337- Insulin resistance masterclass: The full body impact of metabolic dysfunction, treatment & more

A researcher at Michigan collaborating with Dr. Luke Norton on epigenetic studies of muscle insulin resistance.

A researcher whose group in Denmark showed that glucotoxicity impairs the beta cell's ability to respond to GIP, but not necessarily GLP-1.

The first SGLT2 inhibitor brought to market, whose development was influenced by Dr. DeFronzo's early work on phlorizin. Shown to lower glucose, improve insulin sensitivity, and beta cell function.

A National Institutes of Health-sponsored study that reaffirmed earlier findings that a sequential, single-agent approach to diabetes treatment (starting with Metformin and adding other drugs one by one) is largely ineffective long-term.

A journal where Dr. DeFronzo published a series of papers on glucose and phosphate transport, and later, a study with Giovan Gulli on early defects in type 2 diabetes predisposition.

A colleague in Dr. DeFronzo's division at UT, working with Steve Parker, who is using muscle insulin resistance as a specific phenotype to identify causal genes through epigenetics and single-cell analysis.

A gene that is 'pretty clear' as being causally associated with type 2 diabetes, unlike many other genes found through associations.

Referred to as the 'father of insulin resistance', Dr. Ren was one of the first people to suggest that diabetics were insulin resistant, a concept further definitively shown by Dr. DeFronzo's clamp studies.

An Italian fellow who worked with Dr. DeFronzo in San Antonio on a JCI paper identifying the earliest defects in children predisposed to type 2 diabetes.

A study that, along with the San Antonio Heart Study and VEGAS study, reproduced the finding that a 1-hour glucose level >155 mg/dL during an OGTT is a strong predictor of type 2 diabetes.

Dr. Cahill was the guest, Ralph DeFronzo's, mentor at Harvard Medical School who specialized in intermediary metabolism and greatly influenced his career path.

A physician in New York who was the first to use tritiated glucose to trace metabolic pathways, inspiring Dr. DeFronzo's use of this technique in insulin clamp studies.

One of the largest genetic studies Dr. DeFronzo was involved in 20 years ago, aiming to define genes responsible for diabetes, which found limited success with GWAS due to diabetes's heterogeneous nature.

A gene previously described by Dr. Michael Stern and others, which Dr. DeFronzo's team also found to be associated with type 2 diabetes through GWAS, though associations in non-coding regions are complex.

Another SGLT2 inhibitor mentioned alongside dapagliflozin for its ability to increase glucose excretion and improve glycemic control.

A molecule inside the cell that interacts with the insulin receptor and gets phosphorylated, initiating the insulin signaling pathway. A defect here is an early sign of insulin resistance.

A glucose transporter in the kidney that reabsorbs 90% of filtered glucose. In diabetics, it is paradoxically upregulated.

A fellow who worked with Dr. DeFronzo on early animal studies showing that SGLT2 inhibition led to normalization of beta cell function and improved insulin sensitivity.

A hypothesis that predicted SGLT2 inhibitors would be beneficial for kidney health, which has since been proven correct.

A study (2005) that, like UKPDS and GRADE, demonstrated the limitations of stepwise, single-agent diabetes treatment.

A new GLP-1 agonist from Novo Nordisk, mentioned as part of the pipeline of even more effective drugs coming soon.

A framework developed by Dr. DeFronzo in 2008 (Banting Lecture) describing eight key pathophysiological defects contributing to Type 2 Diabetes, expanding on the earlier 'triumvirate'.

Another SGLT2 inhibitor mentioned that broadly does the same thing as other sglt2 inhibitors.

A colleague of Dr. DeFronzo at UT who is involved in mapping neurocircuitry using functional MRI to understand brain dysfunction related to food intake and obesity.

An older biguanide drug that had a powerful effect on lactate levels, causing safety concerns and influencing the initial hesitation to bring metformin to the US.

An early study (1990) that showed the ineffectiveness of a sequential, single-agent approach to diabetes treatment, a finding reiterated in later studies.

A cardiovascular safety study for pioglitazone involving 5,238 participants, which showed that the drug positively impacted major adverse cardiovascular events (MACE), with weight gain being a predictor of reduced mortality.

