Does Sugar Cause Inflammation? What Your Numbers Can Show

Yes. Fructose, half of table sugar and most of high-fructose corn syrup, switches on metaflammation: low-grade, whole-body inflammation with no pain, no swelling and no off switch. A standard checkup rarely shows it; waist size, body composition, fasting insulin and high-sensitivity CRP come closer.

Fructose does more than add calories. It tells your cells a famine is coming, and the inflammation that follows brings no pain, no swelling and no warning on a standard checkup.

Does sugar cause inflammation? For one sugar in particular, the answer goes well past calories. In the chapter video, Fructose Turns the Famine Signal On, Dr. Padda explains why fructose, half of table sugar and most of high-fructose corn syrup, switches on a survival program built for scarcity, and why the inflammation that follows is the kind nobody feels. Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service. It measures; it does not treat. So the useful question is narrower: if this is happening inside you, what would show it, and what does a routine visit leave out?

How does sugar cause inflammation?

Most foods give a cell more energy to work with. Fructose takes energy away. The enzyme that handles it works quickly and has no brake, unlike the one that handles glucose, so the cell burns through its energy currency, ATP, faster than it can rebuild it. Uric acid is left behind. For an animal facing a hard season, that sudden energy drop carries a message: lay down fat, let the muscles resist insulin so the brain keeps its glucose, turn the mitochondria down, and go find more food. Ripe fruit and honey used to show up for a few weeks before winter, and then the message stopped.

Now it never stops. Estimates drawn from U.S. food supply data put fructose at about 15 grams a day for an American before 1900 and about 55 grams by 1994. Added sugars now supply roughly 15% of energy intake, and some groups get 20% or more. Those are availability figures rather than weighed meals, but nobody disputes the direction. The proposal that fructose helps drive Alzheimer’s disease comes from a 2020 hypothesis paper, and several of its authors hold equity in a company building fructose-blocking drugs. It is a serious idea that still awaits a trial, so it has to stand on its mechanism.

Does sugar cause inflammation you can feel?

A cut finger is inflamed on purpose. It turns red and warm, immune cells clean the wound, and the process shuts itself off. Metaflammation, the name researchers gave to inflammation set off by long-running metabolic stress, has no off switch. It is low-grade, spread through the whole body, and silent. You learn about it years later, as a diagnosis rather than a symptom.

Three engines keep it going. The first is biological: fat packed around the abdominal organs acts like a gland. When surgeons sampled the vein draining that fat in 25 adults with extreme obesity, the inflammatory messenger interleukin-6 ran about 50% higher than in an artery, and it tracked with C-reactive protein. The second is biological too: in 12 healthy men, one high-fat meal raised bacterial endotoxin in the blood by about half within hours, and among eight inpatients, a month of Western-style eating raised endotoxin activity 71%. The third is not biology at all. Added sugar is built into a huge share of packaged and restaurant food, so the famine signal arrives several times a day whether or not you chose it. That decision was made in a factory, long before anything reached your kitchen.

Does a routine checkup show inflammation from sugar?

A typical visit records your weight and blood pressure and may include a glucose or an A1C. Those numbers matter, and they tend to move late. Blood sugar can sit in the normal range for years while insulin climbs to hold it there, as described in what insulin resistance looks like before diabetes. Nothing on that short list asks where your fat is stored, how much muscle you carry, or whether your blood shows a quiet inflammatory signal.

Dr. Padda admits he spent years telling patients with borderline A1C results that they were not doing too badly. He was wrong, and the famine program is part of the reason: by the time glucose finally rises, the program has been running for a long time.

Why does waist size matter more than weight?

Body weight lumps two very different tissues into one number. An international consensus statement on visceral obesity reported that a larger waist meant higher mortality within every BMI category from 20 to 50. At the same BMI, each extra 5 centimeters of waist carried about 17% higher mortality in men and 13% in women. Weight and waist together say what neither says alone.

This is where measurement starts to close the gap. Bioimpedance body composition splits your weight into its fat and lean-tissue portions, a distinction no scale or BMI chart can make. Indirect calorimetry measures the energy your body actually burns at rest instead of estimating it from a formula. Neither test looks inside a single cell. Both describe the whole-body terrain where a long-running famine program would leave its marks, and both give you a starting point to compare against later.

What blood tests show inflammation?

Laboratory panels are where silent signals leave fingerprints. Questions to bring to whoever orders your blood work:

• High-sensitivity CRP. Heart-risk bands from the American Heart Association and CDC run under 1 mg/L low, 1 to 3 average and above 3 high, and a result above 10 should be repeated and checked for infection. They are cardiovascular bands, not brain thresholds.
• Uric acid. It rises 0.3 to 2.0 mg/dL within an hour of a fructose load, so it reads that load. It is not a dementia test; large studies point in both directions.
• Fasting insulin, reported as its own number. Glucose tells you the result; insulin tells you how hard the body worked to get it.
• Oxidized LDL with the omega-6 to omega-3 ratio. Among 1,889 adults in the CARDIA study who did not have metabolic syndrome at the start, the top fifth of oxidized LDL carried 3.5 times the odds of developing it within five years.

For help reading the numbers once they come back, see understanding your results.

What to do with the answer

Measurement is not treatment, and none of these numbers diagnoses a disease on its own. Results go to your physician, who decides what they mean for you. What they give you is leverage. A waist measurement, a body composition reading and an inflammation marker taken now become the baseline that shows, a year from now, whether what changed on your plate changed anything in your body. Unmeasured is unmanaged, and a signal that arrives three times a day deserves a number.

The studies behind every figure here are collected in the book companion (the Chapter 7 companion page), and the next article in the series follows inflammation to an unexpected source, the mouth (gum disease and dementia). Your gums are one of the few places that inflammation is visible without a blood draw, the subject of sugar and gum inflammation.

Frequently asked questions

References

• Johnson, R. J., Gomez-Pinilla, F., Nagel, M., Nakagawa, T., Rodriguez-Iturbe, B., Sanchez-Lozada, L. G., Tolan, D. R., & Lanaspa, M. A. (2020). Cerebral fructose metabolism as a potential mechanism driving Alzheimer’s disease. Frontiers in Aging Neuroscience, 12, Article 560865. https://doi.org/10.3389/fnagi.2020.560865
• Abdelmalek, M. F., Lazo, M., Horska, A., Bonekamp, S., Lipkin, E. W., Balasubramanyam, A., Bantle, J. P., Johnson, R. J., Diehl, A. M., Clark, J. M., & the Fatty Liver Subgroup of the Look AHEAD Research Group (2012). Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes. Hepatology, 56(3), 952–960. https://doi.org/10.1002/hep.25741
• Hotamisligil, G. S. (2017). Inflammation, metaflammation and immunometabolic disorders. Nature, 542(7640), 177–185. https://doi.org/10.1038/nature21363
• Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007). Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes, 56(4), 1010–1013. https://doi.org/10.2337/db06-1656
• Erridge, C., Attina, T., Spickett, C. M., & Webb, D. J. (2007). A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. American Journal of Clinical Nutrition, 86(5), 1286–1292. https://doi.org/10.1093/ajcn/86.5.1286
• Pendyala, S., Walker, J. M., & Holt, P. R. (2012). A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology, 142(5), 1100–1101.e2. https://doi.org/10.1053/j.gastro.2012.01.034
• Ross, R., Neeland, I. J., Yamashita, S., Shai, I., Seidell, J., Magni, P., Santos, R. D., Arsenault, B., Cuevas, A., Hu, F. B., Griffin, B. A., Zambon, A., Barter, P., Fruchart, J.-C., Eckel, R. H., Matsuzawa, Y., & Després, J.-P. (2020). Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nature Reviews Endocrinology, 16(3), 177–189. https://doi.org/10.1038/s41574-019-0310-7
• Pearson, T. A., Mensah, G. A., Alexander, R. W., Anderson, J. L., Cannon, R. O., Criqui, M., Fadl, Y. Y., Fortmann, S. P., Hong, Y., Myers, G. L., Rifai, N., Smith, S. C., Taubert, K., Tracy, R. P., & Vinicor, F. (2003). Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation, 107(3), 499–511. https://doi.org/10.1161/01.CIR.0000052939.59093.45
• Holvoet, P., Lee, D.-H., Steffes, M., Gross, M., & Jacobs, D. R. (2008). Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA, 299(19), 2287–2293. https://doi.org/10.1001/jama.299.19.2287
• Zhang, T., An, Y., Shen, Z., Yang, H., Jiang, J., Chen, L., Lu, Y., & Xia, Y. (2024). Serum urate levels and neurodegenerative outcomes: A prospective cohort study and Mendelian randomization analysis of the UK Biobank. Alzheimer’s Research & Therapy, 16(1), Article 106. https://doi.org/10.1186/s13195-024-01476-x

