Astrid L. Libman, Julio Libman

It is designated with the name of diabetes mellitus (or diabetes saccharin) to a complex syndrome whose most prominent characteristic is the elevation of the glycemia. Along with the carbohydrate metabolism disorder, there are alterations in the metabolism of fats and proteins, as well as a marked tendency to develop complications that mainly affect the voluntary and autonomic peripheral nervous system (neuropathy), the large coronary arteries , of the lower and visceral limbs (macroangiopathy), and to the small arterioles and capillaries, mainly of the retina and the kidney (microangiopathy).

Pathophysiology

The hyperglycemia of diabetes results from abnormalities in the secretion and / or action of insulin. Secretion can be deficient, delayed or inappropriate for the circulating glucose level, while the action can be affected by abnormalities of the peripheral tissues at the receptor and / or post-receptor level.

According to its probable etiology, pathophysiology and clinical manifestations, it is possible to recognize different alterations in the metabolism of carbohydrates that are manifested by hyperglycemia. (Table 72.1).

1. Type 1 diabetes. It is characterized by the absolute or almost total lack of endogenous insulin, due to destruction of the beta cells of the pancreas, due to a combination of genetic and environmental factors. Genetic predisposition appears to be related to diabetogenic genes on the short arm of chromosome 6, in close proximity or forming part of the region of the major histocompatibility complex, that is, the region of human leukocyte antigens (HLA). There is an association between type 1 diabetes and immune response genes, also known as class II alleles of the major histocompatibility complex (MHC). These include the HLA-DR, DQ, and DP loci. The HLA-DR3 and DR4 alleles of the DR locus occur most frequently in whites with type 1 diabetes.

Some environmental agents, such as viral infections, chemical toxins or exposure to cow's milk proteins in the first months of life, could initiate the disease process in individuals with genetic predisposition.

The immune destruction of beta cells would be mediated by the TH1 subclass of facilitator lymphocytes, while the TH2 subtype could confer protection. The cell-mediated immune destructive process would involve lymphocytes, NK cells, and macrophages / monocytes, which produce cytokines such as interferon alpha, interleukin-1, and others that damage beta cells.

Different types of antibodies that do not play a pathogenic role can be detected in the circulation several years before diagnosis. These include islet cell antibodies (ICA), glutamic acid decarboxylase (GAD), and an islet tyrosine phosphatase called IA2.

The destruction in a variable time of the beta cells, faster the younger the individual, leads to an absolute lack of insulin, with the more or less abrupt appearance of the clinical manifestations and the tendency to develop ketoacidosis. This type of diabetes can occur at any age, although the largest number of affected patients begins their disease before the age of 25, mainly in childhood and pubertal age.

2. Type 2 diabetes. Patients with this type of diabetes can produce decreased, normal or increased amounts of insulin, but always insufficient in relation to blood glucose levels, with alterations in the dynamics of secretion and delayed release of insulin after glucose stimulation. There is a decrease in the pulsatile secretion of insulin and an increase in the proportion of proinsulin in relation to the insulin that is produced, the former having a much lower biological activity. The presence of a certain amount of circulating insulin, sufficient to inhibit lipolysis, but not to maintain normoglycemia, means that these patients do not develop ketoacidosis under normal conditions.

In most patients there is a coexisting state of insulin resistance associated with compensatory hyperinsulinemia until the eventual depletion of beta cells, with a decrease in the action of this hormone in the liver, muscle and other target tissues, mainly due to Post-receptor alterations in the intracellular signal transmission cascade of insulin.

Even though compensatory hyperinsulinemia can delay or prevent the onset of diabetes in individuals with insulin resistance, the decreased effectiveness of insulin together with the hyperinsulinemia consequence of it, play an important role in the development of a series of alterations associated with an increase in cardiovascular mortality and the process of atherogenesis, which together are designated as metabolic syndrome or insulin resistance syndrome. The most important manifestations of it are detailed in Table 2.

Type 2 diabetes is preceded by two conditions, impaired fasting blood glucose and decreased glucose tolerance, considered risk factors for the development of diabetes and / or cardiovascular disease.

3. Other specific types of diabetes. They are associated with known genetic defects in beta cells or insulin action, diseases of the exocrine pancreas, endocrinopathies, drugs, and infections.

4. Gestational diabetes. It is glucose intolerance that appears in pregnancy, mainly in the second half, because the pancreatic reserve of insulin is not sufficient to counteract the action of the hyperglycemic hormones of this period of gestation (lactogenic placental hormone, free cortisol increased, prolactin).