A specific type of hexokinase (enzyme) in muscle that phosphorylates glucose upon entering the cell. Dr. DeFronzo believes a defect in this enzyme, along with glucose transport, is a primary issue in insulin resistance.

A study conducted by Professor Cahill in the mid-1960s where medical students underwent a water-only fast for 40 days to observe metabolic changes, notably the brain's continued glucose dependency.

A former fellow of Dr. DeFronzo, now back at UT, who was the first author on a paper showing that physiologic rises in free fatty acids obliterate the insulin signal transduction system.

A dual SGLT2 and SGLT1 inhibitor drug.

Co-worker of Dr. DeFronzo on the Qatar study and faculty at UT in the diabetes division, instrumental in training people in sophisticated metabolic studies.

An institution with a formal cooperative agreement with Dr. DeFronzo's team to train personnel in insulin clamp studies and advanced metabolic research.

Developed the 'disposition index' with Dr. Steven Kahn, a sophisticated measure of beta cell function.

A gold-standard technique developed by Dr. DeFronzo to measure insulin sensitivity by infusing insulin and glucose to maintain a constant glucose level while assessing glucose uptake by tissues.

A program (presumably in mice) that has documented the geroprotective nature of SGLT2 inhibitors. (The guest doesn't elaborate beyond 'ITP in mice').

A true insulin sensitizer drug that works by activating PPAR-gamma receptors, improving mitochondrial function, and redistributing fat, leading to improved metabolic outcomes despite causing weight gain.

A journal where Dr. DeFronzo published a definitive study in 2017 showing that pioglitazone improved myocardial blood flow and insulin sensitivity in the heart.

A comprehensive study, led by Dr. DeFronzo, involving 315 diabetic patients followed for 6 years, comparing a triple therapy regimen (Metformin, Exenatide, Pioglitazone) against the ADA's stepwise approach, demonstrating superior outcomes for combination therapy.

A class of drugs that increase endogenous GLP-1 and GIP levels, but are not strong enough to provide a long-lasting effect, as shown in the GRADE study.

Developed the 'disposition index' with Daniel Port many years ago, a sophisticated measure of beta cell function in relation to insulin resistance.

An incretin hormone, similar to GLP-1, released after a meal. Beta cells in type 2 diabetics are refractory to GIP, an effect linked to glucotoxicity.

A molecule that blocks both SGLT2 and SGLT1 glucose transporters in the kidney, initially studied by Dr. DeFronzo for its potential to treat diabetes by inducing glucosuria.

A fellow involved in early animal studies on SGLT2 inhibitors. Later gave a Banting lecture on the role of specific lipids (diacylglycerols) in insulin resistance via PKC activation, a mechanism of lipotoxicity.

A drug available in Europe (not US) that inhibits lipolysis, effectively lowering free fatty acid levels and improving insulin sensitivity and mitochondrial ATP generation.

An older, first-generation GLP-1 (Gen 1) receptor agonist, part of the triple therapy in the EDI Study and Qatar study, described as effective despite its age.

A syndrome mentioned as an example of a specific genetic defect in the glucose transporter of white adipose tissue, leading to diabetes, weight gain, and NAFLD (Nash).

A prospective study whose data showed that a 1-hour glucose level greater than 155 mg/dL during an OGTT is the best predictor of who will develop diabetes.

Pharmaceutical company that collaborated with Dr. DeFronzo and Bristol-Myers Squibb in the development of dapagliflozin (Farxiga).

A class of drugs in phase 2 development aimed at preserving or increasing muscle mass, particularly for sarcopenic adults. There are discussions about their functional benefits beyond just mass increase.

Referred to as a 'top guru in adipose tissue metabolism' in Dallas.

A study conducted in Qatar with 220 people with poorly controlled diabetes (average A1C ~10), demonstrating that combination therapy with exenatide and pioglitazone was significantly more effective than mixed-split insulin regimens, even for symptomatic patients.

An NIH-sponsored study showing that adolescents with diabetes are highly insulin resistant and respond poorly to current drugs, leading to early onset of complications like kidney disease and MIs in their 20s.