"A chronic disorder characterised by raised blood glucose levels, secondary to a complete or relative lack of insulin. Affects 10.5% adults worldwide in 2021." ^[1]

• Complete lack → Type 1 (autoimmune β-cell destruction)
• Relative lack → Type 2 (combination of insulin resistance + progressive β-cell failure)
• The word "relative" is important: in early Type 2, the pancreas may actually produce more insulin than normal, but it's not enough to overcome the resistance.

The lecture states that 50% may be asymptomatic and detected through incidental glycosuria or hyperglycaemia. Treat this as a teaching estimate rather than a universal prevalence. ^[1]

The clinical point is that diabetes—especially type 2 diabetes—may be silent. Do not require the “three Ps” before testing an at-risk or incidentally hyperglycaemic patient.

The cartoon on slide 5 encodes polyuria, polydipsia and polyphagia. Polyuria drives thirst; polyphagia with weight loss reflects an insulin-deficient catabolic state. The triad is memorable but neither necessary nor sufficient for diagnosis.

Diagnosis based on venous plasma glucose OR HbA1c: ^[1]

Why venous plasma glucose? Arterial glucose > venous (tissues consume glucose), and plasma glucose > whole blood (RBCs have lower glucose concentration). The standard is venous plasma. ^[2]

IFG and IGT carry an increased risk of developing diabetes and cardiovascular diseases. ^[1]

Why two different IFG cut-offs? WHO uses 6.1, ADA uses 5.6. The ADA lowered their cut-off because the lower threshold identifies more people at risk, but this comes at the cost of lower specificity. For exams, know both but default to the one asked about.

Non-enzymatic glycosylation of N-terminal valine of Hb β-chain. Clinically used as an objective index of overall blood glucose control in the preceding 2–3 months. ^[1]

The chemically precise term is non-enzymatic glycation; glycosylation is enzyme-mediated.

From first principles: Glucose attaches non-enzymatically to the N-terminal valine of the haemoglobin β-chain throughout the 120-day lifespan of a red blood cell. The more glucose in the blood over time, the higher the percentage of haemoglobin that becomes glycated. This gives you a weighted average of blood glucose over ~2–3 months (more recent weeks contribute more).

The slide describes fructosamine as an index of glycaemia over the preceding 1–3 weeks and says to correct when albumin is low; the unit printed on the slide is wrong—albumin is conventionally reported in g/dL or g/L, not mmol/L. ^[1]

Fructosamine measures glycated serum proteins, mainly albumin, and usually reflects roughly 2–4 weeks. It can help when HbA1c is unreliable, but altered albumin concentration or turnover, nephrotic/protein-losing states and liver disease can bias the result. There is no universally standardised correction formula; interpret the laboratory's method and reference range rather than applying an automatic correction. ^[9][10]

Cluster of metabolic disorders linked by insulin resistance & associated with accelerated atherosclerosis. Diagnosis: presence of ≥ 3 of the following: ^[1]

Why does insulin resistance cause all of these? Insulin resistance means cells (especially muscle, liver, fat) respond poorly to insulin. The pancreas compensates by producing more insulin (hyperinsulinaemia). This hyperinsulinaemia promotes sodium retention (→ hypertension), stimulates hepatic VLDL production (→ hypertriglyceridaemia, ↓ HDL), and fails to suppress hepatic gluconeogenesis (→ hyperglycaemia). Central (visceral) adiposity is particularly metabolically active and drives the inflammatory milieu.

Type 1: β-cell destruction, mostly autoimmune in etiology: life-long insulin dependency. Type 2: reduced insulin secretion & sensitivity: diet ± oral drugs ± insulin. ^[1]

Other Specific Types:

Prediabetes; DM in first-degree relatives; History of GDM; Age over 35; Obesity, hypertension, dyslipidaemia. ^[1]

Type 1 diabetes occurs as a result of islet cell destruction, immunologically mediated. ^[1]

Three pillars:

a) Genetic factors:

• Chromosome 6: HLA-DR and HLA-DQ susceptibility genes
• 20% risk in HLA-identical twins
• Other genes: insulin gene (VNTR polymorphism on chromosome 11)
• Incidence and genetic-risk architecture vary between populations; the slide's ancestry percentages are cohort estimates, not diagnostic probabilities for an individual

b) Environmental factors:

• Exact nature uncertain, likely multi-hit
• Viral and other environmental exposures are under study; association does not establish a direct causal trigger in an individual
• The slide's “cow's-milk protein in infancy” hypothesis remains unproven and should not be presented as a reason to avoid normal infant feeding

c) Immunological factors (evidence):

a) Presence of islet autoantibodies (GAD; IA2; ZnT8; insulin) at onset ^[1] b) Cell-mediated autoimmunity vs islet cells at autopsy ^[1] c) Increased remission/β-cell preservation after immunosuppressants (Cyclosporin/anti-TNF-α) ^[1] d) Teplizumab (anti-CD3 antibody targeting T-cells) delayed onset of T1DM by 2 years in asymptomatic at-risk relatives (Herold et al, NEJM 2019) – FDA-approved Jan 2023 ^[1]

The cyclosporin/anti-TNF line is historical mechanistic evidence, not a recommendation to use non-specific immunosuppression for routine new-onset type 1 diabetes.

The pathophysiology of type 2 diabetes includes three main defects: ^[1]

1. Insulin resistance (peripheral – muscle and fat): ↓ glucose uptake
2. Insulin resistance (hepatic): ↑ hepatic glucose output (gluconeogenesis + glycogenolysis)
3. Insulin deficiency (pancreas): Progressive β-cell failure + excess glucagon from α-cells

The natural history cascade:

Genes + Environment (obesity, physical inactivity, excessive food) → Insulin resistance → Compensatory hyperinsulinaemia with normal glucose tolerance → β-cell decompensation → IGT → Progressive β-cell decline → Hypoinsulinaemia with increasing hyperglycaemia → T2DM ^[1]

Key concept – Glucotoxicity and Lipotoxicity:

Decline is accelerated by glucotoxicity & lipotoxicity. ^[1]

• Glucotoxicity: Chronic hyperglycaemia itself damages β-cells (oxidative stress, ER stress) and worsens insulin resistance → vicious cycle
• Lipotoxicity: Elevated free fatty acids from visceral adiposity are toxic to β-cells and impair insulin signalling in muscle/liver

Reading the Two Type 2 Diabetes Diagrams

• The progression flowchart is a compensation-to-decompensation model: genetic susceptibility and environmental exposures produce insulin resistance; β cells initially raise insulin output enough to preserve normal glucose tolerance, then inadequate compensation produces IGT and eventually overt diabetes. The arrows are a conceptual pathway, not an inevitable one-way fate—weight change, activity and treatment can alter the trajectory.
• The three-organ figure shows why fasting and postprandial glucose rise together: liver insulin resistance permits excess hepatic glucose output, muscle/adipose resistance reduces glucose uptake, and islet dysfunction combines reduced β-cell insulin with inappropriately high α-cell glucagon. The central “hyperglycaemia” box is therefore the convergence of several defects, not simply “too little insulin.”

Diabetic ketoacidosis ± coma; Hyperosmolar nonketotic coma; Infections – pulmonary TB, UTI, others. ^[1]

Must exclude PRECIPITATING FACTORS: Infection; operation; trauma; severe emotional stress; MI; stroke (especially in the elderly); Drug administration e.g. steroid. ^[1]

The "6 Is" mnemonic from senior notes: ^[3]

• Insulin deficiency (missed doses, T1DM)
• Infection (chest, UTI)
• Inflammation (pancreatitis)
• Infarct (silent MI – always get ECG!)
• Iatrogenic (steroids, antipsychotics, SGLT2 inhibitors)
• Ingestion (methamphetamine, cocaine)

1. First manifestation of undiagnosed Type 1 diabetes. 2. Inadequate insulin treatment in known Type 1 diabetic patients. ^[1]

These are classic settings, but DKA also occurs in type 2 diabetes, ketosis-prone diabetes, pancreatic diabetes and with SGLT2 inhibitors. Do not use age, body habitus or a prior type 2 label to rule it out. ^[11]

Acute insulin deficiency leads to unrestrained lipolysis, ↑ free fatty acids, excess hepatic ketone production and metabolic acidosis. ^[1]

From first principles:

