In many diseases, early diagnosis is important for the progression. This also applies to diabetes mellitus. Especially with type 2 diabetes, a timely detection of symptoms may limit the severe consequential damage and help patients to further have an asymptomatic life. Therefore, medical students should have keen senses about the patients with obesity, weight loss, polydipsia, and polyuria.
Type 1 Diabetes

Image: "Type 1 Diabetes" by BruceBlaus. License: CC BY 3.0

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Symptoms of Diabetes Mellitus Type 1

Diabetes and High Blood Sugar

Image: “Diabetes and High Blood Sugar.” by BruceBlaus. License: CC BY 3.0

As a rule, young patients suffer from type 1 diabetes. Therefore, this form of diabetes was formerly known as juvenile diabetes. In rare cases, type 1 diabetes occurs in adulthood. That is why such a name as LADA diabetes (latent autoimmune diabetes in the adult) exists.

An autoimmune reaction leads to the destruction of beta cells of the islets of Langerhans in the pancreas, which are responsible for the production of insulin. Only when 80–90 % of beta cells are destroyed, the first symptoms of type 1 diabetes can be identified. Stressful situations can accelerate the onset of the disease which was not acute before.

As diabetes is only symptomatic at a late stage, the onset of the disease is often sudden and dramatic. Noticeable symptoms are weight loss, polydipsia, and polyuria. Due to the missing insulin, the glucose content in blood is greatly increasing because glucose cannot be absorbed into the cells. In order to reduce the glucose level in blood, glucose is excreted in urine. Starting from the concentration of 160 to 180 mg/dl (or 8.9 to 10 mmol/l), the renal threshold is exceeded, and glucose passes into urine via the kidney.

However, glucose may be absorbed by kidneys only with enough liquid. Therefore, patients often suffer from excessive thirst. At the same time, the urine production increases and leads to frequent miction. Also, enuresis occurs at this stage. Especially children suffer from it, and it must be understood as a warning sign for diabetes. Since glucose cannot be processed as an energy supplier, the body relies on the energy reserves of the fatty tissues, which leads to significant weight loss.

In addition, there may appear unspecific symptoms of the disease, such as malaise, fatigue, anorexia, amenorrhea, impotence problems and dehydration (exsiccosis). Also, consequential harm caused by diabetes already gets apparent in the subsequent course of the disease. Dry skin, pruritus, muscle cramps, wound healing and visual disturbances are the first indications of the progress of the disease.

In emergency cases, type 1 diabetics shall have diabetic coma, which is also called diabetic ketoacidosis. Due to insulin deficiency, fatty acids are transformed into ketone bodies, which can be taken by the cells independently of insulin and supply them with energy. However, ketone bodies are strong acids, whereby the pH value of blood decreases and metabolic acidosis occurs. What is typical of the diabetic coma are acetone-like breath and urine smells in patients.

If loss of unconsciousness is not the matter yet, patients often complain of nausea, vomiting, and abdominal pain. In the case of peritonitis with muscular defense, one should always think of pseudo-peritonitis as part of undiscovered diabetes mellitus type 1. Breathing can also be disturbed and manifests itself in the typical Kussmaul breathing when it comes to hyperventilation at a normal respiratory rate.

Symptoms of Diabetes Mellitus Type 2

While symptoms in type 1 diabetes have a sudden occurrence, the progression of the disease is insidious in type 2 diabetes. Not infrequently is the disease discovered only by chance. Therefore, under certain circumstances, patients suffer for years from an elevated blood glucose level accompanied by damage to the body. Late consequences may be a further reason for diagnosing diabetes mellitus type 2. As in the case of type 1 diabetes, stressful situations may lead to the outbreak of the disease.

Previously, patients complain only about nonspecific symptoms similar to those of type 1 diabetes:

  • Diabetic Retinopathy

    Image: “Diabetic Retinopathy.” by BruceBlaus. License: CC BY 3.0

    Fatigue, exhaustion

  • Concentration problems
  • Headache, dizziness
  • Increased susceptibility to infection (cold, flu)
  • Impaired wound healing
  • Blurred vision
  • Muscle cramps
  • Pruritus
  • Amenorrhea, impotence problems
  • Frequent infections due to increased sugar content, in particular, in urine (fungi, cystitis, etc.)

