Savvy Updates, 8/16/20: Glucose-Responsive Insulin, Once a Week Basal Insulin, Precision Nutrition, The PERFECT Chocolate Chip

OK, here come some technical papers … worth reading!

1103-P: Glucose-Responsive Insulin: An Unprecedented Cleavable Linker Concept was published by Diabetes 2019 Jun, and presented as an abstract at American Diabetes Association, under Clinical Diabetes/Therapeutics.

Here we present an unprecedented GRI concept. The concept is based on the hydrolysis of a cleavable linker that is covalently bound to insulin. The chemical nature of this central linker is designed to rapidly release active insulin when glucose rises above euglycemia (5 mM), and this release of active insulin will increase with increasing blood glucose concentration. The second element of the concept is an albumin-mediated inactivation of the GRI by lipidation. After injection, the GRI will bind to albumin and circulate as a depot, resulting in a slow release of insulin like seen with other basal insulins such as insulin Detemir.

Overall, we have demonstrated the feasibility of providing a GRI approach, which combines the properties of a basal insulin with that of a bolus insulin. With the circulating depot approach the concept also holds a promise for liver preference. Ultimately our approach could provide a safe insulin for the treatment of insulin-dependent diabetes with very low risk of side effects.

Insulin Icodec – the once a week long acting insulin from Novo Nordisk was reported by Tim Street for Diabettech.com, 18 June 2020.

Novo Nordisk announced that at the end of their phase 2 trial, the once weekly insulin, Icodec had performed AS WELL AS LANTUS in their 26 week trial with 247 people with Type 2 Diabetes.

Insulin Icodec is an investigational, long-acting basal insulin analogue with a half-life of 196 hours. Yes, that’s a half life of more than 8 days. It has also gone under the name IA287 in the past, and other trials (including one in people with Type 1) can be found with this name.

Once injected, insulin icodec binds strongly but reversibly to albumin, (a similar behaviour occurs in both Detemir and Degludec, but not to the same extent). This results in a continuous, slow and steady reduction of blood sugar over the week. The injection volume of once-weekly insulin icodec is equivalent to daily insulin glargine U100 due to the concentrated formulation that it uses.

Precision Nutrition—the Answer to “What to Eat to Stay Healthy” was reported by Griffin P. Rodgers, MD and Francis S. Collins, MD, PhD for JAMANetwork.com, 7 August 2020.

Many studies have revealed profound differences among individuals in disease risk and biological responses to diet, making it challenging to fully answer this question. This necessitates moving beyond a one-size-fits-all dietary prescription for optimal health and disease prevention.

Like precision medicine, the field of precision nutrition aims to understand the health effects of the complex interplay among genetics, microbiome, antibiotic and probiotic use, metabolism, food environment, and physical activity, as well as economic, social, and other behavioral characteristics. Only with a firm grasp of the contributions and interrelationships among these factors will it be possible to develop targeted nutrition guidance for diverse individuals in a highly diverse world.

The National Institutes of Health (NIH) is leading efforts to advance the field of precision nutrition as the best strategy to catalyze nutrition science and related fields into meaningful, clinically relevant dietary solutions for both individuals and populations that share physiological, behavioral, or sociocultural features. The 2020-2030 Strategic Plan for NIH Nutrition Research promotes rigorous science to answer fundamental questions about human nutrition, including the following: the role of nutrition in promoting health and reducing the burden of disease throughout life and across generations; interactions of nutrition with other potentially modifiable exposures such as the microbiome; and how to use this holistic knowledge to develop and implement actionable recommendations.

A Tesla engineer designed the perfect chocolate chip was reported by Mark Wilson for FastCompany.com, 5 August 2020.

In the millennial-old tradition of baking, the classic chocolate chip cookie is a remarkably new invention. The cookie itself was developed around 1937 by a baker at Toll House Inn, when Ruth Graves Wakefield first decided to add a chopped chocolate bar to a cookie. They were a hit, and she sold the recipe to Nestlé in 1939. By 1941, Nestlé figured out how to mass-produce chocolate chips, a novel drop of melted chocolate that solidified into a tiny morsel. And the rest is history.

Or is it? Because nearly 80 years later, a Tesla engineer named Remy Labesque teamed up with Todd Masonis, CEO and cofounder of Dandelion Chocolate in San Francisco. The team spent three years reimagining a more perfect chocolate chip. And apparently, it’s a flat, polygonal wafer—or perhaps a square that dreams to be a diamond. Dandelion calls these chocolate bites “facets.”

While the small, round shape of chips makes it easy to mix them into batter—and their dense bottoms thwart heat in the oven to retain some of their shape—chocolate chips are a lousy delivery mechanism to tasting chocolate. Any expert will tell you that chocolate is meant to melt on your tongue luxuriously, while a chip pretty much just gets stuck in your fillings by default.

After countless sketches and many 3D-printed molds to test the flavor and sensation of different shapes, Labesque created the structure you see here. It optimizes the surface area that strikes your tongue, with two of its edges tapered so that they melt instantly. But it has enough verticality and texture that it’s more than a thin, substance-less wafer.

When you bite into one of these chips baked in a cookie, “you’re getting a nice big chunk, but it’s more a horizontal chunk if you will,” says Masonis. “We tried early taste tests. Our chocolate is honestly pretty strong, so we wanted a shape or experience that isn’t too overwhelming. This is a chunk that’s a bit more palatable.”

Most crucially, however, this design is scalable inside a factory. Despite its delicate mouthfeel, this chip can still be mass-produced in molds, and removed from them without cracking.