How Blood Sugar Stays Steady — A Letter to Store, a Letter to Release

A Value That Does Not Run Out Even When You Starve and Sleep

You eat breakfast, eat a late lunch, and go to sleep after eating dinner. While you sleep, you eat nothing for nearly ten hours. Yet, when you draw blood the next morning, the sugar in your blood has not run out, nor is it as high as it was right after dinner the previous night. Blood glucose is the amount of sugar dissolved in your blood. It is that value that always occupies a single line on your health checkup report chart.

How blood glucose actually moves throughout the day can be measured continuously with a sensor attached to the body. When 153 people aged 7 to 80 without diabetes and without obesity lived with such sensors attached for up to ten days, their blood glucose stayed between 70 and 140 mg/dL for 96% of the day (median) (PMID 31127824). This means that for most of the day, the value was within a narrow band, and the time spent outside that band was a few tens of minutes a day.

The first reason the body keeps this value tightly held is the brain. The brain is an organ that works without rest, but it has almost no fuel stored on its own, so it works by relying on sugar carried in the blood (PMID 9642647). Since the fuel the brain normally uses is practically this sugar alone, the supply through the blood must not be cut off (PMID 10500926). However, there is also evidence that when sugar is scarce, the brain can use some alternative fuel (PMID 9642647).

There is also the opposite end. Because blood vessels and tissues are harmed if blood glucose spikes significantly, the body also reduces the amplitude by which blood glucose rises after eating (PMID 33419065). Whether sugar comes in all at once from a large meal or a lot of sugar is used in intense exercise, the body returns that value back within a narrow range (PMID 8379904).

In a healthy body, blood glucose goes up and down, but it goes up and down within a narrow band. This article deals only with the normal operation that guards that band. Diabetes, the case where that operation is broken, is the job of the articles that follow.

Letters, Postal Routes, and Two Letter-Sending Cells

The "sugar" in blood sugar is mostly glucose. Glucose is a sugar created as carbohydrates in rice, bread, and fruit are digested, in a form that cells can immediately burn for fuel. The work of letting the body know everywhere how much glucose is in the blood is handled by substances carried in the blood.

A hormone is a substance made in one part of the body that rides the blood to a distant place and changes what the cells there do. If you compare a hormone to a letter, the blood is the postal route the letter travels on. A receptor is a protein found on cells that recognizes and catches only a specific hormone. Even if the same letter goes around the whole body, only the cells that have the receptor for that letter read its contents.

Letters about blood sugar mostly go out from one organ. The pancreas is an organ lying horizontally behind the stomach that does the work of making digestive juices and sending them to the intestine, and sending hormones that handle blood sugar out into the blood together. The two hormones on the blood sugar side are insulin and glucagon (PMID 39948335). The cells that make the two hormones are gathered together in small clusters of cells inside the pancreas along with several kinds of hormone cells (PMID 32894317).

Insulin is a hormone that comes out of the pancreas when blood sugar rises, and tells the liver, muscles, and fat to "gather up the glucose in the blood and store it". Insulin is the only hormone in the body that lowers blood sugar (PMID 32894317). Glucagon is a hormone that comes out of the pancreas and tells the liver to "take out the stored glucose and send it out into the blood". If insulin works on the side of storing, glucagon works on the side of taking it out and using it, and the two hormones together regulate blood sugar (PMID 34203830, PMID 12626323).

Beta cells are the cells within that cell cluster that make and send out insulin. The only cells in the body that can make insulin are beta cells (PMID 32894316). Alpha cells are the cells within the same cell cluster that make and send out glucagon. The glucagon that alpha cells send out is an essential regulator for the body's metabolic balance (PMID 37367959).

