Life Extension Magazine®

Combating the “Diabesity” Epidemic

Obesity-driven diabetes—now termed “diabesity” by some experts—is expected to affect 366 million people worldwide by 2030, making it the largest epidemic the world has ever faced. Yet conventional medicine largely fails its victims through late detection and inadequate treatment. Life Extension® examines the overlooked factors behind this global health disaster and offers multimodal prevention strategies.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in October 2024. Written by: Julius Goepp, MD.

The combination of diabetes and obesity—now termed “diabesity” by some experts—is the largest epidemic the world has ever faced.1 By some estimates, the total number of individuals with obesity-induced diabetes will escalate to 366 million worldwide by 2030,2 with an 8-10 year3 reduction in their life expectancy.

The harbingers of diabesity can go undetected for years, as conventional medicine persists in late detection by “waiting” for blood markers to reach critical levels, then adopting failed strategies that can worsen the patient’s outlook for survival.4

Aging individuals are told to focus on blood sugar levels without an explanation of the lethal factor linking obesity and diabetes: inflammation.5,6 Fat cells generate inflammatory cytokines. Excess fatty tissue floods the body with these harmful signaling molecules, triggering a pathological cascade across a range of additional bodily tissues, impairing their response to insulin and leptin, and disabling their ability to properly metabolize sugars, fats, and protein.7

Curcumin: Glucose Control and Increasing Insulin Sensitivity

This deadly feedback loop may commence long before full-blown diabetes manifests,8 suggesting the need for a multimodal prevention strategy implemented far in advance of early signs and symptoms.

In this article, you will learn how curcumin imposes an anti-inflammatory blockade via multiple physiological pathways—including those associated with diabetes onset. You will also discover how it enhances glucose control and insulin sensitivity, quells inflammation at the cellular level, and restores balance across a range of systems normally ravaged by diabetes. Adding to the extraordinary benefits of curcumin, new studies have shown that carnitine, vitamin E, and magnesium complement curcumin in controlling the many destructive elements of high blood sugar. Together, all these nutrients can make a significant difference in the battle against diabesity.

Curcumin: Glucose Control and Increasing Insulin Sensitivity

Experiments in type 2 diabetic animals reveal that curcumin suppresses spikes in glucose levels via multiple mechanisms.9-12 A curcumin complex was shown to significantly reduce blood glucose and lipid levels in diabetic rats and restore blood pressure and endothelial function to normal.13 PPAR (peroxisome proliferator-activated receptor) is a group of nuclear receptor proteins that modulate metabolism through helping regulate gene expression and facilitating sugar uptake and utilization from the blood. Activation of PPAR is one way that curcumin exerts its glucose-lowering effects.14

Another way curcumin brings blood sugar under control is in the liver, where it decreases activity of enzymes that make new sugar molecules, while increasing activity of enzymes that break down and store sugar.15,16 To do this curcumin activates a liver complex called AMP-activated kinase (AMPK) at a rate that may be higher than metformin, while simultaneously reducing expression of glucose-producing genes.17

Curcumin further contributes to glucose control in diabetes by increasing the number of insulin receptors on cell membranes and improving their insulin-binding capacity, restoring both to near-normal levels.10 Increasing sugar uptake from blood, decreasing new glucose formation, and increasing insulin’s effectiveness are three entirely independent means by which curcumin lowers blood sugar.

Curcumin Fights Oxidation and AGEs: the Inflammation Blockade

Advanced glycation end-products (AGEs) form when glucose cross-links with functional proteins, rendering them dysfunctional and destroying cell membranes and vital enzyme systems.18 The resulting inflammation produces oxidant stress and further tissue injury.19 Curcumin blocks formation of AGEs and prevents many of their oxidant-induced, inflammation-promoting, tissue-damaging effects.20,21

For example, blindness caused by diabetic retinopathy is a direct result of capillary overgrowth from long-term exposure to high glucose levels and resultant inflammation.22 Curcumin was shown to help suppress some of the AGE-induced inflammatory changes that promote diabetic retinopathy. It also lowered levels of growth factors that promote capillary proliferation.23-27

Curcumin Fights Oxidation and AGEs: the Inflammation Blockade

Cataracts, another vision-threatening consequence of diabetes, result from damage to delicate proteins in the eye’s lens, producing cloudiness and eventually opacity. Curcumin delayed progression and maturationof cataracts in diabetic rats, countering the oxidative stress and reversing changes associated with lipid peroxidation.28,29

