Biochemistry of Diabetes & Why It’s Increasing in India

 

Biochemistry of Diabetes & Why It’s Increasing in India

Diabetes mellitus is one of the most significant metabolic disorders affecting India today. At its core, diabetes is a condition of impaired glucose homeostasis, resulting either from insufficient insulin production or reduced tissue response to insulin. Understanding the biochemical basis of diabetes helps explain both how the disease develops and why its prevalence is rising rapidly in India.

I. Biochemistry of Diabetes

1. Role of Insulin in Glucose Homeostasis

Insulin, produced by the β-cells of the pancreas, is central to regulating blood glucose levels. Its major biochemical actions:

• In the liver
• Decreases gluconeogenesis
• Promotes glycogen synthesis
• Inhibits glycogen breakdown
• In muscle
• Facilitates glucose uptake via GLUT-4 transporters
• Enhances glycogen formation and protein synthesis
• In adipose tissue
• Stimulates lipogenesis
• Inhibits hormone-sensitive lipase, reducing lipolysis

When insulin levels fall or tissues become resistant, these biochemical pathways malfunction, raising blood glucose.

2. Type 1 vs Type 2 Diabetes – Biochemical Differences

Feature	Type 1 Diabetes	Type 2 Diabetes
Cause	Autoimmune destruction of β-cells	Insulin resistance + β-cell dysfunction
Insulin levels	Very low/absent	Normal or high initially, later low
Metabolic issues	Hyperglycemia, ketosis	Hyperglycemia, hyperinsulinemia, dyslipidemia
Biochemical hallmark	Fat breakdown → ↑ ketone bodies	Impaired insulin signaling pathways (IRS/PI3K/AKT)

 

 

3. Insulin Resistance – Core Biochemical Defect in Type 2 Diabetes

Insulin resistance means cells do not respond effectively to insulin, especially:

• ↓ activation of insulin receptor substrate (IRS-1)
• ↓ PI3K/AKT pathway activation
• Reduced GLUT-4 translocation to the cell membrane
• Increased free fatty acids (FFAs) interfere with signaling
• Chronic low-grade inflammation (TNF-α, IL-6) further impairs pathways

This combination leads to chronic hyperglycemia.

4. Biochemical Consequences of Chronic Hyperglycemia

Long-term uncontrolled glucose leads to:

a. Formation of Advanced Glycation End Products (AGEs)

• Glucose binds non-enzymatically to proteins
• Alters protein structure and function
• Damages blood vessels → retinopathy, nephropathy

b. Activation of the Polyol Pathway

• Excess glucose converted to sorbitol
• Causes osmotic stress in nerves, eyes, kidneys

c. Oxidative Stress

• High glucose increases reactive oxygen species (ROS)
• Damages cells, accelerates aging and inflammation

d. Dyslipidemia

• ↑ triglycerides
• ↑ VLDL
• ↓ HDL
• Contributes to cardiovascular risk

II. Why Diabetes Is Increasing in India

India is called the Diabetes Capital of the World, and the numbers continue to rise sharply. The reasons include a mix of genetic, lifestyle, nutritional, and socio-economic factors.

1. Genetic Predisposition

Indians have:

• Lower β-cell reserve
• Higher tendency for abdominal fat accumulation
• Genetic variants (TCF7L2, FTO) linked to insulin resistance
• “Asian Indian Phenotype”:
• Higher body fat % even at normal BMI
• Higher triglycerides
• Lower HDL

This means Indians develop diabetes at younger ages and lower weights than Western populations.

2. Rapid Urbanization & Sedentary Lifestyle

• Decrease in physical activity
• Increase in screen-time and desk jobs
• Limited access to open spaces

Low physical activity directly reduces GLUT-4 expression in muscle → increased insulin resistance.

3. Dietary Changes

Modern Indian diets have shifted to:

• High refined carbohydrates (white rice, maida-based foods)
• High sugar consumption
• Low fiber
• High fried and processed foods

Such diets cause repeated insulin spikes → β-cell exhaustion.

4. Rise in Obesity — Especially Central Obesity

Abdominal (visceral) fat secretes inflammatory cytokines:

• TNF-α
• IL-6
• Resistin

These impair insulin receptor signaling → insulin resistance.

Even people with normal BMI but high waist circumference (common in India) are at risk.

5. Stress & Sleep Deprivation

Chronic stress increases cortisol, which:

• Stimulates gluconeogenesis
• Raises blood glucose levels
• Promotes abdominal fat storage

Modern work hours also reduce sleep → disrupts insulin sensitivity.

6. Environmental & Epigenetic Factors

• Exposure to endocrine disruptors (plastics, pollutants)
• Maternal malnutrition → “thrifty phenotype”
• Early childhood undernutrition linked to adult diabetes

These alter metabolic pathways over generations.

7. Increased Lifespan

More people living longer → more people crossing the age threshold where diabetes risk increases.

8. Underdiagnosis and Delayed Treatment

Many individuals remain undiagnosed for years because:

• Limited screening
• Low awareness in rural areas
• Symptoms often ignored

Prolonged undetected hyperglycemia → increased national burden.

Diabetes in India is rising due to a combination of biochemical, genetic, lifestyle, and environmental factors. While genetics predispose Indians to higher risk, rapid changes in diet, physical activity, urbanization, and stress have accelerated the epidemic.

Understanding the biochemistry behind diabetes helps in recognizing early signs, promoting lifestyle changes, and implementing preventive strategies. As India modernizes, active health awareness and metabolic well-being must grow alongside.