Another classification that was widely used in the past was the one by stages, which divided the pathology into 4 phases:[
· Potential diabetes
· Latent diabetes
· Asymptomatic diabetes
· Clinical diabetes
In 1979 the National Diabetes Data Group proposed a classification[31] later adopted by the largest organizations worldwide (in 1999 the WHO and the European Association for the Study of Diabetes) regarding the etiology of immunological origin.
Currently, diabetes mellitus is divided into "type 1" and "type 2".
· Type 1 diabetes mellitus: characterized by the destruction of pancreatic beta cells, (CD4+ and CD8+ lymphocytes and infiltration of macrophages in the pancreatic islets), usually resulting in association with insulin deficiency.[33] There are two subtypes:
or Type 1A (immune-mediated)
or Type 1B (idiopathic), without a known etiology, affects mostly young Africans and Asians at a younger age compared to the other form.[
It affects about 10% of people with diabetes and generally arises in childhood or adolescence. In type 1 diabetes, the pancreas does not produce insulin due to the destruction of the β cells that produce this hormone: therefore, it is necessary for insulin to be injected every day and for life. The rate of destruction of the β-cells is, however, quite variable, so the onset of the disease can occur rapidly in some people, usually in children and adolescents, and more slowly in adults (in these rare cases it is referred to as a particular form called LADA: Late Autoimmune Diabetes in Adults).
The cause of type 1 diabetes is unknown, but it is characterized by the presence in the blood of antibodies directed against antigens found in the cells that produce insulin, called ICA, GAD, IA-2, IA-2β. This damage, which the immune system induces against the cells that produce insulin, could be linked to environmental factors (among which dietary factors have been implicated) or to genetic factors, identified as a general predisposition to react against external phenomena, including viruses and bacteria. The latter hypothesis is based on studies conducted in monozygotic (identical) twins, which have shown that the risk of both developing type 1 diabetes is 30-40%, while it drops to 5-10% in non-twin siblings and 2-5% in children. Therefore, a "predisposition to the disease" could be transmitted through the inheritance of genes that affect the immune response and that, during a normal immune system response to common infectious agents, also cause a reaction against the β cells of the pancreas, with the production of antibodies directed against them (autoantibodies). This altered immune response causes a progressive destruction of the β cells, so that insulin can no longer be produced and the diabetic disease is thus triggered.
· Type 2 diabetes mellitus: the pathogenesis is not immune-mediated. It is related to the presence of genes near the HLA site on chromosome 6. It is also called non-ketotic.
It has stronger genetic bases than the first form, although the mode of transmission is not known. It accounts for almost all cases, 90-95% of all forms
In addition to the two main forms, there are other forms, identified by the American Diabetes Association, defined as secondary to other diseases.
· Genetic defects of beta cell function: Mody
· Gestational diabetes mellitus (or GDM): in 7% (average among various studies conducted, reaching up to 14%[36]) of pregnancies it happens that the mother develops a condition of DM, this event is completely transitory and easily treatable, however it can cause problems for the newborn[37] ranging from increased birth weight to the death of the unborn child, and for the mother (it represents an important risk factor for developing DM, from 20 to 50% of women who have suffered from GDM develop type 2 DM during their lifetime).
Physical exercise
The diabetes prevention program (DPP, literally the diabetes prevention program) has shown that modest physical exercise is especially beneficial for type 2 diabetes in most cases[ indicating that about 30 minutes of physical exercise for 5 days a week can produce positive effects, both in terms of prevention and in delaying possible effects.[ Unless contraindicated due to the coexistence of other diseases, exercise reduces glucose intolerance glucose (improving insulin sensitivity) and reduces cardiovascular risk factors. The weight loss resulting from exercise is another incentive since reducing body weight is a basic intervention in the therapy of Type 2 diabetes. The positive effect is seen in both sexes and at any age. Contrary to what one might think, it happens that during physical exertion blood sugar increases. What happens is that during activity, hormones such as adrenaline and glucagon are produced, causing an increase in blood sugar. Before and/or after sports activity, it may be appropriate to reduce insulin since physical effort helps the function of insulin; it is estimated that under exertion, the action of insulin is enhanced by 20/30%. Based on the indications of your doctor and possibly on blood glucose findings, it is therefore necessary to make the necessary changes to insulin therapy taking this information into account.
Diabetes Siena
Diabetologist and Endocrinologist Dr. Alice Cadirni, medical doctor specialized in Endocrinology and Metabolic Diseases. Treatment of diabetes, thyroid, and related conditions
Diabetes Siena
Diabetologist Siena, Diabetologist Grosseto, Thyroid Siena, Thyroid Grosseto, Endocrinologist ar, Diabetes ar, Diabetologist gr, Diet, diabetes, thyroid, metabolic diseases, endocrinologist ar
Diet
The Services Diamedica Siena, Strada Massetana Romana 65/15, Siena - tel. 0577051849 - email
diamedicasiena@gmail.com