Diet, Insulin Resistance and Mood

Anxiety and depression improve when insulin resistance is treated in patients whose mood symptoms share a metabolic driver. A diet high in sugar and fat causes inflammation. That inflammation reaches the brain. There it dulls the dopamine system, which runs drive and motivation.

Can anxiety and depression get better, almost by surprise, when insulin resistance is treated? We ask for a reason. More than 90% of the patients seen in this city interventional pain practice have metabolic dysfunction (a body that handles fuel badly). Their mood symptoms move when their metabolism does.

Can diet affect your mood and memory?

Researchers have studied again and again how much diet affects the brain. A diet high in sugar and fat has measurable effects on memory and mood. How it happens is no mystery. Inflammation signals reach the brain. Glucose supply to the brain gets thrown off. Gut bacteria change the brain-active chemicals they make. And the dopamine system that runs motivation takes a hit.

How does inflammation affect dopamine and motivation?

Chronic inflammation directly hits the dopamine system that drives motivation. That helps explain why drive drops in metainflammation (body-wide inflammation fed by metabolism). It also helps explain anhedonia (loss of pleasure). Anhedonia so often comes with diabetes and chronic pain. A patient called unmotivated may be describing a chemical state in the brain. It may not be a flaw in character at all.

How are chronic pain, anxiety and depression connected?

Anxiety and depression are routinely treated as side problems of chronic pain — the expected result of living with it. That view is incomplete. When all three share an inflammatory and metabolic driver, treating the metabolism can improve all three. Treating each one separately can improve none of them for long.

Does this mean anxiety and depression are metabolic conditions?

This does not mean anxiety and depression are metabolic conditions. It does not mean psychiatric care is unnecessary. It means the metabolic piece is worth measuring in anyone whose mood symptoms sit alongside pain and metabolic dysfunction. Why measure it? Because it is treatable, and it is routinely missed.

Frequently asked questions

Can insulin resistance make you feel depressed?

It can. A diet high in sugar and fat causes inflammation that reaches the brain. That inflammation dulls the dopamine system that drives motivation. This helps explain the low drive and the loss of pleasure, called anhedonia. Both are so often seen with diabetes and chronic pain. A patient labeled unmotivated may be describing a chemical state in the brain, not a flaw in character.

Can diabetes cause depression and anxiety?

Diabetes, chronic pain and mood symptoms often travel together. That is because they can share the same inflammatory and metabolic driver. More than 90% of the patients seen in this city pain practice have metabolic dysfunction. Their mood symptoms move when their metabolism does. That shared driver is why anhedonia so often comes with diabetes and chronic pain.

Does treating insulin resistance help anxiety and depression?

In patients whose mood symptoms share a metabolic driver, anxiety and depression improve when insulin resistance is treated. When pain, anxiety and depression share that driver, treating the metabolism can improve all three. Treating each one separately can improve none of them for long. That is why the metabolic side is worth measuring.

Does this mean I can stop psychiatric treatment?

No. Anxiety and depression are not simply metabolic conditions, and psychiatric treatment still matters. The point is narrower. In anyone whose mood symptoms sit alongside pain and metabolic dysfunction, the metabolic piece is worth measuring. That is because it is treatable, and it is routinely missed. Measuring it adds to your care. It does not replace any part of it.

Related reading

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed August 25, 2026

The secret to a healthy weight is insulin, not calorie math. The same calorie is burned or stored depending on the insulin it triggers. Eat less and move more gives poor odds of keeping weight off. Randomized trials show a higher-fat, lower-carbohydrate diet beats a low-fat diet.

Fewer than 12.2% of US adults are metabolically healthy, based on NHANES data from 2009 to 2016. That is about one adult in eight. It is the most useful number for seeing why advice to each person keeps failing.

Is overeating the root cause of obesity?

People wrongly assume that eating too many calories is the root cause of obesity. But a calorie of food energy has different metabolic fates. It depends on the hormones around it when it arrives. The same calorie may be burned or stored depending on insulin. And insulin depends on what the calorie was made of.

Weight depends on many factors. But the one most often left out is insulin’s role in fat storage. Address that, and the math changes. Ignore it, and the math does not work in real life, however sound it looks on paper.

Does eating less and moving more work for weight loss?