Related reading

• B12 Deficiency in the Elderly: A Guide for Adult Children
• Gum Disease and Dementia: What Is Proven and What to Measure
• Bioimpedance Body Composition

B12 Deficiency in the Elderly: A Guide for Adult Children

B12 deficiency in elderly parents is common and often silent: after 60, about 6% are deficient by the usual plasma cutoff and closer to 20% sit in a marginal band just above it. Trouble absorbing B12 from food, acid-suppressing drugs and metformin are the reasons to raise at a parent’s next visit.

An aging brain is no longer being built. It is being maintained, and the supplies for that upkeep get harder to absorb at exactly the age when lost tissue cannot be replaced.

The video above, Two Windows That Never Reopen, makes a case that lands hardest on families: the same missing nutrient can damage a brain being built at the start of life and a brain being kept up at the end. For adult children, B12 deficiency in elderly parents is the version that matters now, and it rarely looks like anything. No pain, no obvious symptom, often no flag on the report.

Early life is a construction window, and pregnancy testing belongs to prenatal care done elsewhere. Later life is a maintenance window. An older brain is no longer growing, but myelin turns over, synapses remodel and worn membranes have to be replaced, every day, with supplies that get harder to absorb.

What causes B12 deficiency in elderly parents?

Most people assume old stomachs simply stop making acid. The measurements say otherwise. Among 248 independently living older adults in Kansas City, nearly 90% could still acidify their stomach contents. The problem sits in a minority: in a study of 359 Boston adults aged 60 to 99, 31.5% had atrophic gastritis, a thinning of the stomach lining, and low serum B12 climbed with its severity.

That changes the question a family should ask. If your father makes normal stomach acid, age is not the explanation for a low B12, and something else is. In older adults, trouble prying B12 loose from food accounts for more than 60% of deficiency, and pernicious anemia, the loss of the protein that carries B12 across the gut, for 15–20%. After 60, about 6% are deficient by the usual plasma cutoff and closer to 20% sit in a marginal band just above it.

Which medications cause B12 deficiency in older adults?

Two of the most common prescriptions in later life touch the same vitamin. Acid-suppressing drugs reduce the acid that frees B12 from food. In Kaiser Permanente records, two or more years of a proton pump inhibitor carried an odds ratio of 1.65 for a B12 deficiency diagnosis, and larger daily doses carried more. Other pooled studies found the average effect small or absent, so the question is genuinely open.

Metformin is not open. In the Diabetes Prevention Program, a randomized trial, low B12 was more common on metformin than on placebo, and each year of use raised the odds further. Nobody should stop either drug on the strength of a web page. The point is narrower and more useful: a parent on either one has a specific reason to have B12 measured properly, and the prescriber is the person to review it with.

Eating alone, eating less, needing more

Intake falls with age for reasons that have nothing to do with willpower. Appetite fades. Meat is often the first food to go, sometimes because of teeth, sometimes because a roast is a lot of work for one person, and sometimes because a parent was told years ago to cut red meat for the heart. A widowed parent eating toast at the kitchen counter is not making a nutrition decision. Isolation is making it for them.

Meanwhile, need rises. An expert group recommends at least 1.0 to 1.2 grams of protein per kilogram of body weight a day for healthy adults over 65, and more during illness, because older muscle responds less to the protein it gets. Sarcopenia, the loss of muscle, builds from small deficits across a lifetime and gets booked as one diagnosis at the end. Low-grade inflammation climbs too, and researchers describe the same machinery in overnutrition as metaflammation. Supply falls while demand rises, in tissue that cannot be replaced.

When do B vitamins help an aging brain?

The VITACOG trial gave high-dose B vitamins or placebo to people over 70 with mild cognitive impairment, the early stage before dementia. Brain shrinkage slowed to 0.76% a year on the vitamins against 1.08% on placebo, and in people with high homocysteine at the start, it was 53% lower. A later trial gave similar vitamins for 18 months to 409 people who already had mild to moderate Alzheimer’s disease. Homocysteine fell. The rate of decline did not change.

The vitamins were the same. The timing was not, and neither were the patients: the Alzheimer’s trial enrolled people whose B12 and homocysteine were already normal, and you cannot replete someone who is not depleted. A struggling neuron can be protected. One that is gone cannot be brought back. The cruel part is psychological. The years when a change still works are the years that feel like “normal for my age,” when nobody is worried enough to measure anything.

What measurement adds for an aging parent

Measura [Cardiometabolic and Autonomic Health Analysis] is built for exactly that stretch of “nothing to worry about yet.” It records numbers, returns them to the parent’s own physician, and treats nothing itself. Three measurements fit this stage of life:

• Laboratory panels, the route for blood markers, with the specific markers chosen by the ordering physician. Families can ask whether methylmalonic acid or holotranscobalamin belongs beside serum B12.
• A cognitive assessment, which records memory and thinking now, so a later change is measured against your parent rather than against other people’s parents.
• Bioimpedance body composition, which separates muscle from fat instead of reporting one weight, the reason a stable number on the bathroom scale can hide shrinking muscle. More on that in body composition, not BMI.

None of these measures B12 deficiency on its own. Together they show whether the maintenance program is keeping up.

Questions to bring to your parent’s next visit

• Can we check methylmalonic acid or holotranscobalamin, not serum B12 alone?
• If B12 is low, is it atrophic gastritis, pernicious anemia or a medication?
• Can the prescriber review the acid suppressor and the metformin with that in mind?
• How much protein is my parent actually eating per kilogram?
• Can we record a cognitive baseline now, while things look fine?

Practical steps for the day itself are on how to prepare. The first half of the story, why a normal B12 can mislead at any age, is in the methylmalonic acid test explained, and the full evidence is in the book companion for Chapter 6 of The Starved Brain. At both ends of life the person at risk cannot ask for the test. You can.