The blood glucose values ​​in venous plasma for the diagnosis of diabetes and other categories of hyperglycemia are detailed in Table 3.

Oral glucose tolerance test.

Hyperglycemia is the most obvious metabolic abnormality in diabetes and appears to play an important role in the development of neurological and vascular complications. One of the basic mechanisms that would act would be the non-enzymatic glycosylation of proteins in vivo, a process that is directly related to glucose levels. An example of this process is the glycosylation of hemoglobin (Hb) with the production of glycosylated Hb, whose normal values ​​are below 6.2% of total Hb. Poorly controlled diabetics present higher figures. Glycated Hb undergoes a series of functional alterations. It has a greater affinity for O2 and releases it to a lesser extent to the tissues, which can cause hypoxia. It also reduces erythrocyte elasticity and deformability,

Hyperglycemia induces irreversible glycosylation of intra and extracellular proteins that results in the formation of advanced glycosylation products of proteins, which play an important role in the development of the aging process and the vascular complications of diabetes.

The increase in the metabolic pathway of polyols at the level of Schwann cells, with an increase in sorbitol and intracellular fructose, can lead to cellular alterations that lead to demyelination and neuropathy.

On the other hand, hyperglycemia inhibits myoinositol uptake in peripheral nerves, producing a deficit of it with the consequent decrease in nerve conduction velocity.

Alterations in plasma lipoproteins that are frequently observed in diabetes, as well as the higher prevalence of arterial hypertension, contribute to the development of vascular diseases. Alterations in the immune mechanism favor the more frequent appearance of infections in patients with poorly controlled diabetes.

Symptoms and signs

Apart from the direct consequences of hyperglycemia, the symptoms and signs of diabetes mellitus are those produced by acute or chronic complications and those of the underlying cause, if there is one.

Direct consequences of hyperglycemia. In an appreciable number of patients, there are no obvious clinical manifestations, except obesity, often of the android type, accompanied by greater insulin resistance, which contributes to the appearance of DM2. In these cases the discovery of diabetes is made by systematic studies of blood and urine. The clinical manifestations include polyuria, determined by glycosuria-induced osmotic diuresis, with consequent polydipsia and polyphagia, attributable in part to the lack of glucose entry into the satiety center, a mechanism that is insulin-dependent. There may be blurred vision due to variations in osmotic pressure and an increase in the anteroposterior diameter of the lens, fatigue,

Manifestations due to the existence of defined causes of diabetes

Pancreatic diseases

Chronic pancreatitis . The presence of mild or relatively constant pain that is usually aggravated by ingestion of food, or of recurrent acute pain located in the epigastrium and upper left quadrant, radiating to the back and with less abdominal tenderness to the examination than expected in relation to its intensity, suggests the existence of chronic pancreatitis. Malabsorption, manifested by the excretion of bulky and foul-smelling stools, and weight loss are associated.

Hemochromatosis . It can be recognized by the characteristic tanned pigmentation of the skin (caused by hemosiderin deposits), hepatomegaly, asthenia, general malaise, chronic abdominal pain, arthropathy, and nonspecific neurological symptoms. The hypogonadism that is part of the picture is usually hypogonadotrophic, manifested by impotence, loss of libido, decreased body hair, and testicular atrophy.

Acute pancreatitis and tumors of the pancreas . The presence of an epigastric scar may be the key to an exploratory laparotomy related to these pathologies.

Extrapancreatic endocrine diseases

Cushing's syndrome. Cushing's syndrome caused by pituitary or adrenal disease, or as a result of chronic administration of corticosteroids in pharmacological doses, is frequently associated with diabetes. This is due to an increase in peripheral insulin resistance and hepatic gluconeogenesis. Examination shows centripetal obesity with roundness of the face and accumulation of adipose tissue on the trunk, supraclavicular areas, and cervicodorsal spine. The skin is fine, ruddy, with thick vinous red streaks. Ecchymosis occurs due to increased capillary fragility. There is hirsutism and menstrual disturbances in women. High blood pressure and osteopenia are common, the latter produced by exaggerated protein catabolism of the protein bone matrix and a negative calcium balance,

