Endocrinology
Question 28 of 180
A 15 year old boy presents to the Emergency Department with a history of polydipsia and weight loss. You suspect diabetes mellitus. Which of the following is typically used as the threshold for diagnosing diabetes mellitus in a symptomatic patient?
Answer:
- Glucose concentration criteria for diagnosing DM:
- In symptomatic individuals (e.g. thirst, polyuria, polydipsia and unexplained weight loss):
- A random venous plasma glucose concentration > 11.0 mmol/L OR
- A fasting plasma glucose concentration ≥ 7.0 mmol/L OR
- Two-hour plasma glucose concentration > 11.0 mmol/L after 75g anhydrous glucose in an oral glucose tolerance test (OGTT)
- In asymptomatic individual:
- At least one of the above criteria fulfilled on two separate occasions
- In symptomatic individuals (e.g. thirst, polyuria, polydipsia and unexplained weight loss):
Diabetes Mellitus and Hypoglycaemia
Endocrinology
Last Updated: 30th August 2022
Diabetes mellitus is a metabolic disorder characterised by persistent hyperglycaemia with disturbances of carbohydrate, protein, and fat metabolism resulting from defects in insulin secretion (leading to insulin deficiency), insulin action (leading to insulin resistance), or both.
Classification
Diabetes mellitus is broadly classified as type 1 or type 2 (although rarer causes of diabetes exist):
- Type 1
- Caused by autoimmune destruction of insulin-producing beta-cells of the pancreas resulting in an absolute insulin deficiency with patients requiring insulin to survive
- Type 2
- Caused by a combination of insulin resistance/insensitivity (where the body is unable to respond to normal levels of insulin) and insulin deficiency (where the pancreas is unable to secrete enough insulin to compensate for this resistance).
- Risk factors include obesity, lack of physical activity, poor dietary habits, family history, certain ethnicities (Asian, African, and Black communities), polycystic ovarian syndrome, metabolic syndrome, certain drug treatments e.g. corticosteroids
Complications
- Macrovascular complications:
- Ischaemic heart disease
- Angina, acute coronary syndrome, heart failure
- Cerebrovascular ischaemia
- TIA, stroke
- Peripheral vascular disease
- Intermittent claudication, acute ischaemic limb, foot ulcers
- Ischaemic heart disease
- Metabolic complications:
- Dyslipidaemia
- Diabetic ketoacidosis (DKA)
- Hyperglycaemic hyperosmolar state (HHS)
- Hypoglycaemia
- Microvascular complications:
- Autonomic neuropathy
- Resting tachycardia, postural hypotension, cardiac ischaemia, sudden cardiac death
- Gastroparesis, constipation/diarrhoea, oesophageal dysmotility
- Erectile dysfunction, neuropathic bladder
- Chronic painful neuropathy
- Glove and stocking distribution, diabetic foot disease
- Diabetic nephropathy
- Chronic kidney disease
- Diabetic retinopathy
- Progressive loss of vision and possible blindness
- Autonomic neuropathy
- Other complications:
- Other autoimmune conditions
- Psychological complications
- Infections and other skin complications (e.g. necrobiosis lipoidica)
- Reduced quality of life
- Reduced life expectancy
Clinical features
- Type 1 DM:
- Diagnose type 1 diabetes on clinical grounds in adults presenting with hyperglycaemia (random plasma glucose more than 11 mmol/L), bearing in mind that adults with type 1 diabetes typically (but do not always) have one or more of the following:
- Ketosis
- Rapid weight loss
- Age of onset younger than 50 years
- Body mass index (BMI) below 25 kg/m2
- Personal and/or family history of autoimmune disease
- Suspect type 1 diabetes in a child or young person presenting with hyperglycaemia (random plasma glucose more than 11 mmol/L) and the characteristic features of:
- Polyuria
- Polydipsia
- Weight loss
- Excessive tiredness
- Diagnose type 1 diabetes on clinical grounds in adults presenting with hyperglycaemia (random plasma glucose more than 11 mmol/L), bearing in mind that adults with type 1 diabetes typically (but do not always) have one or more of the following:
- Type 2 DM:
- Suspect type 2 diabetes in an adult who presents with:
- Persistent hyperglycaemia (HbA1c more than 48 mmol/mol [6.5%] or random plasma glucose more than 11 mmol/L); if the use of HbA1c is inappropriate (for example in people with end-stage chronic kidney disease), type 2 diabetes is diagnosed by a fasting plasma glucose level of 7.0 mmol/L or greater; be aware that the characteristic features (thirst, polyuria, blurred vision, weight loss, recurrent infections, and tiredness) are not usually severe and may be absent
- Risk factors for type 2 diabetes (such as a strong family history, obesity, or Black or Asian family origin)
- Evidence of insulin resistance (for example acanthosis nigricans)
- Think about the possibility of type 2 diabetes in a child or young person who presents with:
- Persistent hyperglycaemia (random plasma glucose more than 11 mmol/L) — be aware that the characteristic features (thirst, polyuria, blurred vision, weight loss, recurrent infections, and tiredness) are not usually severe and may be absent.
