Current diabetes reversal programs fail to understand basics of precision nutrition

Abstract?

100 million Indians are diabetic or have risk of it while 3X of this number are unaware they already developing diabetes?

Over the last 5-7 years, we have seen a flurry of Indian healthtech startups jumping on the diabetes management bandwagon to encash & generate wealth for themselves & their investors to just manage this metabolic syndrome & suppress the symptoms of type 2 diabetes.

Unfortunately these plain vanilla reductionist biology driven diabetes reversal approaches are nothing but a financial model

“ Diabetes reversal” , a strong statement made by these companies,? is an obnoxious claim, which lacks scientific maneuvering. No wonder, there is no fall in number of people developing diabetes & those who have subscribed to these solutions have witnessed just one change” increase in spent on their healthcare cost”

These companies, without understanding of human biochemistry, have just copied models from the west & made people believe that this new toy “ Continuous Glucose Monitoring(CGM) machine is their savior”. What we have not realized is that while this device increases monthly cost of healthcare( aka sickcare) by INR 13,000(CGM strips , INR 6500-7000 per strip) + INR 4000-5000 ( nutritionist), people have not seen any improvement in their hyperglycemic condition.

In order to really regulate our metabolic health, we need to go back to basics & understand how our biochemistry works.

Let us adopt a system biology approach to decode biochemical reactions involved in onset of type 2 diabetes & elucidate why the healthtech startups offering diabetes reversal programs have failed to address the underlying issue in resolving diabetes

The Current situation

While 99.999% of people, coaches, nutritionists & healthcare practitioners may call “ insulin resistance” as the underlying cause of type 2 diabetes, the fact is insulin resistance is an effect of underlying cause- “inflammation & oxidative stress”.

Inflammation is very poorly understood by the scientific community & the focus has always been on effect- insulin resistance.

Since 2019, we have seen an influx of a bouquet of disease management startups for Indian diabetic patients.While all of them used digital advertisements to acquire customers, their marketing narrative had everything but lacked common sense & scientific literacy.

All of them propagate that they had a magic wand to reverse type 2 diabetes with false nutrition claims that “ Oh eat Peanut Butter instead of Banana to suppress blood sugar level( just an example)”.?

?Common sense questions would arise:?

-Do Bananas & peanut butter offer the same nutrients??

-Spinach is recommended as a superfood for you. What if your gut microbes cannot neutralize oxalate in spinach? It would trigger systemic inflammation which would increase risk of type 2 diabetes.

Eat pulses such as bengal gram as it is high in protein. What if your gut microbes could synthesize it into ammonia which may trigger digestive & even neurological issues?

The fact is these companies work in isolation & suppress a particular biochemical function without evaluating the impact of tens of thousands of other biochemical functions on overall physiology.

Understanding the core biochemistry missed out by these no science no tech startups

The following paragraphs will explain the science & biochemistry behind onset of type 2 diabetes & why these CGM solutions are a complete waste of time & money

1.The cellular story: Every cell inside our body has a cell membrane that maintains cell structure & fluidity. To keep a cell in homeostasis, it needs lipids, healthy fats & cholesterol. Therefore our diet should have a lot of healthy fats- saturated fats have zero double bonds & never react with oxygen while monounsaturated fats have single double bonds.?

a.Both these classes of fats as well as cholesterol are really beneficial & help cell membrane do its job. This facilitates intracellular signaling, enabling cells to sense what is outside, potentiate insulin signaling, produce nitric oxide, stimulate mitochondria biogenesis & more.?

b.However, when your dietary choices include inflammatory fatty acids & oils such as those having high amounts of Omega 6, seed oils, vegetable oils, canola oil & more, it makes your cell membrane fragile, impacts your cell structure & fluidity & prevents cells from doing its job. This directly impacts insulin signaling & disrupts nitric oxide production which triggers type 2 diabetes onset(more discussed about this in next point).?