Acromegalia. It is accompanied by frank diabetes or carbohydrate intolerance in at least 25% of patients. Somatotropin excess is associated with increased resistance to insulin action. The signs and symptoms of acromegaly appear slowly. They consist of soft tissue hypertrophy and increased bone apposition, together with visceromegaly. The extremities are enlarged, so that the patient is forced to increase the size of rings, gloves and shoes. The skin thickens, the dermal folds become more prominent, and sweat and sebaceous secretion increase. Fibroma molluscum and acanthosis nigricans are common. There is prognathism with dental diastasis, and increased size of the paranasal sinuses; the latter, together with hypertrophy of the vocal cords, is the cause of a serious voice. A hypertrophic arthropathy occurs which ultimately leads to disfiguring and disabling changes. There is goiter, arterial hypertension and cardiomegaly. The manifestations of the pituitary tumor syndrome may be associated with the existence of the somatotrophic macroadenoma, such as headaches and visual field alterations.

Pheochromocytoma . It is accompanied by intolerance to carbohydrates and less frequently by frank diabetes, due to increased glycogenolysis and peripheral insulin resistance. It is possible to find headaches, palpitations, profuse sweating, weight loss. The symptoms are paroxysmal and are associated with increases in blood pressure. In other cases the hypertension is permanent, but shows notable variations. Hypertensive spikes are associated with episodic catecholamine release.

Primary hyperaldosteronism . Produced by an adrenal adenoma or bilateral adrenal hyperplasia that affects the glomerular zone selectively, it is accompanied by carbohydrate intolerance or frank diabetes. The clinical manifestations are those of arterial hypertension and less frequently those of hypokalemia, such as asthenia, lassitude, polyuria, polydipsia, alkalosis, paresthesias and cardiac arrhythmias.

Chronic adrenal insufficiency . Of autoimmune origin, it can be associated with insulin-dependent diabetes. In these cases, the examination reveals weight loss, asthenia, skin-mucous pigmentation, arterial hypotension, digestive disorders, and a selective appetite for salt.

Glucagonoma . It is a glucagon-producing  cell tumor. It is associated with frank diabetes in 60% of cases, while 30% of patients have carbohydrate intolerance. The syndrome is clinically characterized by an escalating and decreasing skin rash called erythema migrans, diabetes, weight loss, and anemia. The classic skin lesion begins as an erythematous base, becomes indurated and acquires central and superficial vesicles; the vesicles erode and become covered with scabs. Healing can be accompanied by hyperpigmentation. This process takes 7 to 14 days and the lesions appear in one area while healing in others. Glossitis, stomatitis, and cheilitis are often present, and onycholysis and brittle nails may be seen.

Somatostatinoma . It can be accompanied by mild diabetes, cholelithiasis, steatorrhea with malabsorption, dyspepsia, and significant weight loss. Patients may also have watery diarrhea, anemia, and flushing.

Other findings and associations

Uremia . Carbohydrate intolerance is found in most patients with uremia.

Chronic liver diseases . Whatever the type, they can be associated with diabetes mellitus. Jaundice with ascites is evident on many occasions in cirrhosis accompanied by diabetes.

Prader-Willi syndrome . Diabetes mellitus is associated in this syndrome with marked obesity, hypotonia, small penis, and cryptorchidism in boys, hypoplastic lips in girls, small hands and feet (achromyria), mental retardation of variable degree, and hypogonadotrophic hypogonadism and short stature in adulthood. In these patients, a deletion is found at locus q 11-13 on chromosome 15.

DIDMOAD syndrome . Diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and deafness (D) are variably associated with this rare family syndrome. These patients have mutations in the WFSI gene on chromosome 4 p 16.3. It is inherited in an autosomal recessive manner.

Lipoatrophy . Total lipoatrophy associated with diabetes can occur in children and adults. There is almost complete loss of subcutaneous fat. Partial lipoatrophy usually begins in children and young adults, being more frequent in the female sex. Patients lose fat from the face and upper half of the body. In some cases there is hypertrophy of fat in the lower half of the body.

Acute complications

Allergy to insulin . A small number of patients who start insulin treatment experience various local allergic reactions at the injection site. Manifestations consist of local itching, indurated and erythematous lesions, and occasionally small subcutaneous nodules. The frequency of these problems has greatly decreased after the introduction of the newer more purified insulins, porcine or human. Some patients may have systemic reactions, such as generalized urticaria and even anaphylactic reactions.

Hyperlipidemia . In diabetic ketoacidosis the serum may appear milky as a result of marked hyperlipidemia. This alteration may manifest itself in the fundus examination due to the characteristic retinal lipemia.