Curcumin also boosts levels of natural antioxidants that diabetes depletes, including glutathione, superoxide dismutase (SOD), and catalase—restoring them to normal levels.30-32 As a result, curcumin helps reduce the amount of oxidized fat molecules in the circulation, which are major contributors to cardiovascular disease.33 And curcumin’s reduction of AGEs in connective tissue helps reduce the chemical cross-linking that adds unwanted stiffness to blood vessels, skin, and other tissues in diabetics.34

Brain cells in diabetics are especially vulnerable to oxidative stress and lipid peroxidation because of their lipid-rich cell membranes. Curcumin metabolites prevent brain lipid peroxidation in diabetic rats, potentially protecting brain cells from long-term injury.35 Acting by a completely different mechanism, curcumin further protects diabetic brain cells by preventing oxidative damage to mitochondria and boosting levels of the energy compound adenosine triphosphate (ATP) in brain tissue.36

Diabetics undergo acceleration of inflammatory changes in blood vessel walls that produce endothelial dysfunction and ultimately atherosclerosis. Curcumin supplements in animals markedly reduce dangerous markers of inflammation such as interleukin-6 and tumor necrosis factor-alpha (TNF-alpha).11 And curcumin reduces production of inflammatory cytokines in fat tissue itself, helping to lower the overall burden of inflammation and insulin resistance produced by obesity.19,37

What You Need to Know: Diabesity Epidemic

The combination of diabetes and obesity—now termed “diabesity” by some experts—is the largest epidemic in human history.
The harbingers of diabesity can go undetected for years, as conventional medicine focuses on various biomarkers while ignoring the key factor that links obesity and diabetes: inflammation.
Curcumin has been shown to impose an anti-inflammatory blockade across multiple systems ravaged by “diabesity.”
Curcumin was shown to increase glucose metabolism in the liver while simultaneously reducing expression of glucose-producing genes.
Curcumin intervenes at nearly every stage in the process of diabetic progress, enhancing liver, kidney, and endothelial function, providing optimal cardiac defense, and boosting levels of primary antioxidants while suppressing pro-inflammatory cytokines generated by fatty tissue.
Carnitine helps the body burn fat as energy. Formulations of carnitine such as L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine have been found to help improve insulin sensitivity and blood lipid profiles in individuals with diabetes and pre-diabetes.
Vitamin E helps reduce oxidative stress and improve insulin action.
Magnesium is frequently deficient in people with diabetes. Magnesium supplementation has been found to improve insulin sensitivity and promote healthy blood pressure levels.

Advanced Cardiovascular Defense with Curcumin

The over-oxidized environment in diabetics’ blood and tissues puts a huge strain on vascular health. This hyperoxidation is the root cause of diabetics’ markedly increased risk of stroke, heart attack, and peripheral vascular disease.38 Curcumin combats vascular destruction in diabetics in several ways.39

Curcumin decreased blood sugar and simultaneously reduced vessel-damaging lipid peroxidation to near normal in diabetic rats.12 It also normalizes the out-of-control lipid profiles so common in diabetics.40 Animals fed a high-cholesterol diet that were supplemented with curcumin had a decrease in total cholesterol of 21% and of harmful low-density lipoprotein (LDL) by 43%, but an increase in beneficial high-density lipoprotein (HDL) of 50%!41

Curcumin exerts direct effects on blood vessels, which are vulnerable to oxidant and inflammatory damage. It can help to restore the vital vascular reactivity needed to control blood pressure and flow.42 Curcumin supplements in diabetic rats also have beneficial effects on blood vessel tone in heart muscle, and protect small blood vessels in the eye from endothelial dysfunction.43 In addition, curcumin inhibits platelet aggregation that can contribute to heart attacks and strokes.44

In 2008, researchers in India published a landmark human study showing how curcumin improves endothelial function in type 2 diabetics.45 They tested the supplement head-to-head against the prescription cholesterol-lowering drug atorvastatin (Lipitor®) and a placebo. At the end of the study, significant improvement in endothelial function occurred in both the drug and the curcumin supplemented groups to a similar extent, while placebo recipients had no change. At the same time, the supplemented group and the drug-treated group both showed significant reductions in markers of oxidative stress and inflammatory cytokines. This study alone supports routine curcumin supplementation in diabetics, who are at extreme risk for the consequences of endothelial dysfunction.