- Risk factors for type 2 diabetes (such as a strong family history, obesity, or Black or Asian origin)
- Evidence of insulin resistance (for example acanthosis nigricans)
- No additional features of type 1 diabetes
- No features of monogenic diabetes or diabetes secondary to a pathological condition or disease, drug treatment, trauma, or pancreatic surgery
- Suspect type 2 diabetes in an adult who presents with:
- Diabetic ketoacidosis:
- Suspect diabetic ketoacidosis (DKA) in a person with known diabetes or significant hyperglycaemia (finger-prick blood glucose level greater than 11 mmol/L) and the following clinical features:
- Increased thirst and urinary frequency
- Weight loss
- Inability to tolerate fluids
- Persistent vomiting and/or diarrhoea
- Abdominal pain
- Visual disturbance
- Lethargy and/or confusion
- Fruity smell of acetone on the breath
- Acidotic breathing — deep sighing (Kussmaul) respiration
- Dehydration, which can be classified as:
- Mild — only just clinically detectable.
- Moderate — dry skin and mucous membranes, and reduced skin turgor.
- Severe — sunken eyes and prolonged capillary refill time.
- Shock (resulting from severe dehydration). The person is severely ill with:
- Tachycardia, poor peripheral perfusion, and (as a late sign) hypotension (indicating decreased cardiac output)
- Lethargy, drowsiness, or decreased level of consciousness (indicating decreased cerebral perfusion)
- Reduced urine output (indicating decreased renal perfusion)
- Suspect diabetic ketoacidosis (DKA) in a person with known diabetes or significant hyperglycaemia (finger-prick blood glucose level greater than 11 mmol/L) and the following clinical features:
- Hypoglycaemia:
- Hypoglycaemia is the commonest side effect of insulin or sulfonylureas therapy used to treat diabetes mellitus. Hypoglycaemia is a lower than normal level of blood glucose; the absolute blood glucose level at which signs and symptoms begin to occur can vary. For the purposes of hospital inpatients diagnosed with diabetes, anyone with a blood-glucose concentration less than 4 mmol/litre should be treated.
- In mild hypoglycaemia, the person may experience:
- Hunger
- Anxiety or irritability
- Sweating
- Tingling lips
- Irritability
- Palpitations
- Tremor
- In moderate hypoglycaemia, the person may experience:
- Weakness and lethargy
- Impaired vision
- Incoordination
- Reduced orientation
- Confusion
- Irrational behaviour
- Emotional lability
- Deterioration of cognitive function (when blood glucose levels fall lower than 3.0 mmol/L)
- In severe hypoglycaemia, the person may experience:
- Convulsions
- Inability to swallow
- Loss of consciousness
- Coma
Diagnosis
- Glucose concentration criteria:
- In symptomatic individuals (e.g. thirst, polyuria, polydipsia and unexplained weight loss):
- A random venous plasma glucose concentration > 11.0 mmol/L OR
- A fasting plasma glucose concentration ≥ 7.0 mmol/L OR
- Two-hour plasma glucose concentration > 11.0 mmol/L after 75g anhydrous glucose in an oral glucose tolerance test (OGTT)
- In asymptomatic individual:
- At least one of the above criteria fulfilled on two separate occasions
- In symptomatic individuals (e.g. thirst, polyuria, polydipsia and unexplained weight loss):
- HbA1c criteria:
- HbA1c ≥ 48 mmol/mol (6.5%) confirmed with second sample (unless individual is symptomatic with plasma glucose > 11.0 mmol/L when confirmation is not needed)
- N.B. Not to use in children and young people, type 1 DM, symptom onset within 2 months, pregnancy, drugs causing hyperglycaemia (e.g. steroids) or blood conditions affecting Hb (e.g. haemolytic anaemia)
Management of hypoglycaemia
- If the person is conscious and able to swallow:
- Children and young people should be given approximately 0.3 g/kg of a fast-acting carbohydrate.