Hypoglycemia . Hypoglycemia constitutes the exaggeration of the physiological action of insulin; It is observed as a complication of insulin therapy, especially intensified as a result of its excessive administration or inappropriate timing with exercise or food intake. It can also constitute a complication of treatment with oral hypoglycemic agents from the group of sulfonylureas. The clinical findings depend, on the one hand, on neuroglycopenia, and consist of nervousness, irritability, temporospatial disorientation, miscalculations, headaches, seizures and coma, and on the other hand they are an expression of the release of catecholamines, such as profuse perspiration, tremor, anxiety, palpitations with tachycardia, mydriasis, cold skin and hypertension.

Diabetic cetoacidosis.Diabetic ketoacidosis constitutes a clinical emergency that can endanger the life of the patient, who presents a picture of anorexia, nausea, vomiting, polyuria, polydipsia and asthenia. Sometimes abdominal pain is a predominant feature, often due to gastric stasis and distention or irritation of the peritoneal serosa. There may be ketone breath and deep, loud breathing, with long and long inspirations and exhalations, "hunger for air", the so-called Kussmaul breath. As a consequence of the loss of water due to osmotic diuresis, digestive intolerance and tachypnea, the patient presents dehydration that in the clinical examination is reflected by dry skin and mucous membranes, sunken and hypotonic eyeballs, and due to tachycardia, hypotension and oliguria. to hypovolemia. There is a decrease in the tendon reflexes. Left to its spontaneous evolution, the picture worsens with decreased sensorium, disorientation and coma. Absolute or relative lack of insulin leads to hyperglycemia and ketoacidosis due to decreased peripheral glucose utilization and increased glycogenolysis, gluconeogenesis, protein catabolism, lipolysis, and ketogenesis.

Nonketotic hyperosmolar syndrome . The existence in a patient older than 60 years of a clinical picture of severe polyuria, hypovolemia, dehydration, and neurological manifestations such as disorientation, seizures, and slow-onset loss of consciousness should suggest the possibility of a nonketotic hyperosmolar syndrome.

Acute infections. The presence of itchy, reddish-brown lesions in the armpits or in the genitocrural region suggests the diagnosis of erythrasma, caused by a small gram-positive bacillus, Corynebacterium minutissimus. Skin infections can take on the appearance of boils or carbuncles. Lesions such as oral yeast infection (stomatitis, angular stomatitis), and candida balanitis and vulvovaginitis may occur, and the infection may spread to the upper and inner thighs and skin folds. Necrotizing cellulite is a serious complication that can affect the perineum and lower extremities. 25% of patients have subcutaneous emphysema. Dermatophytoses can be, in the diabetic patient, the gateway to serious infections that can lead to foot loss. The first manifestations are pruritus, erythema and maceration in the interdigital spaces. Vesicles and pustules may occur. Open fissures deep in the interdigital spaces or on the plantar surface of the fingers are ideal sites for aggregate bacterial infection, the origin of cellulitis and osteomyelitis. Although the feet are the most commonly affected sites, this can also occur in the hands and groin.

The existence, in varying combinations, of symptoms and signs of frequency, dysuria, burning pain during urination, suprapubic discomfort, excretion of cloudy and sometimes hematuric urine, fever, costovertebral angle hypersensitivity, pain in the lumbar fossa and chills, indicates the presence of an acute urinary tract infection. The association of fever, lumbar and abdominal pain, and kidney failure should lead to suspicion of necrotizing papillitis.

The presence in elderly diabetic patients of a severe clinical picture of persistent ear pain with purulent discharge, swelling and pain in neighboring soft tissues, together with facial paralysis, indicates the probable existence of a malignant external otitis, produced in the majority of patients. the cases by germs of the type of Pseudomonas aeruginosa. It can be complicated by meningitis and venous sinus thrombosis.

Rhinocerebral mucormycosis occurs in more than 75% of cases in acidotic patients, especially with diabetic ketoacidosis. The first clinical manifestations are nasal congestion with traces of blood, swelling, and facial or orbital pain. Examination of the nasal mucosa reveals dirty red or black and necrotic turbinates. There may be facial cellulitis, perforation of the palate or nasal septum, and signs of sinusitis. Spread of infection to the orbit causes orbital cellulitis, proptosis, and impaired vision. Destruction of cranial nerves III, IV and VI, of the ophthalmic branch of the V pair and of the blood vessels that cross the optic foramen and the sphenoid cleft produces complete ophthalmoplegia, fixed and dilated pupil, superior corneal and facial anesthesia, chemosis and conjunctival hemorrhage, and blindness from obstruction of the central retinal artery. The disease usually spreads to involve the internal carotid artery and sometimes the cavernous sinus, lamina cribrosa, meninges, brain, and skull bones. Cerebral infarction caused by vascular disorder is frequent.

