After reading this note you will be able to describe how diabetes presents, list the local risk factors, interpret the key investigations and outline a safe step‑wise management plan – remembering to verify doses and local protocols against the Kenya MoH guideline and your hospital formulary.
Definition
A chronic metabolic disorder characterised by persistent hyperglycaemia resulting from absolute insulin deficiency (type 1), relative insulin deficiency and/or insulin resistance (type 2), or other specific causes (e.g., drug‑induced, endocrine disease). Diagnosis is made when any of the following criteria are met on two separate occasions:
| Criterion | Value |
|---|---|
| Fasting plasma glucose | ≥7.0 mmol/L |
| 2‑hour OGTT | ≥11.1 mmol/L |
| Random plasma glucose with symptoms | ≥11.1 mmol/L |
| HbA1c | ≥48 mmol/mol (6.5 %) |
Anatomy and physiology you need
- Pancreatic β‑cells: synthesize, store and secrete insulin in response to rising glucose.
- Insulin receptors on muscle, adipose and hepatic cells mediate glucose uptake, glycogen synthesis and inhibition of gluconeogenesis.
- Glucagon‑producing α‑cells: raise blood glucose during fasting.
- Kidney: reabsorbs filtered glucose via SGLT2; contributes to fasting glucose regulation.
- Incretin system (GLP‑1, GIP): augment glucose‑dependent insulin secretion.
Understanding these sites helps explain why β‑cell loss, receptor down‑regulation or renal glucose reabsorption become therapeutic targets.
Causes and risk factors
| Category | Local relevance in Kenya |
|---|---|
| Genetic | Family history, African ancestry (higher insulin resistance) |
| Lifestyle | Urbanisation, sedentary work, high‑calorie diets, tobacco use |
| Obesity | Central adiposity common in peri‑urban populations |
| Infections | HIV (ART‑induced insulin resistance), TB (steroid therapy), chronic malaria (stress hyperglycaemia), hepatitis C |
| Hematologic | Sickle cell disease (β‑cell stress), thalassaemia (iron overload) |
| Medications | Protease inhibitors, corticosteroids, some antipsychotics |
| Endocrine | Cushing’s, acromegaly, pheochromocytoma |
| Pregnancy | Gestational diabetes (risk for later type 2) |
| Socio‑economic | Limited access to healthy foods, delayed screening |
Pathophysiology
Type 1: Autoimmune β‑cell destruction → ↓ insulin → ↑ hepatic glucose output + ↓ peripheral uptake → hyperglycaemia.
Type 2: Chronic caloric excess + genetic predisposition → adipocyte hypertrophy → ↑ free fatty acids & inflammatory cytokines → insulin resistance in muscle & liver → ↑ insulin demand → β‑cell exhaustion → relative insulin deficiency → hyperglycaemia.
Other specific: Drug‑induced (e.g., protease inhibitors) → mitochondrial toxicity → impaired insulin signalling; endocrine tumours → excess counter‑regulatory hormones → hepatic gluconeogenesis ↑.