Frequently asked questions

References

• Krasinski, S. D., Russell, R. M., Samloff, I. M., Jacob, R. A., Dallal, G. E., McGandy, R. B., & Hartz, S. C. (1986). Fundic atrophic gastritis in an elderly population: Effect on hemoglobin and several serum nutritional indicators. Journal of the American Geriatrics Society, 34(11), 800–806. https://doi.org/10.1111/j.1532-5415.1986.tb03985.x
• Hurwitz, A., Brady, D. A., Schaal, S. E., Samloff, I. M., Dedon, J., & Ruhl, C. E. (1997). Gastric acidity in older adults. JAMA, 278(8), 659–662. https://doi.org/10.1001/jama.1997.03550080069041
• Andrès, E., Loukili, N. H., Noel, E., Kaltenbach, G., Abdelgheni, M. B., Perrin, A. E., Noblet-Dick, M., Maloisel, F., Schlienger, J.-L., & Blicklé, J.-F. (2004). Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ, 171(3), 251–259. https://doi.org/10.1503/cmaj.1031155
• Lam, J. R., Schneider, J. L., Zhao, W., & Corley, D. A. (2013). Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA, 310(22), 2435–2442. https://doi.org/10.1001/jama.2013.280490
• Bauer, J., Biolo, G., Cederholm, T., Cesari, M., Cruz-Jentoft, A. J., Morley, J. E., Phillips, S., Sieber, C., Stehle, P., Teta, D., Visvanathan, R., Volpi, E., & Boirie, Y. (2013). Evidence-based recommendations for optimal dietary protein intake in older people: A position paper from the PROT-AGE Study Group. Journal of the American Medical Directors Association, 14(8), 542–559. https://doi.org/10.1016/j.jamda.2013.05.021
• Smith, A. D., Smith, S. M., de Jager, C. A., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K. M., Jacoby, R., & Refsum, H. (2010). Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: A randomized controlled trial. PLoS ONE, 5(9), Article e12244. https://doi.org/10.1371/journal.pone.0012244
• Aisen, P. S., Schneider, L. S., Sano, M., Diaz-Arrastia, R., van Dyck, C. H., Weiner, M. F., Bottiglieri, T., Jin, S., Stokes, K. T., Thomas, R. G., Thal, L. J., & Alzheimer Disease Cooperative Study. (2008). High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: A randomized controlled trial. JAMA, 300(15), 1774–1783. https://doi.org/10.1001/jama.300.15.1774
• Lindenbaum, J., Rosenberg, I. H., Wilson, P. W., Stabler, S. P., & Allen, R. H. (1994). Prevalence of cobalamin deficiency in the Framingham elderly population. The American Journal of Clinical Nutrition, 60(1), 2–11. https://doi.org/10.1093/ajcn/60.1.2
• Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., Wojcicki, T. R., Mailey, E., Vieira, V. J., Martin, S. A., Pence, B. D., Woods, J. A., McAuley, E., & Kramer, A. F. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3017–3022. https://doi.org/10.1073/pnas.1015950108
• Aroda, V. R., Edelstein, S. L., Goldberg, R. B., Knowler, W. C., Marcovina, S. M., Orchard, T. J., Bray, G. A., Schade, D. S., Temprosa, M. G., White, N. H., Crandall, J. P., & Diabetes Prevention Program Research Group. (2016). Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. The Journal of Clinical Endocrinology & Metabolism, 101(4), 1754–1761. https://doi.org/10.1210/jc.2015-3754

Related reading

• Methylmalonic Acid Test: When a Normal B12 Is Not Enough
• Does Sugar Cause Inflammation? What Your Numbers Can Show
• Laboratory Panels

Type 3 Diabetes: What a Normal Blood Sugar Test Can Miss

Type 3 diabetes is a proposed name, not a chart diagnosis, for a brain that stops responding to insulin. A normal blood sugar test misses it because insulin resistance runs for years before fasting glucose moves.

A normal fasting glucose reports on the last system to fail. The insulin problem underneath it, including the one in the brain, can run for years before that number moves.

Type 3 diabetes is a name, not a diagnosis your doctor can put in your chart, and the researchers who proposed it were careful to say so. It grew out of a 2005 Brown University study of brain tissue from people who died with Alzheimer’s disease, where the insulin machinery was badly damaged: fewer receptors, weaker signaling, and less of the brain’s own insulin. That idea anchors Chapter 3 of The Starved Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and in the chapter video he puts the consequence bluntly: a brain can run short of fuel while a blood sugar test reads perfect. For Measura [Cardiometabolic and Autonomic Health Analysis], that is a measurement problem before it is anything else.

What does type 3 diabetes mean?

Most people know insulin as the hormone that moves sugar out of the blood. In the brain it has other work. Its receptors cluster in the hippocampus, where new memories form, and in the cortex. There, insulin helps the connections between nerve cells strengthen, helps those cells stay alive, and takes part in keeping two troublesome proteins, amyloid and tau, under control. The enzyme that breaks down insulin also breaks down amyloid, so a brain bathed in insulin all day may have less of that enzyme available for cleanup. In animals, the shared enzyme is shown; in the human brain, the competition is still a hypothesis.

The evidence tier, stated once: type 3 diabetes is a hypothesis with substantial support, not settled science. Some researchers see brain insulin resistance as a cause of Alzheimer’s disease; others see it as a result. What few serious people dispute is that the Alzheimer’s brain has a fuel problem and that the problem begins early.

Why does a normal blood sugar test miss insulin resistance?

Think of insulin as a message that should arrive after a meal, get heard, and go quiet. Feed a body carbohydrate from breakfast to bedtime and the message never stops. Cells react the way you would to a smoke detector that will not shut off: they stop listening. The pancreas answers by sending more insulin, which keeps glucose in range and makes the deafness worse.

That is why the number most people are handed is a late one. In the Whitehall II study of 6,538 British civil servants, the 505 who later developed diabetes lost insulin sensitivity steeply across the five years before their diagnosis, while fasting glucose rose sharply only in the final three. Sensitivity failed first, then the pancreas strained, then the sugar broke. A glucose test sits at the far end of that line.

Dr. Padda has said he spent years telling patients with borderline results that their A1C was not too bad. The physiology changed his mind. A reassuring glucose describes how hard the pancreas is still working to hide a problem, not whether a problem exists.

What does a standard checkup test, and what does it miss?

A routine visit usually checks fasting glucose, sometimes hemoglobin A1c, and a cholesterol panel. None of them asks how much insulin it takes to hold the glucose where it is. In 2,439 adults from the Framingham Offspring Study who did not have diabetes, fasting insulin tracked smaller brain volume, and hemoglobin A1c did not. Among 683 older adults in Manhattan, people with high insulin levels had about twice the risk of Alzheimer’s disease, and that risk was highest in those who had no diabetes diagnosis at all.

The brain side is harder to see. The scan that shows regional glucose uptake falling is a PET scan with a glucose tracer, and it is a research tool. It has found the pattern in young carriers of the APOE4 risk gene still in their twenties and thirties, and in families with inherited Alzheimer’s disease fourteen to nineteen years before symptoms were expected. Measura does not perform PET imaging, and routine care does not order it for someone whose memory is fine. So the practical question becomes: what can be measured in the same person, now, that shows whether the insulin problem is already running?

Part of the gap is structural. The food supply delivers carbohydrate around the clock, visits are short, and medicine is organized by organ. Insulin resistance gets called diabetes in the blood, fatty liver in the liver, polycystic ovary syndrome in the ovary, and memory trouble in the neurology office. One upstream failure collects four names and four waiting rooms, and nobody is assigned to the upstream part.

What can be measured instead of blood sugar alone?