Acute neuropathy . It can generally be seen during or following a period of poor metabolic control. Sometimes it is the first manifestation of an unknown diabetes. A variety of neuropathic syndromes involving motor and sensory nerves of the upper and lower extremities can be found, including multiple mononeuritis. Thus, for example, radial paralysis can produce a gouty hand.

Paralysis of the oculomotor, external ocular motor, common ocular and pathetic motor nerves, as well as that of the facial, is observed frequently. The involvement of the ocular motor nerves is installed abruptly and is accompanied by eye pain; there are no pupillary modifications.

Chronic complications

Insulin lipodystrophy. Lipoatrophy and lipohypertrophy . They occur at the injection sites of insulin. The first, attributed to impurities in the insulin preparation, is mainly observed with insulin of bovine origin, and consists of the disappearance of the subcutaneous cellular tissue, mainly in young women. The hypertrophy is attributed to the local lipogenic action of the injected insulin. In advanced cases, the underlying tissue may be fibrous and less vascular, for which there is anesthesia of the overlying skin. This circumstance explains why many patients prefer the affected areas to apply insulin.

Peripheral vascular disease . Peripheral artery disease in the lower limbs can be asymptomatic, being revealed only by examination and stress tests, or it can be expressed by intermittent claudication, rest pain and / or necrosis and gangrene.

The pain of intermittent claudication characteristically appears with walking and calms down with rest. The most common location is at the calf level, indicating a femoropopliteal lesion. Aortoiliac obstructions are manifested by pain in the gluteal area and the thigh; the popliteas and the tibiofibular trunk due to pain in the ankle and foot.

Rest pain indicates that the ischemia is more severe. It appears when the patient adopts the horizontal position and something is relieved in a sitting position, with the legs hanging, which would favor blood flow due to the action of gravity. On the other hand, this position can cause the appearance of edema, which would aggravate the ischemia. Rest pain worsens with cold and wandering. In the fluxometric study by Doppler effect, an ankle / arm index greater than 0.50, and / or an absolute pressure greater than 80 mm Hg, exclude the possibility of ischemia as a cause of pain. The signs obtained in the clinical examination include decreased or disappearance of peripheral pulses, presence of murmurs, lack of hair, decreased growth and trophic alterations of the nails, atrophic, shiny and thin skin, paleness,

The pulses can be normal and the murmurs may not exist at rest, the former disappearing and the latter becoming evident after an exercise (walking, climbing stairs, etc.). Elevation of the lower limbs to 45º produces an increase in skin pallor and venous emptying. With the legs pending without touching the ground, a venous filling time greater than 15 to 20 seconds, accompanied by redness and sometimes a cyanotic tint, indicates arterial insufficiency.

Coronary heart disease. Coronary heart disease can present clinically as angina pectoris, acute myocardial infarction, heart failure, or sudden death. It is important to highlight that the painful manifestations of myocardial ischemia are absent in a significant proportion of cases (25%), probably due to the concomitant compromise of cardiac innervation.

Nephropathy . Examination of the diabetic patient with renal failure and uremia may reveal high blood pressure, pericarditis, anemia (paleness, tachycardia, systolic ejection murmur that is best heard in the lung area, and angina pectoris in patients with underlying coronary disease), bleeding diathesis (epistaxis, metrorrhagia, post-traumatic ecchymoses), infections, gastrointestinal disorders (anorexia, nausea, vomiting, digestive bleeding), osteodystrophy, lung disease, myopathy and pruritus. The existence of a nephrotic syndrome is clinically manifested by the presence of edema.

Chronic neuropathy . Peripheral diabetic neuropathy. Sensory manifestations include pain and paresthesia. Pain is a primary symptom of neuropathy; It is localized in the lower limbs and it is present or exacerbated during rest, and it is burning and glowing. It can compromise the general condition of the patient, since it does not allow rest.

The paresthesias that topographically appear in the same areas as the pain and at the distal ends of the lower limbs, are accentuated with decubitus and rest, and are relieved by exercise, walking and cold.