The two cells change their secretion amounts in opposite directions depending on the glucose concentration in the blood (PMID 8379904). Beta cells mainly respond to glucose to send out insulin, and other nutrients like fatty acids and amino acids amplify that response (PMID 22974359). Alpha cells send out glucagon right away when blood sugar drops (PMID 18640586). However, one review summarizes that glucagon secretion is more sensitive to changes in the concentration of certain amino acids in the blood than to blood sugar (PMID 36932176). The two cells also send letters back and forth to their neighbors. Substances sent out by beta cells suppress the work of alpha cells, and substances sent out by alpha cells help beta cells secrete insulin (PMID 32894317).

The places that receive insulin letters and do the work are mainly three: muscles, liver, and fat (PMID 30067154). Letters in the opposite direction do not end with just glucagon. When the body is cornered—like when blood sugar drops, when injured, or during intense exercise—other hormones and nerves also step in to make the liver send out more glucose (PMID 8379904). Adrenaline, a hormone that increases in the blood when blood sugar drops (PMID 18220670); cortisol and growth hormone, hormones that surge while sleeping (PMID 33419065); and the sympathetic nervous system, a neural system that encourages the liver to newly make glucose (PMID 24692138) take on that share. The letter that lowers blood sugar is just one pack of insulin, while the letters that raise it are multiple. This asymmetry will come up again later when blood sugar gets close to rock bottom.

After Eating — 「Collect and Store」

When you eat a bowl of rice, its carbohydrates are digested into glucose and enter the blood from the gut. The speed at which the stomach empties food, the speed at which the gut absorbs glucose, gut hormones, insulin, and glucagon all work together to regulate the ups and downs of post-meal blood sugar (PMID 33419065). One of these letters comes from the gut.

Incretins are hormones that gut cells release when food touches the gut, letting the pancreas know in advance that something has been eaten (PMID 17498508). Incretins are released within minutes of eating. When glucose is eaten by mouth, more insulin is released than when glucose is put directly into a blood vessel to match the exact same blood sugar level, and incretins create that difference (PMID 34310013). The insulin response when eating by mouth is typically two to three times greater than when infused into a blood vessel (PMID 29364588). Incretins cause more insulin to be released than the absorbed nutrients themselves draw out (PMID 11713984).

This letter comes with a condition. Blood sugar must already be raised to a certain degree for incretins to increase insulin secretion (PMID 21701075). Incretins are a warning letter that calls for more insulin only when blood sugar rises.

The two representative incretins are GIP, which comes from the upper part of the small intestine, and GLP-1, which comes from the lower part (PMID 29364588). In healthy people, GIP plays a larger role in increasing insulin, while GLP-1 slows down the speed at which the stomach empties food and suppresses glucagon secretion to reduce the amplitude of post-meal blood sugar spikes (PMID 34310013, PMID 17928588). The name GLP-1 is heard more often nowadays as the name of a drug, and that story continues in the article covering obesity and GLP-1.

Insulin released by beta cells is first loaded into blood vessels heading to the liver. In a small study where blood coming out of the liver was directly drawn and measured in five healthy adults who had fasted overnight and were receiving glucose through a blood vessel, about 80% of the insulin was cleared right there when it first passed through the liver (PMID 15919785). The first destination of the insulin letter is the liver, and the amount going on to the rest of the body after passing through the liver is the remainder (PMID 15919785).

When the liver receives insulin, it suppresses the work of newly making glucose or releasing stored portions, and begins stacking up incoming glucose (PMID 15061128). Glycogen is a storage form in which multiple glucoses are linked together like a chain and piled up in the liver and muscles. In the post-meal state when insulin concentration is high, glycogen and fat are made together in the liver (PMID 39231651).

In muscle, insulin pulls glucose channels that had been put away inside cells up to the cell surface, and glucose enters through those channels. This channel step usually determines the speed at which muscle takes up glucose (PMID 40173020). In fat tissue, insulin causes fatty acids to be piled up in the form of neutral fat (PMID 34751700).