Measura measures; it does not treat, and findings go to your physician. For a brain-fuel question, the useful measurements describe the terrain that insulin resistance builds:

• Laboratory panels: blood work that can describe how your body is handling fuel, beyond a single glucose value. It is worth asking your physician whether fasting insulin has ever appeared in your results.
• Bioimpedance body composition: how much of you is muscle and how much is fat, which a bathroom scale and a BMI chart cannot separate.
• Arterial stiffness and endothelial function: how stiff your arteries are and how well the lining of the vessels responds. The link between diabetes and dementia is strongest for vascular dementia, so the vessels belong in the brain’s story.
• Cognitive assessment: a structured record of memory, attention and thinking speed today, so a later change is measured against you instead of guessed at.

None of these is a brain scan, and none diagnoses Alzheimer’s disease. Together they answer what a glucose test cannot: is the terrain that produces insulin resistance already in place? Type 2 diabetes carries roughly 1.5 to 2 times the risk of dementia, and metabolic health is rarer than most people assume. Fewer than 12.2% of US adults were metabolically healthy on NHANES 2009–2016, and under 7% on the tighter criteria applied after 2021.

Why does finding insulin resistance early matter?

The finding that shifts the prognosis is about a second fuel. In small dual-tracer PET studies of 29 people with mild Alzheimer’s disease, the brain took up 11 to 13 percent less glucose than in matched peers, yet no less of the ketone acetoacetate. Brain tissue that still absorbs an alternative fuel is not dead; it is short of the fuel it normally relies on. Whether supplying that fuel changes the disease is a separate question that clinical trials still have to answer.

For you, the point is timing. Insulin trouble is measurable years before glucose moves, and the brain’s fuel gauge falters years before memory does. A normal glucose means the last alarm has not sounded yet. It does not mean the building is sound. Unmeasured is unmanaged, and knowing your numbers earlier gives you and your physician more years to decide what to do with them. The evidence, study by study, is in the book companion for Chapter 3, and what insulin resistance looks like before diabetes walks through the body-wide version of the same story.

What to ask at your next visit

• My glucose is normal. Has my fasting insulin ever been measured?
• Does anything in my results suggest insulin resistance, even without diabetes?
• Do we have a baseline of my memory and thinking to compare against later?
• Diabetes or dementia runs in my family. Does that change what we should measure?

More questions worth bringing are collected in questions worth asking your doctor. What the brain tissue itself shows, and where the name came from, is set out in brain insulin resistance in Alzheimer disease.

Frequently asked questions

References

• Tabák, A. G., Jokela, M., Akbaraly, T. N., Brunner, E. J., Kivimäki, M., & Witte, D. R. (2009). Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: An analysis from the Whitehall II study. The Lancet, 373(9682), 2215–2221. https://doi.org/10.1016/S0140-6736(09)60619-X
• Tan, Z. S., Beiser, A. S., Fox, C. S., Au, R., Himali, J. J., Debette, S., DeCarli, C., Vasan, R. S., Wolf, P. A., & Seshadri, S. (2011). Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: The Framingham Offspring Study. Diabetes Care, 34(8), 1766–1770. https://doi.org/10.2337/dc11-0308
• Luchsinger, J. A., Tang, M.-X., Shea, S., & Mayeux, R. (2004). Hyperinsulinemia and risk of Alzheimer disease. Neurology, 63(7), 1187–1192. https://doi.org/10.1212/01.wnl.0000140292.04932.87
• Castellano, C.-A., Nugent, S., Paquet, N., Tremblay, S., Bocti, C., Lacombe, G., Imbeault, H., Turcotte, É., Fulop, T., & Cunnane, S. C. (2015b). Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer’s disease dementia. Journal of Alzheimer’s Disease, 43(4), 1343–1353. https://doi.org/10.3233/JAD-141074
• Croteau, E., Castellano, C. A., Fortier, M., Bocti, C., Fulop, T., Paquet, N., & Cunnane, S. C. (2018). A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Experimental Gerontology, 107, 18–26. https://doi.org/10.1016/j.exger.2017.07.004
• Steen, E., Terry, B. M., Rivera, E. J., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease—is this type 3 diabetes?. Journal of Alzheimer’s Disease, 7(1), 63–80. https://doi.org/10.3233/jad-2005-7107
• Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proceedings of the National Academy of Sciences, 101(1), 284–289. https://doi.org/10.1073/pnas.2635903100
• Gordon, B. A., Blazey, T. M., Su, Y., Hari-Raj, A., Dincer, A., Flores, S., Christensen, J., McDade, E., Wang, G., Xiong, C., Cairns, N. J., Hassenstab, J., Marcus, D. S., Fagan, A. M., Jack, C. R., Hornbeck, R. C., Paumier, K. L., Ances, B. M., Berman, S. B., … Benzinger, T. L. S. (2018). Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: A longitudinal study. The Lancet Neurology, 17(3), 241–250. https://doi.org/10.1016/S1474-4422(18)30028-0
• Chatterjee, S., Peters, S. A. E., Woodward, M., Mejia Arango, S., Batty, G. D., Beckett, N., Beiser, A., Borenstein, A. R., Crane, P. K., Haan, M., Hassing, L. B., Hayden, K. M., Kiyohara, Y., Larson, E. B., Li, C.-Y., Ninomiya, T., Ohara, T., Peters, R., Russ, T. C., … Huxley, R. R. (2016). Type 2 diabetes as a risk factor for dementia in women compared with men: A pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia. Diabetes Care, 39(2), 300–307. https://doi.org/10.2337/dc15-1588
• Willette, A. A., Bendlin, B. B., Starks, E. J., Birdsill, A. C., Johnson, S. C., Christian, B. T., Okonkwo, O. C., La Rue, A., Hermann, B. P., Koscik, R. L., Jonaitis, E. M., Sager, M. A., & Asthana, S. (2015). Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer disease. JAMA Neurology, 72(9), 1013–1020. https://doi.org/10.1001/jamaneurol.2015.0613

Related reading

• Ketosis vs Ketoacidosis: What the Numbers Actually Mean
• Statins and Memory Loss: What to Measure Before Anyone Guesses
• Laboratory Panels

Ketosis vs Ketoacidosis: What the Numbers Actually Mean

The difference is insulin. Nutritional ketosis runs between about 0.5 and 3 mmol/L of blood ketones with normal blood sugar and pH; ketoacidosis happens when insulin is missing, and ketones can climb as high as 20 mmol/L, usually with high blood sugar.

One is a regulated fuel state your brain uses readily. The other is a medical emergency. They share half a name, and the difference comes down to one hormone and a handful of numbers.

Ketosis vs ketoacidosis is one of the most misunderstood comparisons in everyday medicine, and the mix-up is not harmless. People get warned away from a normal fuel state because it sounds like an emergency, while others on certain diabetes drugs miss a real emergency because their blood sugar looks fine. In the video Your Brain Was Built for Ketones, Not Sugar, Dr. Padda argues that the brain was designed to use ketones well. The numbers below explain what that means for you, and where the line into danger actually sits.

Measura [Cardiometabolic and Autonomic Health Analysis] does not put anyone into ketosis or treat anything. It measures the metabolic terrain that decides how your body handles fuel, and sends those results to your physician.

How does your brain use ketones?

Ketones are made by the liver from fat when carbohydrate is scarce. Unlike glucose, which the brain pulls in according to how busy its neurons are, ketones enter roughly in proportion to how much is in the blood. When nine healthy adults fasted for 3.5 days, both their blood ketones and the flow of ketones into the brain rose more than 10 times.

