Cortisone Shot Blood Sugar: What a Knee Injection Does to Your Numbers

A cortisone shot raises blood sugar for days after the injection, and in people with type 2 diabetes the rise is steep; a review of 7 studies found a rise in every one. Glucose is worth watching for up to a week, and A1c is worth knowing before the next shot.

A steroid injection is aimed at one joint, but the drug travels. For anyone with diabetes, prediabetes or extra weight, both the days after the shot and the success of the next treatment show up in measurable numbers.

A cortisone shot into a painful knee is sold as a local fix, but the drug does not stay in the joint. Anyone searching cortisone shot blood sugar is asking a fair question, and the answer has been measured: in people with type 2 diabetes, a single immediate-release knee injection pushed the highest glucose reading up by a median of 169.1 mg/dL over the next three days. The video above, The Goal Was Never to Manage Your Pain Forever, covers chapter 15 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. Its subject is injections, which Measura does not perform. The subject here is the numbers surrounding them, and every study is laid out in the book companion for chapter 15.

How much does a cortisone shot raise blood sugar?

That figure comes from continuous glucose monitors worn by people whose hemoglobin A1c already sat between 6.5 and 9.0 percent. With the ordinary immediate-release drug, 93 percent climbed above 250 mg/dL, the share of time spent in the 70 to 180 target range dropped to 48 percent, and the median time to reach 250 was 6 hours. The extended-release form did less harm, a median rise of 92.3 mg/dL with 50 percent crossing 250. The study was small and its analysis came after the fact, but an older review of 7 studies found a glucose rise in every one of them, with peaks as high as 500 mg/dL in the first days, and advised watching glucose for up to a week.

Blood sugar is not the only system that notices. An epidural dose of 40 milligrams switched off the body’s own stress-hormone axis for about 19.7 days, against 8.0 days for 20 milligrams, and the bigger dose relieved no more pain. Among older Medicare patients with sciatica, whose mean age was 76, those given epidural steroid had fractures at a rate of 49.1 per 1,000 person-years compared with 35.2 among those who were not. None of that makes the injection the wrong choice. It makes each injection a withdrawal from an account that deserves a balance check before the next one.

Why doesn’t the injection visit check your blood sugar?

A standard injection visit examines the joint: swelling, range of motion, perhaps an x-ray. It rarely examines the person attached to the joint. Three drivers keep it that way. The first is insulin resistance, which can hide behind a normal fasting glucose for years while the pancreas pushes out more insulin to hold that number in place. The second is fat stored around the organs and the slow, body-wide inflammation it feeds, which the book calls metaflammation, and which weight and body mass index describe poorly. The third is how care is organized. The visit is built around the procedure, relief comes quickly, and nobody is scheduled to ask what glucose did on day two or what the shrinking gap between shots is saying.

Dr. Padda is blunt that he spent years telling patients with an A1c in the prediabetic band that the number was not too bad. He now treats that number as one of the first things to measure, because the injection data below make the old reassurance hard to defend.

The same numbers predict whether a regenerative injection works

The book’s alternative to repeated steroid is platelet-rich plasma, and here the case for measuring gets sharper. In 120 patients with Achilles or patellar tendon pain treated with plasma, patients living with diabetes or prediabetes were 2.41 times as likely to fall short of a meaningful gain, and with every one-unit step up in hemoglobin A1c the odds of a poor result climbed 1.16-fold. A higher body mass index pushed the odds up as well. The platelets were not the weak link: in knee arthritis patients, growth-factor levels in the preparation did not differ between leaner and heavier groups. What differed was the tissue receiving them. The book pictures the injection as a seed and the body as the field, and the field has lab values.

What a measurement shows that a scale does not

Measura [Cardiometabolic and Autonomic Health Analysis] is a testing service. It performs no injections and provides no treatment. It measures, and every result goes to your physician. Two of its measurements speak directly to the terrain described above.

• Laboratory panels. Blood work that describes the metabolic picture, including hemoglobin A1c, the three-month blood sugar average, instead of a single glucose reading taken the morning of a procedure.
• Bioimpedance body composition. A measurement of fat and lean compartments, which says more about the load on a knee and the muscle available to protect it than height and weight can.

Why measure if your numbers are probably fine? Because probably fine is rarely true. On NHANES 2009–2016, under 12.2% of US adults met the criteria for metabolic health, and under 7% on the tighter criteria applied after 2021. In our own clinic the figure is under 3% overall and under 1% of chronic pain patients, practice-reported figures from our own population, not trial outcomes, and individual results vary. What insulin resistance looks like before diabetes describes the pattern behind those numbers.

What works better than a steroid shot for knee arthritis?

A measurement is only useful if it points somewhere. In a trial of 273 patients with knee arthritis and meniscal tears, twelve months of physical therapy built on exercise outscored a steroid injection by 22.70 points on a standard knee arthritis questionnaire. In an 18-month trial of 454 overweight and obese adults aged 55 and over, diet plus exercise removed 11.4 percent of body weight and produced the lowest pain scores, while interleukin-6, an inflammatory signal in the blood, measured 2.7 in the diet groups against 3.1 with exercise alone. Muscle answers to load, fat answers to food and insulin, and both show up on a body composition report and a lab panel long before they show up as a knee that fails the next injection. Chronic pain and metabolic health goes further into that link, and physicians can read metabolic screening before repeat joint injections.

What to ask before the next shot

• How many steroid injections have I had in this joint, and how long did each one last?
• If I have diabetes or prediabetes, how should I watch my glucose during the week after the injection, and who do I call if it climbs?
• What was my most recent hemoglobin A1c, and has anyone measured my body composition rather than just my weight?
• If platelet-rich plasma is offered, do my metabolic numbers change the result I should expect?
• What is the plan for the months of relief, so the next interval is longer than the last one?

Do not adjust diabetes medication or skip a planned injection on your own. Take these questions to the physician who ordered it, and see questions worth asking your doctor for more.

Frequently asked questions

References

• Spitzer, A. I., Rodbard, H. W., Iqbal, S. U., Nakazawa, M., DiGiorgi, M., & Winston, R. (2024). Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus. The Journal of Arthroplasty, 39(9 Suppl 2), S218-S223.e1. https://doi.org/10.1016/j.arth.2024.05.055
• Choudhry, M. N., Malik, R. A., & Charalambous, C. P. (2016). Blood Glucose Levels Following Intra-Articular Steroid Injections in Patients with Diabetes: A Systematic Review. JBJS Reviews, 4(3), e5. https://doi.org/10.2106/JBJS.RVW.O.00029
• Sim, S. E., Hong, H. J., Roh, K., Seo, J., & Moon, H. S. (2020). Relationship Between Epidural Steroid Dose and Suppression of Hypothalamus-Pituitary-Adrenal Axis. Pain Physician, 23(4S), S283-S294. https://pubmed.ncbi.nlm.nih.gov/32942788/
• Yun, H., Liu, Y., Curtis, J. R., Saag, K., D’Erasmo, G., Haseltine, K., & Stein, E. M. (2025). Epidural steroid injections and fracture incidence among older individuals with radiculopathy. Journal of Bone and Mineral Research, 40(2), 176–183. https://doi.org/10.1093/jbmr/zjae162
• Abate, M., Paganelli, R., Pellegrino, R., Di Iorio, A., & Salini, V. (2024). Platelet Rich Plasma Therapy in Achilles and Patellar Tendinopathies: Outcomes in Subjects with Diabetes (A Retrospective Case-Control Study). Journal of Clinical Medicine, 13(18), 5443 (article number from DOI; PubMed record lists volume 13, issue 18). https://doi.org/10.3390/jcm13185443
• Wiciński, M., Szwedowski, D., Wróbel, Ł., Jeka, S., & Zabrzyński, J. (2022). The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis. International Journal of Environmental Research and Public Health, 20(1), 40 (article number from DOI; PubMed record lists volume 20, issue 1). https://doi.org/10.3390/ijerph20010040
• Lee, M., Jing, C., & Lee, K. (2025). Physical therapy vs. glucocorticoid injection in patients with meniscal tears and knee osteoarthritis: a multi-center, randomized, controlled trial. BMC Medicine, 23(1), 277. https://doi.org/10.1186/s12916-025-04113-y
• Messier, S. P., Mihalko, S. L., Legault, C., Miller, G. D., Nicklas, B. J., DeVita, P., Beavers, D. P., Hunter, D. J., Lyles, M. F., Eckstein, F., Williamson, J. D., Carr, J. J., Guermazi, A., & Loeser, R. F. (2013). Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA, 310(12), 1263-1273. https://doi.org/10.1001/jama.2013.277669

Related reading

• Insulin Resistance and Tendon Pain: What Your Numbers Can Show
• Orthostatic Blood Pressure: What a Seated Reading Misses
• Laboratory Panels

Insulin Resistance and Tendon Pain: What Your Numbers Can Show

Insulin resistance is tied to tendon pain: an A1c in the prediabetic band carried about three times the rate of leg tendon injury, and Achilles tendinopathy tracks high triglycerides and low HDL even at a matched weight. The numbers to ask for are A1c, triglycerides, HDL and body composition.

A tendon that stays painful for years is treated as a local problem. The blood work and body composition around it may explain why the same exercise program helps one person and stalls in another.

Tendon pain that lasts for years is usually handled as a problem at one spot: the elbow, the heel, the point of the hip. The insulin resistance tendon connection says the spot sits inside a larger system, and that system shows up in blood work and body composition long before anyone calls it disease. The video above, Wash Out the Lesion, Don’t Jam the Signal, covers chapter 14 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. The procedures it describes are done by an interventional physician. What follows is about the numbers that sit around that decision, and the full study detail is in the book’s companion for chapter 14.

Why does tendon pain last for years?

The word most people hear is tendinitis, which suggests a hot, inflamed tendon that rest will cool. Under the microscope, a chronically painful tendon looks different: disorganized collagen, cells that have turned cartilage-like, and new blood vessels and nerve fibers growing into damaged tissue. There is inflammation, but it is the low, unfinished kind rather than a flare. The book’s word for that slow burn across the whole body is metaflammation.

Tendon also rebuilds far more slowly than people assume. Carbon dating from atmospheric bomb tests showed the core collagen of adult Achilles tendons was laid down at a median of 8 years after birth and essentially not renewed afterward. Plantar fasciitis confirmed on ultrasound was still present in 80.5 percent of patients one year after onset and in 45.6 percent at ten years. Pain that stays that long is not bad luck. It is a repair process that never got what it needed to finish.

Is insulin resistance linked to tendon pain?

Several separate lines of evidence point at metabolism. In a Danish population cohort, a hemoglobin A1c above 5.7 percent, the prediabetic band, was tied to about three times the rate of tendon injury in the legs, and the metabolic syndrome roughly two and a half times the risk in both arms and legs. People with Achilles tendinopathy showed higher triglycerides, lower HDL cholesterol and a higher ratio between the two than controls matched for body mass index, which is the lipid pattern of insulin resistance. Pooled across studies, people with tendon pain or altered tendon structure ran 0.33 millimoles per liter higher in triglycerides and 1.00 higher in LDL cholesterol.

These are observational findings, so they show association rather than proof of cause. They are also consistent, and they describe exactly the person who is told everything looks fine because no single value crossed a diagnostic line.

Can tendon pain be metabolic at a normal weight?

