• Diabetes has reached epidemic proportions globally. According to the International Diabetes Federation (IDF, 2023), 537 million adults (aged 20–79 years) live with diabetes — roughly 1 in 10 adults.
• The number is projected to rise to 643 million by 2030 and 784 million by 2045. Type 2 diabetes accounts for more than 90% of all cases.
• Nearly half of all people with diabetes remain undiagnosed, particularly in low- and middle-income countries.
• The disease contributes significantly to premature mortality, cardiovascular disease, chronic kidney disease, and vision loss.
• Economic burden: The global healthcare expenditure on diabetes exceeded USD 970 billion in 2022, and continues to rise with increasing obesity and sedentary lifestyles.

The key mechanisms underlying diabetes include:

1. Insulin Resistance: Target tissues (muscle, liver, adipose tissue) fail to respond to normal insulin levels. Glucose uptake by muscle decreases, while hepatic glucose output increases.
2. β-cell Dysfunction: Progressive loss of insulin secretion capacity due to oxidative stress, lipotoxicity, and glucotoxicity. In Type 1 diabetes, autoimmune destruction is the main cause; in Type 2, it’s progressive exhaustion.
3. Abnormal Glucose Metabolism: Reduced glucose utilization and increased hepatic gluconeogenesis. Elevated fasting and postprandial blood glucose levels.
4. Incretin Hormone Deficiency: Impaired GLP-1 (Glucagon-Like Peptide-1) response reduces post-meal insulin secretion.
5. Chronic Inflammation and Endothelial Dysfunction: Low-grade inflammation contributes to vascular damage and insulin resistance.

Non-Modifiable Factors:

• Family history of diabetes
• Genetic susceptibility
• Age >45 years
• Ethnicity (Middle Eastern, South Asian, African, and Hispanic populations at higher risk

Modifiable Factors:

• Overweight and obesity (especially visceral adiposity)
• Unhealthy diet high in refined sugars and saturated fats
• Physical inactivity
• Hypertension and dyslipidaemia
• Smoking and excessive alcohol intake
• Chronic stress and sleep deprivation

Symptoms may develop gradually (especially in Type 2 DM) or suddenly (in Type 1 DM).

Common manifestations include:

• Polyuria: Frequent urination due to glucose-induced osmotic diuresis.
• Polydipsia: Excessive thirst caused by dehydration.
• Polyphagia: Increased hunger due to cellular glucose deprivation.
• Fatigue and weakness Blurred vision from lens swelling due to hyperglycemia.
• Unintended weight loss, particularly in Type 1 DM. Slow-healing wounds, recurrent infections, or skin changes.
• Tingling, numbness, or burning in hands and feet (diabetic neuropathy)

1. Laboratory Criteria (ADA/WHO Guidelines):

Prediabetes:

• FPG: 100–125 mg/dL
• HbA1c: 5.7–6.4%
• 2-hour OGTT: 140–199 mg/dL

2. Additional Assessments:

• C-peptide levels to assess endogenous insulin production.
• Autoantibody testing (GAD, ICA, IAA) for Type 1 DM.
• Urinalysis for glucose, ketones, and microalbuminuria.
• Lipid profile, liver function tests, and renal function tests for metabolic evaluation

The goal is multifactorial control — managing hyperglycaemia, blood pressure, and lipid levels while preventing complications and preserving β-cell function.

1. Lifestyle and Non-Pharmacological Management

Medical Nutrition Therapy (MNT):

• Individualized meal planning with a focus on whole grains, lean proteins, healthy fats, fruits, and vegetables.
• Limiting simple carbohydrates and sugary beverages.
• Emphasis on low-glycaemic-index foods to improve glycaemic variability.

Physical Activity:

• Minimum of 150 minutes of moderate aerobic activity per week (e.g., brisk walking, swimming, cycling).
• Strength/resistance training twice weekly.

Weight Reduction:

• Losing 5–10% of body weight can significantly improve insulin sensitivity.

Behavioral Interventions:

• Smoking cessation, stress management, and sleep hygiene.

Patient Education and Self-Management:

• Regular self-monitoring of blood glucose (SMBG).
• Recognition and management of hypoglycemia and hyperglycemia.
• Adherence to medication and follow-up appointments.

2. Pharmacological Management

A. Type 1 Diabetes:

• Insulin therapy is essential for survival. Basal-bolus regimen (long-acting + rapid-acting insulin).
• Continuous subcutaneous insulin infusion (insulin pump).
• Newer hybrid closed-loop insulin delivery systems are emerging.