How much of the brain’s energy that covers depends on the level. At about 1 mmol/L, ketones supply 10–15% of brain energy. After four days on a strict ketogenic diet, an estimated 33%. In three adults studied after 38–41 days of total starvation, 58%. A well-fed brain with trace ketones is running mostly on glucose, and some glucose is always needed. Your liver makes that glucose from protein and the glycerol in fat, which is why carbohydrate, about half of the calories in the American diet at 50.5% in a 2016 survey of U.S. adults, has no established minimum requirement.

What blood ketone level means nutritional ketosis?

Nutritional ketosis starts once blood ketones pass 0.5 mmol/L and usually runs between 0.5 and 3. Blood sugar stays normal. Blood pH stays normal. Insulin is low but present, and it acts like a governor on an engine: it lets the liver make ketones without letting production run away. Ketones even help apply their own brake, through a receptor that slows the release of fat when levels rise.

This is not exotic. Healthy adults reach about 1 mmol/L after prolonged exercise or 24 hours without food, and 76% of breastfed newborns in one study crossed 0.5 mmol/L in their first days. Neurology has used ketogenic diets to treat epilepsy since the 1920s.

What is ketoacidosis, and why is insulin the difference?

Diabetic ketoacidosis happens when insulin is missing or nearly so. With the governor gone, ketones can climb to as high as 20 mmol/L, several times and sometimes more than ten times the levels of nutritional ketosis, usually with high blood sugar and acid building up in the blood. British diabetes guidelines treat ketones above 3.0 mmol/L, together with a pH below 7.3 and low bicarbonate, as the emergency zone. It happens classically in type 1 diabetes and can occur in type 2.

There is one exception every reader should know. A class of diabetes drugs called SGLT2 inhibitors can cause ketoacidosis while blood sugar looks normal. On one of those drugs, or on insulin, a normal glucose reading is not reassurance, and any plan to cut carbohydrate is a conversation to have with your prescribing physician first. Do not start, stop or change a medication on your own.

Ketosis vs ketoacidosis: why do people mix them up?

Two biological facts get blurred: ketones as a regulated fuel, and ketones as a symptom of insulin failure. A third driver is social. For decades the American food supply has delivered carbohydrate at every meal, so most adults rarely experience ketosis after infancy, and clinicians see ketones mainly in emergency rooms. Dr. Padda has his own history here. He spent years as a strict vegetarian defending dietary guidelines he later abandoned when the physiology stopped supporting them.

What can a blood ketone number tell you?

Beta-hydroxybutyrate, the main blood ketone, can be read with a fingerstick meter or ordered by your physician. That is a different test from those in Measura’s library. A single value tells you where you are at that moment; it says nothing about why, and it should always be read next to a glucose value.

The bigger question is whether your body can switch fuels at all. High insulin keeps the liver from making ketones, and insulin can run high for years while glucose stays normal. That is where measurement helps:

• Laboratory panels show the metabolic picture in your blood work, as numbers rather than flags.
• Bioimpedance body composition uses a weak electrical signal to split your weight into its fat and muscle compartments.
• Indirect calorimetry measures the oxygen you use and carbon dioxide you breathe out at rest to calculate your resting metabolic rate, instead of guessing it from a formula. See measured versus estimated metabolic rate.

For the full study-by-study evidence, including the pregnancy and newborn data, read the Chapter 2 companion to The Starved Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP. Unmeasured is unmanaged, and knowing your own numbers turns a debate about diets into a decision you make with your physician.

Frequently asked questions

References

• Volek, J. S., Noakes, T., & Phinney, S. D. (2015). Rethinking fat as a fuel for endurance exercise. European Journal of Sport Science, 15(1), 13–20. https://doi.org/10.1080/17461391.2014.959564
• Gershuni, V. M., Yan, S. L., & Medici, V. (2018). Nutritional ketosis for weight management and reversal of metabolic syndrome. Current Nutrition Reports, 7(3), 97–106. https://doi.org/10.1007/s13668-018-0235-0
• Puchalska, P., & Crawford, P. A. (2017). Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics. Cell Metabolism, 25(2), 262–284. https://doi.org/10.1016/j.cmet.2016.12.022
• Mustafa, O. G., Haq, M., Dashora, U., Castro, E., Dhatariya, K. K., & Joint British Diabetes Societies (JBDS) for Inpatient Care Group (2023). Management of Hyperosmolar Hyperglycaemic State (HHS) in adults: An updated guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care Group. Diabetic Medicine, 40(3), Article e15005. https://doi.org/10.1111/dme.15005
• Dhatariya, K. K., & Joint British Diabetes Societies for Inpatient Care (2022). The management of diabetic ketoacidosis in adults—An updated guideline from the Joint British Diabetes Society for Inpatient Care. Diabetic Medicine, 39(6), Article e14788. https://doi.org/10.1111/dme.14788
• Hasselbalch, S. G., Knudsen, G. M., Jakobsen, J., Hageman, L. P., Holm, S., & Paulson, O. B. (1995). Blood-brain barrier permeability of glucose and ketone bodies during short-term starvation in humans. American Journal of Physiology, 268(6 Pt 1), E1161–E1166. https://doi.org/10.1152/ajpendo.1995.268.6.E1161
• Courchesne-Loyer, A., Croteau, E., Castellano, C.-A., St-Pierre, V., Hennebelle, M., & Cunnane, S. C. (2017). Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study. Journal of Cerebral Blood Flow & Metabolism, 37(7), 2485–2493. https://doi.org/10.1177/0271678X16669366
• Owen, O. E., Morgan, A. P., Kemp, H. G., Sullivan, J. M., Herrera, M. G., & Cahill, G. F., Jr. (1967). Brain metabolism during fasting. Journal of Clinical Investigation, 46(10), 1589–1595. https://doi.org/10.1172/JCI105650
• Shan, Z., Rehm, C. D., Rogers, G., Ruan, M., Wang, D. D., Hu, F. B., Mozaffarian, D., Zhang, F. F., & Bhupathiraju, S. N. (2019). Trends in dietary carbohydrate, protein, and fat intake and diet quality among US adults, 1999–2016. JAMA, 322(12), 1178–1187. https://doi.org/10.1001/jama.2019.13771

Related reading

• Can You Be Overweight and Malnourished? What Your Numbers Show
• Type 3 Diabetes: What a Normal Blood Sugar Test Can Miss
• Laboratory Panels

Can You Be Overweight and Malnourished? What Your Numbers Show

Yes. A diet can deliver plenty of energy and still come up short on the molecules cells need, so a heavy body can run low on B12, omega-3 and vitamin D at the same time.

A bathroom scale measures how much fuel you have stored. It says nothing about whether your cells, and your brain most of all, are getting the specific molecules they need to keep building.

Can you be overweight and malnourished at the same time? Yes, and in a metabolic practice it is closer to the rule than the exception. In the chapter video Overfed and Starving, Dr. Padda describes a man in his late fifties, forty pounds heavy, who has never gone hungry in his adult life. His blood work shows low-normal B12, a low omega-3 index, raised homocysteine, too little vitamin D and insulin resistance, and his cognitive screening score has slipped over three years. The scale said well fed. Everything else said short of supplies.

Measura [Cardiometabolic and Autonomic Health Analysis] was built for exactly that gap between what a body looks like and what it holds. Measura measures; your own physician interprets the results and decides on care.

What does malnourished mean if you are overweight?

Malnutrition literally means bad nutrition, not too little food. Global nutrition researchers describe a double burden: undernutrition and overnutrition sitting in the same population, and often in the same person. Most of us picture a famine photograph when we hear the word, so a full plate and a wide waistline switch the question off entirely.