Dietitians and physicians usually tell you to eat less and move more. That advice does not give good odds for losing weight and keeping it off. This is what the outcomes show. It is not a criticism of anyone’s effort.

Evidence from multiple randomized controlled trials indicates that a higher-fat, lower-carbohydrate diet beats a low-fat diet. It wins for both weight loss and cutting cardiovascular risk.

Why is it harder to lose weight each time you diet?

Weight regained after a loss often exceeds what was lost. Each new attempt gets harder. The process has a name — relapse-induced hyperplasia of adipose tissue. People call it rubber-banding or the fat yo-yo. Repeated cycles raise the number of fat cells that can store fat, and the next diet does not reverse that.

Smoking or obesity: which carries the higher hazard ratio?

A hazard ratio compares hazard rates between conditions. In context, smoking and obesity are closer than most people expect. For several outcomes, obesity does not come out ahead. This is a useful correction for anyone who sees obesity as a cosmetic issue and smoking as a medical one.

A generational and national problem

Blue Cross Blue Shield studied millennial health. It found health index scores dropped fast after a certain age, with metabolic conditions prominent. Obesity is also the leading medical reason people fail to qualify for US military service. Among young people aged 17 to 24, 27% are too obese to serve.

Around the world, chronic non-communicable disease makes up most of the disease burden. Most of it is associated with diet. The dual burden is real. Hunger persists in some groups while excess kills in others, and both are malnutrition.

How does sitting in front of the TV affect your health?

On average, every hour of TV watched after age 25 cuts life expectancy by an estimated 21.8 minutes. (Br J Sports Med. 2012 Oct;46(13):927-30.) Inactivity is not just a lack of exercise. Long stretches of sitting have their own metabolic effects.

The epidemic framing

Reversing obesity, prediabetes and type 2 diabetes is the most important public health challenge right now. When every species in a setting gets the same disease, the setting is the exposure. That matters more than whether we call it an epidemic or a pandemic.

Frequently asked questions

Why am I finding it so hard to lose weight?

Because the usual plan ignores insulin. The same calorie may be burned or stored depending on insulin. And insulin depends on what the calorie was made of. Eat less and move more does not give good odds of losing weight and keeping it off. Each regain can add fat cells, so every new attempt starts from a harder place.

How can I trigger my body to burn fat?

Change what you eat, not just how much. Whether a calorie is burned or stored depends on the insulin it triggers. That depends on what the food is made of. Evidence from multiple randomized controlled trials indicates that a higher-fat, lower-carbohydrate diet beats a low-fat diet. It wins for both weight loss and cutting cardiovascular risk.

What is yo-yo dieting?

Yo-yo dieting is the cycle of losing weight and gaining it back, often ending heavier than before. The process has a name: relapse-induced hyperplasia of adipose tissue. It is also called rubber-banding or the fat yo-yo. Repeated cycles raise the number of fat cells that can store fat. The next diet does not reverse that, and each attempt gets harder.

Related reading

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed August 25, 2026

Insulin resistance is the stage in which the pancreas has to make more and more insulin to keep blood sugar normal. That excess insulin, called hyperinsulinemia, is itself inflammatory. It shuts down fat burning and drives fat into storage, including in the liver. That fatty liver makes still more metabolic inflammation.

Most of what goes wrong in type 2 diabetes happens years before blood sugar turns abnormal. The driver is insulin itself. It stays high for years, it quietly feeds inflammation, and it is mostly invisible on the tests most people get.

What does insulin actually do?

Insulin is widely described as the hormone that pushes glucose into cells by opening a channel. That description leaves out so much that it misleads. Insulin is mainly a fat-storage hormone. It shifts the body away from burning fat for energy and toward storing it.

Without insulin, the default state is lipolysis: fat comes out of storage and turns into usable energy. When insulin is present, lipolysis stops and lipogenesis begins. Lipogenesis turns the glucose in your blood into stored fat. The more insulin present, the more fat builds up.

At the enzyme level, insulin turns on hexokinase. Hexokinase tags glucose with a phosphate and traps it inside the cell. Insulin also blocks glucose-6-phosphatase, which would otherwise let the glucose back out. It turns on phosphofructokinase and glycogen synthase too, which drives glycogen building. With plenty of glucose coming in, the liver fills its glycogen stores fast. Then it turns the extra into fat.

