Dr. Ralph DeFronzo - Father of current day Diabetes Management....

I don't lecture as often as I would love to.....and this is driven by a host of reasons including lack of time, breaks in the day-to-day continuity (since these are adhoc engagements) and what my #Mentor calls Impassioned Buoying - his polite way of pointing out how I tend to get carried away when confronted with the enticing combination of an engaging topic, an engaging audience and a microphone!!!

However, sometimes, I get roped in for spur-of-the-moment events and sessions.....and if I have time in hand, I usually accept.....this was one of them.

It started off with a startup asking me to conduct an orientation for its Healthcare Data Analytics team - their topic of interest was Diabetes Mellitus (Type 2).....and I was chosen because of a combination of factors including unnamed references (though I don't know them, they have my gratitude), my "prolific" presence on LinkedIn (whatever that means, it was said politely, so....) and their insistence to make it less about the clinical and more about the human aspect - touching on the #Innovation side would be a great add-on!

So, after thinking for a day, I decided to talk about the requested, opening a 2 hours session: 90 minutes of discussions led by me followed by 30 minutes of question time!

After the introductions were done (audience comprised of 1 VP, 1 Co-founder, and 25 Data Analytics professionals with varying levels of control and experience in all things numbers!)......I started off with the usual about how T2DM is a menace of epic proportions, the statistics of disease burden, and the compounding effect of covid2019 and the ageing population confronted with poor reimbursement, poorer access and a clinical pool that is short-staffed, short in supply, and tetering on the brink of burnout!

Then, I followed up with the therapies and their basis of use, feeling unsure if I was already in "Impassioned Buoying" mode! That's when, 40 minutes later, the moderator pinged about "making it less clinical and more interesting with a slant on innovation"....so, I introduced them to Dr. Ralph DeFronzo.

Here's a summary of what made my brilliant audience (a little) happier than (they were) 40 minutes ago......

"Diabetes mellitus, at its core, is a consequence of Insulin resistance afflicting the triad comprising of:

1. The beta cells of the pancreas (progressive dysfunction & failure starts fairly early in the course of the disease)

2. The muscle cells (impaired glucose uptake after a meal containing carbohydrates)?

3. The hepatocytes.

Besides impaired glucose uptake mainfested by the foregoing, there is:

4. Accelerated loss of Adipocytes (lipolysis) which makes the patient lose weight and girth

5. Incretin deficiency (or resistance) in the GI tract

6. Incretin deficiency (or resistance) in the brain. The brain's inability to leverage (or respond to) incretins lead to the brain cells' inability to process glucose, causing starvation and death - while this is amenable to alternative sources of fuel (like Medium Chain Triglycerides), the usage has to be monitored carefully since the liver is not functioning either normally or optimally

7. Onset of hyperglucagonemia (caused by dysfunctioning alpha cells of the pancreas) makes the already affected mechanism and function of insulin comparatively ineffective

8. An effect on the Kidney, resulting in an increased reabsorption of glucose, affecting not just structural and functional integrity but overall wellbeing as the glucose now stays in the bloodstream, reaching other sensitive organs in higher concentration."

I quickly explained that in a diabetes patient, the foregoing (except #1) lay stress on functioning Beta cells and they respond by producing progressively more insulin (till eventual failure - a burnout/breakdown in lay terms).

For Dr. DeFronzo's cue, I stated, "BTW, the above 8 are recognized as the Ominous Octet of Type 2 Diabetes mellitus (Dr. Ralph DeFronzo, 2008)."

Just for complete context, I also pointed out that the top three represent the Triumvirate of Type 2 Diabetes (T2DM).

Moving on, I conveyed that thanks to elucidating the above eight and a decades-long pursuit of managing Diabetes patients, Dr. DeFronzo - whom many regard as the "Father of current-day Diabetes" - was awarded the Prince Mahidol 2022 Award in Medicine in Jan. 2023!

Here's a summary of the highlights from Dr. DeFronzo that I shared:

"As of today, it is globally acknowledged that Dr. DeFronzo proposed the link between insulin resistance, atherosclerotic cardiovascular disease, and Diabetes.

This was later proved by the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) trial conducted in Drug-na?ve new patients"...(readers can see it here: https://clinicaltrials.gov/study/NCT01107717).

Here, I talked about how being a rare, gifted and prolific intellectual, Dr. DeFronzo started making outstanding contributions early on, talking about the following:

In 1975, Dr. DeFronzo kicked off an outstanding run with the innovation of the Insulin Clamp - the gold standard for assessing Insulin Sensitivity - the hallmark for glycemic status in both norml and affected individuals.

Around 1995, Dr. DeFronzo's research was instrumental in giving the world Metformin - a first-line pharmacotherapy that inhibits hepatic glucose production, lowering HbA1C.

Around 2012, Dr. DeFronzo gave the world Dapagliflozin besides a formidable volume of translational research for the entire SGLT-2 inhibitor class that carried them from pre-clinical bench to patients hands. His research was in collaboration with #AstraZeneca, making #dapagliflozin the first SGLT-2 inhibitor ever approved (in 2012 in the UK, in 2014 in the US).

I also pointed out that it stands to Dr. DeFronzo's and AstraZeneca's credit that a renoprotective glycemic controller like Dapagliflozin was approved - a novel approval for Type 2 Diabetes after nearly two decades!

In 2021, the EDICT results were published, vindicating Dr. DeFronzo's assertion that the three pathological factors (insulin resistance, atherosclerotic cardiovascular disease, and Diabetes) should be tightly managed right from the beginning in patients of T2DM.

In 2022, the American Diabetes Association declared support for combination therapy in managing T2DM,quoting EDICT (and VERIFY : https://clinicaltrials.gov/study/NCT01528254 for readers)!

I also touched upon how Dr. DeFronzo's contributions have been acknowledged globally, represented by an array of awards and recognitions including those from both the ADA and the European Association for the Study of Diabetes!

As I closed, I got a few applause icons (17 at last count, I think).....and quite a few questions, including about my latest posts on #Semaglutide.....

Then, came an observation that I didn't have a redy answer to:

"Sir, it makes one wonder.....would a Nobel Prize have been too out of place for Dr. DeFronzo?"

Thankfully, the moderator closed before the buoying could kick in.....

An hour ago, I was assured by the VP that my inputs were well received by the team....and Dr. DeFronzo was Googled quite a bit!

So, what was your Saturday like?????

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