Your body does not run on calories in general. It runs on particular molecules with particular jobs. B12 keeps the methylation cycle turning, which is how cells repair DNA and make neurotransmitters. DHA is part of the fat structure of the brain. Choline becomes a memory chemical. Cholesterol builds membranes and the insulation around nerves. A diet can deliver plenty of energy and still come up short on every one of them.

How can a full plate leave you malnourished?

Three forces stack on top of each other. The first is economic. Refined flour, added sugar and industrial seed oils became the cheapest calories in the store, and decades of public health advice steered families away from eggs, liver and red meat, the richest sources of B12, choline, retinol and heme iron. Appetite has a ceiling, so each cheap refined calorie takes the seat of a nutrient-dense one. The shortfall comes from what was pushed off the plate.

The second force is insulin resistance. When cells respond poorly to insulin, the pancreas makes more of it, and the fuel you eat in abundance struggles to reach the cells that need it. The third is methylation running low on parts: as B12 and related nutrients fall, homocysteine rises and the repair work that depends on that cycle slows. Too much stored energy, poor delivery and missing materials, all in one body.

How common are nutrient shortfalls in heavier bodies?

This is not one unlucky patient. Among 26,010 U.S. adults in NHANES 2001–2010, 28.9% were vitamin D deficient, and deficiency was 3.09 times as common with obesity. The first nationally representative red-blood-cell omega-3 measurement, NHANES 2021–2023, put the average U.S. adult index at 4.25%, with 97.6% of adults below 8%, and obesity predicted a lower index on its own. Among 12,335 adults in NHANES 1999–2004, 2.2% had clearly low B12 and another 13% sat in a low-normal band.

These are snapshots, so they show that heavier bodies tend to hold less of these nutrients, not that weight alone causes the shortfall. The practical lesson is simpler anyway: nobody finds a deficiency they never test for.

Why the brain pays first, and quietly

Your brain is about 2% of adult body weight yet uses roughly 20% of resting energy, and it keeps almost no fuel in reserve. It holds about a quarter of the body’s cholesterol. Most of its neurons are never replaced, so harm accumulates instead of being cleared away. And there is no pain signal when a connection fails to form.

That silence can be measured. In young adults carrying the APOE4 gene, average age about 30, glucose use was already lower in the brain regions Alzheimer’s disease later targets, with thinking still normal, roughly four decades before dementia usually appears. In 107 cognitively normal older adults scanned every year for five years, those in the lowest third of blood B12, below 308 pmol/L, had 6.17 times the odds of landing among the fastest brain-volume losers. None of them were deficient by the usual 150 cutoff. The shortfall that matters can sit completely inside a normal lab range.

What does a routine checkup miss?

A typical checkup records your weight and blood pressure and orders a basic panel built around glucose, HbA1c and cholesterol. Those numbers count. But HbA1c climbs late, after the pancreas can no longer cover the strain, and a scale or BMI cannot tell fat from muscle. In 2,439 adults from the Framingham Offspring Study, higher fasting insulin went with smaller total brain volume even after people with diabetes were excluded, while HbA1c showed no such link. The test ordered most often was the one that saw nothing.

Dr. Padda is blunt about his own part in that pattern. For years he told patients with prediabetes that their A1C was not too bad. He was wrong, and the physiology of insulin resistance is what changed his mind.

What measurement adds

Three Measura measurements fit the overfed-and-undernourished picture most directly:

• Laboratory panels show the metabolic picture in your blood, read as actual values rather than a pass or fail flag.
• Bioimpedance body composition estimates how much of your weight is fat, muscle and water, which a scale cannot separate. More on that in body composition, not BMI.
• Cognitive assessment scores memory, attention and thinking in a structured way, so a future result can be compared with your own starting point instead of a population average.

None of these diagnoses a nutritional deficiency by itself, and every result goes to your physician. What they do is turn feeling tired, foggy or heavier into a record that can be followed over time.

Questions to bring to your next appointment

• Can my B12 be checked with methylmalonic acid or holotranscobalamin, not serum B12 alone? This matters more if you take metformin.
• What is my fasting insulin, as a number?
• What are my homocysteine, omega-3 index and 25-hydroxyvitamin D?
• Do I have a cognitive baseline on file, and when should it be repeated?

More prompts are in questions worth asking your doctor. Every study behind these figures is laid out in the fully referenced Chapter 1 companion to The Starved Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP. Unmeasured is unmanaged. Once the numbers exist, the conversation about food, movement and repair starts from facts, and the next question is what the brain was built to run on. If surgery is on the calendar, the weeks before it are when these numbers can still change, covered in nutrition before surgery.

Frequently asked questions

References

• Liu, X., Baylin, A., & Levy, P. D. (2018). Vitamin D deficiency and insufficiency among US adults: Prevalence, predictors and clinical implications. British Journal of Nutrition, 119(8), 928–936. https://doi.org/10.1017/S0007114518000491
• Powers, C. D., Sternberg, M. R., Mineva, E. M., Clifton, C. C., Leachman, J. R., Wambogo, E., & Pfeiffer, C. M. (2026). Over half of the United States population had an undesirably low Omega-3 Index based on erythrocyte membrane measurements: Results from the cross-sectional NHANES from August 2021 to August 2023. Current Developments in Nutrition, 10(6), 107715. https://doi.org/10.1016/j.cdnut.2026.107715
• Mineva, E. M., Sternberg, M. R., Bailey, R. L., Storandt, R. J., & Pfeiffer, C. M. (2021). Fewer US adults had low or transitional vitamin B12 status based on the novel combined indicator of vitamin B12 status compared with individual, conventional markers, NHANES 1999-2004. The American Journal of Clinical Nutrition, 114(3), 1070–1079. https://doi.org/10.1093/ajcn/nqab122
• Raichle, M. E., & Gusnard, D. A. (2002). Appraising the brain’s energy budget. Proceedings of the National Academy of Sciences of the United States of America, 99(16), 10237–10239. https://doi.org/10.1073/pnas.172399499
• Reiman, E. M., Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., & Hardy, J. (2004). Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proceedings of the National Academy of Sciences of the United States of America, 101(1), 284–289. https://doi.org/10.1073/pnas.2635903100
• Vogiatzoglou, A., Refsum, H., Johnston, C., Smith, S. M., Bradley, K. M., de Jager, C., Budge, M. M., & Smith, A. D. (2008). Vitamin B12 status and rate of brain volume loss in community-dwelling elderly. Neurology, 71(11), 826–832. https://doi.org/10.1212/01.wnl.0000325581.26991.f2
• Tan, Z. S., Beiser, A. S., Fox, C. S., Au, R., Himali, J. J., Debette, S., DeCarli, C., Vasan, R. S., Wolf, P. A., & Seshadri, S. (2011). Association of metabolic dysregulation with volumetric brain magnetic resonance imaging and cognitive markers of subclinical brain aging in middle-aged adults: The Framingham Offspring Study. Diabetes Care, 34(8), 1766–1770. https://doi.org/10.2337/dc11-0308
• Popkin, B. M., Corvalan, C., & Grummer-Strawn, L. M. (2020). Dynamics of the double burden of malnutrition and the changing nutrition reality. The Lancet, 395(10217), 65–74. https://doi.org/10.1016/S0140-6736(19)32497-3

Related reading

• Ketosis vs Ketoacidosis: What the Numbers Actually Mean
• Laboratory Panels

What insulin resistance looks like before diabetes

Glucose is the measurement everyone knows and it is a late one. Insulin rises first, for years, keeping glucose in range by working harder.