c.While you may hear certain trainers promote these oils propagating that these oils are not overheated, the fact is the way these oils are produced & processed involve a lot of toxic chemicals which are heated beyond our imagination & even a 2 teaspoon of oil is sufficient to react with oxygen & cause oxidative stress.?

d.Besides, these chemicals stay in your body for a long time further triggering oxidative stress & systemic inflammation. This oxidative stress oxidizes certain enzymes, proteins & a co-factor required for nitric oxide production- Tetrahydrobiopetrin which shuts down nitric oxide production, resulting in low glucose uptake & creates a vicious cycle of hyperglycemia.

We did a talk on inflammatory oils a few months back. A must listen: https://www.youtube.com/watch?v=Re8BwOQfd4E

2.Nitric oxide Production: Nitric oxide is a signaling molecule, a gas which plays a key role in various biochemical processes. It sends biochemical signals to various cells, tissues & organs in the body to perform various processes.?

• Facilitate how our cells inside the body communicate
• Dilate blood vessels & control oxygen & nutrient uptake & delivery in every cell
• Controls cellular respiration
• Regulates mitochondrial biogenesis & ATP production
• Regulates insulin signaling
• Promotes blood flow
• Controls length of telomeres which predicts longevity
• Improves exercise performance

There are two pathways our body produces nitric oxide.?

a.Endothelial nitric oxide synthase enzyme(eNOS), when coupled with endothelial cells, synthesizes L-arginine, produced inside our body via Urea Cycle, into Nitric oxide & L-citruline. Oxidative stress & gut/oral microbiome induced inflammation can uncouple this enzyme & disrupts the production of nitric oxide. Besides overconsumption of L-arginine creates a competition between L-arginase & eNOS & the enzyme produces superoxide instead of nitric oxide, causing oxidative stress which further disrupts nitric oxide production via oxidation of tetrahydrobiopterin(BH4).

b.The most important pathway is the oral microbiome. Microbes in your mouth synthesize nitrate in green vegetables into nitrite which mixes with? stomach acid to produce nitric oxide. The remaining nitrite is oxidized into nitrate which is again synthesized into nitric oxide. A lot of it is stored in the salivary gland.

Nitric oxide is the most important molecule to prevent the onset of type 2 diabetes.?

The following chronological process explains this nitric oxide driven insulin signaling

1. We ingest a meal which is predigested by microbes in our mouth. These microbes send a biochemical signal via metabolite to pancreas to be ready to release insulin.
2. Pancreas releases insulin which binds to insulin receptors on most cells but specifically fat cells, liver cells & muscle cells which starts intracellular cascades & activates AMP Kinase & PI3 ATP Kinase
3. As a terminal step, AMP Kinase/ PI3 ATP Kinase will communicate with ENOS to activate protein GLUT4 which will go to the cell membrane, bind to glucose & remove it from circulation by transporting it to cells for storage or energy.
4. Activating GLUT4 needs a signal. This signal is nothing but nitric oxide.
5. If eNOS is uncoupled due to oxidative stress or gut microbiome driven inflammation or there is low nitric oxide production due to oral microbial dysbiosis, the process of glucose transport is impaired. This raises glucose level, leading to hyperglycemia
6. Pancreas senses it & releases more insulin. What happens next is a vicious cycle, triggering wave of hyperinsulinemia & hyperglycemia, causing insulin resistance & type 2 diabetes

If you consume a lot of inflammatory oils or sugar, it causes oxidative stress which shuts down nitric oxide production via the eNOS pathway. If you use mouthwash,fluoride laden toothpaste or? consume lot of artificial sweeteners, it causes oral microbial dysbiosis & disrupts nitric oxide production

The real science based mechanism behind precision nutrition?