Weight matters. Obesity raised the odds of Achilles tendinopathy 3.81-fold in class I and 6.56-fold in class III. But the lipid study above matched patients and controls for body mass index, and the metabolic difference remained. Two people at the same weight can carry very different amounts of muscle and fat, and store that fat in very different places.

That is what bioimpedance body composition measures: fat mass, lean mass and body water, estimated from a small, painless electrical signal. Lean mass is the part that loads a tendon well, and fat mass is the part tied to the metabolic pattern. Body composition is not the same as weight, and for tendon pain that difference is the point.

Why does rehab help one tendon and stall in another?

Tendon rebuilds in response to load. Cells sense force and answer it with repair, which is why a structured loading program is the core treatment rather than an afterthought. In a trial of people with gluteal tendon pain at the hip, education plus exercise worked for 51 of 66 people by week eight; a steroid shot worked for 38 of 65, and waiting for 20 of 68.

Metabolism changes how well that program works. When patients with the metabolic syndrome went through the same eccentric exercise program as matched controls, their pain stayed higher throughout, satisfaction was lower, and they used more pain medication. In the other direction, after bariatric surgery and a 51.0 percent loss of excess weight, 90 percent of patients with plantar fasciitis saw their symptoms resolve. That study could not separate less load from better metabolism, but both moved together.

There is a behavioral trap under all of this. A lab threshold turns a gradient into a yes or a no. A person told they are not diabetic hears that nothing needs to change, keeps eating and sleeping the same way, and keeps loading a tendon that sits in the same terrain. The label ends the conversation the numbers were trying to start.

Where a procedure fits, and where measurement fits

For a damaged tendon that has not responded to loading, removing degenerated tissue with a needle-based device is one option, and the book is candid that its evidence is early and has no sham-controlled trial yet. In one series, physical therapy after the procedure accounted for 60 percent of the reduction in elbow pain, while only 44 percent of published tenotomy studies prescribed a structured rehabilitation program. The procedure opens a window. The loading, and the metabolism underneath it, decide what fills it.

Measura [Cardiometabolic and Autonomic Health Analysis] does not perform that procedure or any treatment. It measures, and the results go to your physician. The measurements that fit here are laboratory panels for the metabolic picture and body composition for the tissue picture, taken before a procedure decision and repeated as rehabilitation goes on.

What to ask your physician for

• My hemoglobin A1c as a number, not only whether it was flagged.
• My triglycerides and HDL, and the ratio between them.
• A fasting insulin, which the book treats as the starting point for a tendon rehabilitation plan.
• A body composition measurement, so lean and fat mass are tracked separately from weight.
• A review of my medication list. Fluoroquinolone antibiotics raised the odds of Achilles tendinitis 3.95-fold in pooled studies. Discuss any concern with your physician and do not stop anything on your own.

If those numbers look like the pattern above, insulin resistance before diabetes explains what the early stage looks like. Physicians can read the screening version for practices.

Frequently asked questions

References

• Skovgaard, D., Siersma, V. D., Klausen, S. B., Visnes, H., Haukenes, I., Bang, C. W., Bager, P., Grävare Silbernagel, K., Gaida, J., Magnusson, S. P., Kjaer, M., & Couppé, C. (2021). Chronic hyperglycemia, hypercholesterolemia, and metabolic syndrome are associated with risk of tendon injury. Scandinavian Journal of Medicine & Science in Sports, 31(9), 1822–1831. https://doi.org/10.1111/sms.13984
• Gaida, J. E., Alfredson, L., Kiss, Z. S., Wilson, A. M., Alfredson, H., & Cook, J. L. (2009). Dyslipidemia in Achilles tendinopathy is characteristic of insulin resistance. Medicine and Science in Sports and Exercise, 41(6), 1194–1197. https://doi.org/10.1249/MSS.0b013e31819794c3
• Tilley, B. J., Cook, J. L., Docking, S. I., & Gaida, J. E. (2015). Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review. British Journal of Sports Medicine, 49(23), 1504–1509. https://doi.org/10.1136/bjsports-2015-095100
• Macchi, M., Spezia, M., Elli, S., Schiaffini, G., & Chisari, E. (2020). Obesity Increases the Risk of Tendinopathy, Tendon Tear and Rupture, and Postoperative Complications: A Systematic Review of Clinical Studies. Clinical Orthopaedics and Related Research, 478(8), 1839–1847. https://doi.org/10.1097/CORR.0000000000001261
• Park, Y. H., Kim, W., Kim, J. Y., Choi, G. W., & Kim, H. J. (2021). Clinical Impact of Metabolic Syndrome on Eccentric Exercises for Chronic Insertional Achilles Tendinopathy. Journal of Foot and Ankle Surgery, 61(4), 726–729. https://doi.org/10.1053/j.jfas.2021.03.020
• Boules, M., Batayyah, E., Froylich, D., Zelisko, A., O’Rourke, C., Brethauer, S., El-Hayek, K., Boike, A., Strong, A. T., & Kroh, M. (2018). Effect of Surgical Weight Loss on Plantar Fasciitis and Health-Care Use. Journal of the American Podiatric Medical Association, 108(6), 442–448. https://doi.org/10.7547/15-169
• Mellor, R., Bennell, K., Grimaldi, A., Nicolson, P., Kasza, J., Hodges, P., Wajswelner, H., & Vicenzino, B. (2018). Education plus exercise versus corticosteroid injection use versus a wait and see approach on global outcome and pain from gluteal tendinopathy: prospective, single blinded, randomised clinical trial. BMJ, 361, k1662. https://doi.org/10.1136/bmj.k1662
• Hansen, L., Krogh, T. P., Ellingsen, T., Bolvig, L., & Fredberg, U. (2018). Long-Term Prognosis of Plantar Fasciitis: A 5- to 15-Year Follow-up Study of 174 Patients With Ultrasound Examination. Orthopaedic Journal of Sports Medicine, 6(3), 2325967118757983. https://doi.org/10.1177/2325967118757983
• Chalian, M., Nacey, N. C., Rawat, U., Knight, J., Lancaster, T., Deal, D. N., & Pierce, J. (2021). Ultrasound-guided percutaneous needle tenotomy using Tenex system for refractory lateral epicondylitis; short and long-term effectiveness and contributing factors. Skeletal Radiology, 50(10), 2049–2057. https://doi.org/10.1007/s00256-021-03778-9
• Alves, C., Mendes, D., & Marques, F. B. (2019). Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis. European Journal of Clinical Pharmacology, 75(10), 1431–1443. https://doi.org/10.1007/s00228-019-02713-1

Related reading

• Blind Injection Accuracy: What a Failed Shot Does and Doesn’t Prove
• Cortisone Shot Blood Sugar: What a Knee Injection Does to Your Numbers
• Bioimpedance Body Composition

Polypharmacy and Chronic Pain: What Your Medication List Measures

Most people with chronic pain take five or more medications, and a list that long often grows through cascades in which a new drug treats the side effect of an earlier one. Bring the list to your physician for a structured review, ask for measurements of the body underneath it, and never stop a medication on your own.

A chart can hold a dozen procedures and seven prescriptions and still contain no measurement of the body underneath the pain. The length of the list is a signal worth reading.

Polypharmacy and chronic pain travel together so reliably that researchers call it the rule rather than the exception. In a Quebec cohort of 1,342 adults with chronic pain, five or more medications were the norm for 71.4 percent, and ten or more for 25.9 percent. A list that long is a measurement in its own right: it records how many problems were answered with a prescription, and how few were answered with a question. The Chapter 12 video of The Pained Brain, from Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, argues that a system built to count procedures and prescriptions will keep producing longer lists. The useful response is to start counting different things.

What does polypharmacy look like in a chronic pain chart?

The book opens its twelfth chapter with a composite: a sixty-one-year-old man on his ninth epidural in three years, each at the same spinal level, each good for about six weeks. Between injections he takes seven prescriptions, and three exist to handle side effects of the other four. He has had imaging, a nerve study and a surgical consultation. What his chart lacks is just as telling. Nobody has checked his fasting insulin. Nobody has asked what he eats or how he sleeps.

Dr. Padda is blunt that he has given that injection himself and will defend it as a bridge, a few weeks bought so a person can rehabilitate, sleep, move and change the terrain under the pain. The ninth injection, with nothing planned on the far side, is not a bridge. It is a routine, and routines do not generate measurements.

What causes polypharmacy in chronic pain?

Long lists grow through cascades, where a new prescription answers a side effect of an earlier one. In 23,544 nursing-home residents who began a gabapentinoid, a loop diuretic was added within ninety days for 4.2 percent, at a median of 36 days, a sequence consistent with treating the swelling the first drug can cause. Among older hospital inpatients who had chronic noncancer pain and polypharmacy, 24.5 percent were taking an opioid together with a sleeping medication. In United States survey data, adults whose pain interferes with work faced 1.47 times the odds of an emergency visit with every five added medications.

None of those studies proves a single prescription wrong. They show the list itself carries risk that deserves a structured review with the physician who writes it. Never stop or change a medication on your own.

What gets counted, and what does not

The system counts some things very well. Epidural injections in traditional Medicare grew by 103 percent per 100,000 enrollees between 2000 and 2010. In commercial claims covering 196,332 patients, the busiest tenth of providers performed 36.6 percent of all spinal procedures. Since 2019 those curves have bent downward, yet the counts carry no reason for the procedure and no outcome, so a smaller number cannot show whether patients now have plans or simply fewer appointments.

What almost never gets counted is the terrain. Two biological drivers sit under most long lists: metaflammation with insulin resistance, and the side-effect load of the drugs themselves. The third driver is the incentive: when the service count is what gets rewarded, a chart fills with procedures and stays empty of measurements. The patient can change that third driver by asking for numbers.

What should be measured when your medication list is long?

Measura [Cardiometabolic and Autonomic Health Analysis] measures; it does not treat or prescribe, and findings go to your physician. These are the gaps a chart like his leaves open:

• Laboratory panels: blood markers of metabolic health, the category the composite patient never had drawn
• Bioimpedance body composition: muscle and fat compartments rather than weight alone
• Cognitive assessment and vestibular and balance testing: a baseline for memory and steadiness, worth raising when a list combines sedating medications
• Autonomic nervous system testing: how the involuntary nervous system is regulating heart rate and blood pressure

A baseline earns its place because it can be repeated. A plan that works should move a number you can see; a routine moves only the next appointment date. For background, read chronic pain and metabolic health and why body composition is not the same as weight.

Proof that a lifelong label can move

One landmark trial opened by calling type 2 diabetes a disorder needing lifelong treatment, then assigned primary care practices to run a structured weight-management program. After twelve months, remission had been reached by 46 percent of the program group and 4 percent of usual care, and by 86 percent of people who lost 15 kilograms or more. After twenty-four months the split was 36 against 3 percent, and diabetes medication was still being taken by 40 percent of the program group against 84 percent of controls. Some people relapsed, and the trial studied diabetes, not pain. Its lesson for a long list is that the medications followed the terrain.

Pain programs point the same direction on a smaller scale: in 134 older adults finishing interdisciplinary rehabilitation, medication use fell across every drug class by discharge.

What should I ask my doctor about my medications?

• Which medications on my list were started because of another medication?
• What measurement will show this plan is working, and when do we repeat it?
• Has my fasting insulin ever been checked?
• Given what I take, would a balance or memory baseline help?
• What should be different before the next procedure?