What is insulin resistance?

Insulin resistance means the tissues respond less to insulin, so the pancreas produces more of it to achieve the same effect. For a long time that works. Glucose stays normal, hemoglobin A1c stays normal, and an annual panel comes back reassuring — while insulin levels are well above where they started.

A fasting glucose of 92 mg/dL tells you the system is still compensating. It does not tell you how much effort that is taking, and only measuring insulin does.

Can insulin resistance cause damage before diabetes?

Nerve injury associated with impaired glucose tolerance and the metabolic syndrome begins during it. That injury preferentially affects the small unmyelinated fibers, and nerve conduction studies are relatively insensitive to it — which is why skin biopsy measuring intraepidermal nerve fiber density has traditionally been used to confirm the diagnosis, and why sudomotor testing is useful non-invasively.

Vascular consequences appear during the same phase. Endothelial function is tightly coupled to insulin signaling in the vessel wall, which is why endothelial markers behave as insulin-resistance markers, and why they sit alongside prothrombotic and pro-inflammatory measures. Arterial stiffness and endothelial function.

How many Americans are metabolically healthy?

Analysis of the National Health and Nutrition Examination Survey for 2009 to 2016 defined optimal metabolic health as optimal waist circumference, glucose and hemoglobin A1c, blood pressure, triglycerides and HDL cholesterol, with no medication for any of them. By that definition, under 12.2% of American adults met it in 2009 to 2016, and under 7% do on the tighter criteria applied after 2021 — so more than nine in ten US adults do not. Fewer than one in three normal-weight adults met it; the figure fell to 8.0% among overweight adults and 0.5% among adults with obesity.

In the Padda Institute patient population the picture is starker still: fewer than 3% of patients overall, and fewer than 1% of chronic pain patients, meet the same definition of metabolic health. Those are practice-reported figures from our own population, not trial outcomes, and individual results vary.

How do you test for insulin resistance?

• Fasting insulin alongside glucose and hemoglobin A1c — the single highest-yield addition to a standard panel.
• C-peptide and fructosamine, which describe the same process from different angles.
• Triglycerides and HDL cholesterol, and lipid particle analysis rather than total cholesterol alone.
• Waist circumference, which is part of the definition and takes ten seconds.
• Body composition, because normal weight with low muscle mass is a distinct and common pattern.
• Sudomotor and vascular measurements, because the consequences appear before the diagnosis does.

The genuinely encouraging part

Every component of that metabolic health definition responds to changes in what people eat, how they move and how they sleep. Not equally, not in everyone, and not overnight — but triglycerides and fasting glucose move within weeks to months, and being able to watch them move is itself part of what makes a change stick.

Frequently asked questions

What are the symptoms of insulin resistance?

Often none you would notice. During the compensating phase, glucose and hemoglobin A1c stay normal and a routine panel looks reassuring. The early consequences are quiet: injury to the small nerve fibers and changes in how blood vessels work begin during this phase, which is why sudomotor and vascular measurements can pick them up before diabetes is ever diagnosed.

How can I know if I am insulin resistant?

A standard panel will not tell you, because glucose stays in range while insulin works harder to hold it there. A fasting glucose of 92 mg/dL says the system is still compensating, not how much effort that takes. Adding fasting insulin to glucose and A1c, along with waist circumference, triglycerides and HDL cholesterol, shows what glucose alone hides.

How do you lower insulin resistance?

By changing what you eat, how you move and how you sleep. Every part of the metabolic health definition responds to those changes. Not equally, not in everyone and not overnight, but triglycerides and fasting glucose move within weeks to months, and watching them move on repeat measurements is part of what makes a change stick.

Is insulin resistance the same as diabetes?

No. Insulin resistance comes first, often by years. The tissues respond less to insulin, so the pancreas makes more of it, and that extra effort keeps glucose and hemoglobin A1c in the normal range. A routine panel looks reassuring while insulin climbs. Glucose is the late signal, and nerve and blood vessel changes are already starting during this compensating phase.

References

• Araújo J, Cai J, Stevens J. Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016. Metabolic Syndrome and Related Disorders. 2019;17(1):46–52. doi:10.1089/met.2018.0105
• Cortez M, Singleton JR, Smith AG. Glucose intolerance, metabolic syndrome, and neuropathy. Handbook of Clinical Neurology. 2014;126:109–122. doi:10.1016/B978-0-444-53480-4.00009-6

Related reading

• Insulin resistance and metabolic health
• Laboratory panels
• Small-fiber versus large-fiber neuropathy

Measured versus estimated metabolic rate

An estimated metabolic rate comes from an equation that returns the average for people of your age, sex, height and weight. A measured rate comes from indirect calorimetry, which records your own oxygen use and carbon dioxide output at rest, after an overnight fast.

Almost every calorie target in existence comes from an equation. It is possible to measure the thing the equation is guessing at, in about ten minutes.

How accurate are metabolic rate calculators?

A predictive equation takes your age, sex, height and weight and returns the average resting energy expenditure of people who share those characteristics. That is a genuinely useful starting point and it is a population regression, which means it carries the variance of the population it was built on.

For someone near the center of that population it works acceptably. For anyone away from it — a lot of muscle, very little muscle, a large weight loss in the past, thyroid disease, advanced age — the estimate diverges from reality, and the divergence is not detectable without measuring.

What happens during a resting metabolic rate test?

You breathe normally for about ten minutes, at rest, after an overnight fast. Oxygen consumption and carbon dioxide production are recorded, and from those two figures the device calculates your resting energy expenditure and your respiratory quotient. Results are available within minutes.

What does a resting metabolic rate test measure?

Resting energy expenditure

The energy your body uses at rest, which is the large majority of what most people use in a day. This is the number a nutrition plan should be built on. It is also the number that changes as lean mass changes, which is why a target set at the start of a program may no longer be right six months in.

Respiratory quotient

The ratio of carbon dioxide produced to oxygen consumed. Because fat and carbohydrate are oxidized with different proportions of oxygen consumed to carbon dioxide released, this ratio indicates which fuel is predominantly being used at rest — lower for fat, higher for carbohydrate. It is a description of that moment under the recorded conditions, not a fixed trait, which is why the fasting requirement is absolute.

Read it against lean mass

Resting energy expenditure is produced overwhelmingly by lean tissue, so the absolute number means little on its own. A low value in someone with low muscle mass is a finding about muscle. That is why body composition is measured first.

How should you prepare for a metabolic rate test?

A recent meal, a cup of coffee, a cigarette or a brisk walk from the parking lot will all change the result. So will talking, dozing off or a leaking mask. The measurement is easy; getting the conditions right is the part that requires discipline. How to prepare.

What people usually find out

Most often, that the equation was wrong in one direction or the other, and that a plan built on the equation was therefore aimed at the wrong target. That is a more useful answer than either “you must be eating more than you think” or “your metabolism is broken,” and it is testable rather than assumed.

Frequently asked questions

Is a resting metabolic rate test worth it?

For most people, yes. The usual finding is that the equation behind their calorie target was wrong in one direction or the other, so the plan built on it was aimed at the wrong number. A measurement replaces both “you must be eating more than you think” and “your metabolism is broken” with an answer that can be tested rather than assumed.

What is a good resting metabolic rate?

There is no single good number, because resting energy expenditure is produced overwhelmingly by lean tissue. The absolute figure means little until it is read against your lean mass. A low value in someone with low muscle mass is a finding about muscle, not about metabolism, which is why body composition is measured first.

