Chai Shots #006: The Signal Fire and The Missing Mechanics
The Double Hit of Inflammation and Failed Repair in South Asians
Welcome back to Chai Shots, a series where we distill the latest science on South Asian health optimization.
In previous editions, we’ve been building a map of the South Asian metabolic phenotype. We’ve talked about the Fragile Engine (our smaller pancreatic beta-cell reserve), the Overflow Tank (our limited capacity to store fat safely), and the Adiponectin Deficit (the missing metabolic brake).
Today, we are adding two critical new pieces to this puzzle, courtesy of research published just this past year. If you’ve ever wondered why heart disease seems to strike the South Asian diaspora so aggressively, often decades earlier than our neighbors, these two papers provide deep insight.
It turns out we aren’t just fighting a fragile engine. We are fighting a system that is constantly overheating (inflammation) while running with a depleted pit crew (repair cells).
Grab some chai.
Paper No. 1: The Signal Fire (IL-6)
Title: Ethnic differences in the association between interleukin-6 and the risk of type 2 diabetes
Authors: Henson, J. et al.
Journal, Year: eBioMedicine (The Lancet), 2025
Understanding why inflammation drives diabetes faster in South Asians.
What They Found:
We have known for a while that Type 2 Diabetes is an inflammatory disease. But this study clarifies how that inflammation differs for us. The researchers found that South Asians have significantly elevated baseline levels of Interleukin-6 (IL-6) compared to White Europeans.
The study established that each standard deviation (SD) increase in IL-6 was associated with a 47% higher risk (HR 1.47; 95% CI 1.32–1.64) of developing type 2 diabetes in the fully adjusted model for the entire cohort.
For South Asians specifically, higher IL-6 levels were strongly predictive of diabetes onset, reinforcing inflammation as a key driver of metabolic risk in the population.
Why It Matters:
Think of Il-6 as a “signal fire.” In the short term (like during exercise), it’s good, it mobilizes energy. But when it’s chronically elevated at rest, it’s a distress signal. It tells your body it’s under attack.
For South Asians, this chronic IL-6 elevation is likely coming from that “overflowing” visceral fat we’ve discussed. This fat isn’t just sitting there; it is biologically active tissue pumping out inflammatory signals. This constant background noise of inflammation desensitizes your insulin receptors. It effectively “jams” the signal between your insulin and your cells, forcing your already Fragile Pancreas to work double-time to compensate.
Paper No. 2: The Missing Mechanics (Vascular Regenerative Cells)
Title: Vascular Regenerative Cell Deficiencies in South Asian Adults
Authors: Krishnaraj, A., Verma, S., et al.
Journal & Year: Journal of the American College of Cardiology (JACC), 2024
Why our blood vessels age faster.
This might be one of the most important papers of the decade for South Asians.
What They Found:
The researchers looked at Endothelial Progenitor Cells (EPCs). Think of these cells as your body’s “road repair crew.” When a blood vessel gets damaged (by high sugar, pressure, or inflammation), these cells rush in to patch the pothole and heal the lining.
The study found that South Asians have markedly lower frequencies of these regenerative cells compared to White Europeans. Specifically, South Asian participants had 23% fewer pro-angiogenic progenitor cells (measured as ALDHhiSSCmidCD14+CD163+ cells), even after adjusting for age, BMI, and glucose levels.
Furthermore, the cells we do have are less functional, they are essentially “tired mechanics.” This deficit was observed even in South Asians without established cardiovascular disease, suggesting it is an intrinsic vulnerability rather than just a consequence of illness. It fundamentally challenges the idea that our heart risk is solely due to lifestyle, pointing instead to a compromised biological repair system.
Since we can’t easily measure these “repair crew” cells directly yet, keeping an eye on markers like hs-CRP (inflammation) and microalbumin (vessel leakage) can serve as a practical proxy for this hidden damage.
The South Asian Connection:
This explains the “accelerated aging” we see in South Asian heart health.
In a typical body, damage happens, and repair happens. It’s a balance.
In the South Asian body, we have a Double Hit:
High Damage: The elevated IL-6 and insulin resistance cause constant wear and tear on the vessel walls.
Low Repair: The repair crew (EPCs) is understaffed and overwhelmed.
The result? The potholes don’t get fixed. Plaque builds up faster. Arteries harden earlier.
This is why a South Asian male in his 40s might have the vascular age of a European male in his 60s.
The Burn and Crash Model
When we integrate these findings into our Zinda Framework, the full picture of our metabolic risk emerges not as a list of symptoms, but as a sequential chain of events:
Fragile Engine: We begin with a smaller beta-cell reserve.
Overflow Tank: Subcutaneous fat capacity is limited, causing early visceral spillover.
Signal Fire: This visceral fat releases excess IL-6, causing chronic inflammation that blocks insulin signaling.
Repair Deficit: When blood vessels are damaged by this inflammation, we lack the regenerative cells (EPCs) needed to fix them efficiently.
This isn’t a defect; it’s a mismatch. Our biology is optimized for a low-inflammation, high-activity environment, and it is colliding with a modern world that offers neither.
Why Zone 2 Works (A Deeper look at The Physiology)
A great way to fix this is zone 2 cardio. Yes, we’ve mentioned it a few times and countless times do we hear this said. But why? Intentionality is vital.
To understand why Zone 2 cardio is non-negotiable for our phenotype, we have to look at the source of the static. The Signal Fire isn’t just abstract inflammation, it is a physical distress signal originating from overflowing visceral fat. This tissue is not inert energy storage. It’s biologically active, pumping out cytokines like IL-6 that desensitize your insulin receptors and jam the communication lines between insulin and your cells.
Because of this the phenotype’s tendency to accumulate this specific type of fat earlier and at lower body weights, we create a much longer and pronounced period of inflammation than other populations.
Zone 2 cardio, performed at 60 - 70% of your maximum heart rate, functions as the drainage mechanism for this reservoir of visceral fat. Unlike high-intensity intervals which primarily burn glycogen, Zone 2 intensity maximizes fat oxidation and upregulates mitochondrial transporters like CPT1A. These transporters act like gates, allowing lipids to move into the mitochondria to be burned. By draining the fuel source of the signal fire, we lower the baseline “background noise” of chronic IL-6.
This creates a critical distinction between “good” and “bad” inflammation.
The chronic IL-6 from visceral fat is a distress signal indicating the body is under attack. However, the acute release of IL-6 during exercise is a healthy metabolic trigger.
The goal of Zone 2 is to silence the chronic noise so that the body can once again “hear” the acute, healthy signals of exercise and insulin, effectively unclogging the jammed signaling pathways.
And thats Zone 2.
-Omar
Dr. Omar Saleem is a double board-certified physician dedicated to health optimization, especially within the South Asian community. He runs Zinda - A South Asian Health Initiative, building the framework for South Asian precision medicine.