Type I diabetes mellitus (T1DM) is an autoimmune condition that results in a complete deficiency of insulin.
Pathophysiology
- Insulin is an anabolic (promotes synthesis of complex molecules from simple ones) hormone responsible for lowering the amount of circulating glucose in the body. It does this by promoting the synthesis of glycogen in the liver, which are long chains of glucose used as energy stores by the body.
- In states of high blood glucose e.g. following a meal, glucose enters the beta-cells of the pancreas via GLUT2 channels and triggers the release of insulin.
- There are two main things that insulin does.
- Insulin can be thought of as a key, because you need insulin for cells to actually use glucose. It facilitates glucose uptake by various body tissues including muscle and adipose tissues via GLUT4 transporters which are present on the cell membrane of various cells in the body, thus acting to lower glucose levels.
- Anabolic Action:
- Glycogenesis: Formation of glycogen from glucose (thus lowering circulating glucose levels)
- Lipogenesis: Formation of fatty acids from glucose
- Promoting protein formation using amino acids
- The actions of insulin are opposed by the hormone glucagon, released by alpha cells in the pancreas. It works to increase blood glucose levels and is released in low blood glucose states e.g., fasted states. It has the following actions:
- Glycogenolysis: Breaking down stored glycogen in the liver back into glucose.
- Gluconeogenesis: Converting amino acids and glycerol into glucose.
- Whilst glucagon is the main counter-regulatory hormone, other hormones do work to help increase glucose levels such as adrenaline (which is why patients with hypoglycaemia can get shaking/sweating/palpitations as the body releases adrenaline in response to the hypoglycaemic state).
In T1DM, an autoimmune process results in the destruction of the beta-cells in the islets of Langerhans of the pancreas, which results in completely absent or very, very low amounts of insulin in the body.
Risk Factors
- Genetics: Family history increases the risk of developing T1DM
- Individuals from Northern geographical regions
- Caucasian ethnicity
- Other autoimmune conditions
Clinical Features
High glucose in the blood draws water from cells resulting in an osmotic diuresis, and also makes patients thirsty, resulting in the following cardinal features of diabetes:
- Polydipsia (excessive thirst)
- Polyuria (excessive urination)
- Nocturia (urinating at night)
Other features include:
- Younger age
- Fatigue and lethargy
- Blurred vision
- Weight loss: Due to breakdown of muscle and fat tissues as an alternative when carbohydrate based energy cannot be used
- Genital thrush infections: Higher sugar makes it easier for yeast infections to grow
Some patients may only be found to have T1DM following a presentation of diabetic ketoacidosis (DKA), a serious complication of T1DM. The features of DKA include nausea, vomiting, abdominal pain and altered consciousness. To find out more about DKA, see the notes on the topic.
Associated Conditions
As T1DM is an autoimmune condition, patients may have co-existing autoimmune conditions such as:
- Coeliac disease
- Hashimoto’s Thyroiditis
- Grave’s disease
- Addison’s disease
- Multiple sclerosis
- Pernicious anaemia
Investigations
Bedside
- Urinalysis: Looking for glucosuria or ketonuria
Bloods
The following glycaemic values are based on the WHO criteria for hyperglycaemia.
- Random plasma glucose: ≥ 11.1 mmol/L
- Fasting plasma glucose: ≥ 7.0 mmol/L
- Oral glucose tolerance test: Patient asked to have 75g oral dose of glucose. If plasma glucose concentration is ≥ 11.1 mmol/L 2 hours after the test, it’s positive for diabetes
- HbA1c ≥ 6.5% or 48mmol/L
- C-peptide: This is cleaved off of endogenous insulin i.e., insulin made by the body. This is not used routinely in practice, but you would expect patients with T1DM to have low levels of C-peptide.
Management
As patients lack insulin, treatment is mainly aimed at replacing this insulin as well as controlling the risk of developing further complications.
Replacing Insulin
NICE recommend a basal-bolus regime as first line for insulin replacement in type I diabetics. A basal-bolus regime is designed to mimic normal insulin physiology whereby:
- Basal Dose: A long-acting, basal amount of insulin to help control blood glucose between meals, usually given twice daily.
- NICE suggest: Twice-daily insulin detemir or once-daily insulin glargine if the former is not tolerated.
- Bolus Dose: A shorter-acting, bolus amount of insulin used to clear glucose following meals. It is injected before the meal.
- NICE suggest: Rapid-acting insulin analogues before meals.