There is a decrease in tactile and thermoalgesic sensitivity, responsible for burns that occur as a result of the use of hot water bottles, and trophic lesions of the feet, as well as a decrease in vibratory sensitivity (apalestesia).

Less frequent motor alterations consist of a feeling of insecurity in walking, asthenia and decreased strength, paresis, and rarely paralysis, followed by muscle atrophy. Hyporeflexia and areflexia are a fundamental sign of peripheral neuropathy. The most frequently affected reflex is the Achilles, followed in order of frequency by the patellar.

Muscle alterations can be secondary to the nerve injury or primary. Secondary lesions occur especially in the distal extremities of the limbs, mainly the lower ones. The atrophy of the muscles of the foot produces structural alterations due to modification of the lines of force and support points, which determines the appearance of hyperkeratosis that can easily ulcerate at the level of the heads of the first and fifth metatarsals and the ball of the feet. fingers, constituting the gateway for infections. The initial blister or blister can evolve into a painless ulcer, the plantar perforator disease.

Primary diabetic amyotrophy is clinically characterized by the presence of muscle atrophy at the level of the scapular and pelvic girdles, accompanied by muscle pain and dysesthesias.

Autonomic neuropathy . When there is a neurogenic bladder, the patient may complain of prolonged, spaced urination, with a weak stream and a sensation of hypogastric heaviness. The apparent incontinence of urine may be an expression of overflow urination. Patients with a neurogenic bladder often apparently improve from a previous nocturnal frequency. When the first morning urination is measured, abnormally high volumes of urine are found, because patients literally urinate into their own bladder during the night, and pass urine when they get up. The volume of the first morning urination is an important data to evaluate the existence of a neurogenic bladder.

Sexual impotence generally coexists with other signs and symptoms of peripheral and visceral neuropathy, especially with a neurogenic bladder. The patient may also refer to retrograde ejaculation as an expression of autonomic nervous system injury due to failure of the internal bladder sphincter closure. The pressure of the testicles does not cause pain.

The clinical manifestations of cardiac neuropathy include fixed resting tachycardia without response to the Valsalva maneuver, orthostatic hypotension, with dizziness and syncope episodes when suddenly assuming the upright position, and the production of a myocardial infarction that frequently occurs without pain.

There may be changes in sweating. Patients present with hyperhidrosis and heat intolerance in the upper half of the body, especially the face, neck, armpits, and hands. This is in contrast to anhidrosis below the navel, with dry, cracked and easily flaking skin, which is easily infected.

Digestive disorders are manifested by delayed evacuation and retention and gastric hypotonia, resulting in nausea, bloating, and general postprandial malaise. Since this syndrome alters eating habits and food absorption, hypoglycemic episodes can occur.

There may be diarrhea, appearing at night, accompanied by sphincter incontinence; they evolve in episodes and are sometimes accompanied by steatorrhea. They are produced by a decreased intestinal motility, with exaggerated bacterial overgrowth.

Regarding pupillary alterations, a reduction in the pupillary diameter at rest, a lazy reflex to light and small fibrillar contractions (hippus) is observed.

Osteoarticular alterations. Neuropathy (Charcot arthropathy). Diabetes mellitus is the most common cause of Charcot arthropathy. It usually develops in patients with long-standing poorly controlled diabetes and concomitant peripheral neuropathy. There is usually no vascular insufficiency. The feet are particularly affected, especially the ankle and metatarsophalangeal and metatarsal joints. Characteristically minor trauma is followed by painless swelling. When some type of pain or discomfort is present, they are of much lower hierarchy considering the degree of deformity of the foot. Often there is subluxation of the midtarsal region or metatarsophalangeal joints. The foot does not appear ischemic, has a normal temperature, and can be anhydrotic or hyperhydrotic. The pulses are usually palpable. There is some degree of joint hypermobility.

Diabetic hand syndrome. It is known by a variety of terms, including "joint stiffness" and "limited joint mobility." Common in juvenile diabetics, it is characterized by limited mobility of small and large joints. It can be demonstrated by asking the patient to try to bring both hands together in prayerful accuracy, opposing the palmar surfaces of the proximal and distal interphalangeal joints. The inability to achieve contact with the palmar surfaces of these joints demonstrates their limited mobility. May be associated with thick, tight, waxy-looking skin, particularly on the back of the hands. It is also very often accompanied by diabetic microangiopathy.