Reviews differ on who receives how much of the eaten glucose and how they count it. There is a review stating that the liver processes over half of the eaten glucose (PMID 33419065), and a review stating that muscles take 80% of the glucose cleared from the blood after a meal (PMID 32940941). The former counts the entire eaten glucose, while the latter counts the portion cleared from the blood, so they cannot be read combined into one. What the two numbers together tell us is that a large share of post-meal glucose goes to the liver and muscles.

Muscles have one more pathway to open glucose channels. When muscles contract, the same channels rise to the cell surface (PMID 23899560). The signal used here is different from the insulin signal, and glucose uptake by muscles increases up to 50-fold during exercise (PMID 27739515). During exercise, insulin secretion decreases so the storage signal is turned off, and after exercise, the worked-out muscles respond better to insulin to refill the emptied glycogen (PMID 34751700).

The letter after eating is a single sentence: 「Collect and Store」, and the liver, muscles, and fat execute that sentence in their own ways.

When Fasting — "Take It Out and Use It"

Several hours after eating dinner, glucose coming in from the gut stops. Yet the brain keeps using sugar. The organ that props up blood sugar at this time is the liver. The liver exports glucose while fasting, and stores it after eating (PMID 28731034).

When insulin drops due to fasting, the liver unlocks glycogen and starts making new glucose (PMID 39231651). Glucagon spurs both of these tasks to make the liver export glucose, thereby preventing blood sugar from dropping too low (PMID 15061128). The signal to "take it out and use it" comes from two directions together: the side where glucagon increases and the side where insulin decreases.

The glucose that the liver exports has two sources. One is unpacking stored glycogen back into glucose. Gluconeogenesis is the work of making new glucose from materials that are not glucose, and the liver handles this mainly. Those materials are mainly lactic acid and some amino acids (PMID 8379904). When resting after fasting through the night, the glucose that the liver exports comes from the two sources in roughly equal halves (PMID 8379904). As the fasting time gets longer, gluconeogenesis becomes the main source (PMID 24692138). The kidneys also make and contribute some glucose (PMID 33419065).

Fat helps too. While fasting, adipose tissue unpacks fat to export fatty acids, and the liver turns some of them into other fuels to send to tissues outside the liver (PMID 24692138). When blood sugar is in short supply, fatty acids become a fuel that muscles and the liver can use instead of glucose (PMID 33419065).

While asleep, growth hormone and cortisol surge, and the body gradually becomes less responsive to insulin. Because of this change, muscles shift toward burning fatty acids instead of glucose, and the glucose production of the liver and kidneys is regulated so that blood sugar stays in the normal range all night (PMID 33419065).

Fasting blood sugar is blood sugar measured before breakfast after eating nothing all night. The core process that regulates blood sugar in the state of resting without eating is the liver exporting glucose (PMID 8379904). Blood sugar is kept steady by the balance of the glucose the body harvests and uses, and the glucose the body makes on its own (PMID 26549348). A single line of fasting blood sugar on a checkup report is the value matched between the glucose the liver exported overnight and the glucose the body used.

When the Bottom Nears — Hypoglycemia and Defense Lines

If you skip meals for a long time or take medications that lower blood sugar, your blood sugar can drop further (PMID 10500926). Hypoglycemia is a state where blood sugar has fallen below the normal range. Because the brain must receive glucose from the blood without interruption, preventing hypoglycemia means protecting the brain's metabolism and the survival of the entire body (PMID 10500926).

Counter-regulation is a defensive response in which the body deploys multiple hormones and nerves together to push blood sugar back up when it starts to fall. The drop in blood sugar is read by glucose sensors in the brain and throughout the body, and the brain gathers that information to coordinate hormonal, neural, and behavioral responses (PMID 21039590).