The studies behind every figure here, with their limits, are in the Chapter 12 companion. The next question in the series, whether the needle lands where it is aimed, is taken up here, and the physician version of this topic is measuring before the next procedure.

Frequently asked questions

References

• Zahlan, G.; De Clifford-Faugère, G.; Nguena Nguefack, H. L.; Guénette, L.; Pagé, M. G.; Blais, L.; Lacasse, A. (2023). Polypharmacy and Excessive Polypharmacy Among Persons Living with Chronic Pain: A Cross-Sectional Study on the Prevalence and Associated Factors. J Pain Res, 16, 3085–3100. https://doi.org/10.2147/JPR.S411451
• Hayes, K. N.; Belanger, E.; Oganisian, A.; Joshi, R.; Wang, X. J.; Grove, L. R.; Corcoran, K. L.; Zullo, A. R. (2025). Predictors of a Gabapentinoid-Loop-Diuretic Prescribing Cascade in U.S. Nursing Home Residents. J Am Geriatr Soc, 74(2), 336–344. https://doi.org/10.1111/jgs.70219
• Goetschi, A. N.; Verloo, H.; Wernli, B.; Wertli, M. M.; Meyer-Massetti, C. (2024). Prescribing pattern insights from a longitudinal study of older adult inpatients with polypharmacy and chronic non-cancer pain. Eur J Pain, 28(10), 1645–1655. https://doi.org/10.1002/ejp.2298
• Qeadan, F.; Barbeau, W. A.; Kroth, P. J. (2026). Polypharmacy, pain-related disability, and treatment fragmentation among U.S. adults without clinician advice to limit alcohol or tobacco use: A cross-sectional analysis of the 2022 Medical Expenditure Panel Survey. Medicine (Baltimore), 105(21), e48927. https://doi.org/10.1097/MD.0000000000048927
• Abbott, Z. I., Nair, K. V., Allen, R. R., & Akuthota, V. R. (2012). Utilization characteristics of spinal interventions. The Spine Journal, 12(1), 35–43. https://doi.org/10.1016/j.spinee.2011.10.005
• Lean, M. E.; Leslie, W. S.; Barnes, A. C.; Brosnahan, N.; Thom, G.; McCombie, L.; Peters, C.; Zhyzhneuskaya, S.; Al-Mrabeh, A.; Hollingsworth, K. G.; Rodrigues, A. M.; Rehackova, L.; Adamson, A. J.; Sniehotta, F. F.; Mathers, J. C.; Ross, H. M.; McIlvenna, Y.; Stefanetti, R.; Trenell, M.; … Taylor, R. (2018). Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet, 391(10120), 541–551. https://doi.org/10.1016/S0140-6736(17)33102-1
• Lean, M. E. J.; Leslie, W. S.; Barnes, A. C.; Brosnahan, N.; Thom, G.; McCombie, L.; Peters, C.; Zhyzhneuskaya, S.; Al-Mrabeh, A.; Hollingsworth, K. G.; Rodrigues, A. M.; Rehackova, L.; Adamson, A. J.; Sniehotta, F. F.; Mathers, J. C.; Ross, H. M.; McIlvenna, Y.; Welsh, P.; Kean, S.; … Taylor, R. (2019). Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol, 7(5), 344–355. https://doi.org/10.1016/S2213-8587(19)30068-3
• Schumann, M. E.; Lapid, M. I.; Cunningham, J. L.; Schluenz, L.; Gilliam, W. P. (2020). Treatment Effectiveness and Medication Use Reduction for Older Adults in Interdisciplinary Pain Rehabilitation. Mayo Clin Proc Innov Qual Outcomes, 4(3), 276–286. https://doi.org/10.1016/j.mayocpiqo.2020.01.004

Related reading

• Cluster Headache Misdiagnosis: The Measurement No Scan Can Make
• Blind Injection Accuracy: What a Failed Shot Does and Doesn’t Prove
• Laboratory Panels

Cortisol and Belly Fat: What Chronic Stress Leaves You Can Measure

Chronic stress and belly fat are linked: stress drives fat storage at the waist, and that visceral fat carries an enzyme that turns inactive cortisol back into the active hormone. What a test can read is the record stress leaves: body composition, blood fats such as triglycerides, and heart rate variability.

The stress hormone and the fat around your middle feed each other. A single cortisol number rarely catches that loop, but the body keeps a record you can measure.

The link between cortisol and belly fat is real, and it runs in a circle. Years of stress push the body to store fat around the middle, and that fat then produces active cortisol inside itself, which keeps the loop turning. The piece almost nobody measures is everything in between: the rhythm of the hormone, how your cells answer it, and what the fat and muscle underneath the waistline are actually doing.

The video above, Chronic Stress Is Not in Your Head. It’s in Your Pain Threshold, is Chapter 8 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. The angle here is measurement: what stress writes into your body, and which marks a test can read.

Is cortisol always bad for you?

Before cortisol is a problem, it is protection. When 23 healthy volunteers were given a bacterial toxin, their temperature rose 1.9 degrees and the inflammatory signal tumor necrosis factor peaked at 155 picograms per milliliter. Given the same toxin during a stress-dose infusion of hydrocortisone, fever peaked at just 0.8 degrees and the cytokine dropped below detection. A short burst of the hormone shuts inflammation down.

Timing turns the brake into an accelerator. When the toxin came half a day to a week after the hormone instead, the inflammatory response roughly quadrupled. Stretch the exposure over years and tissue response dulls. Among 33 family caregivers of glioblastoma patients, the inflammatory switch NF-κB ran 1.65 times more active in their immune cells while the cortisol receptor’s gene program ran at 0.68 times normal, even though their cortisol levels were normal. The hormone was present. The tissue had tuned it out.

How does chronic stress put fat on your belly?

Hair holds a record of cortisol over months, and that record tracks the waist. Across 10,289 people, ongoing stress raised hair cortisol by 43 percent, and hair cortisol rose with body mass and waist-to-hip ratio. A three-year Dutch study of 1,604 adults found the same pattern: more hair cortisol, a waist 5.36 centimeters wider, higher interleukin-6, and body mass creeping up about 0.58 percent per year afterward. Women who already carried fat at the waist released more cortisol under laboratory stress than lean women did.

Then the fat joins in. Visceral fat carries an enzyme that turns inactive cortisol back into the active hormone inside the tissue itself, so the fat keeps its own supply regardless of what the adrenal glands are doing. The downstream bill is metabolic: among 10,308 London civil servants followed for fourteen years, three or more exposures to chronic work stress meant 2.25 times the odds of the metabolic syndrome, and across 334,132 workers job strain raised the hazard of type 2 diabetes 1.16-fold, 1.35-fold in women.

Why does one cortisol test miss stress belly fat?

If cortisol drives belly fat, why not just test it? Because the level is the least informative part of the system. Healthy cortisol runs high after waking and falls to a low, quiet evening. Across 80 studies and 36,823 people, what tracked worse health, most strongly inflammation, was a flatter daily slope, and the flat curve carried a mortality hazard of 2.40, falling to 1.63 without two outlier studies. In 4,560 older English adults with chronic pain, hair cortisol ran higher at both the low end and the high end of the range and showed no difference in the middle.

The non-obvious finding came from a study that set out to predict chronic low back pain. In 140 young volunteers with occasional pain, hair cortisol did not predict who would develop chronic pain a year later. What did predict it was a mix of blood and body readings: triglycerides, an inflammatory cytokine, a stress catecholamine, the resting heart rate and the ratio of waist to hips. The stress system showed up clearly. The cortisol number did not. The body logs chronic stress in the waist, the blood fats and the heart long before a single hormone draw reflects it.

Who carries the load, and why it is dismissed

Stress is not evenly distributed. In a British birth cohort, people under the heaviest money strain at age 43 carried 4.44 times the relative risk of widespread chronic pain by 68. Among 315,197 UK Biobank participants, the feeling of loneliness carried a 1.32 hazard for developing low back pain; simply living alone did not.

The medical response has too often been a shrug. In a survey of people with chronic pain, 77 percent reported being dismissed or doubted by a provider, and those reports went with poorer day-to-day function. Dr. Padda’s position is that the fault lies with his own profession: calling something just stress names the mechanism and then declines to measure or treat it. In a random population sample of 2,199 Danes, those reporting high stress needed less pressure on the trapezius, the muscle across the top of the shoulder, before it hurt. That threshold is checked with a pressure gauge in a clinic, which is a different test from the ones below.

What tests show what chronic stress has done to your body?

Measura [Cardiometabolic and Autonomic Health Analysis] reads these marks and reports them to your physician; the numbers inform care rather than replace a diagnosis. Four tests cover different parts of the stress-and-fat record:

• Bioimpedance body composition splits body weight into fat mass and lean mass. A waist measurement is only a proxy for the fat inside; body composition adds the muscle side that stress and inactivity erode.
• Laboratory panels read the blood markers where the metabolic cost of stress appears, including glucose and triglycerides, the same blood fats that turned up in the back pain prediction work.
• Heart rate variability looks at the variation between heartbeats, a reading of the autonomic half of the stress response. Across 52 studies of chronic primary pain, higher cortisol came alongside lower heart rate variability during recovery.
• Autonomic nervous system testing looks more broadly at how the involuntary nervous system regulates heart rate, blood pressure and sweating.

These readings earn their keep when repeated. The research on the stress system itself shows movement that can be tracked: in 342 adults with chronic low back pain, an eight-week mindfulness course left 60.5 percent functioning meaningfully better at 26 weeks, compared with 44.1 percent on usual care, and in 73 adults with both PTSD and chronic pain, six weeks of heart rate variability biofeedback cut pain interference by 24.9 percent. Whether any of that fits your situation is a conversation for your physician, and a baseline makes that conversation concrete.

Questions to bring to your physician

• Can we track the shape of my stress response, not just one morning cortisol value?
• Can my body composition be measured so we know whether my weight is fat, muscle or both?
• What are my triglycerides, glucose and waist this year, and can we repeat them next year?
• Can the exposures in my life, such as caregiving, work strain or loneliness, go in my chart as part of the picture?

Unmeasured is unmanaged. The full study list, with what each one does and does not show, is in the Chapter 8 companion supplement built for your doctor. The sleep side of the same body clock is in what short sleep does to blood sugar before glucose moves, background on reading results is in understanding your results, and clinicians can find the screening view in the physician edition.

