Diabetes Mellitus: A Clinical Guide
Definition
Diabetes Mellitus (DM) is a group of chronic metabolic disorders characterised by the cardinal feature of hyperglycaemia, resulting from defects in insulin secretion, insulin action, or both (4). This is not merely a laboratory abnormality but a systemic disease process where chronic hyperglycaemia inflicts long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels (4, 7.2).
Epidemiology
Malaysia faces a critical public health crisis, with one of the highest rates of diabetes in Asia (12.1). The 2019 National Health and Morbidity Survey (NHMS) revealed a staggering national prevalence of 18.3% among adults, translating to roughly one in five Malaysians living with the condition (12.1). Alarmingly, nearly half (49%) of these individuals were unaware of their diagnosis, placing them at high risk for developing severe complications (12.1). The prevalence of prediabetes is also high, creating a large pool of individuals poised to progress to overt diabetes (1). This epidemic exhibits significant ethnic disparities, with the highest prevalence observed among ethnic Indians, followed by Malays, and then ethnic Chinese (11.1).
Globally, the situation is equally dire. The number of adults with diabetes has surged to 537 million in 2021, with projections reaching 783 million by 2045 (5). Low- and middle-income countries bear the brunt of this pandemic (5). Diabetes is a leading cause of blindness, kidney failure, heart attack, stroke, and lower-limb amputation worldwide (5).
Pathophysiology
The underlying pathology of diabetes dictates its management. The main types are distinguished by their causative mechanisms.
Type 1 Diabetes Mellitus (T1DM)
T1DM is a disease of absolute insulin deficiency caused by the autoimmune destruction of pancreatic β-cells (2.2). In genetically susceptible individuals, an environmental trigger, such as a viral infection, is thought to initiate a T-cell-mediated attack on the islets of Langerhans (2.2). Clinical symptoms manifest only after 80-90% of β-cell mass is destroyed, necessitating lifelong insulin replacement therapy (2.2).
Type 2 Diabetes Mellitus (T2DM)
T2DM, accounting for over 90% of cases, is defined by the dual defects of insulin resistance and a progressive decline in insulin secretion (6.1). Initially, peripheral tissues (muscle, liver, fat) become resistant to insulin's effects, often driven by obesity, particularly visceral adiposity (6.1, 7.2). The pancreas compensates by increasing insulin production (hyperinsulinemia), but over time, the β-cells become exhausted and fail, a process exacerbated by glucotoxicity and lipotoxicity (7.1). This leads to overt hyperglycaemia when insulin secretion can no longer overcome resistance (7.1).
Gestational Diabetes Mellitus (GDM)
GDM is glucose intolerance first recognised during pregnancy (4). It arises when the mother's pancreas cannot produce enough insulin to overcome the physiological insulin resistance created by placental hormones (4). While it may resolve post-delivery, GDM is a significant predictor for the future development of T2DM in the mother (7.1).
Clinical Presentation
The clinical presentation varies significantly by the type and severity of diabetes.
Diagnostic Clues
Classic osmotic symptoms (Polyuria, Polydipsia, Polyphagia): These are hallmarks of significant hyperglycaemia, driven by osmotic diuresis when blood glucose exceeds the renal threshold (7.1).
Acanthosis Nigricans: Hyperpigmented, velvety skin thickening in flexural areas (neck, axillae) is a strong cutaneous marker of insulin resistance and T2DM (7.1).
Diabetic Ketoacidosis (DKA): An acute presentation with nausea, vomiting, abdominal pain, Kussmaul breathing, and a fruity breath odour is a classic, life-threatening presentation of T1DM (8.1).
Common Symptoms (>50%)
Type 1 Diabetes: Acute onset of polyuria, polydipsia, polyphagia, and significant, unexplained weight loss over weeks to months (2.1). Patients are often lean and young (2.2).
Type 2 Diabetes: Often insidious and asymptomatic for years (6.1). May present with non-specific fatigue, recurrent infections (especially vulvovaginal candidiasis or balanitis), or blurred vision (6.1).
⚠️ Red Flag Signs & Symptoms
Altered mental status, confusion, or coma: May indicate severe DKA or Hyperglycemic Hyperosmolar State (HHS) (8.1).
Deep, laboured (Kussmaul) respirations: A sign of metabolic acidosis in DKA (8.1).
Profound dehydration and hypotension: Key features of both DKA and HHS requiring urgent fluid resuscitation (8.1).
New focal neurological deficits or seizures: Can occur in HHS (8.1).