B. Type 2 Diabetes:

• First-line therapy: Metformin — improves insulin sensitivity and reduces hepatic glucose output.
• Second-line oral and injectable agents: Sulfonylureas / Meglitinides: Stimulate insulin secretion.
• DPP-4 inhibitors: Enhance incretin effect and insulin secretion.
• SGLT2 inhibitors: Promote urinary glucose excretion and provide cardiorenal protection.
• GLP-1 receptor agonists: Enhance insulin secretion, delay gastric emptying, and induce satiety (supporting weight loss).
• TZDs (Thiazolidinediones): Improve insulin sensitivity at the cellular level.
• Insulin therapy: Added when oral or injectable therapies fail to maintain glycaemic targets.

C. Adjunctive Therapies:

• Antihypertensives: Especially ACE inhibitors or ARBs for kidney protection.
• Lipid-lowering agents: Statins to reduce cardiovascular risk.
• Antiplatelet therapy: For patients with atherosclerotic disease.

3. Disease-Modifying and β-cell Protective Approach

Just as chondroprotective therapy in osteoarthritis focuses on preserving cartilage, modern diabetes care increasingly emphasizes preservation of pancreatic β-cell function and protection of target organs

Goals of β-cell Protection:

• Reduce oxidative stress and inflammation in pancreatic tissue.
• Prevent β-cell apoptosis and maintain insulin secretory capacity.
• Slow disease progression to insulin dependence

Mechanisms and Strategies:

• Early combination therapy: Reduces glucotoxicity and β-cell exhaustion.
• Use of incretin-based therapies (GLP-1 agonists, DPP-4 inhibitors): Enhance endogenous insulin production and inhibit β-cell apoptosis.
• SGLT2 inhibitors: Offer renal and cardiovascular protection, reducing long-term morbidity.
• Nutraceuticals and antioxidants: Alpha-lipoic acid, vitamin D, and omega-3 fatty acids show potential β-cell support benefits.
• Lifestyle optimization: Weight control and anti-inflammatory diets reduce stress on β-cells. This β-cell–protective paradigm represents a shift from treating glucose levels alone to modifying the disease trajectory through metabolic and organ protection.

4. Surgical Interventions

For obese individuals (BMI ≥35 kg/m²) with poorly controlled Type 2 diabetes: Metabolic or bariatric surgery (e.g., gastric bypass, sleeve gastrectomy) can significantly improve insulin sensitivity and even induce partial remission of diabetes.

1. Acute Complications:

• Hypoglycemia: Resulting from excessive insulin or medication.
• Diabetic Ketoacidosis (DKA): Life-threatening emergency, primarily in Type 1 DM.
• Hyperosmolar Hyperglycemic State (HHS): Severe dehydration and hyperglycemia, usually in elderly Type 2 DM patients.

2. Chronic Complications:

a. Microvascular:

• Retinopathy (leading cause of blindness).
• Nephropathy (progresses to end-stage kidney disease).
• Neuropathy (sensory loss, pain, autonomic dysfunction).

b. Macrovascular:

• Coronary artery disease, stroke, peripheral artery disease.

c. Foot ulcers and amputations.

d. Increased infection susceptibility due to immune dysfunction.

Primary Prevention:

• Maintain a healthy weight and active lifestyle.
• Balanced diet with reduced sugar and saturated fat intake.
• Regular screening for at-risk individuals (over 40 years, obese, family history).

Secondary Prevention:

• Early detection through fasting glucose and HbA1c monitoring.
• Aggressive management of prediabetes through lifestyle and pharmacologic intervention.

Tertiary Prevention:

• Prevent or delay complications via strict glycaemic, blood pressure, and lipid control.
• Routine annual screening for eyes, kidneys, and feet.

Seek medical evaluation if you experience:

• Persistent fatigue, thirst, or frequent urination.
• Blurred vision or unexplained weight changes.
• Tingling or numbness in extremities.
• Slow-healing wounds or frequent infections.
• Family history of diabetes and early signs of high blood glucose.
• Routine check-ups and early diagnosis are key to preventing irreversible complications.

• International Diabetes Federation. IDF Diabetes Atlas. 10th edition.
• American Diabetes Association. Standards of Medical Care in Diabetes – 2024. Diabetes Care.
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• DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88:787–835.
• Wiviott SD, et al. Cardiovascular and renal outcomes with SGLT2 inhibitors. N Engl J Med.
• Marso SP, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med.