Frequently asked questions

References

• Barber, A. E., Coyle, S. M., Marano, M. A., Fischer, E., Calvano, S. E., Fong, Y., Moldawer, L. L., & Lowry, S. F. (1993). Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man.
• Miller, G. E., Murphy, M. L. M., Cashman, R., Ma, R., Ma, J., Arevalo, J. M. G., Kobor, M. S., & Cole, S. W. (2014). Greater inflammatory activity and blunted glucocorticoid signaling in monocytes of chronically stressed caregivers.
• Adam, E. K., Quinn, M. E., Tavernier, R., McQuillan, M. T., Dahlke, K. A., & Gilbert, K. E. (2017). Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis.
• Stalder, T., Steudte-Schmiedgen, S., Alexander, N., Klucken, T., Vater, A., Wichmann, S., Kirschbaum, C., & Miller, R. (2017). Stress-related and basic determinants of hair cortisol in humans: A meta-analysis.
• van der Valk, E. S., van der Voorn, B., Iyer, A. M., Mohseni, M., Leenen, P. J. M., Dik, W. A., van den Berg, S. A. A., de Rijke, Y. B., van den Akker, E. L. T., Penninx, B. W. J. H., & van Rossum, E. F. C. (2021). Hair cortisol, obesity and the immune system: Results from a 3 year longitudinal study.
• Chandola, T., Brunner, E., & Marmot, M. (2006). Chronic stress at work and the metabolic syndrome: prospective study.
• Morgan, S. A., Hassan-Smith, Z. K., & Lavery, G. G. (2016). MECHANISMS IN ENDOCRINOLOGY: Tissue-specific activation of cortisol in Cushing’s syndrome.
• Vyverman, J., De Baere, R., Timmers, I., Coppieters, I., Van Oosterwijck, J., & Moerkerke, M. (2026). The stress-pain connection in chronic primary pain: A systematic review and meta-analysis of physiological stress markers in relation to experimental pain responses.
• Skovbjerg, S., Jørgensen, T., Arendt-Nielsen, L., Ebstrup, J. F., Carstensen, T., & Graven-Nielsen, T. (2016). Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish General Population: The DanFunD Study.
• Chadwick, T. M., Tatschl, J. M., Fujiyama, H., Drummond, P. D., & Mathersul, D. C. (2025). Heart rate variability biofeedback improves co-occurring posttraumatic stress disorder and chronic pain symptoms: A randomised waitlist controlled trial.

Related reading

• Can Lack of Sleep Raise Blood Sugar? What the Numbers Show First
• Central Sensitization Symptoms: What Your Numbers Can Show
• Bioimpedance Body Composition

Can Lack of Sleep Raise Blood Sugar? What the Numbers Show First

Short sleep does push blood sugar up, but glucose is the last number to move. Insulin, muscle and the nervous system shift first, and a routine visit rarely measures any of them.

Can lack of sleep raise blood sugar? Yes, and faster than most people expect: a handful of short nights is enough to make healthy young adults handle sugar the way an aging body does. The catch is where the damage shows up first. Glucose is the number the body defends hardest, so it tends to be the last reading to drift, long after insulin, muscle and the stress wiring have already changed.

That measurement problem sits underneath Why Pain Is Worst at 3 a.m., Chapter 7 of The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. The video argues from the pain side. The questions below are narrower: what a broken night does to your numbers, which of those numbers a standard visit checks, and which ones it leaves in the dark.

Can lack of sleep raise blood sugar? Insulin moves first

The first clean experiment was run in 1999. Eleven healthy young men were limited to four hours in bed for six nights. By the end their glucose tolerance had slipped to a level the researchers likened to normal aging, their evening cortisol was up, and their sympathetic nervous system, the fight-or-flight half, was running hot. In clamp studies of healthy adults, five nights of four hours cut whole-body insulin sensitivity by 25 percent and raised 24-hour cortisol by 21 percent. When fat tissue was biopsied from seven healthy adults after four nights of short sleep, their fat cells needed nearly three times as much insulin to respond.

Notice what those studies measured: insulin sensitivity, cortisol, nerve activity. Blood sugar moved as well, but the body covers for it. When healthy adults had their whole day pushed 12 hours out of phase, glucose rose only 6 percent, and it took 22 percent more insulin to hold it there. Three of eight produced after-meal glucose in the prediabetic range. The pancreas is working overtime well before a fasting glucose on a lab slip turns red.

Does night-shift work raise blood sugar?

Hours are only half the story. When healthy adults slept the same short amount but at the wrong time of day, the schedule of a night-shift worker, the drop in insulin sensitivity nearly doubled in men, 58 percent against 32, and the inflammatory marker hsCRP climbed far more. The same meal eaten in the biological evening raised glucose 17 percent more than in the biological morning, because the pancreas keeps a clock of its own.

This is where biology meets the way we live and work. Pooled across cohort studies, night-shift work raised the hazard of type 2 diabetes 1.30-fold. Among 84,790 people who wore wrist light sensors, those with the brightest nights developed diabetes at 1.53 times the hazard of those who slept in the dark. An economy that runs around the clock, on screens and shift rosters nobody chose, is running a metabolic experiment on the people who keep it open.

How does losing muscle raise blood sugar?

Sleep loss also costs muscle, and muscle is where insulin sends most of the sugar you eat. In a two-week diet study of overweight adults, the short-sleep arm (5.5 hours a night against 8.5) shed 60 percent more lean mass, 2.4 kilograms against 1.5, and under half as much fat. The scale said the diet worked. The body composition said the opposite.

That loss matters for blood sugar. In a national survey analysis of 13,644 Americans, people with 10 percent more muscle for their size showed 11 percent lower insulin resistance, and the researchers estimated muscle with electrical impedance, the same basic principle a body-composition test relies on. Low muscle also travels with pain: sarcopenia, the wasting of muscle, carries 1.26 times the odds of chronic pain. A person who sleeps badly, hurts, and moves less is losing the very tissue that would have protected both the blood sugar and the back.

What does a routine checkup miss about sleep and blood sugar?

A typical checkup for someone who sleeps poorly and hurts looks at weight, blood pressure, and perhaps a fasting glucose or HbA1c. Those numbers are useful and late. Weight hides the trade of muscle for fat. Fasting glucose is the number the body protects by spending insulin. And few visits ask the two sleep questions that carry the most information: how many hours, and how many times you wake. In women whose sleep was broken by repeated awakenings, the body’s own pain brakes failed, while women who lost the same hours in one block kept them. Across six months of daily diaries in 801 adults, sleep quality, not hours, predicted the next day’s pain.

Dr. Padda is blunt that the failure starts in his own specialty. Opioids make people feel they sleep better while the sleep lab records less deep sleep, and in a Canadian pain-clinic study of opioid-treated patients who completed a sleep study, 58.8 percent had sleep apnea. A sleep study is a different test, done elsewhere, and any question about a medication belongs with the physician who prescribes it.

What measurement can show in the same person

Measura [Cardiometabolic and Autonomic Health Analysis] puts numbers on hidden change like this and hands them to your physician, who makes any diagnosis or treatment call. Sleep studies are outside its library. For the terrain a broken clock leaves behind, several tests read the damage directly:

• Laboratory panels read blood markers, which is where asking for fasting insulin next to glucose, HbA1c and triglycerides makes the insulin cost of a normal glucose visible instead of assumed.
• Bioimpedance body composition separates lean mass from fat mass, the exact trade that sleep loss makes while the scale stays quiet.
• Heart rate variability reads the beat-to-beat rhythm of the heart, a window on autonomic balance, the same fight-or-flight system that ran hot after six short nights.
• Indirect calorimetry measures resting metabolic rate. In pooled trials of partial sleep loss it did not change while next-day intake rose about 385 calories, so a normal reading points toward appetite and meal timing, not a slow metabolism.

None of those numbers is a verdict. Their value is in the pattern and in the repeat: the same markers, measured again after the nights change, show whether the terrain is moving. One small crossover in eight men with prediabetes shows why the repeat has to include insulin. Eating every meal inside a six-hour morning window, with no weight loss, lowered their insulin and their blood pressure, yet their glucose did not change. A glucose-only follow-up would have scored that as a failure.

Questions worth bringing to your appointment

Unmeasured is unmanaged, and the night is the least measured part of most people’s health. Before your next visit, consider asking:

• Can my sleep history be recorded next to my pain history, with hours and awakenings written down separately?
• Can fasting insulin be checked alongside glucose and HbA1c, and rechecked once my sleep changes?
• Can we measure muscle and fat, not just weight?
• If I take a nightly sedating medication, should I be screened for sleep apnea?

More questions like these are gathered in questions worth asking your doctor. Every study behind these numbers, with its limits spelled out, is in the companion supplement written to hand to your physician. What the same clock hormone does when stress keeps it high for years is covered in how stress cortisol shows up around the waist, and the screening side for clinicians is in the physician edition.

Frequently asked questions

References

• Spiegel, K., Leproult, R., & Van Cauter, E. (1999). Impact of sleep debt on metabolic and endocrine function.
• Rao, M. N., Neylan, T. C., Grunfeld, C., Mulligan, K., Schambelan, M., & Schwarz, J.-M. (2015). Subchronic sleep restriction causes tissue-specific insulin resistance.
• Broussard, J. L., Ehrmann, D. A., Van Cauter, E., Tasali, E., & Brady, M. J. (2012). Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study.
• Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009). Adverse metabolic and cardiovascular consequences of circadian misalignment.
• Leproult, R., Holmbäck, U., & Van Cauter, E. (2014). Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss.
• Nedeltcheva, A. V., Kilkus, J. M., Imperial, J., Schoeller, D. A., & Penev, P. D. (2010). Insufficient sleep undermines dietary efforts to reduce adiposity.
• Srikanthan, P., & Karlamangla, A. S. (2011). Relative muscle mass is inversely associated with insulin resistance and prediabetes.
• Al Khatib, H. K., Harding, S. V., Darzi, J., & Pot, G. K. (2017). The effects of partial sleep deprivation on energy balance: a systematic review and meta-analysis.
• Sutton, E. F., Beyl, R., Early, K. S., Cefalu, W. T., Ravussin, E., & Peterson, C. M. (2018). Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.
• Wasef, S., Mir, S., Ryan, C., Waseem, R., Bellingham, G., Kashgari, A., Wong, J., & Chung, F. (2021). Treatment for patients with sleep apnea on opioids for chronic pain: results of the OpSafe trial.

Related reading

• Frozen Shoulder and Diabetes: The Numbers Worth Checking
• Cortisol and Belly Fat: What Chronic Stress Leaves You Can Measure
• Laboratory Panels

Do Seed Oils Cause Inflammation? Why Your Blood Test May Say No

In trials of healthy adults, seed oils did not raise C-reactive protein or other blood markers of inflammation, but that is not the whole answer. In adults with abdominal obesity, added omega-6 turned up inflammatory genes in fat tissue while the blood markers stayed quiet.

A normal C-reactive protein can sit on top of inflamed tissue. The real question is not only what you eat, but where anyone is looking for the damage.

Do seed oils cause inflammation? Most cardiologists say no, and the blood work behind that answer is real. What that blood work sampled is the interesting part. The video above is Chapter 5 of The Pained Brain, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. The question here is practical: what would show omega-6 harm in a real person, and what the usual test misses.

Do seed oils cause inflammation? The blood test says no

The case against the seed-oil story rests largely on C-reactive protein, the inflammation marker most people have had drawn at some point. When researchers reviewed 15 randomized trials in healthy adults, adding linoleic acid, the main omega-6 fat in soybean, corn and sunflower oil, did not raise CRP or any other inflammatory marker in the blood. A pooling of 30 trials and 1,377 participants agreed, which is why vegetable oil keeps its heart-healthy reputation.

Now look at who was in those trials: healthy volunteers, studied for weeks, with blood drawn from an arm. That is a poor stand-in for someone who has lived with sore joints, a thick waist and high insulin for a decade.

Can seed oils inflame tissue while blood tests look normal?

One randomized crossover trial did look deeper. Thirty-nine adults with abdominal obesity spent seven weeks with added omega-6 and seven weeks with added marine omega-3. Blood markers did not separate between periods; fat biopsies did. During the omega-6 weeks, linoleic acid in the tissue rose by 4.91 percent and inflammatory genes were turned up. During the omega-3 weeks, those genes were turned down.