- Examples of rapid-acting insulins: Insulin aspart, insulin lispro and insulin glulisine.
There are, however, other options that can be used such as mixed insulin which contains a mix of rapid and intermediate/longer-acting insulins, or even continuous subcutaneous insulin infusions (CSII) which are insulin pumps. There is no one size fits all, so shared-decision making is important to find out what suits the patient best.
Glycaemic Control
- HbA1c is measured every 3-6 months at a minimum, with a target of ≤ 6.5% (48mmol/L)
- T1DM target blood glucose levels during acute illness/surgery: 5-8 mmol/L
- Patients are also recommended to test their own glucose at a minimum of 4 times a day (before each meal, and before bed)
- Can support patients to record blood glucose up to 10 times a day if for example they are unwell/before and after sports/pregnant/breastfeeding/if they feel hypoglycaemic/before driving
- Fasting glucose aim: 5-7mmol/L on waking
- Glucose before meals/other times of the day: 4-7 mmol/L
Cardiovascular Risk Control
As individuals with diabetes are at an increased risk of cardiovascular disease, it is important to control risk factors such as:
- Optimising blood pressure control: ACE inhibitors are usually started as first-line if the blood pressure is greater than or equal to 135/85.
- Smoking cessation
- Exercise
- Lipid modification e.g. with statins
Diet Management
Patients diagnosed with T1DM are offered education e.g. through the dose-adjustment for normal eating (DAFNE) programme, which helps educate individuals on how to carbohydrate count. This is important as the bolus doses of insulin are calculated based on the carbohydrate intake.
Complications
- Diabetic ketoacidosis (DKA): A serious medical emergency that occurs due to a complete absence of insulin.
- Diabetic neuropathy: A peripheral neuropathy caused by chronic hyperglycaemia which has a ‘glove and stocking’ distribution i.e. affecting the peripheral limbs first.
- Diabetic nephropathy: Kidney disease secondary to diabetes – patients should have their urine tested usually once a year and the serum creatinine/eGFR monitored.
- Diabetic retinopathy: Disease affecting the eye which can ultimately result in blindness if not treated. When diagnosed, patients with T1DM should be referred to local eye screening services and then repeated screenings annually.
- Charcot’s foot: Charcot’s foot is a condition affecting the bones and tissues of the feet/ankles secondary to long-term trauma.
- If a person injures their foot in a certain way but also has diabetic neuropathy in that they can’t feel it the injury, they won’t be able to employ protective measures.
- Over time with repetitive injuries, the bones of the feet can fracture, and joints can become distorted, resulting in feet deformities.
- If the bones of the midfoot become involved and collapse, it results in the commonly known ‘rocker-bottom’ deformity, where the bottom of the foot appears rounded.
- Hypoglycaemia: Going the other way on the spectrum whereby blood sugar levels are too low – this might occur if someone takes their insulin but doesn’t eat enough/takes too much insulin/exercises too much
Driving and Diabetes
Patients are required to notify the DVLA regarding their diabetes if it is treated by insulin i.e. T1DM. Patients at risk of developing hypoglycaemia, or those who develop disabling hypoglycaemia must also notify the DVLA of their condition.
Sick Day Rules
If someone is unwell and also has T1DM, there are some ‘sick-day rules’ which can apply. The NICE CKS outline the following sick-day rules:
- Individuals should be advised to continue taking their insulin although it may be necessary to adjust the dose.
- Increasing blood glucose checks
- Monitoring blood/urinary ketones
- Drinking at least 3L of fluid to prevent dehydration
- Try to maintain oral intake of food. Can replace meals with carbohydrate-containing drinks such as juice or milk.
References
http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html
https://www.ncbi.nlm.nih.gov/books/NBK551501/
https://surgery.ucsf.edu/conditions--procedures/charcot-foot.aspx
https://bnf.nice.org.uk/treatment-summary/insulin-2.html
https://www.nice.org.uk/guidance/ng17/chapter/1-Recommendations#insulin-therapy-2
https://dafne.nhs.uk/about-dafne/what-is-dafne
https://www.diabetes.org.uk/diabetes-the-basics/related-conditions#thyroid
https://www.diabetes.org.uk/professionals/position-statements-reports/diagnosis-ongoing-management-monitoring/new_diagnostic_criteria_for_diabetes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892884/
https://cks.nice.org.uk/topics/diabetes-type-1/management/management-adults/
https://www.nice.org.uk/guidance/ng17/chapter/Recommendations#diagnosis-and-early-care-plan
