Summary

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterised by hyperglycaemia resulting from progressive insulin resistance and relative insulin deficiency. It is the most common form of diabetes, accounting for 90-95% of all cases. T2DM is strongly associated with obesity, physical inactivity, and genetic factors. The condition leads to microvascular complications (retinopathy, nephropathy, neuropathy) and macrovascular complications (cardiovascular disease, stroke, peripheral arterial disease). Management focuses on lifestyle modification, glycaemic control, and cardiovascular risk reduction. SGLT2 inhibitors and GLP-1 receptor agonists have transformed treatment due to their proven cardiovascular and renal benefits beyond glycaemic control.

Key Facts

• Definition: Fasting glucose ≥7.0 mmol/L, HbA1c ≥48 mmol/mol (6.5%), or OGTT 2h glucose ≥11.1 mmol/L
• Prevalence: ~10% of adults globally; rapidly increasing
• Pathophysiology: Insulin resistance + progressive beta-cell dysfunction
• Complications: Microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (CVD, stroke, PAD)
• Treatment Target: HbA1c <7% (individualised); BP <130/80 mmHg; LDL <2.0 mmol/L (high CVD risk)
• First-Line: Metformin + lifestyle modification

Clinical Pearls

"Cardio-Renal Protection First": For patients with established CVD, heart failure, or CKD, prioritise SGLT2 inhibitors or GLP-1 receptor agonists regardless of HbA1c.

"The Ominous Octet": T2DM is not just about beta-cell failure — eight pathophysiological defects contribute to hyperglycaemia.

"Prevent Before Treating Complications": Annual screening for retinopathy, nephropathy, and neuropathy is essential to catch complications early.

Why This Matters Clinically

T2DM is a leading cause of cardiovascular death, blindness, renal failure, and amputation. Early diagnosis, aggressive risk factor management, and modern glucose-lowering agents with proven benefits can significantly reduce morbidity and mortality.

Structured Approach

General:

• BMI, waist circumference
• Blood pressure
• Signs of insulin resistance (acanthosis nigricans)

Cardiovascular:

• Peripheral pulses
• Bruits (carotid, femoral, renal)
• Signs of heart failure

Neurological:

• Peripheral neuropathy (10g monofilament, vibration sense)
• Autonomic neuropathy (postural BP)

Feet (Annual Exam):

• Inspection: Ulcers, calluses, deformity, infection
• Pulses: Dorsalis pedis, posterior tibial
• Sensation: Monofilament, vibration

Eyes:

• Fundoscopy (refer for annual retinal screening)

Natural History

T2DM is a progressive disease. Beta-cell function declines over time, often requiring intensification of therapy. Good glycaemic, BP, and lipid control significantly reduce complications.

Outcomes

Prognostic Factors

• Duration of diabetes
• Glycaemic control (HbA1c)
• Presence of complications
• Cardiovascular risk factors
• Medication adherence

Key Guidelines

1. ADA Standards of Care in Diabetes (2024) — Comprehensive guidance.

2. ADA/EASD Consensus Report on Management of Hyperglycaemia (2022) — CV-centric approach.

Landmark Trials

UKPDS (1998) — Intensive glycaemic control

• Key finding: Intensive control reduced microvascular complications
• Clinical Impact: Established HbA1c targets

EMPA-REG OUTCOME (2015) — Empagliflozin

• Key finding: Empagliflozin reduced CV death by 38% in T2DM with CVD
• Clinical Impact: Cardioprotection with SGLT2i

LEADER (2016) — Liraglutide

• Key finding: Liraglutide reduced CV death by 22%
• Clinical Impact: GLP-1 RA for CV protection

DAPA-CKD (2020) — Dapagliflozin in CKD

• Key finding: Dapagliflozin reduced CKD progression regardless of diabetes
• Clinical Impact: Renal protection with SGLT2i

Evidence Strength

What is Type 2 Diabetes?

Type 2 diabetes is a condition where your body doesn't use insulin properly. Insulin is a hormone that helps sugar from your food get into your cells for energy. When insulin doesn't work well, sugar builds up in your blood.

What causes it?

Main factors include:

• Being overweight, especially around your middle
• Not being physically active
• Family history of diabetes
• Getting older
• Certain ethnic backgrounds

How is it treated?

1. Lifestyle changes: Healthy eating, regular exercise, weight loss — the most important first step
2. Medications: Tablets or injections to help control blood sugar
3. Monitoring: Regular blood tests (HbA1c) and check-ups

What to expect

• Diabetes is a lifelong condition
• With good control, you can live a long, healthy life
• You'll need regular check-ups for eyes, kidneys, feet, and heart
• Treatment may need to change over time

When to seek urgent help

Go to A&E or call your doctor immediately if:

• You feel very unwell with high blood sugar (thirsty, confused, drowsy)
• You have signs of severe low blood sugar (confusion, shaking, sweating, not responding)
• You have a new foot ulcer or signs of infection
• You have sudden vision changes