1. Insulin action becomes inadequate: insulin-dependent tissues reduce glucose uptake while hepatic glucose production continues; this is not literally zero glucose entry into every cell
2. Counter-regulatory hormones surge (glucagon, cortisol, catecholamines, GH)
3. Hyperglycaemia pathway: ↑ gluconeogenesis + ↑ glycogenolysis (liver) + ↓ peripheral glucose uptake → blood glucose soars
4. Ketosis pathway: Insulin deficiency removes the brake on hormone-sensitive lipase → unrestrained lipolysis → ↑ free fatty acids flood the liver → β-oxidation → acetyl-CoA → overwhelms Krebs cycle capacity → shunted into ketogenesis → acetoacetate, β-hydroxybutyrate, acetone
5. These ketoacids are strong organic acids → consume bicarbonate → high anion gap metabolic acidosis (HAGMA)
6. Hyperglycaemia → osmotic diuresis → dehydration + electrolyte losses

The slide says serum sodium and potassium are “usually normal” on admission. In practice either may be low, normal or high: the measured extracellular values do not reveal the total-body deficits. ^[1]

Hypokalaemia becomes evident after rehydration and insulin therapy (insulin-stimulated glucose transport into cell is accompanied by inward K+ shift). ^[1]

Why can K+ look “normal” or high despite depletion?

• Osmotic diuresis → K+ lost in urine (total body K+ deficit)
• BUT: Insulin deficiency → K+ stays extracellular (no insulin-driven K+ uptake); acidosis → H⁺/K⁺ exchange pushes K+ out of cells
• So serum K+ looks normal or even high, masking a profound total body deficit
• When you give insulin → K+ rushes back into cells → serum K+ plummets → potentially fatal hypokalaemia with arrhythmias

Glucose-related dilutional hyponatraemia: hyperglycaemia shifts water extracellularly and may lower measured sodium. Correction factors are estimates and vary at extreme glucose levels; interpret sodium together with measured/calculated osmolality and its trajectory rather than relying on one formula. A sodium rise during initial treatment can be expected as glucose falls. ^[11]

All three DKA domains—diabetes/hyperglycaemia, ketosis and acidosis—must be present. All four HHS domains must be present. Mixed DKA/HHS is common, and SGLT2-associated DKA may be euglycaemic; therefore a glucose threshold alone is unsafe. Prefer quantitative blood β-hydroxybutyrate and a venous blood gas. ^[11]

The slide summarises fluids, potassium, IV insulin, treatment of the precipitant and close monitoring. Its fixed “5–10 units/hour” and saline-only wording should not replace a current weight-based local protocol. ^[1]

Step-by-step rationale:

1. Resuscitate and assess: ABC, circulation, mental state, fluid balance, ECG and precipitant. In adults without cardiac/renal compromise, start isotonic saline or a balanced crystalloid promptly; use smaller boluses with frequent reassessment in older adults, pregnancy, heart failure or kidney disease. ^[11]
2. Potassium before/during insulin: If K⁺ is < 3.5 mmol/L, begin replacement and delay insulin until K⁺ is > 3.5. Once K⁺ falls below 5.0, potassium is commonly added to fluids to maintain about 4–5 mmol/L, adjusted for renal function and local protocol. ^[11]
3. Suppress ketogenesis: Standard adult IV insulin is weight-based (usually 0.1 units/kg/hour). When glucose is < 13.9 mmol/L, add 5–10% dextrose and reduce insulin (usually 0.05 units/kg/hour) so insulin can continue until ketoacidosis resolves. Selected uncomplicated mild/moderate DKA may use a validated subcutaneous rapid-acting protocol. ^[11]
4. Bicarbonate is not routine: Fluid and insulin usually correct acidosis. Consider bicarbonate only for severe acidaemia (pH < 7.0) under the treatment protocol. ^[11]
5. Find and treat the trigger: examine for infection, missed/interrupted insulin, myocardial ischaemia, stroke, pancreatitis, drugs and psychosocial barriers; order tests to match the presentation rather than reflexively prescribing antibiotics.
6. Monitor the biology: bedside glucose every 1–2 hours and electrolytes, creatinine, β-hydroxybutyrate and venous pH about every 4 hours during treatment, with more frequent checks when clinically indicated. ^[11]

Ketosis usually absent (just sufficient insulin to suppress lipolysis and ketogenesis; severe hyperosmolality may ↓ lipolysis). ^[1]

Relative insulin availability is often enough to limit marked lipolysis/ketogenesis but not hyperglycaemia. “Non-ketotic coma” is obsolete shorthand: modest ketonaemia may occur and the patient need not be comatose.