In healthy people, this defense overlaps in multiple layers. Insulin secretion drops, glucagon increases, the adrenergic nervous system turns on, and growth hormone and cortisol increase. As a result, the liver first releases glycogen and later makes new glucose, while muscles use less glucose and more fatty acids. Hunger is also part of this response, making you eat. One review paper summarizes that this entire system is organized to secure as much glucose for the brain to use as possible (PMID 18220670). The "Many Letters Are Sent to Raise It" we saw earlier becomes these overlapping defense lines here.

In one type of diabetes, several of these layers are damaged (PMID 18220670), and if insulin is excessive, life-threatening hypoglycemia can occur (PMID 32894316). That story continues in the article dealing with diabetes.

One Lap a Day — From Breakfast to Breakfast the Next Day

At seven-thirty in the morning, I eat breakfast with rice and side dishes. Within minutes, cells in the gut release incretins (PMID 17498508). Digested glucose enters the blood and blood sugar starts to rise, and because blood sugar is up, the advance warning from incretins takes effect (PMID 21701075). Beta cells send out more insulin than would come out from the absorbed glucose alone (PMID 11713984).

Insulin reaches the liver first, and judging by a small study measuring five people in fasting and glucose-infusion states, most of it is cleared there (PMID 15919785). The liver suppresses its job of sending out glucose and builds up glycogen (PMID 15061128). Passing the liver, insulin travels all over the body and reaches muscles, and muscles bring glucose channels to the surface to take in glucose from the blood (PMID 40173020). At the same time, signals from GLP-1 and the beta cell side press down on alpha cells to work toward reducing glucagon (PMID 17928588, PMID 32894317). Another incretins hormone, GIP, is summarized as actually increasing glucagon secretion (PMID 34310013).

These events run together to reduce the magnitude by which post-meal blood sugar rises (PMID 33419065). The same events repeat at lunch and dinner.

I fall asleep at eleven at night. When the glucose from the last meal has fully entered and insulin drops, the liver unpacks glycogen and starts making new glucose (PMID 39231651). While sleeping, growth hormone and cortisol surge so muscles shift toward burning fatty acids, and blood sugar stays in the normal range (PMID 33419065). Adipose tissue releases fatty acids to supply alternative fuel for muscles and the liver to use (PMID 33419065).

At seven the next morning, the fasting blood sugar measured in a body that has fasted for close to ten hours is the matched value of the glucose the liver sent out overnight and the glucose the body used (PMID 8379904, PMID 26549348). When I eat breakfast, one lap starts all over again from the beginning.

The Amplitude of Swings — A Healthy Person's Real Day

Even a healthy person's blood sugar briefly rises above 140 mg/dL during the day. In the sensor records of 153 non-obese healthy individuals seen earlier, the median time spent above 140 was 30 minutes a day (PMID 31127824). In another study that intensively measured blood sugar in people without diabetes over several weeks, most of them crossed this line at least once (PMID 20396998).

Some stay above it for a long time. Among the participants in that study, 7 had risen to about 200 mg/dL. About 1 in 10 spent more than 2 hours a day above 140, and these people had higher age, body mass index, fasting blood sugar, and test values reflecting long-term average blood sugar (PMID 20396998). This was true even though the participants were chosen to have very low fasting blood sugar. The authors wrote that these people spent a considerable amount of time at blood sugar levels considered to be prediabetes, and warned that dividing people by a single measured blood sugar value like fasting blood sugar fails to properly reveal such exposure (PMID 20396998). These records show that a healthy person's blood sugar also swings up and down above the band, but they do not judge whether those swings are harmful or harmless. What the line of 140 means in testing is the role of the article handling blood sugar test numbers.

The response to the same meal varies from person to person. In a single study giving the exact same meal to 1,002 British twins and healthy adults, post-meal blood sugar responses were widely scattered among people. Nutritional composition of the meal and personal factors like gut microbes explained only a small fraction of that difference, with the meal's nutritional composition explaining more of it between the two. The results were verified separately in another American cohort, and the authors wrote that this can serve as a reference for creating personalized diet strategies (PMID 32528151).