Curcumin Provides Kidney and Liver Protection

Diabetes wreaks havoc on vital organs, particularly those with high blood flows such as the kidney and liver. End-stage renal disease (ESRD) is a tremendous cause of suffering and death among diabetics; while non-alcoholic steatohepatitis (also called “fatty liver disease”) begins its damaging effects even in early-stage insulin resistance.46 No drug exists to effectively prevent progression of these diabetic complications, but curcumin’s multi-targeted capabilities offer distinct protection.

Dietary curcumin supplements significantly reduced kidney lesions in diabetic laboratory animals and slowed progression of the illness.47 Treatment with curcumin significantly reduced both kidney dysfunction and oxidative stress in diabetic rats.48,49 A 2009 study revealed one of the ways it works: curcumin’s powerful anti-inflammatory, gene expression-modulating activities were blocking production of growth factors and other proteins that lead to damaged kidney tissue.50

Curcumin prevents dietary-induced fatty liver, prevents activation of the liver inflammatory cells that produce the condition, and can also ameliorate fatty liver caused by alcohol intake in diabetic rats.46 In a laboratory study, diabetic rats displayed abnormal liver function tests. Curcumin supplementation for 45 days reversed these abnormalities to near normal.49 This suggests that curcumin may be helpful for people with diabetes, who have a higher incidence of liver function test abnormalities than people who do not have diabetes.51 In 2009, it was shown that curcumin achieves these effects by suppressing destructive lipid-handling genes, simultaneously stimulating PPAR-gamma activity to improve liver cells’ energy utilization.52

Curcumin Protects Nerve and Brain Cells

Nerve and brain tissue come under direct attack by high sugar levels in diabetic patients, resulting in severe pain called diabetic neuropathy and in cognitive disturbances ranging from memory loss to severe diabetic encephalopathy and dementia. Curcumin has proven effective in preventing or mitigating both.

Neuropathic pain is recognized as one of the most difficult to treat, and frustrates patients and physicians alike. Indian researchers experimentally induced the condition in diabetic rats, then supplemented them with curcumin.53 The treatment significantly attenuated excessive painful response to mild stimuli (hyperalgesia). The effects were even more pronounced when supplementation was combined with insulin.54

Diabetic encephalopathy is a complex and poorly-understood process of accelerated brain aging and cognitive decline related both to high glucose levels and insulin deficiency in brain tissue.55,56 Chronic treatment with curcumin reversed the extreme oxidant damage and inflammation in the brains of diabetic rats, and markedly improved their performance on tasks of memory and cognition.56

Carnitine Improves Blood Sugar and Lipids in Diabetes

Carnitine is a small amino acid-derived molecule used by cells to shuttle fats into mitochondria, where they are burned for energy.57,58 Diabetic tissue, especially cardiac muscle, can accumulate lipids that impair function.59,60 Both aging and obesity reduce carnitine levels, contributing to mitochondrial aging and loss of metabolic control.61 That makes carnitine a very appealing supplement for its ability to promote mitochondrial health and fat/sugar utilization before problems arise.58,62

One gram of L-carnitine orally three times daily over 12 weeks significantly lowered fasting blood sugar in middle-aged adults with type 2 diabetes.

Human carnitine studies in diabetes are compelling. Given intravenously to insulin-resistant diabetics, L-carnitine or acetyl-L-carnitine improved insulin sensitivity, glucose uptake and effective utilization from the bloodstream, while improving efficiency of energy utilization.58,63 One gram of L-carnitine orally three times daily over 12 weeks significantly lowered fasting blood sugar in middle-aged adults with type 2 diabetes.64

Curcumin Directly Blocks Obesity, Consequences

Curcumin offers a host of multi-targeted benefits that fight both the diabetes and the obesity components of diabesity. Late-breaking discoveries now show how curcumin can actually prevent obesity in the first place, and block its consequences even before they arise.

The most remarkable discovery is that curcumin acts as an antagonist to human appetite-promoting receptors.101 By binding to those receptor sites, curcumin prevents natural molecules from attaching and stimulating appetite. The researchers recognized their breakthrough, suggesting that curcumin “might be developed as novel, nontoxic… therapeutics for obesity.”101

There’s plenty of evidence about how curcumin prevents obesity and its inflammatory consequences in animal studies. Curcumin normalized lipid profiles and insulin sensitivity in non-diabetic hamsters on a high-fat diet, and ramped up liver fat-burning activity. 102 Curcumin also directly inhibits growth of fat cells by reducing their blood supply, resulting in reduced weight gain and body fat in live animal models.

