Diabetes mellitus

Diabetes mellitus (DM) is a group of disorders characterised by chronic hyperglycaemia due to abnormal carbohydrate metabolism. There are many types, but the most common types are type 1 diabetes mellitus and type 2 diabetes mellitus. DM is a very common disease, and the most common form, type 2, is associated with inactivity and obesity, which are increasing globally. Chronic hyperglycaemia causes severe long-term and short-term complications which may be lethal or cause significant morbidity.

There exists state of "prediabetes" where the carbohydrate metabolism is abnormal but not (yet) to such an extent that diabetes mellitus has manifested.

Types

• Type 1 diabetes mellitus
  • Type 1A (autoimmune) (almost all cases of T1D)
  • Type 1B (idiopathic) (autoantibodies absent; very rare)
  • Latent autoimmune diabetes in adults (LADA)
• Type 2 diabetes mellitus
• Other types of diabetes mellitus
  • Maturity onset diabetes of the young (MODY)
  • Pancreoprivic diabetes (diseases of exocrine pancreas)
    • Cystic fibrosis
    • Chronic pancreatitis
    • Hereditary haemochromatosis (bronze diabetes)
  • Endocrinopathies
    • Cushing syndrome
    • Acromegaly
  • Drug-induced diabetes
    • Glucocorticoids
    • Antipsychotics
    • +++
• Gestational diabetes

Diagnosis and evaluation

There are several ways to diagnose diabetes mellitus. If one fulfills any of the diagnostic criteria, they have DM.

Random plasma glucose

If one measures plasma glucose "randomly", i.e. without any preparation or fasting, and the result is > 11.1 mmol/L, they fulfill the diagnostic criterium of diabetes mellitus but only if they also have symptoms of diabetes mellitus. A random plasma glucose of 11.1 or higher in the absence of DM symptoms does not fulfill the criterium

Oral glucose tolerance test

The oral glucose tolerance test (OGTT) involves measuring blood glucose before and 2 hours after ingestion of 75 g oral glucose in a patient who has fasted for 12 hours, usually from the day before. It is mostly used to screen for gestational diabetes. If the blood glucose after 2 hours is 7.8 - 11.1, the patient has "impaired glucose tolerance" and is at risk for diabetes. If the blood glucose is > 11.1, the diagnostic criterium for diabetes is filled.

Fasting plasma glucose

Fasting plasma glucose (FPG) refers to measurement of plasma glucose after an overnight fast. If the FPG is 6.1 - 7.0, the patient has "impaired fasting glucose" and is at risk for diabetes. If the FPG is > 7.0, the diagnostic criterium for diabetes is filled.

HbA1c

Haemoglobin A1c (HbA1c) is a form of haemoglobin A with a glucose molecule bound to a specific point on its beta chain. The higher the serum blood glucose, the more haemoglobin A will be glycated, and the HbA1c level will increase. Because RBCs have a lifespan of around 120 days, the HbA1c level is proportional to the average blood glucose level for the last 120 days (3 months). Nowadays, the unit for HbA1c is mmol/mol (mmol of HbA1c divided by mol of regular Hb A), whereas previously one used a percentage unit.

The HbA1c is normally > 39 mmol/mol (< 5.7%). A result of 39 - 48 mmol/mol (5.7 - 6.5%) is significant for prediabetes, while 48 mmol/mol (6.5%) or higher fulfills the diagnostic criterium for diabetes mellitus.

Fructosamine and glycated albumin

It's possible to measure fructosamines (total glycated proteins in the serum) as well as glycated albumin levels to monitor 30-day average blood glucose level, but because these depend on the albumin level in the serum they are not reliable and are therefore rarely used. HbA1c is better suited.

Acute complications

Hypoglycaemia

Hypoglycaemia occurs more commonly in type 1 diabetes than type 2, although it occurs in both. It can occur when taking too much antidiabetic or insulin, after skipping meals, after exercising, after stress, after alcohol consumption, etc. Insulin, sulfonylureas and meglitinides are the antidiabetics with highest risk for hypoglycaemia.

Hypoglycaemia causes symptoms directly related to decreased glucose supply to the brain (neuroglycopaenic symptoms), as well as symptoms related to the autonomic response to hypoglycaemia (autonomic symptoms). The neuroglycopaenic symptoms include confusion, dizziness, weakness, and possibly delirium. The autonomic symptoms include tremor, palpitations, anxiety, sweating, and hunger.