Arrows:
``` Obesity → ↑ FFAs → ↓ insulin receptor signalling → insulin resistance → ↑ glucose → β‑cell hyperstimulation → β‑cell failure → ↓ insulin → hyperglycaemia ```
Clinical features
| Domain | Key questions / findings | Why it occurs |
|---|---|---|
| Polyuria | “How many times do you urinate each day? Do you wake at night to go?” | Hyperglycaemia exceeds renal tubular re‑absorption capacity → osmotic diuresis. |
| Polydipsia | “Do you feel unusually thirsty? How much water/fluids do you drink?” | Loss of water with osmotic diuresis triggers thirst centre. |
| Polyphagia | “Has your appetite increased? Are you eating more than usual?” | Cells perceive intracellular glucose deficiency → hunger signals. |
| Weight change | “Unintentional weight loss or gain? Recent diet changes?” | Catabolic state (type 1) or insulin resistance with adiposity (type 2). |
| Fatigue | “Do you feel unusually tired even after rest?” | Impaired glucose utilisation and dehydration reduce energy. |
| Blurred vision | “Any recent changes in eyesight?” | Hyperosmolarity draws fluid into lens, altering refractive index. |
| Infections | “Frequent skin, urinary, or genital infections?” | Hyperglycaemia impairs neutrophil function and promotes microbial growth. |
| Neuropathy symptoms | “Numbness, tingling, burning in feet or hands?” | Chronic hyperglycaemia damages peripheral nerves. |
| Cardiovascular symptoms | “Chest pain, dyspnoea, claudication?” | Accelerated atherosclerosis in diabetes. |
| Pregnancy history | “History of gestational diabetes or macrosomic infant?” | Prior gestational diabetes is a strong risk factor for type 2. |
| Family & ethnic background | “Any relatives with diabetes? Ethnicity?” | Genetic predisposition; African ancestry has higher risk of type 2. |
| Co‑morbid infections | “Do you have HIV, TB, recurrent malaria, sickle cell disease?” | HIV, TB, chronic malaria and sickle cell can worsen insulin resistance or precipitate hyperglycaemia. |
| Medication history | “Use of steroids, antiretrovirals, protease inhibitors, thiazides?” | Certain drugs increase insulin resistance or impair secretion. |
| Lifestyle | “Physical activity level, diet, alcohol use, smoking?” | Sedentary lifestyle, high‑calorie diet, alcohol and smoking aggravate insulin resistance. |
Examination findings
| Finding | Interpretation |
|---|---|
| Elevated BMI / central obesity | Visceral fat drives insulin resistance (type 2). |
| Acanthosis nigricans (hyperpigmented velvety plaques on neck, axillae) | Marker of chronic hyperinsulinaemia and insulin resistance. |
| Dry skin, fissures | Dehydration from osmotic diuresis; predisposes to infection. |
| Peripheral neuropathy (reduced vibration, pin‑prick sensation) | Long‑standing hyperglycaemia causing nerve damage. |
| Foot deformities / ulcers | Neuropathy + peripheral arterial disease → loss of protective sensation and poor healing. |
| Hypertension | Common comorbidity; contributes to macrovascular risk. |
| Cardiac exam (S4 gallop) | Diastolic dysfunction from hypertension and diabetic cardiomyopathy. |
| Fundoscopic changes (microaneurysms, hemorrhages) | Early diabetic retinopathy; indicates microvascular disease. |
| Signs of infection (erythema, swelling) | Hyperglycaemia impairs immunity; infections may be presenting feature. |
| Hepatomegaly / fatty liver | Non‑alcoholic fatty liver disease common in insulin resistance. |
Differential diagnosis
| Condition | Points toward it | Distinguishing features |
|---|---|---|
| Type 1 diabetes mellitus | Acute onset, weight loss, ketoacidosis, younger age, autoimmune history | Low/absent C‑peptide, positive auto‑antibodies, insulin dependence |
| Type 2 diabetes mellitus | Overweight/obese, gradual onset, family history, metabolic syndrome | Preserved C‑peptide early, insulin resistance signs, older age |
