Type 1 diabetes mellitus

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Type 1 diabetes results from progressive loss of endogenous insulin secretion and can occur at any age. Presentation ranges from screening hyperglycaemia to DKA, while a temporary honeymoon phase after diagnosis can reduce insulin needs without removing the requirement for continuing basal replacement. NICE recommends diabetes-specific autoantibodies at initial diagnosis when type is being established. Routine C-peptide is not necessary when the diagnosis is clear, but a non-fasting C-peptide interpreted with simultaneous plasma glucose can help later if antibodies are negative or clinical behaviour is atypical. Classification should remain revisable: adults with slow autoimmune decline may initially look like type 2, and monogenic or pancreatic diabetes may be incorrectly labelled type 1.

Good care combines insulin pharmacology with learning, data and psychosocial support. Basal insulin restrains hepatic glucose output between meals and overnight; rapid-acting insulin covers carbohydrate and corrects excess glucose. The person needs a practical method for insulin-to-carbohydrate ratios, correction factors, injection or infusion technique and adaptation for activity, illness and meals, taught through a quality-assured structured programme. Continuous glucose monitoring supplies direction and time-in-range information, but alarms and algorithms require education and a backup plan for sensor, handset or pump failure. Targets should reduce long-term microvascular risk without recurrent severe hypoglycaemia or intolerable burden. Eating disorders, diabetes distress, fear of hypoglycaemia, cognitive barriers and cost or access constraints are clinical issues requiring proactive, non-judgemental support.

Key points

Type 1 diabetes is autoimmune beta-cell failure requiring insulin replacement; clinical suspicion and metabolic safety take precedence over awaiting classification tests.
Offer diabetes-specific autoantibodies near diagnosis; use paired non-fasting C-peptide later when uncertainty persists because its discrimination improves with time from diagnosis.
A basal-bolus regimen with rapid-acting mealtime insulin and long-acting basal insulin is usual first-line adult therapy, integrated with carbohydrate estimation and dose adjustment.
Structured education, continuous glucose monitoring and equitable access to pump or hybrid closed-loop technology are therapeutic interventions, not optional accessories.
Sick-day rules require extra monitoring, hydration, ketone-directed action and continued basal insulin; vomiting or persistent ketones should trigger early clinical contact.
Hypoglycaemia treatment must be followed by rechecking and prevention review, including insulin timing, exercise, alcohol, renal function and awareness impairment.
Annual review includes HbA1c, blood pressure, lipids, renal function and albuminuria, retinal screening, foot surveillance and assessment for associated autoimmune disease.
Driving, work, exercise, travel, contraception and pregnancy planning need individual anticipatory advice based on current UK rules and the person's insulin system.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Autoimmune beta-cell destruction

Immune-mediated loss of pancreatic beta cells progressively reduces endogenous insulin secretion and can occur at any age.

Inherited susceptibility

Genetic background influences autoimmune risk, but family history may be absent and does not determine an individual's onset.

Atypical or antibody-negative disease

Some clinically insulin-deficient patients lack detectable standard antibodies, making later C-peptide and revisable classification important when behaviour is unusual.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Beta-cell mass declines
Progressive immune injury reduces insulin secretion until it cannot restrain hepatic glucose output or support normal peripheral glucose use.
2
Glucose rises and water is lost
Hyperglycaemia causes osmotic diuresis, thirst, polyuria, weight loss and dehydration as filtered glucose draws water and electrolytes into urine.
3
Ketogenesis becomes unrestrained
Without sufficient basal insulin, lipolysis releases fatty acids that the liver converts to acidic ketone bodies.
4
Exogenous insulin restores essential signalling
Basal and meal-related replacement suppresses glucose and ketone production, but interruption can quickly recreate absolute deficiency.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Insulin-deficient onset

Rapid polyuria, thirst, nocturia, fatigue and weight loss, especially with ketones, point to type 1 diabetes; older age or higher body mass index must not be used to dismiss it.

Hypoglycaemia

Sweating, tremor, hunger and palpitations may progress to confusion, behavioural change, seizure or coma; recurrent episodes can blunt warning symptoms and create impaired awareness.

Developing ketoacidosis

Rising ketones, nausea, abdominal pain, tachypnoea, acetone breath, dehydration and reduced alertness signal inadequate effective insulin and require escalation before glucose becomes extreme.

Technology failure

Pump interruption can remove all rapid-acting basal delivery, causing ketones quickly. Unexpected persistent hyperglycaemia should prompt a blood ketone check, infusion-set review and backup injection plan.