- Adults should promptly consume 10–20 g of a fast-acting carbohydrate, preferably in liquid form.
- Examples include:
- 5 glucose tablets; 6 dextrose tablets; 200 mL (small carton) of fresh fruit juice (not sugar-free or reduced-sugar); 3–4 heaped teaspoonfuls of sugar added to a cup of water; 4 large jelly babies or 7 large jelly beans; 2 tubes of glucose 40% gel (such as Glucogel®, Dextrogel® or Rapilose gel®).
- Note: advise to avoid chocolates and biscuits as they have a lower sugar content, and their high fat content may delay stomach emptying.
- Recheck blood glucose levels after 15 minutes.
- Hypoglycaemia should be reversed in about 10 minutes as simple carbohydrates are expected to raise blood glucose levels within 5–15 minutes.
- Improvements in signs and symptoms may lag behind improvement in blood glucose level.
- If there is no response or an inadequate response, repeat oral intake as above and re-test blood glucose levels after another 15 minutes.
- When symptoms improve or normoglycaemia is restored:
- If the next meal is due, the carbohydrate intake of that meal should be increased (for example with bread, potatoes, or pasta).
- If the next meal is not due soon, the person should immediately eat some long-acting starchy carbohydrate (e.g. two biscuits, one slice of bread, 200–300 mL of milk) to maintain blood glucose. This is not necessary for people on a continuous subcutaneous insulin infusion.
- Hypoglycaemia which does not respond after 30–45 minutes or after 3 treatment cycles, should be treated with intramuscular glucagon or intravenous glucose as below.
- If the person is unconscious and unable to swallow:
- Adults:
- Adults who are unconscious, having seizures, or who are very aggressive, should be treated initially with intramuscular glucagon (dose 1 mg). If glucagon is unsuitable, or there is no response after 10 minutes, glucose 10% intravenous infusion, or alternatively glucose 20% intravenous infusion should be given.
- Children:
- Children who are unconscious or having seizures, and where rapid intravenous access is possible, should be treated with glucose 10% intravenous infusion. A bolus dose using glucose 10% can be given before the glucose infusion to rapidly increase the plasma-glucose concentration, in order to allow glucose to cross the blood brain barrier and alleviate neuroglycopaenia. If intravenous access is not rapidly available, intramuscular glucagon should be given (dose 500 micrograms in children < 8 years/weight ≤ 25 kg, 1 mg for all others).
- Once the patient has recovered and is sufficiently awake and able to swallow safely, they should eat some oral carbohydrate (to replace the body's supply and to prevent relapse of hypoglycaemia).
- Patients who have received glucagon require a larger portion of long-acting carbohydrate to replenish glycogen stores.
- Vomiting is common in the recovery phase, and recurrent hypoglycaemia may recur. Consequently, the person should be closely monitored with regular checking of blood glucose.
- If hypoglycaemia recurs, the person may require additional oral carbohydrate or treatment with IV glucose.
- Hypoglycaemia caused by a sulfonylurea or long-acting insulin, may persist for up to 24–36 hours following the last dose, especially if there is concurrent renal impairment. Blood-glucose monitoring should be continued for at least 24–48 hours.
- Adults:
Diabetic foot
- People with type 1 diabetes should have their feet checked by a primary healthcare professional at diagnosis and at least once a year thereafter, or sooner if any foot problems arise. They should also be advised to check their own feet on a daily basis.
- To examine the feet of a person with diabetes, remove their shoes, socks, bandages, and dressings (as appropriate) and examine both feet for evidence of the following risk factors:
- Neuropathy — use a 10 g monofilament as part of a foot sensory examination
- Limb ischaemia — use ankle brachial pressure index (ABPI) and interpret results carefully because calcified arteries may falsely elevate results
- Ulceration
- Callus formation
- Infection and/or inflammation
- Deformity
- Gangrene
- Charcot arthropathy (an acute, localised inflammatory condition that may lead to varying degrees and patterns of bone destruction, subluxation, dislocation, and deformity)
- Examples of limb-threatening and life-threatening diabetic foot problems include:
- Ulceration with fever or any signs of sepsis
- Ulceration with limb ischaemia
- Clinical concern that there is a deep-seated soft tissue or bone infection (with or without ulceration)
- Gangrene (with or without ulceration)
- Suspicion of an acute Charcot arthropathy, or an unexplained hot, red, swollen foot with or without pain
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
