Insulin Resistance: The root of many diseases

Time of India

2 days ago

Lalit Kapoor is a 1971 graduate from IIT Kanpur and has done his MBA from UCLA. Lalit is a successful serial entrepreneur in Silicon Valley. With age, he developed lifestyle diseases and decided to reverse them by changing diet and lifestyle. This led him to study and research in the field of nutrition and plant-based whole food field. Eventually, he successfully got rid of all his chronic diseases and reinvented himself. Lalit became an inspiration for his IIT-K batch mates and started to guide them with his learnings. Many of them benefitted and successfully reversed their chronic diseases. He further incorporated the Nobel prize winning work by Nobel laureates Dr Yoshinori Ohsumi (2016) on autophagy, Dr Jeffery Hall (2017) on circadian rhythm and Dr Tasuko Honzo (2018) on immunotherapy into his recommendations. He has conducted over 450 course sessions which have been attended by over 150,000 people in over 50 countries with thousands of success stories. He runs over 100 active social groups and his NGO 'Plant Based Wellness Foundation' has over 40 centers worldwide. Lalit has also taught a course as a visiting faculty on Nutrition & Health at IIT Kanpur for one semester. LESS ... MORE
Insulin resistance is the most common metabolic disorder—and one of the least understood. It's often seen as incurable, with treatment focused narrowly on cutting carbs or controlling blood sugar. But insulin resistance is not just a blood sugar problem; it's a systemic issue that affects nearly every major organ in the body.
At its core, insulin resistance is the body's response to chronic sugar overload—especially glucose and fructose. A healthy body contains about 3 grams of glucose in the 5 liters of blood and stores roughly 1,500 calories in muscles and 500 in the liver. Any excess is stored as fat. Fructose and alcohol burden the liver disproportionately, since only the liver can process them.
When people hear 'insulin resistance,' they usually think of type 2 diabetes. But it's also the root cause of many other chronic conditions. This blog explores how insulin resistance operates systemically and underlies numerous diseases.
What is insulin resistance?
Insulin is a hormone produced by the pancreas that helps regulate blood sugar. After we eat, insulin is released into the bloodstream, where it allows glucose to enter cells for energy or storage. Insulin also tells fat cells to store fat when energy is abundant.
In healthy individuals, this system works efficiently. But when cells become resistant to insulin's signal, glucose can't enter as easily. The pancreas compensates by producing more insulin. Over time, this leads to chronically high insulin levels, even if blood sugar appears normal.
One major consequence is disrupted fat metabolism, particularly in visceral fat, which surrounds internal organs. In insulin-resistant individuals, fat cells begin releasing stored fat into the bloodstream instead of holding onto it. Since muscle cells often don't need that fat, it recirculates until the liver processes it. The liver repackages the fat into triglyceride-rich lipoproteins and sends it back out—creating a harmful cycle known as hypertriglyceridemia, a key marker of insulin resistance.
In short, insulin resistance disrupts both glucose and fat metabolism, setting the stage for multiple health issues.
Diseases linked to insulin resistance
Insulin resistance occurs in different tissues and causes different diseases depending on where it manifests:
Liver → Type 2 Diabetes
→ Type 2 Diabetes Ovaries → PCOS
→ PCOS Heart → Cardiovascular Disease
→ Cardiovascular Disease Brain → Alzheimer's Disease
This region-specific nature helps explain the wide variety of disease presentations rooted in the same metabolic dysfunction.
Types of insulin resistance
Insulin resistance comes in several forms, each with distinct underlying mechanisms. Two primary types include:
1. Internal starvation
This form is marked by high blood glucose but low glucose within muscle cells. Insulin receptors malfunction, preventing glucose uptake despite adequate insulin levels. Individuals are often lean and do not have fatty liver. Weight loss doesn't improve the condition. Though not overeating, these individuals often consume refined carbs and sugary drinks, leading to liver fat buildup and visceral fat through rapid fructose metabolism.
2. Overflow paradigm
This form occurs when cells are so full of energy that they reject more glucose. It's common in individuals with obesity and fatty liver. Weight loss usually improves insulin sensitivity.
Other mechanisms include:
Inflammation-induced resistance – Chronic inflammation impairs insulin signaling.
– Chronic inflammation impairs insulin signaling. Lipotoxicity – Excess fatty acids damage the liver and pancreas.