Yet responses fluctuate greatly even within the same person. In a study (preprint before formal review) where 30 people without diabetes ate the same meal twice about 1 week apart while hospitalized, the two responses tracked each other only weakly or moderately, and the repeatability of the response (reliability) was low. The fluctuation when eating the same meal twice was similar to the fluctuation between different meals (PMID 37503002). The authors concluded that an individual's post-meal sensor response to the same meal could not be relied upon, and wrote that providing personalized diet advice based on this requires more reliable methods that aggregate values measured multiple times (PMID 37503002). In a small single study involving 23 healthy adults, looking at the 14 who completed all three rounds, the white bread glycemic index (white bread response compared to the glucose response) varied more greatly within the same person than between people (PMID 17384339).

Both differences between people and fluctuations within the same person have been reported, and it has not yet been settled whether a response to a single meal can be read as a fixed trait of that person.

When the Balance Slips, and Where to Look Further

Diabetes is the state where this balance remains disrupted for a long time. In the most common form, tissues respond less to insulin, and beta cells fail to secrete enough extra to compensate for it (PMID 15061128). In diabetes, high blood sugar even after an overnight fast is mainly because the liver releases too much glucose (PMID 8379904). The detailed story of this breakdown is taken up by the article on diabetes, the numbers on your health checkup by the blood sugar test article, and GLP-1 by the article covering obesity and GLP-1.

Some questions remain unsettled. Glucagon was long known only as a hormone that raises blood sugar, but as evidence accumulates that it also handles fat and amino acid metabolism, it has become harder to reduce to a single simple action (PMID 36323234).

The paths the letters travel can be followed in "How the Heart Moves Blood — Four Chambers, Four Doors, Two Loops". Other articles in this series have not yet been released.