Insulin is the disease; glucose is the symptom

For type 2 diabetes to appear, two things must exist together. One is insulin resistance. The other is insulin output that has fallen short of what that resistance demands. Overweight people commonly have insulin resistance without diabetes, because the pancreas makes up for it by making more insulin. Diabetes only appears when that makeup effort fails.

Here is why that matters in the clinic. The makeup period, hyperinsulinemia before insulin production collapses, is not a safe waiting room. It is highly inflammatory. Significant tissue damage builds up all through it, while fasting glucose still reads normal.

Does when you eat affect insulin resistance?

Most people eat from waking until bedtime: three meals, several snacks, and often sweet drinks in between. That pattern keeps insulin output high all day and wears out the insulin receptors. Insulin is a storage hormone. So keeping it high also drives fat buildup in the liver, which makes still more metabolic inflammation.

So giving the body a stretch of time when insulin is truly low is not a fad. It is how stored energy becomes usable again.

How are insulin resistance and inflammation linked?

Hyperinsulinemia is the common link between inflamed fat tissue and metabolic syndrome. The metabolic pattern associated with obesity raises pro-inflammatory cells, M1 macrophages and NK cells. It also holds down anti-inflammatory M2 macrophages, eosinophils and regulatory T cells. Notably, lowering blood insulin partway eases the fat tissue inflammation that excess calories cause. It also improves insulin sensitivity. That points at insulin, not fat mass, as the real driver. (Mol Cell Endocrinol. 2018 Dec 5;477:15-28.)

In diabetes, blood sugar stays high for a long time. That raises reactive oxygen species, which are harmful oxygen molecules. They harm how the beta cells that make insulin work. They also make insulin resistance even worse. The same process adds to the atherosclerosis (clogged, hard arteries) so often seen with diabetes.

Insulin resistance, not LDL, is the cardiovascular signal

Total and LDL cholesterol are poor markers of heart health. High triglycerides with low HDL predict heart risk considerably better. That pattern is also a reliable marker of insulin resistance. The QRISK calculator estimates ten-year heart and blood vessel risk. It does not use LDL at all. It uses the ratio of total cholesterol to HDL.

Preventing insulin resistance in young men would prevent an estimated 42% of myocardial infarctions (heart attacks). That is a bigger drop than correcting high blood pressure, at 36%.

An unrecognized cause of chronic pain

Metabolic inflammation from obesity and hyperinsulinemia is an overlooked driver of pain. Musculoskeletal pain (pain in muscles, bones and joints) affects an estimated 13.5% to 47% of the general population. Roughly 75% of those people report two or more painful areas. Pain in many joints, and its spread, is linked on its own to the inflammatory cascade, not just to mechanical load. That includes joints that bear no weight.

That independence is the point. A joint that bears no weight does not hurt because of body mass. It hurts because it sits in an inflammatory environment. A pain physician who never addresses insulin resistance is treating half the problem.

How do you reverse insulin resistance?

Weight loss and carbohydrate restriction each help reverse diabetes on their own, and combining them works better than either alone. Weight loss helps by easing the crowding in the liver and pancreas, improving blood flow and cutting hormone signals from fat cells. Carbohydrate restriction helps by lowering the insulin signal that drives storage in the first place.

The size of the problem justifies the effort. As obesity has worsened worldwide, type 2 diabetes has followed. One in every two Americans born today is predicted to develop it.

Frequently asked questions

What are the symptoms of being insulin resistant?

Often nothing you notice. Insulin resistance does its damage quietly for years while fasting blood sugar still reads normal. That is because the pancreas keeps pouring out extra insulin to hold it there. That excess insulin is inflammatory and drives fat into storage, including in the liver. One sign worth taking seriously is pain in several joints, even ones that bear no weight. That pain tracks metabolic inflammation, not body mass.

How can I know if I am insulin resistant?

Do not rely on fasting glucose. It stays normal through the damaging years, and the tests most people get miss the problem. Look at your triglycerides and HDL instead. High triglycerides with low HDL is a reliable marker of insulin resistance. That pattern predicts heart risk considerably better than total or LDL cholesterol. Ask your physician to read the pattern, not just your sugar.

What foods increase insulin?