That is the whole measurement problem in one study. A quiet CRP can sit on top of tissue that is anything but quiet. Unmeasured is unmanaged; measured in the wrong place is little better.

How do omega-6 seed oils drive pain and inflammation?

The first driver is chemistry. Your body lengthens linoleic acid into arachidonic acid, stores it in cell membranes, and during injury converts it into prostaglandin E2, a molecule that lowers the firing threshold of pain nerves. Ibuprofen and naproxen block that step. The second driver skips it. Heat or inflamed tissue oxidizes linoleic acid into metabolites that activate TRPV1, the heat-and-pain channel on the nerve ending. When 55 people with chronic headache cut linoleic acid from 6.7 to 2.4 percent of their calories for 12 weeks, those metabolites fell in their blood.

Your red blood cells keep a record of both. Among 605 adults with chronic pain conditions, a higher proportion of arachidonic acid relative to the omega-3 fats EPA and DHA in the red-cell membrane went with worse facial, headache, low back and whole-body pain scores. That is a snapshot, not proof, but it makes the number worth knowing.

The third driver is economic. Between 1909 and 1999, soybean oil consumption in the United States rose more than a thousandfold, and linoleic acid climbed from 2.79 to 7.21 percent of available calories. Cheap oil became the default fat of packaged and fried food, with a health halo because it lowered cholesterol. The body stored what the market sold: the linoleic acid content of American body fat rose 136 percent over half a century.

Are seed oils bad for you if they lower cholesterol?

Cholesterol is the cautionary tale. In Sydney, 458 men who had survived a heart attack were randomized to replace saturated fat with safflower oil, which is nearly pure linoleic acid. Their cholesterol fell. Deaths from any cause reached 17.6 percent, against 11.8 percent in the comparison group. In Minnesota, 9,423 institutionalized people were put on a corn-oil diet. Cholesterol dropped 13.8 percent against 1.0 percent, and no subgroup lived longer for it. In both, a lab value moved the right way while the people moved the wrong way.

The other side of the fat balance rarely appears on a routine panel. The omega-3 index is the share of EPA and DHA in the red blood cell membrane. More than half of Americans measured in the most recent national survey, 54 percent, had an index under 4 percent, and among adults 97.6 percent fell short of the 8 percent target. Whether it belongs on your order is a question for the physician who orders your lab work.

The second factory: the pan, the vessels and the nervous system

Fried again and again, polyunsaturated oil breaks down into aldehydes such as acrolein that damage proteins and DNA. In obese adults, a breakfast cooked in sunflower oil that had been heated twenty times switched on stress and DNA-damage genes in their white blood cells.

This is where the measurement angle becomes concrete. In 54 male restaurant cooks in China, fine particles from cooking-oil fumes went with lower heart rate variability and a faster heart rate over periods of minutes to hours. In 346 nonsmokers, a higher urinary acrolein metabolite went with worse endothelial function. Both are small or cross-sectional, but they point to two things that can be measured in a person: heart rate variability, the beat-to-beat variation that reflects how the autonomic nervous system is balancing itself, and arterial stiffness and endothelial function, how rigid the arteries have become and how well the vessel lining relaxes.

The pill aimed at the same pathway

My own training ran in one direction: the prescription pad first, the plate as an afterthought. Anti-inflammatory painkillers work by blocking the enzyme that turns arachidonic acid into prostaglandins, so they target the product while the grocery cart keeps restocking the raw material. Their risks show up in the heart and kidneys. Across 280 placebo-controlled trials, every NSAID roughly doubled the risk of heart failure. Among 446,763 people, even one week on ibuprofen went with 1.48 times the odds of a heart attack. Chronic use carried a hazard of 1.50 for chronic kidney disease.

None of that is a reason to stop a medication on your own. It is a reason to know your own vascular picture if one of these drugs is part of your daily routine. See finding cardiovascular risk early.

What tests show whether seed oils are affecting you?

• The omega-3 index, as a red-cell measurement, with a retest at about five months. In a dose-response trial of 115 healthy adults, that is roughly how long the red-cell membrane took to reach its new composition.
• Metabolic blood work beyond glucose. Measura [Cardiometabolic and Autonomic Health Analysis] runs laboratory panels that describe the metabolic terrain the oil lands on.
• Body composition, not just weight. The thin-outside, inflamed-inside pattern is invisible on a bathroom scale. Bioimpedance body composition estimates muscle and fat separately.
• Vascular and autonomic measurements if you take anti-inflammatories daily or cook with reused oil.

Measura measures; it does not treat, and results go to your physician. The backdrop matters: under 12.2 percent of US adults met a full definition of metabolic health on NHANES 2009–2016, and under 7 percent do on the tighter criteria applied after 2021. Every study behind these numbers, with its limits, is on the book’s companion page for Chapter 5, written to hand to your doctor. The next measurement question, sugar bonding to collagen, is covered in frozen shoulder and diabetes. Chronic pain and metabolic health connects the threads.

Frequently asked questions

References

• Grytten, E., Laupsa-Borge, J., Cetin, K., Bohov, P., Nordrehaug, J. E., Skorve, J., Berge, R. K., Strand, E., Bjørndal, B., Nygård, O. K., Rostrup, E., Mellgren, G., & Dankel, S. N. (2025). Inflammatory markers after supplementation with marine n-3 or plant n-6 PUFAs: A randomized double-blind crossover study. Journal of Lipid Research, 66(4), 100770. https://doi.org/10.1016/j.jlr.2025.100770
• Johnson, G. H., & Fritsche, K. (2012). Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. Journal of the Academy of Nutrition and Dietetics, 112(7), 1029-41, 1041.e1-15. https://doi.org/10.1016/j.jand.2012.03.029
• Chan, C. C., Lin, L. Y., Lai, C. H., Chuang, K. J., Wu, M. T., & Pan, C. H. (2021). Association of Particulate Matter from Cooking Oil Fumes with Heart Rate Variability and Oxidative Stress. Antioxidants (Basel), 10(8), 1323. https://doi.org/10.3390/antiox10081323
• McGraw, K. E., Riggs, D. W., Rai, S., Navas-Acien, A., Xie, Z., Lorkiewicz, P., Lynch, J., Zafar, N., Krishnasamy, S., Taylor, K. C., Conklin, D. J., DeFilippis, A. P., Srivastava, S., & Bhatnagar, A. (2021). Exposure to volatile organic compounds – acrolein, 1,3-butadiene, and crotonaldehyde – is associated with vascular dysfunction. Environmental Research, 196, 110903. https://doi.org/10.1016/j.envres.2021.110903
• 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
• Ramsden, C. E., Zamora, D., Leelarthaepin, B., Majchrzak-Hong, S. F., Faurot, K. R., Suchindran, C. M., Ringel, A., Davis, J. M., & Hibbeln, J. R. (2013). Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ, 346, e8707. https://doi.org/10.1136/bmj.e8707
• Bally, M., Dendukuri, N., Rich, B., Nadeau, L., Helin-Salmivaara, A., Garbe, E., & Brophy, J. M. (2017). Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ, 357, j1909. https://doi.org/10.1136/bmj.j1909
• Sanders, A. E., Weatherspoon, E. D., Ehrmann, B. M., Soma, P. S., Shaikh, S. R., Preisser, J. S., Ohrbach, R., Fillingim, R. B., & Slade, G. D. (2023). Circulating Polyunsaturated Fatty Acids and Pain Intensity in Five Chronic Pain Conditions. The Journal of Pain, 24(3), 478-489. https://doi.org/10.1016/j.jpain.2022.10.008
• Flock, M. R., Skulas-Ray, A. C., Harris, W. S., Etherton, T. D., Fleming, J. A., & Kris-Etherton, P. M. (2013). Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. Journal of the American Heart Association, 2(6), e000513. https://doi.org/10.1161/JAHA.113.000513
• Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., Majchrzak, S. F., & Rawlings, R. R. (2011). Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. The American Journal of Clinical Nutrition, 93(5), 950-962. https://doi.org/10.3945/ajcn.110.006643

Related reading

• High Insulin, Normal Blood Sugar: What Your Nerves May Be Showing
• Frozen Shoulder and Diabetes: The Numbers Worth Checking
• Heart Rate Variability

High Insulin, Normal Blood Sugar: What Your Nerves May Be Showing

A normal glucose and a normal A1c can sit on top of years of rising insulin. The nerves that carry pain are often among the first tissues to show the cost, and a routine checkup looks at neither.

High insulin, normal blood sugar: a pattern most checkups are not built to catch. Blood sugar stays in range because the pancreas releases more and more insulin to push sugar into cells that have stopped responding well. The glucose number looks reassuring. The effort behind it never appears on a standard panel, and small nerves can be paying for that effort for years.

The video The Hormone Nobody Measured Is Starving Your Nerves covers Chapter 4 of The Pained Brain, by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. Measura [Cardiometabolic and Autonomic Health Analysis] takes the measurement side of it: what a normal result can hide, which parts of the damage can be measured before any diagnosis, and what to ask for at your next visit.

How long can insulin run high before blood sugar rises?

Long-term studies answer this by looking backward from the day diabetes was diagnosed. British civil servants who later developed diabetes were already 34.2% less sensitive to insulin thirteen years earlier, while their fasting glucose barely budged, from 5.47 to 5.79 mmol/L. In a Japanese cohort of 27,392 adults, people who would later be told they had prediabetes already showed lower insulin sensitivity ten years before that label, with fasting sugar of 91.8 mg/dL against 89.6 in people who never progressed. No one would flag a gap that small.

A glucose tolerance test with insulin measured at the same time shows the hidden half. Among 4,185 people whose glucose handling was entirely normal, 2,079 were producing abnormal amounts of insulin to keep it that way. Roughly half of “normal” was compensating, and a glucose-only result could not tell them apart.

Can high insulin damage your nerves and their blood supply?

Insulin opens blood vessels through one signal and tightens them through another. When the body becomes resistant, the opening signal weakens while the tightening one keeps working. In 40 obese adults with no diabetes, the most insulin-resistant third widened their arteries by 9.2% on testing, compared with 18.0% in the least resistant third.

Nerves are fed by tiny vessels that run inside them. Swedish researchers biopsied a leg nerve in a group of men and came back eleven years later. The men who went on to develop diabetes had, at the first biopsy, capillaries inside the nerve with an open channel of 5.5 square micrometers, against 22.8 in the men who stayed healthy. The nerve was short of blood before any diagnosis existed.

The front of the eye shows the same process, and shows that it can turn around. People with impaired glucose tolerance already had fewer corneal nerve fibers than controls, 24.4 against 30.7 per square millimeter. The five who reversed their glucose intolerance grew nerve back, from 25.4 to 29.8. Laboratory work adds a second effect: insulin makes pain-sensing nerve cells fire more readily. That evidence comes from animal tissue, not people, but it explains how a metabolic hormone can turn up the volume on pain.

Why can a routine nerve test come back normal?

Small nerve fibers, the ones that carry pain and temperature, tend to fail before the large fibers that standard nerve conduction studies measure. When Heidelberg researchers tested people with prediabetes, a full sensory battery found nerve damage in 71%. The usual bedside score found it in 11%, and nerve conduction studies missed 58% of what the battery caught. More than half had nerves that were oversensitive rather than numb.