– Excess fatty acids damage the liver and pancreas. Mitochondrial dysfunction – Poor energy production increases insulin resistance.
– Poor energy production increases insulin resistance. Hormonal imbalance – Conditions like PCOS and Cushing's syndrome alter insulin dynamics.
– Conditions like PCOS and Cushing's syndrome alter insulin dynamics. Genetic factors – Rare inherited forms of insulin resistance also exist (e.g., Type A insulin resistance, Donohue syndrome).
These types often overlap, particularly in complex conditions like type 2 diabetes and metabolic syndrome.
What causes insulin resistance?
There are three primary causes of insulin resistance, each driven by different mechanisms:
1. Overloaded subcutaneous fat: Subcutaneous fat (under the skin) can buffer excess calories, but only up to a point. Once its storage capacity is exceeded, fat starts accumulating in places it shouldn't—like the liver and muscles—leading to insulin resistance. This explains why some people can be obese and still metabolically healthy—until this threshold is crossed.
2. Stress and hormonal imbalance: Chronic stress triggers cortisol, which can induce insulin resistance even in the absence of overeating. Patients with clinical depression, for example, often lose subcutaneous fat but gain visceral fat. This type of insulin resistance isn't food-driven, but hormonally driven, similar to what's seen in Cushing's Syndrome.
3. Fatty liver (Non-alcoholic fatty liver disease)
NAFLD affects about 45% of Americans and nearly 25% of the global population. Fat accumulation in liver cells interferes with insulin's ability to function. The liver is 'ground zero' for insulin resistance—explaining why even lean individuals can develop the condition. It also highlights that insulin resistance is not solely a byproduct of obesity. This distinction is crucial. Obesity is increasing globally at 2.78% per year, while diabetes is rising at 4.07%. If diabetes were merely a function of obesity, the rates would track each other. Clearly, there is more to the story.
Insulin resistance and muscle performance
Insulin resistance also compromises muscle health in several important ways:
Reduced glucose uptake – Less energy available for muscle performance. Slower recovery & growth – Impaired protein synthesis delays muscle repair and limits development. Increased fatigue – Muscles switch to slower fat metabolism, leading to early exhaustion. Inflammation – Chronic low-grade inflammation increases soreness and slows recovery. Muscle loss (Sarcopenia) – Over time, insulin resistance accelerates muscle breakdown, reducing strength and coordination.
How to reverse insulin resistance
To improve insulin sensitivity, we must first stop making it worse. Here's how:
Diet and nutrition
Eliminate refined and ultra-processed foods.
Minimise or avoid animal products, including dairy.
Focus on whole, complex carbohydrates.
Exercise
Walk regularly (aim for ~10,000 steps/day or equivalent activity).
(aim for ~10,000 steps/day or equivalent activity). Strength training enhances glucose uptake by muscles independently of insulin.
enhances glucose uptake by muscles independently of insulin. Aerobic exercise boosts mitochondrial function and fat-burning capacity.
Lifestyle
Prioritize sleep (aim for 8 hours of quality rest).
Manage stress, as chronic cortisol impairs insulin sensitivity. Yoga, Pranayama and meditation can help.
Time-restricted eating (Intermittent fasting)
Arguably, the most powerful intervention for reversing insulin resistance is reducing the eating window. Humans evolved eating only during daylight—usually after sunrise and before sunset. However, in the modern world after the advent of electricity, we have increased this window to 14-16 hours. This is too long and reduces insulin sensitivity. Reducing the eating window to 8–10 hours, such as in the 16:8 intermittent-fasting regimen, allows the liver to burn through its limited glycogen stores (~125g or ~500 calories) in about 12 hours. After that, the body shifts to burning fat, including the harmful fat stored in the liver and muscles, that contributes to insulin resistance. This switch to fat-burning helps clear the very lipids that block insulin receptors, restoring proper insulin function.
Final thoughts
Insulin resistance is not just about blood sugar—it's about systemic dysfunction that affects nearly every major organ. The good news is that it is reversible. Through a combination of intermittent fasting, whole-food plant-based nutrition, regular physical activity, adequate sleep, and stress reduction, insulin sensitivity can return. In my experience, many patients with Type 2 diabetes see marked improvements within 4–6 weeks using a consistent 16:8 fasting protocol. It is time to shift the conversation from just managing diabetes to actually reversing insulin resistance at its root.
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Views expressed above are the author's own.