QuestionSBA
QuestionChoice
In asymptomatic patients, two separate readings are required for diagnosis. As this patient has only had one reading, they cannot be diagnosed with type 2 diabetes at this point, but they should have a follow-up reading to confirm the diagnosis
33614
b
No further investigations needed to confirm diagnosis
QuestionChoice
The diagnosis of type 2 diabetes depends on whether the patient is symptomatic or asymptomatic. For symptomatic patients, only one positive HbA1c, fasting glucose or random glucose is used for diagnosis. In asymptomatic patients, two separate readings are required for diagnosis. As this patient has only had one reading, they cannot be diagnosed with type 2 diabetes at this point, but they should have a follow-up reading to confirm the diagnosis
33613
a
Repeat HbA1c
QuestionChoice
In asymptomatic patients, two separate readings are required for diagnosis. NICE CKS recommends the same modality that was used for the original test is used, meaning HbA1c is the most appropriate answer, as this is the test that was originally used
33616
d
Fasting glucose
QuestionChoice
In asymptomatic patients, two separate readings are required for diagnosis. NICE CKS recommends the same modality that was used for the original test is used, meaning HbA1c is the most appropriate answer, as this is the test that was used initially
33617
e
Random glucose
QuestionChoice
This patient is 55 years old; it is very unlikely they will be presenting with type 1 diabetes at this age. This test is not recommended to distinguish between type 1 and type 2 diabetes unless there is diagnostic uncertainty
33615
c
C-peptide
QuestionComment
the old double bluff 
24318
User
subscriber
Migraine Body
Concept
Chapter
# Summary

Type 2 Diabetes Mellitus is a chronic metabolic disorder characterised by pancreatic beta-cell insufficiency and insulin resistance. The resulting hyperglycaemia leads to symptoms such as polyuria, polydipsia and if chronic can have microvascular and macrovascular complications. Key investigations include random and fasting blood glucose, 2-hour glucose tolerance, and HbA1C tests, and diagnosis is based on the results of these +/- symptoms. Management of type 2 diabetes primarily revolves around lifestyle modifications, hypoglycaemic agents, and insulin therapy when necessary, as well as reducing risks for serious complications such as cardiovascular and cerebrovascular disease. Other complications from chronic hyperglycaemia involve the gastrointestinal system, nervous system, peripheral arteries, foot infections, sexual dysfunction, and cardiac system. 

# Definition

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition characterized by inadequate insulin production from pancreatic beta cells, resulting in insulin resistance. This leads to an elevation in blood glucose levels, causing hyperglycaemia.

# Epidemiology

T2DM generally manifests in adults, and it is often associated with a strong familial predisposition. It accounts for approximately 90-95% of all diagnosed cases of diabetes.

# Aetiology

T2DM results from a combination of genetic and environmental factors. Known contributors include:

- Poor dietary habits
- Lack of physical activity
- Obesity

# Signs and symptoms

Individuals with T2DM may initially be asymptomatic, but over time, they may develop:

- Polyuria
- Polydipsia
- Unexplained weight loss
- Blurry vision
- Fatigue

# Differential diagnosis

The primary differentials for T2DM include Type 1 Diabetes Mellitus, Maturity Onset Diabetes of the Young (MODY), and Secondary Diabetes Mellitus. The main distinguishing features of these differentials are:

- Type 1 Diabetes Mellitus: Early onset (typically in childhood or adolescence), often presents with ketoacidosis, and requires insulin therapy from diagnosis.
- 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
- Secondary Diabetes Mellitus: Often presents with other signs of pancreatic disease (e.g., pancreatitis, cystic fibrosis), or due to certain medications (e.g., glucocorticoids, antipsychotics).

# Investigations

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

- Random blood glucose ≥ 11.1mmol/l
- 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.

# Management

Management of T2DM involves patient education, lifestyle modifications, pharmacological interventions, and close monitoring of glucose levels:

- Lifestyle modifications: Advice on diet, regular physical activity, and smoking cessation
- Pharmacological interventions: 
	- Initial drug treatment is usually metformin, with consideration of other agents like Pioglitazone, DPP‑4 inhibitors, sulphonylureas, or SGLT-2 inhibitors for those who cannot take metformin.
	- If on monotherapy HbA1c >58mmol/mol   consider dual therapy with metformin, pioglitazone, a DPP‑4 inhibitor or a sulphonylurea (such as gliclizide).
	- If dual therapy has not controlled drug glucose, triple therapy using the above medications can be considered. Otherwise, starting insulin may be necessary.
- Close Monitoring: Measure HbA1c levels at 3-6 month intervals. If the patient is on insulin or is at risk of hypoglycaemia, self-monitoring of glucose at home is necessary.