Weight and waist matter even without a diabetes diagnosis. In a Michigan cohort, nerve damage turned up in 3.8% of lean adults, 11.1% of obese adults with normal glucose and 29.0% of obese adults with prediabetes. In a German cohort followed for six and a half years, every five centimeters of waist added 22% to the odds of developing neuropathy, with or without diabetes. And in a 2001 study of patients told their painful neuropathy had no known cause, 34% had impaired glucose tolerance that only a sugar drink revealed.

That is where sudomotor testing fits. Tiny nerve fibers switch on the sweat glands in your hands and feet, and this test checks how well that signal works, something a conduction study does not assess. Burning or tingling feet are covered in numbness, burning and tingling.

Why isn’t fasting insulin on a routine blood test?

The honest reason is that the test was never standardized. When the same blood samples were run on twelve commercial insulin assays, results varied by a median of 24%. By 2025, just one of twelve methods matched the laboratory gold standard. Without a standard there are no agreed cutoffs, and current diabetes diagnostic standards define prediabetes by glucose and A1c without naming fasting insulin at all. No standard, no guideline, no routine order. The gap is institutional, not biological.

The number is still useful when it is read with care. In an Iranian cohort followed for nine years, future diabetes became more likely once fasting insulin passed about 9.16 for men or 11.13 for women, well under the top of many printed reference ranges. A value repeated over time on the same assay is the comparison that means something.

What tests show high insulin with normal blood sugar?

A measurement plan for this pattern has several parts, and none of them is a diagnosis on its own:

• Blood work. Laboratory panels can include fasting glucose, HbA1c and triglycerides. Ask whether fasting insulin is on the requisition, because insulin and glucose drawn together allow HOMA-IR to be calculated. C-peptide is the body’s own record of how much insulin it is making, and among 5,249 Danes newly diagnosed with type 2 diabetes it tracked neuropathy more strongly than A1c did.
• Small-fiber nerve function. Sudomotor testing, described above.
• Vessel function. Arterial stiffness and endothelial function testing describes how the artery wall responds, the property insulin resistance wears down.
• Body composition. Bioimpedance body composition separates fat from lean tissue, which a bathroom scale cannot do.

Findings go to your physician. They describe terrain; what to do about it is a clinical conversation. The research on reversal is encouraging. In a randomized trial of 100 adults with type 2 diabetes, a year of supervised exercise regrew small nerve fibers in the leg by 1.5 fibers per millimeter while A1c stayed flat. In 32 people with prediabetes and neuropathy, those whose fibers regrew most after a year of diet and exercise counseling had the largest drop in nerve pain. Movement and food are biology, and they are also schedules, neighborhoods and habits, which is why a measured baseline helps: it turns a vague warning into a number that can be tracked. The full evidence, including the studies that disagree, is in the book companion for Chapter 4, and the imaging side of the same argument is in what degenerative disc disease means.

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. Lancet, 373(9682), 2215–2221. https://doi.org/10.1016/S0140-6736(09)60619-X
• Crofts, C., Schofield, G., Zinn, C., Wheldon, M., & Kraft, J. (2016). Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database. Diabetes Research and Clinical Practice, 118, 50–57. https://doi.org/10.1016/j.diabres.2016.06.007
• Galvao, R., Plavnik, F. L., Ribeiro, F. F., Ajzen, S. A., Christofalo, D. M. de J., & Kohlmann, O. (2011). Effects of different degrees of insulin sensitivity on endothelial function in obese patients. Arquivos brasileiros de cardiologia, 98(1), 45–51. https://doi.org/10.1590/s0066-782×2011005000119
• Mohseni, S., Badii, M., Kylhammar, A., Thomsen, N. O. B., Eriksson, K.-F., Malik, R. A., Rosen, I., & Dahlin, L. B. (2017). Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy. Brain and behavior, 7(8), e00763. https://doi.org/10.1002/brb3.763
• Azmi, S., Ferdousi, M., Petropoulos, I. N., Ponirakis, G., Alam, U., Fadavi, H., Asghar, O., Marshall, A., Atkinson, A. J., Jones, W., Boulton, A. J. M., Tavakoli, M., Jeziorska, M., & Malik, R. A. (2015). Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes. Diabetes care, 38(8), 1502–8. https://doi.org/10.2337/dc14-2733
• Kopf, S., Groener, J. B., Kender, Z., Fleming, T., Bischoff, S., Jende, J., Schumann, C., Ries, S., Bendszus, M., Schuh-Hofer, S., Treede, R.-D., & Nawroth, P. P. (2018). Deep phenotyping neuropathy: An underestimated complication in patients with pre-diabetes and type 2 diabetes associated with albuminuria. Diabetes Research and Clinical Practice, 146, 191–201. https://doi.org/10.1016/j.diabres.2018.10.020
• Callaghan, B. C., Xia, R., Reynolds, E., Banerjee, M., Rothberg, A. E., Burant, C. F., Villegas-Umana, E., Pop-Busui, R., & Feldman, E. L. (2016). Association Between Metabolic Syndrome Components and Polyneuropathy in an Obese Population. JAMA Neurology, 73(12), 1468–1476. https://doi.org/10.1001/jamaneurol.2016.3745
• Christensen, D. H., Knudsen, S. T., Gylfadottir, S. S., Christensen, L. B., Nielsen, J. S., Beck-Nielsen, H., Sørensen, H. T., Andersen, H., Callaghan, B. C., Feldman, E. L., Finnerup, N. B., Jensen, T. S., & Thomsen, R. W. (2020). Metabolic Factors, Lifestyle Habits, and Possible Polyneuropathy in Early Type 2 Diabetes: A Nationwide Study of 5,249 Patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Cohort. Diabetes Care, 43(6), 1266–1275. https://doi.org/10.2337/dc19-2277
• Marcovina, S., Bowsher, R. R., Miller, W. G., Staten, M., Myers, G., Caudill, S. P., Campbell, S. E., & Steffes, M. W., for the Insulin Standardization Workgroup (2007). Standardization of insulin immunoassays: report of the American Diabetes Association Workgroup. Clinical Chemistry, 53(4), 711–716. https://doi.org/10.1373/clinchem.2006.082214
• Singleton, J. R., Marcus, R. L., Jackson, J. E., K Lessard, M., Graham, T. E., & Smith, A. G. (2014). Exercise increases cutaneous nerve density in diabetic patients without neuropathy. Annals of Clinical and Translational Neurology, 1(10), 844–849. https://doi.org/10.1002/acn3.125

Related reading

• What Does Degenerative Disc Disease Mean for Your Numbers?
• Do Seed Oils Cause Inflammation? Why Your Blood Test May Say No
• Sudomotor Testing

What Does Degenerative Disc Disease Mean for Your Numbers?

Degenerative disc disease is one of the most common phrases on a spine report. For most adults it describes a normal spine, and the part that matters sits in blood work and blood vessels the scan never sees.

Your MRI report lists “degenerative disc disease,” and the phrase lands like a diagnosis. So what does degenerative disc disease mean? In most adults it names the ordinary wear a spine collects with years of use: discs that have lost some height, bulges, worn facet joints. It tells you what the tissue looks like. It does not tell you why you hurt, and it says nothing about the blood chemistry and blood vessels that feed that tissue.

Dr. Padda’s video Your MRI Is Lying to You lays out the argument from Chapter 3 of The Pained Brain, written by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD. Measura [Cardiometabolic and Autonomic Health Analysis] picks up where the picture stops. The scan shows shape. The question here is which measurements show the terrain around that shape, and why a routine back-pain visit rarely orders them.

What does degenerative disc disease mean when nothing hurts?

Radiologists have been scanning adults without back pain for three decades, and the answer keeps coming back the same. Pooled across 33 studies and 3,110 people with no symptoms, disc degeneration was already present in 37% of twenty-year-olds. By fifty it was 80%. By eighty it was 96%. Bulging discs climbed from 30% to 84% across the same ages, and wear in the facet joints from 4% to 83%.

If most people your age carry the finding and feel fine, the finding cannot be the whole explanation for your pain. Having more wear than your age predicts does not settle it either. Among 382 Japanese community residents, those whose discs looked older than expected reported back pain 17% of the time, and those whose discs matched their age reported it 21% of the time.

How much of your pain can an MRI explain?

Put a number on the link and it shrinks. Across 4,796 adults with arthritic knees, the best MRI-based model could account for no more than 28% of how much their knees hurt, and X-ray features for no more than 15%. Among 180 people already booked for rotator cuff repair, tear length accounted for about 1.2% of their pain. In a large hip cohort, an X-ray showing arthritis had a positive predictive value for hip pain of only 6.0%.

Structure is not meaningless. Inside one body, a badly worn knee hurts more often than the clean knee on the other side. Across different people, though, the same image produces very different pain. In one group of 113 people with knee arthritis, 57 had pain that did not match their X-ray, and those with severe pain but a mild X-ray turned out to have a more sensitive nervous system on formal testing. The camera cannot see how sensitive a nervous system is.

What makes back pain worse without changing the scan?

Several human experiments show pain thresholds shifting across the whole body while the spine stays untouched. Two nights of repeatedly broken sleep lowered heat-pain thresholds in healthy adults, and 34.9% of that change traveled through inflammation produced by their own immune cells. One 37.5-gram glucose drink weakened the nervous system’s ability to turn pain down, more so in people with a higher waist-to-hip ratio. Sleep, sugar and the inflammation they stir up are biological drivers. How people sleep and eat is shaped by work schedules, food environments and stress, which is part of why the same finding behaves so differently from one life to the next.

The most useful of these studies for measurement involved 223 people waiting for knee replacement. Fat mass, measured with bioimpedance, tracked lower pain thresholds at every site tested, including the forehead, which has no arthritis in it. Body mass index tracked none of it. Bioimpedance body composition estimates fat and lean tissue separately, so a normal weight carrying a high share of fat does not get filed as healthy. The difference is explained in body composition, not BMI.

What causes degenerative disc disease besides age?

A spinal disc has no blood supply of its own. It takes in nutrients by diffusion from nearby vessels, so when those vessels narrow, the disc goes hungry. In the Framingham cohort, calcification of the abdominal aorta at a given level predicted breakdown of the disc served by that level 25 years later, with an odds ratio of 1.5. In a pooled analysis of 2,881,170 adults, diabetes came with 1.68 times the odds of degenerated discs. The wear on the report is often a record of the terrain, not only of the years.

A Japanese community study makes the point with two people and one picture. Among residents whose MRI showed the same moderate narrowing of the spinal canal, what separated those with symptoms from those without was not age, sex or body mass index. Diabetes was present in 25.0% of the symptomatic group and 6.4% of the others, and a lower ankle-brachial index also marked the people with symptoms.

Measura does no imaging; the MRI is a different test, done elsewhere. What it can add is the vascular side. An ankle-brachial index compares blood pressure at the ankle with blood pressure at the arm to show how well blood reaches the legs. Arterial stiffness and endothelial function testing describes how the artery wall behaves. Neither photographs a disc. Both describe the circulation that discs and nerves depend on.

What tests should you ask for besides an MRI?

Scans have a real job. Among 1,172 people seen in primary care for back pain, 0.9% had a serious cause, most often a fracture, and radiology’s own criteria reserve imaging for warning signs or for pain that has not improved after about six weeks of care. The imbalance runs the other way: 24.8% of primary-care back-pain visits end in imaging, yet a metabolic panel is rarely drawn the same day. The system is built to photograph the spine, not to measure the person.