An active foot ulcer, especially with signs of infection (redness, warmth, discharge): This is a limb-threatening emergency requiring urgent multidisciplinary assessment (3.2).
Complications
Chronic hyperglycaemia leads to devastating long-term complications.
Microvascular:
Retinopathy: A leading cause of blindness (7.2).
Nephropathy: A major cause of end-stage renal disease (7.2).
Neuropathy: Can cause sensory loss, pain, and contributes to diabetic foot ulcers (9).
Macrovascular:
Coronary Artery Disease: Leading to myocardial infarction (7.2).
Cerebrovascular Disease: Leading to stroke (7.2).
Peripheral Arterial Disease (PAD): A key contributor to foot ulcers and amputation (9).
Acute:
Diabetic Ketoacidosis (DKA): More common in T1DM (8.1).
Hyperglycemic Hyperosmolar State (HHS): More typical in T2DM (8.1).
Prognosis
The prognosis of diabetes depends heavily on the degree of glycaemic control and management of cardiovascular risk factors. Early diagnosis and aggressive management to achieve and maintain glycaemic targets significantly reduce the risk of long-term complications, a concept known as "metabolic memory" (1). However, diabetes remains a major cause of premature death, with nearly half of all diabetes-related deaths occurring before the age of 70 (5).
Differential Diagnosis
Hyperglycaemia in a Young, Lean Patient: While T1DM is most likely, consider Maturity-Onset Diabetes of the Young (MODY). This monogenic form of diabetes can be distinguished by a strong family history across multiple generations (autosomal dominant inheritance) and negative islet autoantibodies. Correctly identifying MODY is critical as some subtypes respond well to oral sulfonylureas instead of insulin (7.1).
Asymptomatic Hyperglycaemia in an Overweight Adult: This is classic for T2DM. However, consider Latent Autoimmune Diabetes in Adults (LADA), a slowly progressing form of autoimmune diabetes. LADA patients may initially be managed as T2DM but will progress to absolute insulin deficiency more quickly. The presence of islet autoantibodies (especially anti-GAD) confirms the diagnosis (7.1).
Hyperglycaemia in a patient on specific medications: Always consider drug-induced diabetes. This is a key differential, especially in patients recently started on glucocorticoids, thiazide diuretics, or atypical antipsychotics. A thorough medication history is essential to distinguish this from de novo T2DM, as hyperglycaemia may resolve upon cessation of the offending drug (7.1, 8.1).
Investigations
Immediate & Bedside Tests
Capillary Blood Glucose: Essential for rapid confirmation of hyperglycaemia, guiding immediate management decisions.
Blood or Urine Ketone Measurement: This is mandatory in any patient with suspected DKA to assess for ketosis (the rationale), which is a defining feature of the condition and guides the intensity of initial therapy (the action) (8.1). Point-of-care blood β-hydroxybutyrate is preferred.
Bedside ECG: Crucial to immediately assess for life-threatening hyperkalaemia (peaked T waves) or hypokalaemia (U waves, T wave flattening) (the rationale), which are common and dangerous electrolyte disturbances in DKA that require urgent correction (the action) (8.1).
Diagnostic Workup
The Malaysian CPG for T2DM recommends a lower HbA1c threshold for diagnosis compared to global standards, a strategy to increase diagnostic sensitivity in a high-prevalence population (1).
First-Line Investigations (Screening & Diagnosis):
Fasting Plasma Glucose (FPG): A value of ≥7.0 mmol/L is diagnostic (1). This test is convenient for routine screening.
HbA1c: An HbA1c ≥6.3% (45 mmol/mol) is diagnostic in Malaysia (1). This reflects average glycaemia over 2-3 months and avoids the need for fasting, making it a practical diagnostic tool.
Gold Standard (in specific situations):
2-hour Oral Glucose Tolerance Test (OGTT): A 2-hour plasma glucose of ≥11.1 mmol/L is diagnostic (1). This is the most sensitive test for diagnosing diabetes, particularly for detecting post-prandial hyperglycaemia when fasting glucose is normal (the rationale), and is essential for diagnosing GDM (the action).
Monitoring & Staging
HbA1c: Performed every 3-6 months to assess long-term glycaemic control (the action), as it directly reflects the average blood glucose and is the primary target for therapy to reduce long-term complication risk (the rationale) (1).