Source Papers

• "Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study." (2019) — PMID 31127824 — 153 healthy non-diabetic individuals (aged 7 to 80), with a median time of 96% in the 70–140 mg/dL range, spending more than 30 minutes a day above 140 and 15 minutes below 70.
• "Carbohydrates as a cerebral metabolic fuel." (1998) — PMID 9642647 — Evidence that the brain has few stored fuels of its own and relies on circulating glucose, making partial use of alternative fuels such as lactate and beta-hydroxybutyrate when glucose is scarce.
• "Physiology of glucose counterregulation to hypoglycemia." (1999) — PMID 10500926 — Since the brain normally uses only glucose, a continuous supply is essential; when blood sugar drops due to prolonged fasting or glucose-lowering drugs, counter-regulatory responses are the first reaction.
• "Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach." (2021) — PMID 33419065 — Hepatic and renal glucose production and muscle disposal, progressive overnight insulin resistance driven by growth hormone and cortisol maintaining blood glucose through the night, and the liver processing over 50% of ingested glucose to limit postprandial rises.
• "Control of glycaemia." (1993) — PMID 8379904 — Maintenance within a narrow range despite fluctuations in supply and demand, reciprocal secretion of insulin and glucagon, hepatic glucose output during fasting (half glycogenolysis and half gluconeogenesis) being key, adrenaline, cortisol, and growth hormone during stress, with diabetic fasting hyperglycemia mainly driven by excessive hepatic output.
• "Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status." (2025) — PMID 39948335 — The pancreas performs a dual function of insulin and glucagon secretion (endocrine) and digestive enzyme secretion (exocrine).
• "Alpha cell regulation of beta cell function." (2020) — PMID 32894317 — Islets are endocrine micro-organs composed of multiple cell types, insulin is the sole hormone that lowers blood glucose, beta-cell products suppress alpha-cells, and alpha-cell products stimulate insulin secretion.
• "Role of Insulin in Health and Disease: An Update." (2021) — PMID 34203830 — Insulin is secreted by beta-cells, regulates blood glucose alongside glucagon (anabolism versus catabolism), and promotes storage in the liver, muscle, and fat.
• "Glucagon and regulation of glucose metabolism." (2003) — PMID 12626323 — Glucagon acts as insulin's counter-regulatory hormone to increase hepatic glucose release.
• "Paracrine regulation of insulin secretion." (2020) — PMID 32894316 — Beta-cells are the only cells that make insulin, excessive insulin can cause fatal hypoglycemia, and a healthy pancreas secretes it to match tens of years and tens of thousands of meals.
• "100 years of glucagon and 100 more." (2023) — PMID 37367959 — Discovered in late 1922, glucagon is an essential regulator of metabolic homeostasis secreted by alpha-cells.
• "Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes." (2013) — PMID 22974359 — Insulin is secreted primarily in response to glucose, with fatty acids and amino acids acting as enhancers.
• "Pancreatic alpha-cell dysfunction in diabetes." (2008) — PMID 18640586 — Glucagon secretion by alpha-cells is an immediate response to hypoglycemia.
• "Revisiting the role of glucagon in health, diabetes mellitus and other metabolic diseases." (2023) — PMID 36932176 — Glucagon secretion is more sensitive to changes in certain amino acid concentrations than to glucose, alongside alpha-beta cell crosstalk.
• "Mechanisms of Insulin Action and Insulin Resistance." (2018) — PMID 30067154 — The three core target tissues of insulin are skeletal muscle, liver, and white adipose tissue.
• "Biology of incretins: GLP-1 and GIP." (2007) — PMID 17498508 — GIP and GLP-1 are secreted within minutes of ingestion, driving glucose-dependent insulin secretion.
• "Incretin hormones: Their role in health and disease." (2018) — PMID 29364588 — The upper (GIP) and lower (GLP-1) small intestine produce 2 to 3 times more insulin with oral compared to intravenous glucose (the incretin effect), though GLP-1's share of the incretin effect is minor even in healthy individuals.
• "Incretin hormones--an update." (2001) — PMID 11713984 — Incretins augment insulin secretion beyond what the absorbed nutrients themselves elicit.
• "Glucose-incretin interaction revisited." (2011) — PMID 21701075 — Stimulus-level blood glucose is an absolute prerequisite for incretins to boost insulin secretion.
• "The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update." (2021) — PMID 34310013 — The incretin effect shows a larger insulin response orally than with isoglycaemic intravenous infusion, GIP has a greater physiological role as an incretin and raises glucagon, while GLP-1 slows gastric emptying to reduce postprandial spikes and suppresses glucagon.
• "The physiology of glucagon-like peptide 1." (2007) — PMID 17928588 — GLP-1 is secreted in response to meals, limiting postprandial glucose fluctuations by stimulating insulin secretion and suppressing glucagon.