Associated autoimmunity

Thyroid disease and coeliac disease occur more often in type 1 diabetes; symptoms such as unexplained glucose instability, weight change, diarrhoea or anaemia should lower the threshold for appropriate testing.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Diabetes-specific autoantibodiesFirst step
Why
Support autoimmune classification near presentation using the locally available antibody panel.
Interpretation and limitations
Positive antibodies strongly support type 1 diabetes. Negative results reduce but do not remove probability and should lead to phenotype review rather than automatic reclassification.
02
Non-fasting C-peptide with paired glucose
Why
Estimate endogenous insulin secretion when diabetes type remains uncertain after initial assessment.
Interpretation and limitations
Very low C-peptide in the presence of adequate glucose stimulation supports severe insulin deficiency. Preserved secretion years after diagnosis suggests revisiting type 2, monogenic or other causes.
03
HbA1c and continuous glucose metrics
Why
Assess longer-term exposure alongside time in range, time below range and glycaemic variability.
Interpretation and limitations
Use trends to adjust the regimen jointly. A satisfactory HbA1c can conceal frequent alternating hypo- and hyperglycaemia, which sensor metrics reveal.
04
Urine albumin-creatinine ratio and eGFR
Why
Screen for diabetic kidney disease and guide renal and cardiovascular risk management.
Interpretation and limitations
Confirm persistent albuminuria outside infection, menstruation, exercise or acute hyperglycaemia; falling eGFR or significant albuminuria changes medicine and referral decisions.
05
Retinal screening and foot assessment
Why
Detect sight-threatening retinopathy and neuropathic, vascular or ulcer risk before symptoms occur.
Interpretation and limitations
Abnormal retinal grade follows the national screening pathway; active ulceration, infection, ischaemia or Charcot concern requires urgent foot-team referral.
06
Thyroid and coeliac assessment
Why
Identify autoimmune comorbidity at guideline-recommended intervals or when symptoms arise.
Interpretation and limitations
Interpret coeliac serology with IgA status and gluten exposure. Thyroid tests require illness and medicine context, with confirmed disease managed alongside insulin adjustment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Type 2 diabetes

Preserved C-peptide, absent autoimmunity and durable response without insulin support type 2 disease, though body mass and age are insufficient alone.

Latent autoimmune diabetes

Slower adult autoimmune decline may initially avoid insulin but progresses as beta-cell reserve falls, representing a continuum of autoimmune diabetes.

Monogenic diabetes

Strong dominant family history, retained secretion and negative antibodies suggest a single-gene disorder with genotype-specific management.

Pancreatic diabetes

Pancreatitis, pancreatic surgery, malabsorption or imaging abnormalities point to secondary endocrine tissue loss rather than primary autoimmunity.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01StartEstablish insulin and self-managementFirst stepType 1 diabetes is newly diagnosed or strongly suspected without established DKA.

1Involve the specialist diabetes team promptly, begin an individualised basal-bolus insulin regimen and teach injection, storage and glucose-monitoring safety.
2Provide structured carbohydrate-counting and dose-adjustment education, hypoglycaemia treatment, ketone testing and written sick-day rules from the outset.
3Agree glucose and HbA1c goals, offer suitable CGM, assess psychological and social barriers, and ensure early review while insulin requirements evolve.

02Sick dayRespond to illness and ketonesA person with type 1 diabetes is unwell, vomiting, persistently hyperglycaemic or has a pump-delivery concern.

1Continue basal insulin, check glucose and blood ketones more frequently, maintain fluids and follow the person's written supplemental-insulin plan.
2For pump users, inspect the delivery system and use a reliable pen or syringe for corrective insulin when failure is possible, replacing the set according to training.
3Seek urgent help for persistent vomiting, rising ketones, breathing change, drowsiness, inability to hydrate or failure of correction, and use the DKA pathway when indicated.

03OptimiseReduce variability and treatment burdenTargets are not met, hypoglycaemia recurs or the current insulin delivery method is limiting daily life.

1Review sensor traces by time and context, separating basal-pattern problems from mealtime estimation, timing, exercise, alcohol and technique.
2Address impaired awareness, injection sites and psychosocial barriers before or alongside technology changes, using specialist structured education rather than blame.
3Consider pump or hybrid closed-loop eligibility through current NICE guidance, agree expectations and retain a documented backup basal and bolus plan for device interruption.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Covers meal carbohydrate and corrects hyperglycaemia, and in pumps also supplies continuously programmed basal insulin.

