What happens to the food we eat, once we’ve devoured it and wiped our plates clean? It gets chewed, swallowed, and pulverized, as it passes through the esophagus, stomach, and small intestine. Here, at long last, the delicious contents of our plates become things the body can use: water, electrolytes, fatty acids, amino acids, and sugars. These components then cross over from the small intestine into the bloodstream, through a variety of processes, to be utilised by different organs.
Given the largely carbohydrate-based Indian diet, the sugars are the largest end product of digestion, and the primary providers of energy. This sugar can be galactose or fructose, but largely, it is glucose.
Glucose lying around in the blood is bad for us.
There's just one tiny problem: our bodies cannot use all that glucose (or other building blocks like amino acids and fatty acids) all at once. While some is consumed by hungry cells immediately, the rest is stored either as glycogen in liver and muscle cells, or as triglyceride in fat cells. This is, in part, a simple rationing exercise; one cannot use up all energy stores in one go.
But it is also a matter of safety. Glucose lying around in the blood is bad for us. Professor and Head of Department of Physiology at Navi Mumbai’s D.Y. Patil Medical College, Dr. Vivek Nalgirkar explains why: "In the short term, the glucose gets converted to fat and causes weight gain. In the long term, it irreversibly binds with protein structures (like skin) in the body, weakening the body and accelerating ageing." So, glucose needs to be packed away safely.
Lock and key
The pancreas, tucked right behind the stomach, is responsible for detecting this excess glucose, and kickstarting the storage process. Gathered in small clusters of the organ are specialised cells called beta cells, which pick up on the high glucose levels in the bloodstream and release insulin. This hormone acts like a key, opening the doors of liver, muscle, and fat cells, and ushering glucose inside them. It was first isolated in 1921, and shortly after, in January 1922, it was administered as part of diabetes treatment for the first time.
Naturally, there are times (for example, when you skip lunch) when the body needs to dig into its glucose reserves. For this, the pancreas has a different set of specialised cells called alpha cells. They look out for low glucose levels in the bloodstream (i.e. when glucose is gone) and release a hormone called glucagon. Glucagon opens the doors in the reverse fashion, emptying glucose from the cells they are stored in, and back into the bloodstream.
Together, insulin and glucagon ensure that the blood sugar levels remain constant in the body. Too little (hypoglycemia), and your body—your brain especially—buckles under the lack of energy; too much (hyperglycemia), and the excess energy wreaks havoc on your organs.
The link to diabetes and obesity
Trouble begins to brew when insulin does not work like it is supposed to. Sometimes, the immune system thinks that the beta cells responsible for making insulin are dangerous, and destroys them. This results in Type 1 diabetes and requires patients to take insulin supplements.
The more common condition, however, is Type 2 diabetes, where the body becomes insulin-resistant. The beta cells continue to make and release insulin, but the hormone is no longer able to open the muscle, fat, or liver cells and pack away the glucose. "Think of it like trying to open a rusted lock," says preventative diabetologist Dr. Jagruti Parikh. "Naturally, the door won't open.” The ‘rusting’ could be because of various factors like excess fat, infections, or stress.
This hormone acts like a key, opening the doors of liver, muscle, and fat cells, and ushering glucose inside them
Insulin resistance contributes to obesity through various ways. Firstly, the beta cells can continue to sense excess glucose in the blood, and release higher quantities of insulin to try to counteract it. This upsets the balance that insulin and glucagon concentrations usually maintain, and this high insulin concentration is linked with obesity. Second, since the cells are starving despite abundant glucose in the bloodstream, the brain sends out hunger signals and we end up eating more. Lastly, the liver can struggle to process this extra energy and starts accumulating excess fat inside its cells, resulting in fatty liver disease. Insulin resistance is also a foundational issue causing PMOS (previously termed PCOS/PCOD).
Beta cells in the pancreas detect excess glucose in the blood and release insulin.Also read: Food fortification 101: Can foods built in with nutrients counter malnutrition, deficiencies?
The emergence of GLP-1 drugs
The miracle drug of recent times, GLP-1 (which includes the likes of Ozempic), was introduced to control diabetes through weight reduction. GLP-1 stands for glucagon-like peptide-1, and it is a hormone that exists naturally in the body. It acts in the small intestine before digestion is complete. GLP-1 receptor agonists are lab-made medications that are meant to mimic the natural hormone. The first GLP-1 drug was cleared for diabetes treatment by the US FDA in early 2005.
It performs two useful functions for diabetes patients. First, it addresses the issue of excess insulin in blood by restoring the ratio of the hormone to glucagon. "Glucagon is an antagonist (antagonists are substances that block the effect of another substance, or prevent a certain biological response), in a sense. It will normalise the glucagon-to-insulin ratio which is skewed in diabetes patients," says Dr. Nalgirkar. Secondly, GLP-1 reduces hunger at both a biological and psychological level. It affects how the brain ascertains satiety, how quickly the stomach empties food, and even how the liver performs metabolism.
The medication is only prescribed to diabetic patients who match certain diagnostic criteria. "It is never the first line of treatment," says Dr. Parikh. She stresses that GLP-1 drugs are worthless without coordinated changes in lifestyle, otherwise the lost weight will be gained back once the medication is discontinued. Given its prohibitive cost, it is also not a medication most people can afford to take for years together. Dr. Nalgirkar also warns that our understanding of the medication is still in nascent stages.
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GLP-1 drugs find alternate ways to balance blood sugar levels, but there also exists the possibility of reversing insulin resistance. Though the mechanism behind it is not fully understood yet, study after study has proved that exercise and a mindful diet makes our cells more sensitive to insulin, possibly because they increase the number of receptors (locks) on the cell’s surface.
Beneath its 'wonder drug' status, GLP-1 is simply a medication that is prescribed in specific use cases, and approached with the caution of any drug in its early years. In a fat-fearing society such as the one we inhabit, the history and purpose of the medication can serve as an important reminder to not get carried away by its promises of weight loss.
India’s diabetes burden is only growing, with a recent study finding that the country tops the Asia Pacific region in Type 2 diabetes, both in terms of absolute burden and mortality. It is imperative to focus on lifestyle, both diet and exercise, to buck the trend.
Cover art by Pratik Bhide
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