• Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency
• Typically presents in childhood/adolescence
• Features: polyuria, polydipsia, weight loss, ketosis, DKA
• Associated with other autoimmune diseases (e.g. coeliac, thyroid)
• Requires lifelong insulin therapy
• Antibodies: anti-GAD, anti-IA2, ZnT8
• Combination of insulin resistance and relative insulin deficiency
• Risk factors: obesity, family history, sedentary lifestyle, South Asian/Afro-Caribbean ethnicity
• Often asymptomatic or mild osmotic symptoms
• Management (stepwise):
1. Lifestyle modification
2. Metformin (1st-line, unless contraindicated)
3. Add SGLT2 inhibitor or GLP-1 RA (if CVD/weight loss benefit)
4. Add insulin or SU/DPP4i if needed
• Any one of the following (in symptomatic patients):
o HbA1c ≥ 48 mmol/mol (6.5%)
o Fasting glucose ≥ 7.0 mmol/L
o 2h glucose ≥ 11.1 mmol/L on OGTT
o Random glucose ≥ 11.1 mmol/L with symptoms
• If asymptomatic: confirm with second abnormal test
• Pancreatic: chronic pancreatitis, haemochromatosis, pancreatic cancer
• Endocrine: Cushing’s syndrome, acromegaly, phaeochromocytoma, glucagonoma
• Drug-induced: steroids, antipsychotics, thiazide diuretics
• Monogenic (AD) form of non-insulin dependent diabetes
• Onset <25 years, strong FHx, not obese
• Often misdiagnosed as T1/T2
• Subtypes:
o HNF1A/4A: sensitive to sulfonylureas
o GCK: mild stable fasting hyperglycaemia, no treatment needed
• Microvascular:
o Retinopathy: background → pre-proliferative → proliferative ± maculopathy
o Nephropathy: microalbuminuria → proteinuria → CKD
o Neuropathy: distal symmetrical sensory loss ("glove and stocking")
• Macrovascular:
o ↑ risk of MI, stroke, PAD
• Autonomic neuropathy:
o Gastroparesis, erectile dysfunction, postural hypotension, bladder dysfunction
• Prevention: tight glucose, BP, lipid control; annual screening
• Includes gestational diabetes and pre-existing diabetes
• Risks: macrosomia, pre-eclampsia, neonatal hypoglycaemia
• Insulin is treatment of choice
• Oral hypoglycaemics usually stopped (some units use metformin)
• Monitor closely with growth scans and glucose targets
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Author & Educational Disclaimer
Author:
Dr Phillip Cockrell BM FRCP DipClinEd
Dr Phillip Cockrell is a UK Consultant Physician in Internal Medicine, currently working at Queen Alexandra Hospital, Portsmouth University Hospitals NHS Trust. He has previously worked as a registrar across Intensive Care Medicine, Gastroenterology, Cardiology, Stroke Medicine, Acute Medicine, and Respiratory Medicine.
He has held senior leadership roles including Associate Clinical Director of the Acute Medical Unit, Clinical Director of Internal Medicine, and Chief of Medicine. Dr Cockrell has over 15 years’ experience in postgraduate medical education, having lectured extensively across the MRCP syllabus and contributed to MRCP revision teaching and course development.
Dr Cockrell holds a Bachelor of Medicine (BM), Fellowship of the Royal College of Physicians (FRCP), and a Diploma in Clinical Education (DipClinEd). His teaching approach is based on structured consolidation of complex medical topics to support efficient and effective revision for postgraduate examinations.
Purpose of this content:
The material on this page is intended solely for educational purposes to support revision for the MRCP (UK) Part 1 examination. It reflects examination-relevant principles of internal medicine and is designed to aid learning and pattern recognition.
Medical disclaimer:
This content is designed for postgraduate medical examination revision and does not constitute medical advice, diagnosis, or treatment guidance and must not be used as a substitute for professional clinical judgement, local guidelines, or specialist consultation. Clinical decisions should always be made in the context of individual patient circumstances and current national guidance.