Also, in type 2 diabetes, the renal threshold can be exceeded due to high glucose levels. That is why, in some cases, polyuria, polydipsia, and glucosuria may occur. However, these symptoms are more frequent in type 1 diabetes. Type 2 diabetes often occurs in connection with the so-called metabolic syndrome, or affluent syndrome. It includes obesity, elevated triglyceride levels, insulin resistance, and hypertension.

Due to the increasing frequency in childhood and adolescence obesity (adiposity), not only the elderly but also younger people, are affected by type 2 diabetes. However, the majority of patients are over 40 years old.

Acanthosis nigricans

Image: “Acanthosis nigricans” by Madhero88. License: CC BY-SA 3.0

In emergency cases, diabetes mellitus type 2 may lead to hyperosmolar coma, which is also called a diabetic coma, but it is different from a ketoacidotic coma. In the case of hyperosmolar coma, the increased fluid needs cannot be satisfied by drinking due to the high urinary excretion. It leads up to the loss of consciousness. In type 2 diabetes, the hyperosmolar coma occurs less common than the ketoacidotic coma in type 1 diabetes.

If diabetes mellitus types 2 is not recognized for a long time or inadequately treated, the first symptoms of micro- and macroangiopathy appear. These include visual disturbances, polyneuropathy, and impaired wound healing.

Note: Acanthosis nigricans of the inguinal and axillary region is typical for the insulin resistance, especially in young patients.

Symptoms of Gestational Diabetes

In most cases, gestational diabetes is asymptomatic. Therefore, an oral glucose tolerance test is recommended during the 24th to 28th week of pregnancy. Untreated gestational diabetes can lead to developmental problems in the fetus, which result in an increased birth weight of over 4 kg, respiratory distress syndrome, hypoglycemia, hyperbilirubinemia, and a cesarean section. In emergency cases, the fetus may suffer from injury syndrome – diabetic embryopathy.

During pregnancy, due to hydramnios, a larger than average fetus, urinary tract infections, and preeclampsia can be noticed. Usually in gestational diabetes, we deal with diabetes mellitus type 2, because the hormonal changes lead to insulin resistance in 3–5 % of females. In rare cases, the pregnancy is a trigger for diabetes mellitus type 1.

Symptoms of Diabetes Mellitus Type 3

All the forms of diabetes grouped under type 3 are not easy to see in practice. They are often diagnosed with diabetes types 1 or 2, as the symptoms are similar. Which type of diabetes we exactly deal with can just be revealed with the help of specific diagnosis.

Under WHO, all the forms which are not applicable to type 1, 2 and gestational diabetes refer to type 3 diabetes. A total of eight groups can be distinguished. They are distinguished according to different causes that occur very rarely in diabetics in their frequency. Therapeutic measures are similar to type 1, 2 and gestational diabetes.

Diabetes due to genetic defects in beta cells of the islets of Langerhans

This group is part of the so-called MODY diabetes (Maturity Onset Diabetes of the Young), which is caused due to genetic defects in glucose metabolism and occurs mainly in adolescence. These specific gene defects are monogenic autosomal dominant disorders. Eleven different forms of MODY diabetes have been specified so far:

  • MODY 1: mutation in chromosome 20, defect of the hepatic transcription factor HNF4A
  • MODY 2: mutation in chromosome 7, defect in the enzyme glucokinase
  • MODY 3: mutation in chromosome 12, defect of the hepatic transcription factor HNF1A
  • MODY 4: mutation in chromosome 13, defect of PDX1
  • MODY 5: mutation in chromosome 17, defect of the hepatic transcription factor TCF2
  • MODY 6: mutation in chromosome 2, defect of NEUROD1
  • MODY 7: mutation in chromosome 2, defect of KLF11
  • MODY 8: mutation in the chromosome 9, defect of CEL
  • MODY 9: mutation in chromosome 7, defect of PAX4
  • MODY 10: mutation in chromosome 11, defect of INS
  • MODY 11: mutation in chromosome 8, defect of BLK

If MODY diabetes is early examined, initial treatment with oral hypoglycemic agents such as Sulfonylureas is sufficient. However, it is quite probable that the dose of insulin might become necessary within time.

Diabetes due to genetic defects in insulin action

Two types have been distinguished in this group so far. They are both insulin-resistant by genetic defects. For type A insulin resistance syndrome, there are typical disorders: hyperinsulinemia, skin disorder – acanthosis nigricans (hyperpigmentation and hyperkeratosis (cornification), mostly in groin and armpits) and hyperandrogenism in women. The Lawrence syndrome, or Lipodystrophy, is characterized by a massive reduction of subcutaneous fat, which is accompanied by insulin resistance out of the previously undiscovered reason.