Carbohydrates drive the insulin signal that pushes fuel into storage. That is why cutting them is one of the two independent factors that reverse diabetes. When you eat matters as much as what you eat. Three meals, several snacks and sweet drinks from waking to bedtime keep insulin high all the time and wear out the insulin receptors. A daily stretch of truly low insulin makes stored energy usable again.

Related reading

Sources

  1. Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017. PMID 28179656
  2. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. Journal of Clinical Investigation. 2006. PMID 16823477

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed August 25, 2026

Nutritional ketosis is the state in which reduced insulin shifts the body toward burning its fat stores instead of adding to them. It is not diabetic ketoacidosis. Ketone levels are an order of magnitude lower, and blood pH stays normal.

Every approach on this page works through one mechanism. It lowers insulin long enough for stored fat to become reachable again. The differences between them are practical, not biochemical.

Ketosis is not ketoacidosis

Mention a ketogenic diet and some doctors go into a tailspin. That is because doctors are trained to focus on diabetic ketoacidosis — a life-threatening emergency. Nutritional ketosis is a whole different state. Its ketone level differs by an order of magnitude, and blood pH stays normal.

Nutritional ketosis is arguably the default human metabolic state. Eating mostly carbs is the exception, not the baseline. The body’s machinery for running on fat is intact in everyone.

What happens once insulin falls

In nutritional ketosis, low insulin shifts the body’s metabolic pathways toward burning stored fat first, rather than adding to it. That produces weight loss. It can also reverse the symptoms of type 2 diabetes — not by pushing glucose down, but by removing the storage signal that comes before it.

Time-restricted feeding

Time-restricted feeding lowers high insulin levels and can reverse type 2 diabetes. The logic is simple once you see insulin as a storage hormone. A body that never has a low-insulin stretch never gets to what it has stored.

Most people eat from waking to bedtime — three meals, several snacks, and often sweet drinks in between. Shrinking the eating window has a measurable effect even if you change nothing about what you eat. Changing both works much better.

Intermittent fasting

Intermittent fasting has gained attention for good reasons rooted in how the body works. The benefits reported most consistently relate to insulin sensitivity and glucose control. That is just what you would expect from an approach that keeps insulin low for long stretches.

The cheat day, and metabolic flexibility

A single high-carb day interrupts ketosis. More important, it interrupts the body’s adjustment. Metabolic flexibility — the ability to switch between fuels with ease — is built by doing the same thing every day. Swinging back and forth weakens it. The cheat day costs more than its calorie count suggests.

Hara hachi bu

The Japanese phrase hara hachi bu — eat until you are 80 percent full — is a practical rule older than any of the science above. The body’s fullness signal lags behind eating by some minutes. Stopping when you are comfortably satisfied, rather than full, makes up for that delay. It is a cultural answer to a lag in the body’s signals, and it works.

Related reading

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed August 25, 2026

Insulin for type 2 diabetes lowers blood glucose, but these patients already run high insulin levels. The extra insulin makes insulin resistance worse. It also adds to fat storage and metainflammation. In the studies cited below, a low-carbohydrate ketogenic diet improved hemoglobin A1c more over one year than a low-fat, calorie-restricted diet.

Insulin is the most popular drug treatment for type 2 diabetes. It was once used only sparingly. Today it makes lots of money for the companies that make it. Thanks to drug company marketing and a lack of time, many physicians prescribe insulin. They do it instead of nutrition counseling or lifestyle management.

Before the 1920s, Diabetes treatment mainly aimed to control glycosuria (sugar spilling into the urine). Glycosuria happens when blood glucose goes above about 160–180 mg/dL, and it is easy to measure. The diet advice back then was “meats, poultry, game, fish, clear soups, gelatin, eggs, butter, olive oil, coffee, tea” and held 5% carbohydrates, 20% protein, and 75% fat. This is much like the Low Carbohydrate Ketogenic Diet (LCKD). That advice was very different from today’s low-fat, high-carbohydrate advice for people with diabetes. Also note that people rarely ate breakfast back then, and factory-made snacks did not exist yet. That gave 2 small glucose spikes a day, compared with today’s 5-6 spikes. And vegetable oils were not widely sold before the 1940s and 1950s.