Annual Urine Albumin-to-Creatinine Ratio (UACR): This is the key screening test for diabetic nephropathy (the action), as it detects microalbuminuria, the earliest clinical sign of kidney damage, allowing for early intervention with ACE inhibitors or ARBs to slow progression (the rationale) (1).
Annual Dilated Fundoscopy / Retinal Photography: Performed to screen for diabetic retinopathy (the action), as early detection and treatment with laser photocoagulation or anti-VEGF injections can prevent vision loss, which is often asymptomatic in its early stages (the rationale) (1).
Comprehensive Annual Foot Examination: Includes inspection, neurological testing with a 10g monofilament, and vascular assessment (pedal pulses) to stratify the patient's risk of ulceration (the action), which allows for targeted education and preventative measures to prevent limb-threatening complications (the rationale) (3.2).
Management
Management Principles
The management of diabetes is multifaceted, focusing on achieving individualised glycaemic control to prevent acute decompensation and reducing the risk of long-term microvascular and macrovascular complications, thereby preserving quality of life (1).
Acute Stabilisation (The First Hour of DKA/HHS)
Airway/Breathing: Administer high-flow oxygen via a non-rebreather mask to maintain SpO2 >94% (the action), which is crucial to correct tissue hypoxia resulting from poor perfusion and potential respiratory compromise (the rationale).
Circulation: Secure two large-bore IV cannulas and administer a stat fluid bolus of IV Normal Saline 0.9% 1,000mL over the first hour (the action) to rapidly restore intravascular volume and improve tissue perfusion, which is severely compromised by osmotic diuresis (the rationale) (8.1).
Disability/Exposure: Check capillary blood glucose and ketones immediately to confirm the hyperglycaemic emergency. Draw blood for urgent laboratory investigations including venous blood gas, urea and electrolytes, and FBC before starting insulin therapy (the action), as these results are critical for diagnosing the severity of acidosis and electrolyte imbalance that will guide subsequent management (the rationale).
Electrolytes: Do not start insulin until the serum potassium level is known and is >3.3 mmol/L. Starting insulin with low potassium can drive potassium into cells, causing fatal cardiac arrhythmias (the rationale). If K+ is <3.3 mmol/L, potassium replacement must be initiated first (the action) (8.1).
Definitive Therapy
Type 1 Diabetes: Management requires lifelong replacement with a basal-bolus insulin regimen to mimic physiological secretion (2.2). This involves a long-acting basal insulin (e.g., Glargine, Detemir) once or twice daily and rapid-acting bolus insulin (e.g., Aspart, Lispro) with each meal, with doses adjusted based on carbohydrate counting and blood glucose levels (2.2).
Type 2 Diabetes (following Malaysian CPG T2DM 6th Ed.):
First-Line Treatment: Lifestyle modification plus Metformin is the initial therapy for all newly diagnosed patients unless contraindicated or not tolerated (1).
Second-Line/Escalation: If the HbA1c target is not met, the choice of a second agent is guided by comorbidities (1):
With established Atherosclerotic Cardiovascular Disease (ASCVD), Heart Failure, or Chronic Kidney Disease (CKD): Add an SGLT2 inhibitor (e.g., Dapagliflozin, Empagliflozin) or a GLP-1 receptor agonist (e.g., Liraglutide, Semaglutide) with proven cardiorenal benefit, irrespective of HbA1c (1). These agents are now considered organ-protective first, and glucose-lowering second (1).
To minimise hypoglycaemia risk: Add a DPP-4 inhibitor, GLP-1 RA, or SGLT2 inhibitor (1).
For weight loss: Add a GLP-1 RA or SGLT2 inhibitor. The dual GIP/GLP-1 receptor agonist Tirzepatide has shown superior weight loss effects (1, 10.1).
If cost is a major issue: A sulfonylurea (e.g., Gliclazide) is an effective option, but carries a higher risk of hypoglycaemia and weight gain (1).
Injectable Therapy: If oral agents are insufficient, initiate injectable therapy, starting with a GLP-1 RA or basal insulin (e.g., Insulin Glargine 10 units at bedtime or 0.1-0.2 U/kg/day) (1).
Supportive & Symptomatic Care
Painful Diabetic Neuropathy: First-line agents include amitriptyline, duloxetine, or pregabalin/gabapentin (3.2).
Nutrition: All patients require Medical Nutrition Therapy (MNT). For T2DM, a focus on achieving 7-10% weight loss is crucial (1). The "Quarter-Quarter-Half" plate method is a practical tool for portion control.