| Diabetes secondary to HIV/ART | HIV infection, use of protease inhibitors, lipodystrophy | Temporal relation to ART initiation, high triglycerides, central fat loss |
| Tuberculosis‑associated hyperglycaemia | Active TB, weight loss, fever, pulmonary signs | Hyperglycaemia improves with TB treatment; may be stress‑induced |
| Malaria‑related hyperglycaemia | Recent severe malaria, fever, haemolysis | Transient hyperglycaemia resolves after malaria cure |
| Sickle cell disease with pancreatic involvement | Sickle cell history, vaso‑occlusive crises, abdominal pain | Imaging shows pancreatic infarction; may have episodic hyperglycaemia |
| Cushing’s syndrome | Central obesity, moon face, striae, hypertension | Elevated cortisol, abnormal dexamethasone suppression test |
| Hyperthyroidism | Weight loss, tremor, tachycardia, heat intolerance | Suppressed TSH, elevated free T4/T3 |
| Medication‑induced (steroids, thiazides) | Recent start of offending drug | Hyperglycaemia coincides with drug exposure; resolves after withdrawal |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Fasting plasma glucose (FPG) | Baseline glucose status | ≥7.0 mmol/L = diabetes; 5.6‑6.9 mmol/L = pre‑diabetes |
| 2‑hour oral glucose tolerance test (OGTT) | Glucose handling after load | ≥11.1 mmol/L = diabetes; 7.8‑11.0 mmol/L = impaired glucose tolerance |
| HbA1c | Average glycaemia over 2‑3 months | ≥6.5 % = diabetes; 5.7‑6.4 % = increased risk |
| Random plasma glucose (RPG) with symptoms | Diagnostic in symptomatic patients | ≥11.1 mmol/L with classic symptoms = diabetes |
| C‑peptide (fasting or stimulated) | Endogenous insulin secretion | Low → insulin deficiency (type 1); normal/high → insulin resistance (type 2) |
| Auto‑antibodies (GAD‑65, IA‑2, ZnT8) | Autoimmune etiology | Positive = type 1 or LADA |
| Lipid profile | Cardiovascular risk | Elevated LDL, TG, low HDL common in type 2 |
| Renal function (eGFR, urine albumin‑creatinine ratio) | Diabetic kidney disease | Albuminuria >the protocol dose/g or reduced eGFR indicates nephropathy |
| Liver function tests & ultrasound | NAFLD assessment | Elevated ALT/AST, fatty infiltration on US |
| Fundoscopy (or retinal photography) | Diabetic retinopathy | Microaneurysms, hemorrhages, exudates |
| Foot assessment (monofilament, pulses) | Neuropathy & peripheral arterial disease | Loss of sensation or absent pulses → high ulcer risk |
| HIV test, TB screening (GeneXpert, chest X‑ray) | Co‑morbid infections influencing glucose | Positive results guide integrated management |
| Pregnancy test (women of reproductive age) | Exclude gestational diabetes | Positive → refer for obstetric evaluation |
Diagnosis and severity
- Confirm diabetes using any two of:
- FPG ≥ 7.0 mmol/L
- 2‑h OGTT ≥ 11.1 mmol/L
- HbA1c ≥ 6.5 %
- RPG ≥ 11.1 mmol/L with classic symptoms
- Classify type:
- Type 1 – low C‑peptide, positive auto‑antibodies, usually younger, rapid onset.
- Type 2 – preserved C‑peptide, insulin resistance features, older or obese.
- Secondary – clear precipitating condition (HIV/ART, TB, drugs, endocrine disorders).
- Assess severity (glycaemic control and organ involvement):
| Category | Glycaemic marker | Target | Complication risk |
|---|---|---|---|
| Well‑controlled | HbA1c <7 % (or <53 mmol/mol) | Near‑normal glucose | Low micro‑ and macro‑vascular risk |
| Moderately uncontrolled | HbA1c 7‑9 % | Requires treatment intensification | Rising risk of retinopathy, nephropathy |
| Poorly controlled | HbA1c >9 % | High risk of ketoacidosis (type 1) or hyperosmolar state (type 2) | Advanced micro‑vascular disease, cardiovascular events |
- Stage organ damage using:
- Nephropathy: albuminuria categories (normo‑, micro‑, macro‑) and eGFR.
- Retinopathy: none, mild non‑proliferative, moderate, severe, proliferative.
- Neuropathy: absent, peripheral, autonomic.
- Cardiovascular: presence of coronary artery disease, stroke, peripheral arterial disease.