The slide depicts severe hyperglycaemia, dehydration and hyperosmolality with possible depression of consciousness. Its “> 340” line is a teaching association, not a required diagnostic threshold. ^[1]

HHS has high mortality because it often affects older or medically complex people, evolves over days and produces profound dehydration; the precipitating illness also drives outcome. Neurological dysfunction should broadly track osmolality—marked impairment out of proportion to it warrants investigation for stroke, infection or another cause. ^[11]

Effective serum osmolality = 2[Na⁺] + [glucose] (all in mmol/L); total calculated osmolality also includes urea. Current HHS criteria use effective osmolality > 300 mOsm/kg or total osmolality > 320 mOsm/kg. ^[11]

The slide correctly emphasises a larger water deficit and lower insulin requirement than DKA, but its routine CVP/pulmonary-wedge monitoring, sodium-triggered half-normal saline and ancestry-specific thrombosis statement are not current practice rules. ^[1]

• Controlled fluids are the priority: begin isotonic saline or a balanced crystalloid, with smaller boluses and frequent clinical/biochemical reassessment when fluid overload is a risk. A rising sodium as glucose falls is expected and is not by itself an indication for hypotonic fluid.
• Control the rate: aim for glucose decline no faster than about 5–6.7 mmol/L/hour, osmolality fall 3–8 mOsm/kg/hour and sodium fall no faster than 10 mmol/L in 24 hours. Consider 0.45% saline only if osmolality is not falling despite adequate positive fluid balance and appropriate insulin—not from a single sodium threshold. ^[11]
• Insulin is lower-dose in pure HHS: use a fixed-rate IV infusion around 0.05 units/kg/hour; treat mixed DKA/HHS with the DKA dose. Follow local protocol and potassium safeguards. ^[11]
• Thrombosis risk is clinical, not ancestry-based: assess for VTE and use prophylaxis according to the crisis protocol and contraindications. Central venous or pulmonary-artery pressure monitoring is reserved for selected critically ill patients, not routine HHS.

Too much sulphonylurea or insulin; too little carbohydrate; too much exercise; exclude renal impairment. ^[1]

Why renal impairment? Reduced renal insulin clearance and gluconeogenesis, reduced intake/illness and accumulation of some insulin secretagogues or active metabolites can all increase hypoglycaemia risk. Risk differs between drugs and rises as kidney function declines, so review the exact agent and dose rather than treating all sulfonylureas as equivalent.

The slide groups palpitations, sweating and tremor as autonomic warning symptoms, and altered behaviour, drowsiness and coma as neuroglycopenia. Hunger and anxiety can overlap; symptom groups are not perfectly exclusive. ^[1]

Why two categories? When glucose drops, the body first releases adrenaline/noradrenaline (adrenergic response – this is the "warning system"). If glucose continues to drop, the brain itself is starved of fuel (neuroglycopenia – this is the "danger zone"). In long-standing diabetes, patients may lose the adrenergic warning signs (hypoglycaemia unawareness) and present directly with neuroglycopenic symptoms.

The slide lists oral carbohydrate, glucagon and intravenous glucose. Route depends first on whether the person can safely swallow. ^[1]

Level 1 hypoglycaemia is < 3.9 mmol/L, level 2 is < 3.0 mmol/L, and level 3 is defined clinically by the need for another person's assistance—not by a lower numerical threshold. One level 2 or 3 event should trigger review of treatment, education, awareness and technology needs. ^[12]

The older device image advertises “up to 15 days” recording and shows multi-day traces used to identify nocturnal lows and postprandial highs. Wear duration is device-specific and no longer a general definition of CGM. ^[1]

How to read the figures: the daily profile's central line is the median glucose, with darker/lighter ribbons showing progressively wider percentile bands. A wide band at a particular time means high day-to-day variability even if the median looks acceptable. The receiver image adds a current value, trend arrow and recent trace; treatment decisions use the direction and rate of change, not the number alone. Confirm with capillary glucose when symptoms do not match the sensor, readings are changing rapidly or the device warns of inaccuracy. ^[14]

The slide invokes the historical Somogyi phenomenon (rebound morning hyperglycaemia after nocturnal hypoglycaemia). Do not assume it from a fasting high: inspect overnight CGM/BGM data and consider insufficient basal insulin, dawn phenomenon, meals, illness and sensor error before changing insulin.