Insulin given by injection to treat Diabetes arrived in the 1920s. That began the shift from controlling diabetes with lifestyle to controlling it with drugs. It has gone so far that many type 2 Diabetic patients now eat too many carbohydrates, knowing they can chase them with insulin. Sadly, these patients already have a high insulin level. The extra insulin only makes the insulin resistance worse. On top of that, insulin tells the body to store fat. That makes the metainflammation worse, and the patient’s obesity too. This is like a fat dog chasing its tail. The glucose is the tail, the mouth is the insulin, and the fat dog is the broken metabolism.

 

Several recent studies have taken a fresh look at cutting carbohydrates in type 2 Diabetes. They confirmed again that the Low Carbohydrate Ketogenic Diet (LCKD) is safe and works. Over one year, hemoglobin A1c (a measure of average blood sugar) improved more on a low-carbohydrate diet. It improved less on a low-fat, calorie-restricted diet. Put simply, people’s glycohemoglobin improved more on the low-carbohydrate diet. It improved less on a eucaloric low-fat diet (one with the same calories).  LCKD can be very good at lowering blood glucose. Because of that, patients on diabetes medication who use this diet should be under close medical supervision or able to adjust their medication.

 

  • Allen FM, Stillman E, Fitz R: Total dietary regulation in the treatment of diabetes: monograph No. 11. 1919, New York, The Rockefeller Institute for Medical Research Google Scholar
  • Stern L, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams M, Gracely EJ, Samaha FF: The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004, 140: 778-785.View Article Google Scholar
  • Samaha FF, Iqbal N, Seshadri P, Chicano K, Daily D, McGrory J, Williams T, Williams M, Gracely EJ, Stern L: A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003, 348: 2074-2081. 10.1056/NEJMoa022637.View Article Google Scholar  
  • Gannon MC, Nuttall FQ: Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes. 2004, 53: 2375-2382.View Article Google Scholar
  • Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005, 142: 403-411.View Article Google Scholar
  • Nielsen JV, Jonsson E, Nilsson AK: Lasting improvement of hyperglycaemia and bodyweight: low-carbohydrate diet in type 2 diabetes. A brief report. Ups J Med Sci. 2005, 110: 179-183. Google Scholar
  • Yancy WS, Vernon MC, Westman EC: Brief report: a pilot trial of a low-carbohydrate, ketogenic diet in patients with type II diabetes. Metabolic Syndrome and Related Disorders. 2003, 1: 239-244. 10.1089/154041903322716723.View Article Google Scholar

So, we know that patients with type 2 diabetes have the symptom of too much glucose. But their actual disease is too much insulin, with cells that are insulin resistant. Yet we treat them with more insulin. That raises the question: why, and who benefits? (This does not in any way suggest insulin is bad. Insulin is a lifesaving drug. It means patient care should first focus on lifestyle changes, and insulin should be the rescue drug.)

Making lifestyle changes and counseling patients takes time and energy, which most healthcare providers lack. Physicians are one of the key decision makers. So they remain a main target for drug company sales. The drug industry uses many marketing and promotion efforts to shape what doctors prescribe. This starts early in medical school, even in the first years of study before patient care. This marketing goes on through a physician’s whole career. Drug companies hand out gifts and benefits, from cheap gifts to costly trips and grants. That leads to poorer prescribing choices and pushes more expensive care. One could argue that most physicians are simply a marketing tool the drug companies use to sell their products. They are a sales team that is paid indirectly.

Drug companies often launder their education efforts through patient advocacy groups. On the surface, these groups appear to be trusted authorities, such as The American Diabetes Association.

Clearly, Big Pharma will not be likely to pay for studies that cut use of its products. Those studies would favor lifestyle changes that no one gets paid for. Academics funded by the same interests are also unlikely to do that kind of evidence-based research. The whole health care industry seems built to medicalize treatment rather than improve lifestyle. Lifestyle change would radically disrupt the status quo.  Big Pharma is everywhere in the academic world of policy and thought leaders. So it is no longer considered a “conflict of interest” to recommend a drug that paid that policy or thought leader. It is now simply considered a “duality of interest.”

Related reading

Medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP
Interventional pain physician, addiction medicine specialist and obesity medicine diplomate.
Licensed in Missouri and Illinois.
Last reviewed June 17, 2026