Diabetes as a result of pancreatic disease

All the disorders of the exocrine pancreatic secretion, as a defect of the pancreas itself, or as a consequence of another disease, may lead to diabetes. There are such diabetic symptoms in this case:

  • Pancreatitis
  • Trauma or pancreatectomy
  • Neoplasms in pancreatic cancer
  • Cystic fibrosis
  • Hemochromatosis

Diabetes due to disturbed hormone production or regulation (Endocrinopathy)

Diabetes can occur as an accompanying disease in the case of the following hormonal imbalances:

  • Pheochromocytoma

    Image: “Body Szintigrafie 24 hours after intravenous administration of 123Iod-MIBG. Physiological occupancy of the thyroid, liver and bladder. Pathological accumulation in a tumor of the left adrenal glands (pheochromocytoma). Left: from the front. Right: from behind.” by Drahreg01. License: CC BY-SA 3.0

    Acromegaly (disturbance of the growth hormone somatotropin)

  • Aldosteronoma (elevated aldosterone production)
  • Glucagonoma (tumor which relates to A-cells of the islets of Langerhans)
  • Hyperthyroidism (overactive thyroid)
  • Cushing’s disease (increased ACTH production)
  • Pheochromocytoma (tumors of the adrenal medulla)
  • Somatostatinoma (tumor of the pancreas or duodenum with increased somatostatin production)

Diabetes due to drugs or chemicals

Even taking certain chemicals and drugs can result in a side effect of diabetes. We have discovered the following so far:

  • Alpha interferon (for protection against viral diseases)
  • Beta adrenergic agonists (for stimulation of beta receptors of the sympathetic nervous system)
  • Diazoxide (hyperglycemia)
  • Glucocorticoids (against inflammations, overactive immune system, inflammatory rheumatic diseases)
  • Nicotinic acid (for decreasing increased blood cholestorol)
  • Pentamidine (antiprotozoic, commonly used in tropical medicine)
  • Phenytoin (for epilepsy, cardiac arrhythmia)
  • Thyroid hormones
  • Thiazide diuretics
  • Vacor (rat poison)

Diabetes due to viral infection

Congenital rubella is caused by the rubella virus, and it is common in children. As a result of the disease, the islet cells of the pancreas may be destroyed. It results in the lack of insulin production, which consequently characterizes type 1 diabetes. Also, human cytomegalovirus (HCMV) can contribute to the development of diabetes, as pancreatitis may occur in the disease progression.

Diabetes due to immunological defects

In autoimmune disease, stiff person syndrome (SPS), endocrine glands may be harmed as well. Therefore, the disease negatively influences the cells of the pancreas, which can lead to type 1 diabetes. Other immunological defects that cause diabetes are the anti-insulin receptor antibodies. They block the insulin receptors of the cells, and thus the absorption of insulin gets hindered.

Diabetes due to genetic disorders

Previously diabetes was observed as a side effect with numerous genetic syndromes:

  • Huntington’s disease (HD)
  • Down syndrome
  • Myotonic dytsrophy
  • Friedreich’s ataxia
  • Klinefelter’s syndrome (KS)
  • Porphyria
  • Prader-Willi-Labhart syndrome
  • Turner syndrome
  • Wolfram syndrome

Popular Examination Questions

The correct answers can be found below the references.

1. What is one of the symptoms of ketoacidotic coma?

  1. Kussmaul breathing
  2. Hypoglycemia
  3. pH value > 7.65
  4. Sweating
  5. Anuria

2. What is not typical of a newborn with diabetic embryofetopathy?

  1. Hypoglycemia
  2. Increased risk of developing diabetes mellitus in children and adults
  3. Shoulder dystocia
  4. Respiratory distress syndrome
  5. Reduced birth weight

3. A 64-year-old man with a BMI of 29 k/m² attends a medical appointment because of recurrent urinary tract infections. A urologist has already excluded the urinary tract as a cause. Upon questioning, he indicates to have had erysipelas on the right lower leg last year. He has also felt tired and exhausted for quite a long period of time, as his work has been stressful. You suspect that the patient could suffer from undiscovered diabetes mellitus type 2. What is the most suitable diagnostic tool in this case?

  1. Determination of HbA1c
  2. Oral glucose tolerance test
  3. Determining the amount of C-peptide in blood
  4. Determining the amount of glucose in urine
  5. One-time measurement of fasting plasma glucose
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