QuestionSBA
QuestionChoice
T1DM is characterised by an absolute lack of insulin, unlike Type 2 diabetes where there is insulin resistance. For this reason, the insulin that the body is lacking must be replaced directly with subcutaneous insulin injections
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a
Insulin
QuestionChoice
Glucagon injections are used in the acute management of severe episodes of hypoglycaemia. It acts to raise sugar levels by triggering conversion of glycogen to glucose in the liver. It is not used to manage hyperglycaemia
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d
Glucagon
QuestionChoice
A pancreas transplant is not a first line treatment due to the significant risks of both transplants and major surgery in general. It is considered in some patients with T1DM who have severe renal disease (and may be carried out at the same time as a kidney transplant) or those with hypoglycaemic episodes that are unmanageable and pose significant risk to warrant the surgery
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e
Pancreatic transplant
QuestionChoice
Gliclazide is a sulphonylurea, which acts to enhance secretion of pancreatic insulin. In T1DM where there is an inherent lack of insulin (due to destruction of the secretory beta cells within the pancreas) Gliclazide would be ineffective and is not used - its role is in type 2 diabetes treatment
33365
c
Gliclazide
QuestionChoice
Metformin acts to reduce hyperglycaemia by reducing hepatic gluconeogenesis and over time, can help increase insulin sensitivity. It is the first line anti-diabetic medication for adults with type 2 diabetes where lifestyle measures are unable to control sugar levels. In T1DM the fundamental problem is an absolute lack of insulin, so without replacing this directly there would be little or no effect on glycaemic control
33364
b
Metformin
Concept
Chapter


# Summary

Type 1 diabetes mellitus (T1DM) is an autoimmune condition involving the destruction of insulin-producing pancreatic cells, resulting in insulin deficiency. It presents with signs such as polyuria, polydipsia, and weight loss, and mostly affects children and young adults. It's often associated with other autoimmune conditions such as thyroid disease and coeliac disease. Diagnostic tests involve assessing blood glucose, HbA1c, and urine ketones, as well as testing for the presence of auto-antibodies (e.g. anti-GAD, ICA, IAA). Management strategies involve tailored insulin therapy, close monitoring of blood glucose levels, and addressing both short-term and long-term complications.

# Definition

Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterized by the destruction of the insulin-producing beta cells within the pancreas, leading to insulin deficiency. 

# Epidemiology

T1DM predominantly affects children and young adults but can occur at any age. The incidence varies worldwide, with higher rates observed in northern Europe and in individuals with a family history of T1DM or other autoimmune diseases.

# Aetiology

T1DM is thought to be caused by a combination of genetic predisposition and environmental triggers. Genes associated with the human leukocyte antigen (HLA) system contribute to susceptibility. Environmental triggers, such as viral infections, are proposed but not definitively identified.

# Signs and Symptoms

Patients with T1DM often present with classic symptoms of insulin deficiency:

- Polyuria
- Polydipsia
- Weight loss - a distinguishing factor between T1DM and T2DM

In severe cases, patients may present with diabetic ketoacidosis (DKA), characterised by hyperglycemia, metabolic acidosis, and ketonemia.

# Differential Diagnosis

Other conditions presenting with similar symptoms include:

- Diabetes insipidus: Presents with polyuria and polydipsia, but without hyperglycemia or glucosuria.
- MODY (Maturity Onset Diabetes of the Young):
	- MODY 3 is the commonest cause, occurring due to a mutation in HNF1A. It is characterised by a very high blood sugar (10-20), and is very sensitive to sulphonylureas (e.g. gliclazide.) Insulin is the next line of treatment if it doesn't respond.
	- MODY 2 is the second commonest cause, occurring due to a glucokinase mutation. Blood sugars rarely rise above 7-8, over many years. Patients are generally well with few complications and the diabetes often responds to diet alone.
	- MODY 5 is associated with HNF1 beta mutation, and is associated with pancreatic atrophy, renal cycsts (causing palpable kidneys), epidydymal cysts, a bicornuate uterus, and abnormal LFTs
- Hyperthyroidism: Can present with weight loss and increased appetite, but usually also includes symptoms such as tachycardia, tremor, and heat intolerance.

# Investigations

Diagnosis involves first confirming diabetes and then identifying the underlying cause as type 1. Diabetes can be diagnosed either with or without symptoms:

If symptomatic, one of the following results is sufficient for diagnosis:

- Random blood glucose ≥ 11.1mmol/l or Fasting plasma glucose ≥ 7mmol/l
- 2-hour glucose tolerance ≥ 11.1mmol/l
- HbA1C ≥ 48mmol/mol (6.5%)

If the patient is asymptomatic, two results are required from different days.

To confirm T1DM, the following investigations can be done:

- Autoantibody testing: Identification of specific antibodies (e.g. anti-GAD, ICA, IAA) contributes to confirming the autoimmune nature of T1DM.
- C-peptide levels: Evaluation of C-peptide production helps assess endogenous insulin secretion.
- Urine ketone testing: Presence of ketones may suggest concurrent DKA.