Severity grading guides urgency of glycaemic control, choice of drug class (e.g., insulin for type 1 or severe hyperglycaemia, metformin‑based regimens for insulin‑resistant type 2, SGLT2 inhibitors or GLP‑1 receptor agonists when cardiovascular/renal protection is needed) and frequency of monitoring.
Management
Immediate stabilisation
- Severe hyperglycaemia / DKA – give rapid‑acting insulin infusion, replace fluids with isotonic saline, correct electrolytes (especially potassium) and monitor blood gases.
- Hypoglycaemia – administer glucose (IV dextrose if unconscious, oral glucose if conscious) and reassess cause.
Definitive treatment
| Goal | First‑line agents (class) | Rationale |
|---|---|---|
| Lower fasting glucose | Metformin (biguanide) | Reduces hepatic gluconeogenesis, improves peripheral insulin sensitivity; weight neutral. |
| Post‑prandial control | DPP‑4 inhibitor or GLP‑1 receptor agonist | Enhance incretin effect, low hypoglycaemia risk; GLP‑1 also promotes weight loss. |
| Established cardiovascular disease / CKD | SGL‑2 inhibitor (if eGFR acceptable) | Lowers glucose, reduces CV events and slows renal decline. |
| When HbA1c remains >9 % despite oral agents | Add basal insulin (long‑acting) | Provides steady background insulin, easy titration. |
| Pregnancy or severe insulin resistance | Rapid‑acting insulin + basal insulin regimen | Tight control needed, oral agents contraindicated. |
Monitoring
- Glycaemia: capillary glucose 4‑hourly in acute phase, then fasting & 2‑hour post‑meal glucose daily; HbA1c every 3 months until stable, then 6 months.
- Renal function: eGFR and urine albumin‑creatinine ratio every 6 months.
- Lipids: full lipid profile annually; statin therapy as per risk.
- Blood pressure: target <130/80 mmHg; ACE‑inhibitor/ARB if proteinuria.
- Weight & BMI: at each visit; counsel on diet & activity.
Safety & contraindications
- Metformin: avoid in eGFR < 30 ml/min/1.73 m², acute heart failure, or hepatic decompensation.
- SGL‑2 inhibitors: contraindicated in recurrent genital infections, eGFR < 45 ml/min/1.73 m², and in type 1 diabetes (risk of ketoacidosis).
- GLP‑1 agonists: avoid in personal/family history of medullary thyroid carcinoma or MEN‑2.
- Insulin: monitor for hypoglycaemia; adjust doses during infection, pregnancy, or steroid therapy.
Complications and prognosis
- Microvascular: retinopathy (leading cause of blindness), nephropathy (progresses to end‑stage renal disease), neuropathy (painful distal symmetric, autonomic dysfunction).
- Macrovascular: accelerated atherosclerosis → coronary artery disease, stroke, peripheral arterial disease.
- Acute: diabetic ketoacidosis, hyperosmolar hyperglycaemic state, severe hypoglycaemia.
- Infection risk: especially urinary, skin, and fungal infections; TB and HIV co‑infection worsen control.
Prognosis improves markedly with early, sustained glycaemic control, blood pressure and lipid optimisation, and regular screening for complications. In Kenya, addressing co‑morbid infections and ensuring access to affordable medicines are pivotal for long‑term outcomes.
High‑yield exam points
- Look‑alike conditions:
- Stress hyperglycaemia vs. new‑onset diabetes – check repeat fasting glucose/HbA1c after acute illness.
- Cushing’s syndrome vs. type 2 diabetes – look for centripetal obesity, striae, hypertension.
- Commonest wrong first step: Starting insulin without correcting severe dehydration or electrolyte imbalance in DKA.
- Bedside examiner questions:
- “What is the next immediate action for a patient with a random glucose of 28 mmol/L, K⁺ 3.2 mmol/L, and a pH 7.1?”