Mild hypoglycaemia is treated by giving complex carbohydrates like bread. Moderate hypoglycaemia is treated by giving oral liquid glucose. Severe hypoglycaemia is treated by administering IV glucose. If IV access is not available, intramuscular or intranasal glucagon is used.

Hyperglycaemic crisis

The two hyperglycaemic crises in diabetes are diabetic ketoacidosis (DKA) and hyperosmolar-hyperglycaemic state (HHS). DKA occurs in type 1 diabetes while HHS occurs in type 2 diabetes. Both are characterised by severe hyperglycaemia, causing osmotic diuresis with resulting dehydration and loss of electrolytes. Hyperglycaemic crises can be triggered by infections, cardiovascular accidents, alcohol abuse, or inappropriate antidiabetic therapy. DKA may be the first manifestation of type 1 diabetes.

Diagnosis of DKA is based on the presence of:

• Hyperglycaemia
  • Usually between 10 – 15 mM
• High anion gap metabolic acidosis
  • Acidosis (pH < 7,30)
  • Elevated anion gap (> 10 mM)
  • Decreased bicarbonate (< 18 mM)
• Ketonuria

Diagnosis of HHS is based on the presence of:

• Hyperglycaemia
  • Usually > 33,3 mM
• Elevated serum osmolality
• Normal pH
• Normal anion gap

Physical examination may show decreased skin turgor, Kussmaul breathing (in DKA), tachycardia, hypotension, and abdominal pain. Glucometers should not be used to measure blood glucose in hyperglycaemic crises as they can’t measure above around 15 mM.

Treatment of a hyperglycaemic crisis involves getting IV access. Administer 1 litre physiological saline in the first hour, and later continue administering fluids according to the fluid deficit. If potassium level is < 3,3 mM, it must be repleted before administering insulin. Potassium must be closely monitored and should be kept above 5,3 mM. When potassium is above 5,3 mM, administer 0,1 units/kg insulin per hour. Don’t let blood glucose level go below 8 mM; if it does, add glucose infusion.

Bicarbonate should only be used if pH goes below 7. Electrolytes, pH, creatinine, and glucose should be monitored regularly (every 2 – 4 hours) during the treatment.

Chronic complications

Patients with diabetes mellitus, especially type 2, experience both macrovascular and microvascular complications. The best way to prevent these complications is by strict long-term glucose control, as well as control of blood pressure and lipid levels, use of aspirin, and smoking cessation.

The macrovascular complications include coronary heart disease, cerebrovascular disease, peripheral artery disease, and diabetic foot.

The microvascular complications include diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy.

To prevent chronic complications, patients with diabetes should be

Patients with type 2 diabetes also have increased risk for some cancers, especially liver and pancreas. Diabetes causes delayed wound healing, which might be evidenced after an operation

Cutaneous manifestations

• 30% of all diabetes patients will experience skin symptoms
• Non-specific skin conditions
  • Impetigo
  • Candida intertrigo
  • Psoriasis
  • Necrotizing fasciitis
  • Acanthosis nigricans
• Specific skin conditions
  • Diabetic dermopathy
    • Reddish, oval/round scaly patches
    • Often on the shins
  • Diabetic bullae
    • Painless bullae
    • Can be very large
    • Intraepidermal bullae
      • More common
      • Filled with clear fluid
      • Heal without scarring or atrophy
    • Subepidermal bullae
      • Less common
      • Filled with blood
      • Heal with scarring and atrophy
  • Diabetic sclerosis
    • In diabetes type 1
    • Sclerosis of finger skin -> restricted mobility
  • Foot ulcers (diabetic foot)
  • Necrobiosis lipoidica diabeticorum
    • Erythematous patches on lower legs
    • May ulcerate and become infected

Follow-up

Patients with diabetes should have regular follow-up to prevent complications. Examination is usually 2 – 4 times yearly. The body parameters, examination of the feet, HbA1c, and blood pressure should be measured. Kidney function tests, electrolytes, and liver function tests should be checked. A detailed eye examination should be done annually. Urinary albumin-to-creatine ratio should also be measured annually, to screen for diabetic nephropathy.