A practical list to bring to your physician: HbA1c, fasting glucose, triglycerides and HDL cholesterol, which are standard laboratory panels; a body composition measurement rather than body mass index alone; a circulation check if walking brings on leg pain; and an honest answer about how you sleep. Results go to your physician, who reads them next to your examination and the scan. The study-by-study evidence is in the book companion for Chapter 3, and more prompts are in questions worth asking your doctor.

The picture records where the tissue has been. Blood work and vessel measurements show where it is heading, and they can be repeated to see whether it changes. The hormone upstream of much of this is the subject of high insulin with normal blood sugar.

Frequently asked questions

References

• Brinjikji, W., Luetmer, P. H., Comstock, B., Bresnahan, B. W., Chen, L. E., Deyo, R. A., Halabi, S., Turner, J. A., Avins, A. L., James, K., Wald, J. T., Kallmes, D. F., & Jarvik, J. G. (2015). Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. AJNR. American Journal of Neuroradiology, 36(4), 811–816. https://doi.org/10.3174/ajnr.A4173
• Watanabe, T., Otani, K., Sekiguchi, M., & Konno, S. I. (2022). Relationship between lumbar disc degeneration on MRI and low back pain: A cross-sectional community study. Fukushima Journal of Medical Science, 68(2), 97–107. https://doi.org/10.5387/fms.2022-17
• Hill, B. G., Eble, S., Moschetti, W. E., & Schilling, P. L. (2025). The Discordance Between Pain and Imaging in Knee Osteoarthritis. The Journal of the American Academy of Orthopaedic Surgeons, 33(14), e786–e794. https://doi.org/10.5435/JAAOS-D-24-00509
• Finan, P. H., Buenaver, L. F., Bounds, S. C., Hussain, S., Park, R. J., Haque, U. J., Campbell, C. M., Haythornthwaite, J. A., Edwards, R. R., & Smith, M. T. (2013). Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis and Rheumatism, 65(2), 363–72. https://doi.org/10.1002/art.34646
• Irwin, M. R., Olmstead, R., Bjurstrom, M. F., Finan, P. H., & Smith, M. T. (2023). Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial. Pain, 164(5), 1128–1137. https://doi.org/10.1097/j.pain.0000000000002811
• Meert, L., Vervullens, S., Heusdens, C. H. W., Smeets, R. J. E. M., Meeus, M., & Mertens, M. G. C. A. M. (2024). Unravelling relationships between obesity, diabetes, and factors related to somatosensory functioning in knee osteoarthritis patients. Clinical Rheumatology, 43(8), 2637–2645. https://doi.org/10.1007/s10067-024-07022-2
• Kauppila, L. I., McAlindon, T., Evans, S., Wilson, P. W., Kiel, D., & Felson, D. T. (1997). Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham. Spine, 22(14), 1642-1647; discussion 1648-1649. https://doi.org/10.1097/00007632-199707150-00023
• Maeda, T., Hashizume, H., Yoshimura, N., Oka, H., Ishimoto, Y., Nagata, K., Takami, M., Tsutsui, S., Iwasaki, H., Minamide, A., Nakagawa, Y., Yukawa, Y., Muraki, S., Tanaka, S., Yamada, H., & Yoshida, M. (2018). Factors associated with lumbar spinal stenosis in a large-scale, population-based cohort: The Wakayama Spine Study. PLoS One, 13(7), e0200208. https://doi.org/10.1371/journal.pone.0200208
• Wang, X., Gao, Z., Chen, K., Huang, C., & Li, Y. (2024). Diabetes Mellitus and Intervertebral Disc Degeneration: A Meta-Analysis. World Neurosurgery, 188, e81–e92. https://doi.org/10.1016/j.wneu.2024.05.043
• Henschke, N., Maher, C. G., Refshauge, K. M., Herbert, R. D., Cumming, R. G., Bleasel, J., York, J., Das, A., & McAuley, J. H. (2009). Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain. Arthritis and Rheumatism, 60(10), 3072–3080. https://doi.org/10.1002/art.24853

Related reading

• Monofilament Test: What It Means When You Can’t Feel Your Feet
• High Insulin, Normal Blood Sugar: What Your Nerves May Be Showing
• Bioimpedance Body Composition

Fasting Insulin Test: What a Normal A1c Can Hide When You Hurt

A normal A1c can hide years of rising insulin. A fasting insulin test shows the extra insulin the body is making to keep glucose in range, and that excess injures blood vessels and makes nerves quicker to fire, which is why it belongs in a chronic pain workup.

Your A1c came back fine and your back still hurts. The number that connects the two is usually the one nobody ordered.

A fasting insulin test measures how hard the pancreas is working to hold blood sugar steady, and it can show metabolic strain years before glucose moves. Most people who have lived with chronic pain for years have never had one drawn.

The video The Cost of Pain Is Paid in Years, from The Pained Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, and Dr. KrisJay Fucanan, MD, argues that long-lasting pain often lives inside a body running on high insulin. The practical question for you is what would show that in your own numbers, what a routine visit checks, and what it leaves unmeasured.

Why don’t doctors order a fasting insulin test?

A standard visit usually looks at fasting glucose, sometimes hemoglobin A1c, blood pressure, weight and cholesterol. Those are useful numbers. They are also late numbers. Insulin is the hormone that moves sugar out of the blood and into cells. When cells start ignoring it, the pancreas simply makes more, and glucose stays inside its normal range for years while insulin keeps rising. A normal A1c tells you the system is still coping. It does not tell you what the coping is taking.

That hidden phase is not rare. Among American adults without diabetes, high fasting insulin reached 41.4 percent in 2017-2018, up from 28.2 percent in 1999-2000, while measurable insulin resistance reached 38.4 percent, up from 24.8 percent. In that national survey work, high fasting insulin meant a level above 10 µU/mL. That is a population cut point, not a diagnosis. The earlier stages are laid out in what insulin resistance looks like before diabetes.

Dr. Padda has said he spent years telling patients with prediabetes that their A1c was not too bad. The physiology changed his mind. By the time glucose finally rises, the pancreas has been straining for a long while, and blood vessels and nerves have been soaking in the extra insulin the entire time.

Is chronic pain linked to insulin resistance?

In the latest national survey, 24.3 percent of American adults had pain on most days. It is far more common where metabolic disease already sits, at 37.7 percent of adults with diabetes and 40.7 percent of adults with coronary heart disease. The overlap has a biological basis. Excess insulin injures the inner lining of blood vessels, cuts the blood supply that nerves depend on, and makes a nerve quicker to fire. A second driver is visceral fat, the fat packed around the organs, which acts less like storage and more like a gland releasing inflammatory signals around the clock.

The traffic runs in both directions. In 84,565 British adults over sixty with no diabetes at the start, pain at four to seven body sites raised the hazard of later type 2 diabetes to 1.198, and weight gain accounted for close to half of that. Hurting limits movement, less movement adds fat, fat drives insulin up, and insulin sharpens the pain. That loop is the reason chronic pain and metabolic health are worth measuring side by side.

Biology is not the only engine. Among Americans without a four-year degree, pain at age 52 was reported by 40 percent of the 1965 birth cohort compared with 32 percent of the 1955 cohort, and body mass explained only about a quarter of that rise. Schooling and work shape who hurts, and the food, sleep and movement that push insulin up.

Does a normal CRP mean there is no inflammation?

The blood marker most often ordered to look for inflammation is C-reactive protein, or CRP. A normal result is easy to read as a quiet body, and the research does not back that reading. In 5,905 American adults scored for visceral fat, the top quarter carried 1.87 times the odds of chronic pain seen in the bottom quarter, and CRP accounted for only 7.4 percent of that association. Studies using inherited gene variants find no causal effect of higher CRP on spinal pain.

What seems to matter is inflammation that switches on and never switches off, which the book calls metaflammation. In 98 people with new low back pain, those who recovered showed a large immune response that rose and then settled, while those whose pain turned chronic showed no such wave. One marker on one morning cannot capture that, so the useful move is to measure the terrain that keeps it smoldering.

Can you be insulin resistant at a normal weight?

Weight and body mass index miss the same problem from a different angle. In a nine-year study of 3,546 Chinese adults with an average BMI of 23.76, squarely normal, each unit rise in a bedside insulin-resistance index built from fasting triglycerides and glucose raised the odds of new severe chronic pain 1.51-fold. East Asian and South Asian adults often carry more fat in the liver and around the organs at the same BMI, the pattern known as skinny fat: thin outside, insulin resistant inside.

That is where bioimpedance body composition earns its place. It estimates how much of your weight is fat and how much is lean tissue, which a bathroom scale cannot separate. It is not a diagnosis; it shows a compartment total weight conceals, which is why body composition is not the same as weight.

What Measura adds to a standard panel

Measura [Cardiometabolic and Autonomic Health Analysis] collects measurements and sends every result to your physician, who decides what they mean; the service neither treats nor diagnoses by itself. For someone whose pain has been handled one joint at a time, three measurements speak directly to the terrain described above.

• Laboratory panels. Blood work that can add fasting insulin to glucose and A1c, along with the triglyceride and HDL pattern that feeds the insulin-resistance index.
• Body composition. Fat and lean tissue as separate numbers, so a normal weight cannot hide a high fat share.
• Arterial stiffness and endothelial function. How flexible the arteries are and how well the vessel lining responds, the same lining that excess insulin damages.

None of these explains why a particular joint hurts. Together they describe the body the pain is living in, the part no scan of the joint can show. See how to read your Measura report.

What to ask for at your next visit

The next step is small and specific. Ask for the fasting insulin number itself, not only the glucose. Ask whether a triglyceride-glucose index can be calculated from labs you already have; it needs just fasting triglycerides and fasting glucose. Ask to have your waist measured in centimeters, since the metabolic-health definition sets it below 102 cm for men and 88 cm for women. And ask that the number of places you hurt be written into your chart.

By every criterion at once, fewer than 12.2 percent of US adults counted as metabolically healthy in NHANES 2009–2016 data; judged by the stricter post-2021 yardstick, the share falls below 7 percent. In Dr. Padda’s practice, fewer than 1 percent of chronic pain patients meet that definition; these are practice-reported figures from our own population, not trial outcomes, and individual results vary. Unmeasured is unmanaged. Nothing here is a reason to change a medication, so bring the numbers to your physician. The studies behind every figure are in the Chapter 1 supplement, and the next piece of the argument is what losing feeling in the feet tells you.

