Welcome to the Blood Sugar Hub

Insulin binds to insulin receptor sites on the cells. This initiates signal transduction via insulin receptor substrate proteins. In insulin resistance, there is impaired activation of the Phosphoinositide 3-Kinase - Protein Kinase B Pathway (PI3K-Akt), leading to reduced Glucose Transporter Type 4 (GLUT4) translocation in muscle and adipose tissues.

The Mitogen-Activated Protein Kinase (MAPK) pathway remains active, contributing to inflammation and vascular dysfunction.

Hepatic insulin resistance leads to increased gluconeogenesis and lipid accumulation, known as Non-Alcoholic Fatty Liver Disease.

Genetic factors: Family history, polymorphisms in IRS1, PPARG, and other genes.

Obesity: Excess adipose tissue, particularly visceral fat, secretes pro-inflammatory cytokines (TNF-α, IL-6, resistin) and free fatty acids (FFAs), which impair insulin signalling.

Sedentary lifestyle: Reduced glucose uptake due to lower muscle metabolism. Dietary factors: A high intake of refined carbohydrates, added sugars and saturated fats. Fructose also contributes to hepatic insulin resistance.

Hormonal imbalances: Polycystic ovary syndrome, Cushing’s syndrome, growth hormone excess, hypothyroidism.

Chronic inflammation: Systemic inflammation contributes to insulin receptor dysfunction.

Medications: Glucocorticoids, thiazides, beta-blockers, antipsychotics.

Metabolic: Hyperglycaemia, hyperinsulinaemia, dyslipidaemia, central obesity.

Cardiovascular: Hypertension, endothelial dysfunction, atherosclerosis.

Dermatologic: Acanthosis nigricans, skin tags.

Endocrine / reproductive: PCOS, infertility, erectile dysfunction.

Hepatic: Non-alcoholic fatty liver disease (NAFLD).

Fasting insulin and glucose: Raised fasting insulin and glucose levels.

Homeostatic model assessment for insulin resistance (HOMA-IR) Oral glucose tolerance test (OGTT): Delayed glucose clearance, high insulin levels. 

Insulin tolerance test (ITT): Measures insulin sensitivity through glucose disposal rate. 

Clamp studies (gold standard): hyperinsulinemic-euglycemic clamp (assesses insulin sensitivity directly).

Type 2 Diabetes Mellitus (T2DM) begins with insulin resistance, where cells lose sensitivity to insulin, causing the pancreas to produce more. Over time, progressive β-cell dysfunction leads to insufficient insulin production, resulting in high blood sugar levels.

Cardiovascular disease: Increased risk of myocardial infarction and stroke. 

Non-alcoholic fatty liver disease (NAFLD/NASH): Can progress to cirrhosis. 

Hypertension: Enhanced sodium retention and endothelial dysfunction.

Polycystic ovary syndrome (PCOS): Hyperandrogenism, infertility. 

Neurodegenerative Disorders: Increased risk of Alzheimer’s disease (‘Type 3 diabetes’).

Diet: Low-glycaemic index, Mediterranean or ketogenic diet, and reduced sugar intake. 

Exercise: Aerobic and resistance training improves insulin sensitivity. 

Weight loss: Reduces visceral fat and pro-inflammatory cytokines.

• Regular physical activity and maintaining a healthy weight. 
• Avoid processed foods and refined sugars. 
• Early screening in at-risk individuals (e.g. obese, family history of T2DM).