# Management


- **Insulin Therapy**: Individualised insulin regimens are essential. Short-acting insulin is administered after meals and snacks, while long-acting insulin is typically given at night-time. Regular adjustments are necessary to maintain blood glucose within target ranges (see below).

- **Glycemic Control**: Tight glycemic control is crucial for preventing complications. Target ranges for blood glucose and HbA1c levels should be individualized but typically aim for:

  - Pre-meal blood glucose: 4-7 mmol/L (72-126 mg/dL)
  - Bedtime blood glucose: 6-10 mmol/L (108-180 mg/dL)
  - HbA1c: Less than 7% (53 mmol/mol) for most adults; individualised targets for children, elderly patients, and those at risk of hypoglycemia.

- **Lifestyle Interventions**: Patients should receive guidance on nutrition, exercise, and alcohol consumption. Dietitians and diabetes educators play a crucial role in helping individuals make informed choices.

- **Blood Glucose Monitoring**: Regular self-monitoring of blood glucose (SMBG) is essential. Patients should check their blood glucose levels multiple times a day, especially around meals and before bedtime.

- **Continuous Glucose Monitoring (CGM)**: In some cases, CGM systems may be recommended to provide continuous real-time data on blood glucose levels and trends.

- **Hypoglycemia Management**: Hypoglycemic episodes should be promptly treated with sugary drinks or snacks for conscious patients. For unconscious individuals, intramuscular glucagon or intravenous dextrose administration is necessary.

- **Regular Follow-Up**: Patients should receive ongoing care and education from diabetic specialist nurses and healthcare providers. Monitoring HbA1c levels at least every three months is crucial to assess long-term glycemic control.

- **Psychosocial Support**: Diabetes can have a significant emotional impact. Patients should have access to psychosocial support and resources to cope with the challenges of living with T1DM.

- **Comprehensive Care**: T1DM management should address both short-term and long-term complications. Regular screening for microvascular complications (e.g. retinopathy, nephropathy, neuropathy) and macrovascular complications (e.g. cardiovascular disease) is essential.

- **Blood Pressure Control**: Stricter blood pressure targets are recommended for individuals with T1DM, aiming for values of less than 135/85 mmHg, or less than 130/80 mmHg in the presence of end-organ damage. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are often preferred as first-line agents.

These management strategies, combined with a patient-centered and holistic approach, aim to optimise glycemic control, improve quality of life, and reduce the risk of complications in individuals living with T1DM.


## The honeymoon period

Immediately after diagnosis, insulin requirements may be very low if the pancreas is still able to produce a significant amount of insulin. This is known as the 'honeymoon period'. It is important that children are closely monitored during this time. This is because insulin requirements can suddenly increase as the remaining beta cells are destroyed. Additionally, as the blood glucose may be normal in this period on very low insulin doses, parents may incorrectly think that the condition has gone away.

# 'Sick day' rules

1. **Temporary Medication Adjustments**: During acute illness, consider temporarily stopping certain medications until the person is eating and drinking normally for 24–48 hours. 
	- **Angiotensin-Converting Enzyme Inhibitors (ACEIs), Diuretics, and NSAIDs**: Stop treatment if there is a risk of dehydration to reduce the likelihood of acute kidney injury (AKI).


7. **Insulin Therapy**: Do not stop insulin treatment; instead, consider adjusting the dose with guidance from the specialist diabetes team.

8. **Blood Glucose Monitoring (if indicated)**: 
   - Increase monitoring frequency to at least every 3–4 hours, including overnight.
   - Adjust insulin doses based on results.
   - Continue careful monitoring until blood glucose levels return to baseline.
   - Seek urgent medical advice if blood glucose remains uncontrolled.

9. **Ketone Monitoring (Blood or Urinary)**: 
   - Check ketone levels regularly (at least every 3–4 hours, including overnight).
   - Seek immediate medical advice if urine ketone level is greater than 2+ or blood ketone level is greater than 3 mmol/L.

10. **Maintain Normal Meal Pattern**: Encourage maintaining regular meals and fluids, including carbohydrates, if appetite is reduced.

11. **Fluid and Carbohydrate Replacement**:
    - If unable to eat or vomiting, replace meals with carbohydrate-containing drinks (e.g. fruit juices, sugary drinks).
    - Adjust fluid intake based on blood glucose levels (sugar-free fluids for high levels, sugary fluids for low levels).


# Associations

- Growth and pubertal development (delay in puberty and obesity)
- Associated illnesses:
  - Thyroid disease (most associated; screening recommended)
  - Coeliac disease

# NICE Guidelines

[NICE CKS - T1DM](https://cks.nice.org.uk/topics/diabetes-type-1/)

# References 
[NHS choices - T1DM](https://www.nhs.uk/conditions/type-1-diabetes/)

[Diabetes UK - T1DM](https://www.diabetes.org.uk/diabetes-the-basics/what-is-type-1-diabetes)
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Diabetes Mellitus Type 1
Topic
5
Endocrinology
6673
A 19-year-old man presents to the GP with lethargy. After a period of investigation, a new diagnosis of type 1 diabetes mellitus (T1DM) is made.

What is the most appropriate first line treatment for this patient?
a