How accurate is a resting metabolic rate test?

It measures your own oxygen use and carbon dioxide output instead of guessing from age, sex, height and weight, but only if the conditions are right. A recent meal, a cup of coffee, a cigarette, a brisk walk, talking, dozing off or a leaking mask will all change the result, which is why the overnight fast is absolute.

How do I check my resting metabolic rate?

Measure it rather than calculate it. An online calculator runs an equation that returns the average for people of your age, sex, height and weight. Indirect calorimetry records your own oxygen use and carbon dioxide output while you breathe normally at rest for about ten minutes after an overnight fast. Results are available within minutes and are read against your body composition.

Related reading

• Metabolic rate and energy
• Indirect calorimetry
• Body composition is not the same as weight

Body composition is not the same as weight

Two people at the same height and weight can have completely different amounts of muscle, fat and water — and completely different risk. A scale cannot tell them apart.

Is BMI an accurate measure of health?

Body mass index divides weight by height squared. It is a reasonable way to describe a population and a poor way to describe a person, because it treats all weight as equivalent.

Two failure modes matter. A muscular person is classified as overweight while being metabolically healthy. And a person of entirely normal weight carries very little muscle and a great deal of visceral fat — a pattern with the metabolic consequences of obesity and none of its visibility.

The second is the one worth finding. In the survey analysis behind the standard metabolic health figures, fewer than one in three normal-weight adults met the full definition of metabolic health — so normal weight is not a reassuring finding on its own.

What does a body composition test measure?

The arithmetic is straightforward: intracellular plus extracellular water gives total body water; add protein and you have soft lean mass; add minerals and you have lean body mass; add fat mass and you have body weight.

Why does leg muscle matter?

Muscle loss in the legs shows up before it shows up on a scale, and it is one of the stronger predictors of losing independence. It also connects to everything else in a cardiometabolic assessment: less leg muscle means worse balance, less glucose disposal, and less capacity to recover from a stumble.

It is the denominator for metabolic rate

Resting energy expenditure is produced overwhelmingly by lean tissue. A measured resting expenditure without a lean mass figure beside it is not interpretable — a low value in someone with low muscle mass is an expected finding about muscle rather than a finding about metabolism. That is why body composition is measured first. Measured versus estimated metabolic rate.

How can you tell if your body composition is changing?

Hydration is the dominant confounder, followed by a recent meal, recent exercise and even a full bladder. The measurement is highly reproducible under standardized conditions, which is exactly what makes it useful for tracking change — and useless when the conditions differ between measurements.

Frequently asked questions

What does body composition mean?

Body composition is what your weight is actually made of: fat mass, lean body mass (muscle, protein and mineral), and the water inside and outside your cells. Added together they make up your body weight. Two people at the same height and weight can carry very different amounts of each, and very different risk, which is exactly what a scale cannot show.

Can you be a normal weight and still be metabolically unhealthy?

Yes. A person of entirely normal weight can carry very little muscle and a great deal of visceral fat, a pattern with the metabolic consequences of obesity and none of its visibility. In the survey analysis behind the standard metabolic health figures, fewer than one in three normal-weight adults met the full definition of metabolic health.

How is body composition measured?

Bioimpedance separates fat mass, lean body mass, and the water inside and outside your cells, and it shows how muscle is distributed, including whether the legs are losing muscle first. It is taken under standardized conditions, because hydration, a recent meal and recent exercise all shift the reading, so that a later measurement can be compared fairly with the first.

Is body composition testing worth it?

It is if you want to know what your weight is made of. A scale cannot separate muscle from fat, so it misses the normal-weight person carrying little muscle and a great deal of visceral fat. The test also shows leg muscle loss before the scale moves, and it supplies the lean mass figure without which a measured metabolic rate cannot be read.

How should you prepare for a body composition test?

Keep the conditions the same every time. Hydration shifts the reading more than anything else, followed by a recent meal, recent exercise and even a full bladder. The measurement is highly reproducible when those conditions are standardized, which is what lets a later result be compared fairly with the first, and what makes it useless when the conditions differ between visits.

References

• Araújo J, Cai J, Stevens J. Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016. Metabolic Syndrome and Related Disorders. 2019;17(1):46–52. doi:10.1089/met.2018.0105

Related reading

• Body composition, not BMI
• Bioimpedance body composition
• Measured versus estimated metabolic rate

Why metabolic health belongs in a pain practice

Chronic metabolic inflammation damages exactly the tissues a pain practice spends its time on — nerves, vessels and the autonomic system — and almost nobody measures it.

What is chronic metabolic inflammation?

It is inflammation without infection: a whole-body, low-grade inflammatory state driven by metabolic disturbance rather than by injury. It is not the inflammation of a sprained ankle, which is local, acute and resolves. It is systemic, it persists, and it alters both how pain is generated and how it is perceived.

Which tissues does metabolic inflammation damage in chronic pain?

The tissues most affected are the ones a pain practice already works with.

• Small unmyelinated nerve fibers, which are damaged early by high glucose, inflammation and impaired skin microcirculation — and which carry pain and temperature.
• The autonomic nervous system, which regulates vascular tone, and which interacts with pain in both directions.
• The endothelium, whose function is tightly coupled to insulin signaling.
• Joint tissue, where metabolic abnormality including obesity and type 2 diabetes is strongly linked to osteoarthritis in both weight-bearing and non-weight-bearing joints — which points at a mechanism more complicated than mechanical load alone.

How common is poor metabolic health?

In the general adult population, under 12.2% of American adults met a full definition of optimal metabolic health in the National Health and Nutrition Examination Survey for 2009 to 2016, and under 7% do on the tighter criteria applied after 2021 — so more than nine in ten US adults do not. In the Padda Institute patient population the picture is starker still: fewer than 3% of patients overall, and fewer than 1% of chronic pain patients, meet the same definition of metabolic health. Those are practice-reported figures from our own population, not trial outcomes, and individual results vary.

Read those two carefully, because they describe different populations and must not be blended. The survey figure is about US adults. The clinic figures are about patients who have already sought care, and among chronic pain patients specifically.

Does this mean chronic pain is caused by weight?

No. This page is not saying pain is caused by weight. It is not saying structural disease is imaginary, or that a herniated disc is really a metabolic problem. Injuries are real, nerve damage is real and degenerative change is real.

What it says is narrower and more useful: a measurable, modifiable contributor is present in most of this population and is routinely left out of the assessment. Measuring it takes an hour and changes what can be offered.

What changes when metabolic health is measured?

Three things. The patient with burning feet and normal imaging stops being a diagnostic dead end, because small-fiber function can be measured directly. The metabolic contribution becomes a tracked number rather than general advice. And dietary, sleep and activity changes acquire a feedback loop, which is the difference between advice that is followed and advice that is nodded at.

The patient-facing version and the specialty applications page.

Frequently asked questions

References

• Araújo J, Cai J, Stevens J. Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009–2016. Metabolic Syndrome and Related Disorders. 2019;17(1):46–52. doi:10.1089/met.2018.0105
• Cortez M, Singleton JR, Smith AG. Glucose intolerance, metabolic syndrome, and neuropathy. Handbook of Clinical Neurology. 2014;126:109–122. doi:10.1016/B978-0-444-53480-4.00009-6

Related reading

• Chronic pain and metabolic health
• What insulin resistance looks like before diabetes
• Small-fiber versus large-fiber neuropathy