- “Explain why metformin is contraindicated in this patient with an eGFR of 25 ml/min.”
- “List three modifiable risk factors for macrovascular disease in diabetes.”
Clinical case
Case: 52‑year‑old male farmer presents with polyuria, nocturia, blurred vision for 3 weeks and a 4 kg weight loss. Random capillary glucose 22 mmol/L, HbA1c 10 %. Blood pressure 145/90 mmHg, BMI 28 kg/m². Fundoscopy shows mild non‑proliferative retinopathy. No ketones in urine.
Questions
- What is the most appropriate initial pharmacologic regimen?
Answer: Metformin plus an SGL‑2 inhibitor (if eGFR ≥ 45 ml/min/1.73 m²). Metformin addresses hepatic glucose output; the SGL‑2 inhibitor adds glucose‑independent cardiovascular and renal protection.
- Which investigation should be performed before starting metformin?
Answer: Serum creatinine/eGFR to ensure renal function is adequate (≥ 30 ml/min/1.73 m²).
- What lifestyle advice is essential for this patient?
Answer: Adopt a Mediterranean‑type diet low in refined carbohydrates, engage in at least 150 minutes of moderate aerobic activity weekly, and achieve weight loss of 5‑10 % to improve insulin sensitivity and blood pressure.
Practice questions
Question 1
A 68‑year‑old woman with known type 2 diabetes is admitted with a temperature of 38.5 °C, productive cough, and a random glucose of 30 mmol/L. Urine dipstick is positive for ketones, arterial pH 7.25. What is the next best step?
A. Start oral metformin
B. Initiate IV insulin infusion and fluid resuscitation
C. Give a single dose of subcutaneous regular insulin
D. Wait for culture results before treating
Answer: B. Initiate IV insulin infusion and fluid resuscitation
Explanation: The picture is DKA; rapid insulin and volume replacement are mandatory before any oral agents.
Question 2
A 45‑year‑old man with HIV on antiretroviral therapy presents with fasting glucose 7.5 mmol/L, HbA1c 7.2 %. Which oral agent should be avoided?
A. Metformin
B. Sulfonylurea
C. DPP‑4 inhibitor
D. SGL‑2 inhibitor
Answer: D. SGL‑2 inhibitor
Explanation: SGL‑2 inhibitors increase risk of genital infections and may precipitate euglycaemic ketoacidosis, especially in immunocompromised patients.
Question 3
A patient with type 2 diabetes and eGFR 28 ml/min/1.73 m² is being considered for glucose‑lowering therapy. Which statement is correct?
A. Metformin is first‑line regardless of renal function.
B. A GLP‑1 agonist is contraindicated because of renal impairment.
C. An SGL‑2 inhibitor can be used safely at any eGFR.
D. Insulin therapy is appropriate; oral agents are limited.
Answer: D. Insulin therapy is appropriate; oral agents are limited.
Explanation: With eGFR < 30 ml/min, metformin is contraindicated and SGL‑2 inhibitors are not recommended; insulin remains safe.
Question 4
Which of the following is the most sensitive early screening test for diabetic nephropathy?
A. Serum creatinine
B. Urine dipstick for protein
C. Urine albumin‑creatinine ratio (UACR)
D. Renal ultrasound
Answer: C. Urine albumin‑creatinine ratio (UACR)
Explanation: Microalbuminuria is detected earlier by UACR than by dipstick protein or serum creatinine changes.
Question 5
A 30‑year‑old woman with newly diagnosed type 1 diabetes is pregnant at 10 weeks gestation. Which glucose‑lowering strategy is appropriate?
A. Metformin monotherapy
B. Sulfonylurea tablet
C. Basal‑bolus insulin regimen
D. GLP‑1 receptor agonist
Answer: C. Basal‑bolus insulin regimen
Explanation: Insulin is the only safe and effective therapy for glycaemic control in pregnancy; oral agents are contraindicated.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.