Frequently asked questions

References

• Wu, C., Ke, Y., & Nianogo, R. A. (2025). Trends in Hyperinsulinemia and Insulin Resistance Among Nondiabetic US Adults, NHANES, 1999-2018. Journal of Clinical Medicine, 14(9), Article 3215. https://doi.org/10.3390/jcm14093215
• Zhu, J., Wang, Y., Yu, G., Li, L., He, J., Liao, H., & Wu, X. (2025). Association between metabolic score for visceral fat and chronic pain: a cross-sectional analysis of NHANES 1999-2004. Frontiers in Nutrition, 12, Article 1545774. https://doi.org/10.3389/fnut.2025.1545774
• Zhao, D., Cui, Y., Lu, H., Yang, H., Guo, W., Shan, Z., & Wu, C. (2026). Association Between the Triglyceride-Glucose Index and Incident Chronic Severe Pain in Middle-Aged and Older Chinese Adults: A Nationwide Cohort Study. Pain Research & Management, 2026, 2464060. https://doi.org/10.1155/prm/2464060
• Liang, J., He, X., Ouyang, Y., Song, X., Li, M., Qi, T., Chen, J., Zhang, X., Guo, X., Jia, T., Wu, S., Kou, C., & Bai, W. (2026). Association between chronic pain and type 2 diabetes in older adults: A prospective study in the UK Biobank. The Journal of Pain, 43, 106272. https://doi.org/10.1016/j.jpain.2026.106272
• Rikard, S. M., Strahan, A. E., Schmit, K. M., & Guy, G. P. (2023). Chronic Pain Among Adults – United States, 2019-2021. MMWR. Morbidity and Mortality Weekly Report, 72(15), 379–385. https://doi.org/10.15585/mmwr.mm7215a1
• Suri, P., Tsepilov, Y. A., Elgaeva, E. E., Williams, F. M. K., Freidin, M. B., & Stanaway, I. B. (2025). A Mendelian randomization study finds no evidence for causal effects of C-reactive protein on chronic pain conditions. Pain medicine (Malden, Mass.), 26(4), 222–224. https://doi.org/10.1093/pm/pnae122
• Case, A., Deaton, A., & Stone, A. A. (2020). Decoding the mystery of American pain reveals a warning for the future. Proceedings of the National Academy of Sciences of the United States of America, 117(40), 24785-24789. https://doi.org/10.1073/pnas.2012350117
• Araújo, J., Cai, J., & Stevens, J. (2019). Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009-2016. Metabolic Syndrome and Related Disorders, 17(1), 46–52. https://doi.org/10.1089/met.2018.0105

Related reading

• Monofilament Test: What It Means When You Can’t Feel Your Feet
• Laboratory Panels

Keto Diet and Alzheimer’s: What to Measure Before You Believe It

The ketogenic diet gives modest, real memory gains in mild cognitive impairment and early Alzheimer’s: ten pooled trials raised MMSE scores 1.25 points without changing daily function, and eight used a supplement. Whether it works in you shows in fasting insulin, lipids, blood ketones, a memory baseline and fat versus lean mass.

The ketogenic diet has a century of proof in epilepsy and a smaller, honest record in memory loss. Whether it is doing anything in you comes down to numbers most visits never collect.

If you have searched keto diet Alzheimer’s, you have met two camps: people who call it a cure and people who call it a fad. The evidence sits in neither. In the video One Correction, Many Diseases, drawn from The Starved Brain by Dr. Gurpreet Singh Padda, MD, MBA, MHP, the verdict is stated plainly: established for drug-resistant epilepsy, modest but real for mild cognitive impairment and early Alzheimer’s disease, mixed for Parkinson’s disease, preliminary beyond that. Measura [Cardiometabolic and Autonomic Health Analysis] does not prescribe a diet. It measures the terrain a diet is supposed to change, which is the part of the story that usually goes missing.

Why would a keto diet help an Alzheimer’s brain?

The Alzheimer’s brain has trouble taking up glucose, its usual fuel. On dual-tracer PET scans, brain glucose use ran about 11% lower in people with early Alzheimer’s than in healthy older adults, while ketone uptake did not differ. Picture an engine with two fuel lines: one is clogged, the other still flows. Ketones, which the body makes when insulin is low and carbohydrate is scarce, travel through the open line.

Two more drivers ride along. Chronically high insulin feeds insulin resistance inside the brain; in 683 older Manhattan adults, high insulin levels doubled the risk of Alzheimer’s disease. And beta-hydroxybutyrate, the main ketone, quiets an inflammatory switch called the NLRP3 inflammasome in cell and mouse studies. That last finding is laboratory evidence, not a human trial, and it should be read at that level.

The third driver is not biological at all. The ketogenic diet nearly vanished from epilepsy care once anticonvulsant drugs arrived, not because it failed but because a prescription is easier to write than a diet is to support. The same pressure shapes memory care now. Metabolism gets a pamphlet; the drug gets the appointment.

Does the keto diet help Alzheimer’s? What the memory trials found

Three results carry most of the weight.

• A six-month randomized trial gave 122 adults aged 55 and older with mild cognitive impairment a ketogenic MCT drink or a placebo. Recall, verbal fluency and naming improved, and the gains rose with blood ketone levels. That dose-response pattern is the strongest clue that fuel matters.
• A meta-analysis pooled ten randomized trials in 691 patients. Scores on the MMSE, a standard memory screen, rose 1.25 points on average. Daily function did not change. Eight of the ten trials used a supplement, not a whole diet.
• A whole-diet crossover trial in 26 people with probable Alzheimer’s improved daily function and quality of life, but not cognitive scores.

Modest is the honest word. Nobody in these trials got their old self back. Set against the approved anti-amyloid antibodies, which slowed decline by less than a point on an 18-point scale and carry brain swelling as a known risk, modest and real still deserves attention.

The people the trials left out

Here is the detail most summaries skip. The six-month MCT trial screened out people with uncontrolled diabetes, heart, liver or kidney disease, uncontrolled blood pressure or cholesterol, and B12 deficiency. The whole-diet trial excluded abnormal B12, folate and thyroid results. Put simply, the overfed, insulin-resistant patient with a fatty liver was never in the brain trials.

That cuts both ways. The MCT researchers expected prediabetic older adults to respond somewhat less. Yet a 2026 trial at Washington University in St. Louis, which enrolled exactly that patient, found that liver insulin sensitivity improved two to three times more on a ketogenic diet than on a Mediterranean diet when every group lost the same 10% of body weight. Your result cannot be borrowed from a trial that excluded you. It has to be measured.

What does a standard visit check, and what does it miss?

A routine panel reports fasting glucose and hemoglobin A1c. Both are late signals. In 6,538 British civil servants tracked before a diabetes diagnosis, insulin sensitivity was already sliding years before fasting glucose climbed. A person can carry heavy insulin resistance behind a normal glucose and be told all is well. Dr. Padda’s clinic treats a fasting insulin above 10 µIU/mL as high risk; that is his practice cutoff, not a laboratory range.

A routine visit also seldom records a memory baseline, seldom separates fat from muscle when the scale moves, and seldom follows LDL particles after someone changes how they eat. Those gaps matter, because each one is a number the ketogenic trials actually tracked.

The numbers worth having before and after

If you and your physician decide a supervised trial of ketogenic eating makes sense, these measurements turn it from a hope into a result:

• Fasting insulin and lipids. Laboratory panels show where insulin, glucose and cholesterol sit before any change. Across 62 randomized trials in adults, ketogenic diets lowered triglycerides by about 19.96 mg/dL while raising LDL cholesterol by about 8.49 mg/dL, so the lipid picture deserves a repeat check rather than an assumption.
• Ketone level. In the diet trials with positive results, blood beta-hydroxybutyrate ran between 0.95 and 1.3 mmol/L. Ask your physician how your protocol will check it. A diet called ketogenic but never measured is only a menu.
• Memory and thinking. A cognitive assessment gives you a documented starting point, so a later score has something to be compared against.
• Fat versus lean mass. The whole-diet trial reported weight loss of 2.62 kg. Bioimpedance body composition estimates how much of a change came from fat and how much from muscle, which a bathroom scale cannot tell you.

Measura measures and reports. It does not diagnose Alzheimer’s disease and does not treat it. Results go to your physician, who decides what they mean for you.

Safety, and the family-history question

Ketogenic therapy is a medical intervention. The book’s companion material is explicit that anyone taking medication for diabetes or blood pressure, anyone pregnant or breastfeeding, and anyone with kidney, liver, gallbladder or pancreatic disease or a history of disordered eating needs medical supervision for a significant diet change. Medication questions belong with the prescriber before the first meal changes, never after.

People who carry APOE4, the strongest common genetic risk for late-onset Alzheimer’s, often ask whether any of this applies to them. Among 2,157 Swedish adults, all at least 60 years old, the carriers who ate the most meat, roughly 900 grams a week, did not show the extra dementia risk their genes predicted. That is one observational study, and supplement trials in carriers point in different directions. What the research agrees on is that carriers are unusually sensitive to diet and metabolism. Which way that sensitivity runs in one person is a measurement question. Genes set the odds; terrain has a great deal to say about the outcome.

What to do with this

Unmeasured is unmanaged. The ketogenic record is credible precisely because researchers measured ketones, scores and lipids instead of taking the diet on faith. You deserve the same standard. Ask for a fasting insulin number, a cognitive baseline and a body composition reading before anyone decides what your brain needs, then ask for them again. The trial-by-trial evidence is in the Chapter 9 companion evidence guide, and what an evaluation before symptoms looks like continues in measuring for dementia prevention. The mechanism behind the diet, a fuel the insulin-resistant brain can still take up, is covered in ketones as brain fuel.

Frequently asked questions

References

• Fortier, M., Castellano, C.-A., St-Pierre, V., Myette-Côté, É., Langlois, F., Roy, M., Morin, M.-C., Bocti, C., Fulop, T., Godin, J.-P., Delannoy, C., Cuenoud, B., & Cunnane, S. C. (2021). A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6-month RCT. Alzheimer’s & Dementia, 17(3), 543–552. https://doi.org/10.1002/alz.12206
• Rong, L., Peng, Y., Shen, Q., Chen, K., Fang, B., & Li, W. (2024). Effects of ketogenic diet on cognitive function of patients with Alzheimer’s disease: A systematic review and meta-analysis. The Journal of Nutrition, Health and Aging, 28(8), 100306. https://doi.org/10.1016/j.jnha.2024.100306
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• Croteau, E., Castellano, C. A., Fortier, M., Bocti, C., Fulop, T., Paquet, N., & Cunnane, S. C. (2018a). 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
• Petersen, M. C., Smith, G. I., Farabi, S. S., Palacios, H. H., Shankaran, M., Hellerstein, M. K., Patterson, B. W., & Klein, S. (2026). Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial. Cell Metabolism. Advance online publication. https://doi.org/10.1016/j.cmet.2026.07.020
• Chang, C., Liu, Y., Rohani, P., Khodadadi, N., Prabahar, K., & Sohouli, M. H. (2026). The impact of the ketogenic diet on the lipid profile in adults: A comprehensive review and meta-regression analysis of randomized controlled trials. Endocrine Practice, 32(5), 819–828. https://doi.org/10.1016/j.eprac.2026.01.009
• Norgren, J., Carballo-Casla, A., Grande, G., Börjesson-Hanson, A., Xu, H., Eriksdotter, M., Laukka, E. J., & Garcia-Ptacek, S. (2026). Meat consumption and cognitive health by APOE genotype. JAMA Network Open, 9(3), Article e266489. https://doi.org/10.1001/jamanetworkopen.2026.6489
• 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
• 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
• Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D’Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., Kang, S., Horvath, T. L., Fahmy, T. M., Crawford, P. A., Biragyn, A., Alnemri, E., & Dixit, V. D. (2015). The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine, 21(3), 263–269. https://doi.org/10.1038/nm.3804

Related reading

• Gum Disease and Dementia: What Is Proven and What to Measure
• Dementia Prevention Starts With Numbers You Can Measure Now
• Laboratory Panels