While we have been told that nutrition is all about calorie counting & macros- protein, carbs & fats, the scientific concept of nutrition goes beyond these macros. The entire nutrition ontology is a combination & warehouse of 35000 plus molecules & substrates. When we ingest a meal:

1. Flood of these molecules first interact with microbes in our mouth who pre-digest & pre-process these molecules & send biochemical signals to various organs including gut microbes, pancreas & more, communicating what is coming their way.
2. This helps some of these molecules to be easily absorbed in the small intestine.
3. The larger chunk of molecules moves to the large intestine where they interact with millions of microbial strains( 1000 species with each species having multiple strains). Each of the microbes senses each of these molecules & expresses a particular gene/set of genes that perform a particular function( activates a protein) & synthesize these molecules into chemical byproducts.?
4. These byproducts are either nutrients or certain toxins & inflammatory metabolites which overactivate immune system, trigger inflammation & result in insulin spike. This insulin spike is the first stage of type 2 diabetes. Unfortunately, none of these CGM machines can identify this insulin spike.?
5. As we consume different foods during the course of the day & months,? composition & biochemical functions performed by our gut microbiome changes & therefore a particular molecule in a food which was giving you nutrients earlier now starts triggering inflammation & leads to insulin spike.

Understanding & measuring these thousands of biochemical reactions is key to decode which specific foods we should consume & which ones we should avoid.

Continuous Glucose Monitoring(CGM) Machine- a complete financial model

Onset & progression of type 2 diabetes kick starts decades before Hba1c spikes. Systemic inflammation( caused by gut & oral microbiome) created a situation when first the insulin spike, then glucose spikes & finally Hba1c spikes. The focus should always be to prevent insulin from spiking in the first place.

A continuous glucose monitoring machine uses a sensor that measures the glucose spike in the bloodstream in response to consumption of a particular meal. In practical terms, we always consume a meal- we do not say, first I will consume pulses, then rice, then vegetables. We consume all of this together. As such CGM does not measure response to a particular food

Besides, you may experience an insulin spike due to consumption of certain amino acids which is caused via inflammatory byproducts such as P-cresol( gut microbial metabolism of tyrosine). Unfortunately, CGM cannot identify this insulin spike as it just looks at pressure in the blood stream.

The following flaws in CGM makes it an unpleasant experience for you with no improvement in hyperglycemic situation

1. It does not measure glycemic response to some specific molecules in a particular food or combination of certain molecules in different foods.
2. Your gut microbiome functions & composition changes with your dietary intake every month or quarter & therefore your glycemic response to different molecules in food changes. CGM will tell you glycemic response in a particular meal in a particular month however next very month, the response will change & a food that was good for you? may immediately lead to insulin spike.?
3. This means that to track the glycemic response you have to continuously wear the CGM, necessitating an additional cost of US $ 180-US $ 220 on a monthly basis without any insight into why a particular food caused a spike which was healthy earlier.?
4. CGM can never measure the cellular response of consumption of different types of fats. Therefore you may have a spike to consumption of particular food but your CGM will never be able to tell if its gut microbiome driven LPS production, Fucose or oral microbiome/cellular fragility driven low nitric oxide production?

The human body is the most complex biochemical machinery & in order to identify which specific foods you should consume & which you should miss at a particular point in time, you need to understand & measure these thousands of biochemical functions. No coach, nutritionist of CGM can tell you what should be part of your diet.

We at Genefitletics, are India’s first biotech company that collects & analyzes your molecular data to measure each of these biochemical functions to construct data driven nutrition interventions that regulates your glycemic response. We have built a machine learnt model that predicts insulin response to 300 plus foods based on functional activity of your gut & oral microbiome. More details here: https://genefitletics.com/

Citations?

1.https://www.fda.gov/medical-devices/safety-communications/do-not-use-smartwatches-or-smart-rings-measure-blood-glucose-levels-fda-safety-communication

2.https://theprint.in/health/using-smartwatch-to-monitor-blood-glucose-level-us-fda-strongly-advises-against-it/1980140/?amp

3.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927936/

4.https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1119201/full

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749361/

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