Periarthritis Bursitis and periarthritis, particularly involving the shoulder, often bilaterally, are seen more often in diabetic patients.

Dupuytren's contracture. Contraction of the palmar fascia, with fibrous nodules and inability to extend the fingers, is a relatively common finding in patients with diabetes mellitus.

Skin disorders . Lipoid necrobiosis. The early lesions are made up of slightly raised glossy papules, 1–3 mm in diameter, with well-defined borders. They may show slight scaling or be moderately erythematous. They do not disappear under pressure. Later they are transformed into rounded, oval or irregular shaped plates, with well defined edges, a firm consistency and a surface that simulates stretched cellophane paper. Sometimes they acquire atrophic appearance with circular areas of depression and ulceration. The surface may be mottled yellow and crossed by small blood vessels, or it may have a dark tint that resembles an area of ​​gangrene. Telangiectasias can be prominent.

Diabetic dermopathy (pimple spot). These injuries are common in the tibial region, although they can also be seen on the forearms and thighs. They begin as small reddish papules of 5 to 12 mm in diameter, round or oval, flat, that gradually heal, leaving atrophic and hyperpigmented areas.

Xanthomas. They are an expression of the tissue deposition of lipids in the skin and sometimes in the tendons. There are four clinical varieties of xanthomas: flat, tuberous, eruptive, and tendinous. Diabetic patients with severe hyperlipoproteinemia commonly present with eruptive xanthomas, previously known as xanthomas diabeticorum. They are firm, bright red papules that appear on the gluteal areas and on the extremities, particularly on the lateral and dorsal parts of the forearms and around the elbows and knees. A peripapular inflammatory halo is an important diagnostic sign. The lesions vary in size and can reach a diameter of 5 millimeters. Since they are an expression of severe hypertriglyceridemia, which produces a cloudy milky plasma, retinal lipemia can be observed concomitantly. When flat xanthomas are located on the eyelids, they are called palpebral xanthoma. They are the most common type of xanthomas and begin as small, orange-yellow lesions the size of a pinhead, covered by normal epidermis. Over the months they join and thicken, eventually forming irregular patches that can almost entirely cover the skin of the eyelids. Concomitant hypertriglyceridemia and hypercholesterolemia are common. Over the months they join and thicken, eventually forming irregular patches that can almost entirely cover the skin of the eyelids. Concomitant hypertriglyceridemia and hypercholesterolemia are common. Over the months they join and thicken, eventually forming irregular patches that can almost entirely cover the skin of the eyelids. Concomitant hypertriglyceridemia and hypercholesterolemia are common.

Xanthochromia consists of a yellowish color that is sometimes observable on the skin of diabetic patients, mainly on the palms of the hands, soles of the feet, and nasolabial folds. It is produced by the lower conversion of carotenes into vitamin A in the liver.

Acanthosis nigricans. It is a symmetric, pigmented, verrucous lesion that occurs in the skin folds. It is seen in various malignant conditions and endocrinopathies, including diabetes mellitus. Other types of skin lesions are described in the paragraphs dedicated to acute and chronic complications of diabetes.

Ophthalmological disorders . Variations in visual acuity. Variations in visual acuity are common especially in insulin-dependent patients with widely fluctuating plasma glucose levels; they are produced mainly by differences in osmotic pressure between the lens and the extracellular fluid.

Waterfalls. They are produced specifically by diabetes. They can occur in young patients, be bilateral, with a snowflake-like appearance in the subcapsular region of the lens. Senile cataracts appear more commonly and at an earlier age in individuals with diabetes.

Iridopathy. This alteration is observed in some poorly controlled young diabetics, in whom glycogen is deposited in the pigment epithelium on the posterior surface of the iris. Subsequently a network of new blood vessels develops on the anterior surface of the iris, eventually surrounding the pupil. The end result of this process can be glaucoma.

Retinopathy It can be nonspecific, the result of changes produced by atherosclerosis or arterial hypertension, or be a specific consequence of diabetic microangiopathy. The lesions of diabetic retinopathy include:

1. Venous changes that are initially characterized by generalized venous dilation, followed later by beading, tortuosity along the way, and sheathed varicosities that may precede the development of microaneurysms;
2. Arterial changes consisting of hyalinization and narrowing of the arterioles, resulting in part from atherosclerosis;
3. Microaneurysms, a characteristic finding of diabetes, that resemble pinpoint hemorrhages of variable size distributed at the level of the posterior pole and in the macular region;
4. Hemorrhages, round, red and larger than microaneurysms;
5. Exudates, usually hard and white or yellowish;
6. Lesions in the form of cotton wool. They are retinal infarcts resulting from arterial occlusion and constitute a poor prognostic sign;
7. Macular disease, which is a major cause of blindness; Exudates, microaneurysms or hemorrhages contribute to its development, with macular edema being the main cause of vision impairment;
8. Vitreous hemorrhages, which occur from newly formed vessels as part of the proliferative retinopathy of diabetes. Posterior fibrosis can lead to retinal detachment.