Rapid-acting insulin analogue

Calculate each subcutaneous mealtime and correction dose from the person's specialist-agreed insulin-to-carbohydrate ratio, glucose target, sensitivity factor, active insulin and planned activity; pump settings require equivalent individualisation.

Dose stacking, delayed meals, alcohol and exercise can cause hypoglycaemia. Pump interruption can cause rapid insulin deficiency; ensure backup pens, needles and an emergency dosing plan.

Replaces background insulin to restrain hepatic glucose production and prevent ketosis between meals and overnight.

Long-acting basal insulin analogue

Give the individually titrated subcutaneous daily or twice-daily regimen at consistent times according to preparation and specialist plan; continue during fasting and illness unless explicitly adjusted by the team.

Omission risks DKA, while excess causes fasting or nocturnal hypoglycaemia. Different basal products are not unit-for-unit interchangeable without deliberate clinical review.

Raises glucose rapidly during mild or moderate hypoglycaemia when swallowing is safe.

Fast-acting oral glucose

Use the person's agreed measured carbohydrate treatment for conscious hypoglycaemia, recheck after the locally taught interval and repeat if still low before taking longer-acting carbohydrate when needed.

Do not give orally if consciousness or swallowing is impaired. Chocolate and high-fat foods act too slowly for initial rescue, and recovery still requires analysis of the cause.

Mobilises hepatic glucose for community rescue when intravenous access is unavailable.

Glucagon

A trained person should administer the licensed age-appropriate injectable or nasal emergency preparation when severe hypoglycaemia prevents safe oral treatment, then call for help and follow the recovery plan.

Response may be reduced after prolonged fasting, heavy alcohol use or depleted glycogen. Nausea and vomiting can occur, so protect the airway and provide carbohydrate once safe.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Diabetic ketoacidosis

Insulin omission, pump failure or acute illness permits rapid ketone production, acidosis, dehydration and electrolyte depletion.

Severe hypoglycaemia

Insulin exceeding food, activity or physiological need can cause seizure, coma, injury and impaired future warning awareness.

Microvascular disease

Long-term hyperglycaemia damages retinal, renal and peripheral nerve microvasculature, causing sight loss, kidney disease, neuropathy and foot ulceration.

Cardiovascular disease

Diabetes duration, kidney disease, blood pressure, lipids and smoking combine to increase coronary, cerebral and peripheral arterial risk.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review HbA1c and CGM time in range, below range and variability at an agreed frequency, using data to support shared decisions rather than punitive scoring.
Check injection or cannula sites, insulin timing, storage, device downloads and backup supplies whenever glucose patterns become unexplained.
Complete annual blood pressure, lipid, eGFR, urine albumin-creatinine ratio, foot and retinal review through the relevant national and local programmes.
Ask at every meaningful review about severe hypoglycaemia, impaired awareness, DKA, driving, alcohol, activity, distress and disordered eating.
Screen for thyroid disease and coeliac disease according to NICE and symptoms, and revisit pregnancy planning before conception.
After any emergency attendance, conduct rapid specialist follow-up to identify the system failure and update sick-day or technology plans.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Basal insulin is anti-ketotic

Even when no food is eaten, insulin is needed to suppress lipolysis and ketogenesis. Sick-day dose adjustment must never become unplanned basal omission.

C-peptide needs glucose context

A low value during hypoglycaemia is physiologically appropriate. The paired glucose and time since diagnosis determine whether C-peptide truly demonstrates absent reserve.

Pump failure compresses time

Because most pumps use only rapid-acting insulin, an interruption removes background delivery immediately. Ketone action must begin sooner than after one missed long-acting dose.

HbA1c can hide instability

Frequent highs and lows may average to the target. Time-below-range, variability and the person's lived burden prevent false reassurance from a single aggregate.

Technology requires an exit route

Every pump or automated system user needs written doses and equipment for manual insulin delivery when hardware, software, consumables or electricity fail.

11Common pitfallsFrequent interpretation and management errors.

01
Delaying insulin in a ketotic adult while waiting for autoantibody results to prove type 1 diabetes.
02
Telling an ill person who is not eating to omit basal insulin rather than follow ketone-based sick-day rules.
03
Responding to recurrent hypoglycaemia by accepting chronic hyperglycaemia without offering structured review or technology support.
04
Assuming pump-reported delivery proves insulin entered the body when a kinked cannula or displaced set is possible.
05
Using HbA1c alone and overlooking substantial time below range or impaired awareness.
06
Ignoring driving advice after severe hypoglycaemia or changes in awareness.