**Insulin Therapy**

NICE guidance recommends basal insulin therapy with isophane (NPH) insulin as the first type to be used as it is most cost effective eg. Insulatard. Quick acting insulin analogues eg. Humalog, Novorapid, may be added in with meals if there is a big post meal glucose excursion.

Long acting insulin analogues include Levemir, Lantus, Insulin Degludec and Abasaglar (a biosimilar insulin).

Mixed insulin combination which contain varying proportions of short and intermediate acting insulin such as Novomix 30 (30% short acting, 70% intermediate acting insulin) are more convenient because of fewer injections per day but may not be as successful.

**Blood Pressure targets in Diabetes**

- Blood pressure control needs to be strict in diabetes because these patients are at higher risk of macro- and microvascular complications.
- NICE Hypertension Guidance [CG136] sets the same blood pressure targets as those who do not have diabetes, however in diabetics with HTN, ACE-inhibitors are first line as they are reno-protective

# Complications

Complications of diabetes are diverse, affecting multiple systems:

### Macrovascular:

* **Cardiac Complications** - diabetes significantly increases the risk of cardiovascular disease, contributing to major morbidity and mortality.
* **Peripheral Arterial Disease (PAD)** - patients present with foot discolouration, gangrene, intermittent claudication, rest pain, night pain and absent peripheral pulses (confirmed on doppler).
* **Cerebrovascular disease** - patients with diabetes are at significantly increased risk of TIAs and stroke and as such it is paramount to address the main risk factors (lipids, BP, smoking, obesity) for these as a broader part of management


### Microvascular:

* **Diabetic retinopathy** - characterised by vascular occlusion and leakage in the retinal capillaries, leading to potential sight loss if unmanaged, it is the leading cause of visual loss in adults. See separate section.
* **Diabetic nephropathy** - a leading cause of chronic kidney disease, it is characterised by proteinuria. Prevention of this complication is achieved with ACE inhibitors/ARBs (by managing blood pressure) and SGLT-2 inhibitors.
	* Histological changes include Kimmelstiel-Wilson nodules which are the spherical, eosinophilic, sclerotic nodules characteristic of nodular diabetic glomerulosclerosis 
* **Diabetic neuropathy** - the primary causative factor is chronic hyperglycaemia, which leads to several distinct types neuropathy. See separate section.
	* **Autonomic Neuropathy** - may lead to postural hypotension and associated symptoms like dizziness, falls, and loss of consciousness.
	* **Gastrointestinal Complications: Gastroparesis** - a result of poor glycaemic control leading to nerve damage of the autonomic nervous system. Characterized by delayed gastric emptying, early satiety, abnormal stomach wall movements, and morning nausea.
	* **Foot Complications: Diabetic Foot Infections** - patients with vascular and neuropathic complications are at high risk for diabetic foot ulceration and subsequent infection.
* **Sexual Dysfunction** - caused by a combination of factors including poor glycaemic control, neuropathy, microvascular complications, obesity, hypertension, depression, medication side effects, etc.

# '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).

3. **Metformin**: Stop treatment if there is a risk of dehydration to lower the risk of lactic acidosis.

4. **Sulfonylureas**: Be cautious, as they may increase the risk of hypoglycemia, especially if dietary intake is reduced.

5. **SGLT-2 Inhibitors**: Check for ketones and stop treatment if acutely unwell and/or at risk of dehydration due to the risk of euglycemic diabetic ketoacidosis (DKA).

6. **GLP-1 Receptor Agonists**: Stop treatment if there is a risk of dehydration to reduce the risk of 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).



# NICE Guidelines

[Click here for NICE CKS on T2DM](https://cks.nice.org.uk/topics/diabetes-type-2/)

3260
5398
Diabetes Mellitus Type 2
Topic
5
Endocrinology
6723
A 55-year-old man presents to the general practice after being invited for their 5-yearly NHS health check. They are currently asymptomatic with no past medical history. Their examination and blood results are normal, besides a BMI of 32 and a HbA1c of 53 mmol/mol.

Which of the following investigations is most likely to confirm the diagnosis?
a