Study methodology

Faced with the existence of a family history of diabetes, early arteriosclerotic disease, suggestive obstetric history, obesity and / or fasting blood glucose "border line", it is appropriate to carry out an oral glucose tolerance test to diagnose diabetes or carbohydrate intolerance . The patient should receive a normal diet with at least 200 grams of carbohydrates for three days prior to the test; You should not take medications that may interfere with carbohydrate metabolism or have intercurrent illnesses. While fasting and without doing any physical activity, blood is drawn to quantify the basal glycemia and then 75 grams of glucose in 350 ml of water are administered, evaluating the blood glucose at 60 and 120 minutes. The normal curve shows values ​​less than 110, 200 and 140 mgs / dl at 0, 60 and 120 minutes, respectively. Figures between 140 and 199 mgs / dl at 120 minutes indicate decreased glucose tolerance. Fasting values ​​equal to or greater than 126 mgs / dl and / or 200 mgs / dl at 120 minutes indicate diabetes. The existence of two fasting blood glucose levels equal to or greater than 126 mgs / dl indicates diabetes and makes the performance of an oral glucose tolerance test unnecessary. Fasting blood glucose levels between 110 and 125 mgs / dl indicate the presence of the state known as impaired fasting blood glucose. The American Diabetes Association has recently established the upper limit of normal for fasting blood glucose at a value less than 100 mgs / dl. Figures between 140 and 199 mgs / dl at 120 minutes indicate decreased glucose tolerance. Fasting values ​​equal to or greater than 126 mgs / dl and / or 200 mgs / dl at 120 minutes indicate diabetes. The existence of two fasting blood glucose levels equal to or greater than 126 mgs / dl indicates diabetes and makes the performance of an oral glucose tolerance test unnecessary. Fasting blood glucose levels between 110 and 125 mgs / dl indicate the presence of the state known as impaired fasting blood glucose. The American Diabetes Association has recently established the upper limit of normal for fasting blood glucose at a value less than 100 mgs / dl. Figures between 140 and 199 mgs / dl at 120 minutes indicate decreased glucose tolerance. Fasting values ​​equal to or greater than 126 mgs / dl and / or 200 mgs / dl at 120 minutes indicate diabetes. The existence of two fasting blood glucose levels equal to or greater than 126 mgs / dl indicates diabetes and makes the performance of an oral glucose tolerance test unnecessary. Fasting blood glucose levels between 110 and 125 mgs / dl indicate the presence of the state known as impaired fasting blood glucose.

In a patient in whom diabetes has already been diagnosed, the assessment of the degree of metabolic control is done mainly by measuring fasting and postprandial blood glucose levels, either in the laboratory or by self-monitoring, and quantifying glycosylated proteins, which measure control metabolic rate over a one-week period, or glycated hemoglobin, which reflects control over the preceding 6 to 8 weeks. In a non-diabetic individual or in a well-controlled diabetic patient, glycated hemoglobin is less than 6.2% of total hemoglobin.

Semi-quantitative determination of glycosuria by dipstick may be useful to assess metabolic control if it is done two or three times daily and the renal threshold for glucose is normal.

In all diabetic patients, it is necessary to quantify the levels of plasma lipids, total cholesterol, HDL cholesterol and triglycerides, since dyslipoproteinemias constitute another risk factor for the development of arteriosclerotic macrovascular disease.

Considering the neurological and vascular complications to which patients with diabetes are susceptible, a fundus with retinofluoresceinography should be performed periodically, an evaluation of renal function including the quantification of microalbuminuria, mainly in insulin-dependent patients with apparently normal urine, and studies of evaluation of coronary, cerebral and lower extremity circulation, the magnitude of which will be indicated by the presence of symptoms and clinical judgment. If symptoms and signs of neuropathy are observed, a measurement of the conduction velocity of the peripheral nerves can be made.