Cardiovascular Risk Reduction: Aggressively manage blood pressure (target 130-139/70-79 mmHg) and lipids (LDL-C target <2.6, <1.8, or <1.4 mmol/L depending on risk) (1). Prescribe a statin for nearly all patients with T2DM over 40 years old.
Key Nursing & Monitoring Instructions
Strict hourly monitoring of vital signs, GCS, and fluid input/output for patients in DKA/HHS.
Capillary blood glucose monitoring every 1-2 hours during an acute crisis.
Inform medical staff immediately if urine output is <0.5mL/kg/hr or if there is any deterioration in conscious level.
For ward patients, ensure regular foot inspection, especially if they are high-risk or bed-bound.
Long-Term Plan & Patient Education
Structured, ongoing diabetes self-management education (DSME) is critical, covering diet, exercise, medication adherence, and sick day rules (2.1).
Teach patients how to recognise and manage hypoglycaemia (2.2).
Emphasise the importance of daily foot self-inspection (3.2).
Schedule an annual comprehensive diabetes review to screen for all complications (1).
When to Escalate
Call Your Senior (MO/Specialist) if:
A patient presents with signs of DKA or HHS.
The patient develops new or worsening neurological signs, chest pain, or significant ECG changes.
There is severe electrolyte derangement (e.g., K+ <3.3 mmol/L or >6.0 mmol/L).
Lactate fails to clear or acidosis does not improve despite adequate fluid resuscitation.
A patient is found to have a diabetic foot ulcer with deep infection, abscess, or wet gangrene.
Referral Criteria:
Endocrinologist: For all new T1DM diagnoses, difficult-to-control T2DM, or when considering complex therapies like insulin pumps (2.2).
Diabetic Foot Multidisciplinary Team: Refer urgently (within 24 hours) for any high-risk foot problem, such as a new ulcer or suspected Charcot neuroarthropathy (3.2).
Nephrologist: For patients with rapidly declining eGFR or significant proteinuria.
Ophthalmologist: For any signs of vision loss or if screening reveals sight-threatening retinopathy.
Cardiologist: For management of established cardiovascular disease.
References
Ministry of Health Malaysia. (2020). Clinical Practice Guidelines: Management of Type 2 Diabetes Mellitus (6th Edition). Putrajaya: MOH. https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Endocrine/QR_T2DM_6th_Edition_QR_Guide_Digital.pdf
Azmi, S., & Ramachandran, V. (2018). Management of T1DM in children and adolescents in primary care. Malaysian Family Physician, 13(1), 45-51. https://pmc.ncbi.nlm.nih.gov/articles/PMC5802777/
Ministry of Health Malaysia. (2019). Malaysian Clinical Practice Guidelines: Management of Diabetic Foot (Second Edition). Putrajaya: MOH. https://www.moh.gov.my/moh/resources/penerbitan/CPG/CPG%20Management%20of%20Diabetic%20Foot%20%20(Second%20Edition).pdf
American Diabetes Association. (2024). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024. Diabetes Care, 47(Supplement_1), S20–S42. https://doi.org/10.2337/dc24-S002
International Diabetes Federation. (2024). IDF Diabetes Atlas. https://idf.org/about-diabetes/diabetes-facts-figures/
National Institute for Health and Care Excellence. (2022). Type 2 diabetes in adults: management (NICE Guideline 28). https://www.nice.org.uk/guidance/ng28
American Diabetes Association. (2024). Standards of Care in Diabetes—2024 Abridged for Primary Care Providers. https://professional.diabetes.org/standards-of-care
Lizzo, J. M., & Goyal, A. (2024). Diabetic Ketoacidosis. In StatPearls. StatPearls Publishing.
Malik, F. S., & Tadi, P. (2024). Diabetic Foot Ulcer. In StatPearls. StatPearls Publishing.
Frías, J. P., Davies, M. J., Rosenstock, J., Pérez-Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., & Brown, K. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. The New England Journal of Medicine, 385(6), 503–515. https://www.nejm.org/doi/full/10.1056/NEJMoa2107519
Ministry of Health Malaysia. (2023). National Diabetes Registry Report 2023. Putrajaya: MOH. https://www.moh.gov.my/moh/resources/Penerbitan/Laporan/Umum/NDR_Report_2023_Final.pdf
Bernama. (2020, May 30). One in five adult Malaysians has diabetes - NHMS 2019. Astro Awani. https://international.astroawani.com/malaysia-news/one-five-adult-malaysians-has-diabetes-nhms-2019-244852