For many nonpregnant adults, the slide's CGM goals are TIR 3.9–10.0 mmol/L > 70%, time > 10.0 < 25%, time > 13.9 < 5%, time < 3.9 < 4% and time < 3.0 < 1%. These are population targets, not universal prescriptions; older/frail or high-risk patients often need stricter low-glucose avoidance. ^[1][12]

Less than 7% in general. Individualization of treatment goals. Greater risk of hypoglycaemia at extremes of age. Less stringent target if multiple co-morbidities or short life expectancy. ^[1]

Increasing prevalence due to obesity. Majority onset at 10–14 years; often asymptomatic (76% in HK). More rapid deterioration of β-cell function and earlier development of complications than adult-onset T2D. ^[1]

This is an alarming point: childhood-onset T2DM is more aggressive than adult-onset T2DM, with faster β-cell decline and earlier complications.

The slide adds age-approved GLP-1 receptor agonist or SGLT2 inhibitor therapy to metformin and uses insulin when needed. Exact product approval, age, contraindications and funding vary by jurisdiction; symptomatic/ketotic youth or A1c ≥8.5% generally need insulin at presentation, whereas stable asymptomatic youth below that threshold usually start metformin. ^[1][13]

The slide quotes a local HK new-onset T1:T2 ratio and depicts basal-bolus insulin, pumps and CGM. The ratio is cohort- and year-specific. Current ADA guidance sets < 7% for most children/adolescents; selected patients may safely aim below 6.5%, but pump use alone does not determine the target. CGM and automated insulin-delivery systems should be offered with education according to individual and family needs. ^[1][13][14]

DCCT: Benefits of good control (pump or multiple injections): ^[1]

• Primary prevention: retinopathy ↓ 53%, microalbuminuria ↓ 10%
• Secondary prevention: retinopathy progression ↓ 70%, microalbuminuria ↓ 70%
• Faster motor and sensory nerve conduction velocities
• Lower total cholesterol levels
• BUT: Intensive therapy associated with 2–4 fold ↑ in severe hypoglycaemia

Reading the DCCT slide: it contrasts conventional with the then-intensive regimen (multiple injections or pump). The quoted percentage reductions and 2–4-fold severe-hypoglycaemia increase are historical trial findings, not promises for an individual using modern analogues, CGM or automated insulin delivery. The durable lesson is that improved glycaemia reduces microvascular risk, while technology and education help pursue this safely.

The slide records a QMH paediatric schedule and local prevalence figures. Use the current service protocol in practice; organ-specific screening does not start at one identical time. ^[1]

• Type 1 diabetes: current ADA guidance starts annual kidney screening (UACR and eGFR) and neuropathy/foot review at puberty or age ≥11 years, whichever is earlier, after 5 years' duration. Start retinal examination after 3–5 years' duration once age ≥11 or puberty has begun. ^[13]
• Type 2 diabetes: assess kidney disease, neuropathy/feet and retinopathy at or soon after diagnosis and then at recommended intervals because dysglycaemia and comorbidity may predate recognition. ^[13]
• The slide's “two first-morning microalbumin samples” should be translated into a urine albumin-to-creatinine ratio; confirm persistent elevation because exercise, fever, infection, menstruation and marked hyperglycaemia can transiently raise albumin excretion.

The slide says annual thyroid screening. Current ADA guidance measures TSH soon after type 1 diagnosis once clinically stable, then generally every 1–2 years if normal, or sooner with positive antibodies, symptoms, goitre, altered growth or unexplained glycaemic variability. ^[1][13]

Why? Autoimmune thyroid and coeliac disease are more common with type 1 diabetes. Screen them according to guideline timing and symptoms; Addison disease testing is targeted to compatible clinical features rather than an automatic annual panel.