Type 1 Diabetes Mellitus

Last updated: March 18, 2026Bookmark

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic beta cells. This results in absolute insulin deficiency and hyperglycaemia. It commonly presents in childhood and adolescence with the triad of polyuria, polydipsia and unexplained weight loss.

It is relatively common, with an incidence of 4 cases per 100,000 persons per year. It peaks between 20 and 30 years and affects men and women equally.

Risk factors
- HLA-DR and HLA-DQ2 phenotypes
- Coeliac disease – this is also associated with HLA-DQ2 phenotypes
- Family history of T1DM
- Autoantibodies to islet cells, insulin, islet antigens (IA2 and IA2-beta), glutamic acid decarboxylase (GAD), and zinc transporter ZnT8
- Viral infections
- Cow’s milk ingestion
- Vitamin D deficiency
- Early introduction to cereals
Pathophysiology
- Type IV hypersensitivty where CD4+ T cells and CD8+ T cells attack pancreatic beta cells → decreased insulin production → hyperglycaemia once 90% of islet cells are destroyed
- Pancreatic alpha cell dysfunction → overstimulation of glucagon → gluconeogenesis, glycogenolysis and ketogenesis → hyperglycaemia and diabetic ketoacidosis
- Long-term hyperglycaemia → chronic macrovascular and microvascular damage through oxidative stress, free radical damage, sorbitol production and glycosylation of tissues
Signs and symptoms
- Polyuria
  - Due to osmotic diuresis caused by hyperglycaemia
- Polydipsia
  - Due to dehydration
- Unexplained weight loss
  - Due to depletion of glycogen stores and adipose tissue to compensate for cellular glucose deficiency
- Fatigue
  - Due to impaired glucose utilisation
- Blurred vision
  - Due to changes in lens osmolality
- Glycosuria
  - Due to glucose exceeding the renal threshold for reabsorption
- Ketosis
  - Due to increased fat metabolism
- Nocturnal enuresis
- Genital pruritus or thrush
  - Due to increased susceptibility to infections in a high-glucose environment
Differentials
- Type 2 diabetes mellitus (T2DM)
- Gestational diabetes
- Maturity-onset diabetes of the young (MODY)
- Latent autoimmune diabetes in adults (LADA)
- Drug-induced diabetes
  - Antipsychtics
  - Corticosteroids
  - Tacrolimus
  - L-asparaginase
- Exocrine pancreas insufficiency
  - Cystic fibrosis
  - Chronic pancreatitis
  - Hereditary hemochromatosis
- Endocrinopathies
  - Cushing’s syndrome
  - Acromegaly
  - Phaechromocytoma
  - Glucagonoma
- Temporary hyperglycaemia
  - Sepsis
  - Drugs
  - Neonatal hyperglycaemia
Investigations
- Fasting plasma glucose ≥ 7.0 mmol/L
- Random plasma glucose ≥ 11..1 mml/L on more than one occasion in the presence of hyperglycaemia
- Plasma glucose ≥ 11 mmol/L 2 hours after a 75 g oral glucose load
- Glycated haemoglobin (HbA1C) ≥ 48 mmol/mol (6.5%) on two separate tests – this is unreliable if the patient has any condition that affects red cell survival
- Urine testing for glycosuria and ketonuria
- Autoantibody testing to confirm the diagnosis. These include:
  - GAD antibodies
  - Islet cell cytoplasmic autoantibodies (ICA)
  - Insulinoma-associated-2 antibdies (IA-2A)
  - Insulin autoantibodies (IAA)
- Low C-peptide measurement < 0.6 ng/mL along with hypoglycaemia suggests T1DM
Treatment
- Monitor HbA1C every 3- 6 months with a target of 48 mmol/mol (65%) or lower
- Self-monitor glucose levels at least 4 times a day – before each meal and before bed. Blood glucose targets include:
  - 5 – 7 mmol/l on waking
  - 4 – 7 mmol/l before meals
- Insulin
  - Twice-daily insulin detemir is the treatment of choice
  - Once-daily insulin glargine or detemir is an alternative
  - Basal-bolus regimens are preferred for adults
- Metformin if BMI ≥ 25 kg/m2
Acute complications
- Diabetic ketoacidosis
- Hypoglycaemia
Chronic complications
- Nephropathy
- Retinopathy
- Neurpathy
- Coronary artery disease
- Peripheral arterial disease
- Stroke

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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