• "Pulsatile insulin secretion dictates systemic insulin delivery by regulating hepatic insulin extraction in humans." (2005) — PMID 15919785 — Direct hepatic vein sampling in 5 healthy individuals during overnight fasting and intravenous glucose infusion showed that about 80% of insulin is cleared on its first pass through the liver, and the amount passing through the liver determines delivery to extrahepatic tissues.
• "Hepatocytes: critical for glucose homeostasis." (2004) — PMID 15061128 — During fasting, glucagon prevents hypoglycemia via hepatic glucose output, after meals insulin suppresses hepatic glucose production and promotes glycogen synthesis, and type 2 diabetes involves insulin resistance plus beta-cell compensation failure.
• "Physiological and pathophysiological actions of insulin in the liver." (2025) — PMID 39231651 — Gluconeogenesis and glycogenolysis occur when insulin is low during fasting, while glycogen and fat synthesis occur when insulin is high postprandially.
• "A comprehensive view of muscle glucose uptake: regulation by insulin, contractile activity, and exercise." (2025) — PMID 40173020 — The rate-limiting step for muscle glucose uptake is membrane passage, with insulin- and contraction-responsive GLUT4 translocating to the cell membrane.
• "Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake." (2020) — PMID 32940941 — Skeletal muscle accounts for 80% of circulating glucose uptake after meals.
• "Interactions between insulin and exercise." (2021) — PMID 34751700 — Insulin promotes glycogen and triglyceride storage, insulin secretion is suppressed during exercise, and muscle insulin sensitivity increases post-exercise to facilitate glycogen resynthesis.
• "Exercise, GLUT4, and skeletal muscle glucose uptake." (2013) — PMID 23899560 — Muscle contraction causes GLUT4 to move to the cell membrane, driving glucose uptake.
• "Exercise-stimulated glucose uptake - regulation and implications for glycaemic control." (2017) — PMID 27739515 — Exercise increases muscle glucose uptake up to 50-fold through signaling pathways distinct from insulin, remaining preserved even in insulin-resistant muscle.
• "Regulation of hepatic glucose metabolism in health and disease." (2017) — PMID 28731034 — The liver produces glucose during fasting and stores it after meals.
• "Energy metabolism in the liver." (2014) — PMID 24692138 — Gluconeogenesis is the primary source during prolonged fasting, during which the liver converts lipolytic fatty acids into ketone bodies to supply fuel for extrahepatic tissues.
• "Sympathetic mechanisms of hypoglycemic counterregulation." (2007) — PMID 18220670 — Counter-regulation in healthy individuals is multiple and redundant (insulin ↓, glucagon ↑, adrenaline, growth hormone, cortisol), transitioning from initial glycogenolysis to later gluconeogenesis, producing hunger, securing maximal brain glucose, and becoming impaired in type 1 diabetes.
• "Neuroendocrine responses to hypoglycemia." (2010) — PMID 21039590 — Peripheral and central glucose sensors relay information to the central nervous system to coordinate neuroendocrine, autonomic, and behavioral responses.
• "Molecular pathophysiology of hepatic glucose production." (2015) — PMID 26549348 — Blood glucose is maintained by a balance between glucose uptake and endogenous production, with the liver playing the leading role.
• "Real-life glycaemic profiles in non-diabetic individuals with low fasting glucose and normal HbA1c: the A1C-Derived Average Glucose (ADAG) study." (2010) — PMID 20396998 — Intensive 12-week monitoring in 80 non-diabetic individuals showed 93% exceeding 7.8 mmol/L (median of 26 minutes per day), 9% exceeding 11.1 mmol/L, 10% spending over 2 hours above it, correlating with higher HbA1c, fasting glucose, age, and BMI, whereas single measurements underestimate exposure.
• "Human postprandial responses to food and potential for precision nutrition." (2020) — PMID 32528151 — In 1,002 individuals consuming identical meals, the inter-individual coefficient of variation for postprandial glucose was 68%, with meal nutritional composition (15.4%) having a larger effect on glucose than the microbiome (6.0%) and genetics (9.5%), validated in 100 US participants.
• "Imprecision nutrition? Duplicate meals result in unreliable individual glycemic responses measured by continuous glucose monitors across four dietary patterns in adults without diabetes." (2023, preprint) — PMID 37503002 — In 30 non-diabetic individuals across 1,056 meal responses consumed in duplicate about 1 week apart, intra-individual correlations were low to moderate with low reliability (ICC 0.14–0.31), duplicate meal variation was comparable to variation between different meals, and single measurements proved unreliable, necessitating repeated measurements.
• "Interindividual variability and intra-individual reproducibility of glycemic index values for commercial white bread." (2007) — PMID 17384339 — Based on 14 out of 23 healthy adults who completed three trials, the intra-individual variation in white bread glycemic index was 42.8%, exceeding the inter-individual variation of 17.8%, highlighting the need to better understand the sources of variation.
• "The past, present, and future physiology and pharmacology of glucagon." (2022) — PMID 36323234 — As glucagon's physiological role expands into lipid and amino acid metabolism, paradoxes remain that resist summary by simple mechanisms.