Acting almost like a benign chemotherapy agent, curcumin also blocks growth and maturation of fat cells and even induces apoptosis, the natural cell-death program.103,104

With additional discoveries about how curcumin favorably modulates fat-signaling molecules such as adiponectin and leptin that control metabolism and distribution of body fat,6,105 and reduce fat cell-mediated inflammation,6,19,37 it’s no wonder that experts are hailing curcumin as a breakthrough in obesity prevention.103

Because of its unique impact on fat utilization, carnitine is also highly effective at improving diabetics’ abnormal lipid profiles, alone or in combination with a statin drug like simvastatin (Zocor®).65-67 That’s big news for diabetics, who must optimize their lipid profiles in order to avoid devastating cardiovascular consequences.

Acetyl-L-carnitine supplements (2 grams daily) safely reduced arterial hypertension, insulin resistance, and impaired glucose tolerance, while boosting levels of the protective fat-produced cytokine adiponectin in non-diabetic patients at risk for developing diabetes.68 Daily supplementation with 2 grams of L-carnitine reduced levels of dangerous lipoprotein(a) and oxidized LDL in patients with type 2 diabetes.69,70

Carnitine’s energy-boosting effects are especially important in heart tissue. Long-term oral supplementation with acetyl-L-carnitine preserved vital cardiac nerve function in diabetic patients, whereas placebo-treated subjects suffered significant loss of function.71 Propionyl-L-carnitine improved cardiovascular function in diabetics undergoing coronary bypass surgery.72

Diabetics frequently suffer painful peripheral vascular disease, the narrowing and hardening of blood vessels in the extremities that makes walking difficult and painful. Supplementation with 2-3 grams/day of propionyl-L-carnitine improves symptoms and performance, increasing mean walking distance, measures of blood perfusion, and pain scores.73,74 One study even showed that patients supplemented with 1,200 mg propionyl-L-carnitine intravenously each day could also reduce doses of their prescription glucose-lowering medications.75 Erectile dysfunction is a very specific form of peripheral vascular disease common in diabetics, and propionyl-L-carnitine added to drug treatment improved performance in men unresponsive to drug treatment alone.76-78

With additional evidence that 1-2 grams acetyl-L-carnitine supplementation daily can mitigate painful diabetic neuropathy, it’s clear that carnitine belongs in a responsible anti-diabetic supplement regimen.79,80

Vitamin E and Magnesium Reduce Inflammation, Improve Insulin Sensitivity

Consistent vitamin E supplementation (500-600 mg daily) helps improve vascular function and increases magnesium levels inside cells in type 2 diabetic patients while reducing elevated oxidative stress markers.81,82 Vitamin E supplementation with gamma-tocopherol also quenches biomarkers of oxidation and inflammation in patients with metabolic syndrome, potentially preventing progression to full-blown diabetes.83

Vitamins E and C together lowered inflammation and improved insulin action in pre-diabetic patients.84 Even more dramatically, an antioxidant vitamin combination rich in vitamin E (800 mg vitamin E, 500 mg vitamin C, 10 mg beta-carotene) improved insulin sensitivity, reduced dangerous endothelial adhesion molecules, and increased protective adiponectin levels in obese young adults.85 This late-breaking news is impressive evidence that we can break the cycle of diabesity.

Oral magnesium supplements improve insulin sensitivity and lower hemoglobin A1c levels in type 2 diabetics and in non-diabetic adults.86,87 A large review of previous studies in 2006 established that oral magnesium supplementation (360 mg/day) can reduce fasting glucose levels and raise beneficial HDL in type 2 diabetic patients.88 And a 2009 study showed that daily oral magnesium supplementation (450 mg) significantly lowered both systolic and diastolic blood pressure in hypertensive type 2 diabetics who were also taking the ACE inhibitor captopril.89

Long term magnesium supplementation (300 mg/day) slowed the development of peripheral neuropathy in type 1 diabetics.90 A clinically important study in 2008 revealed that depressed elderly diabetic patients with low magnesium levels responded to oral magnesium supplements (450 mg/day) as well as they did to the powerful prescription antidepressant imipramine.91

A daily combination supplement including 100-150 mg vitamin E and 200 mg magnesium along with vitamin C and zinc significantly increased HDL in a group of type 2 diabetics.92,93 And very recently we learned that the combination of vitamin E and magnesium also works together to decrease plasma lipids and blood viscosity (thickness) in diabetic rats, heralding even greater cardiovascular benefits of these essential nutrients.94

Antioxidant vitamins and minerals such as vitamin E and magnesium are depleted in diabetes,95,96 while both nutrients have been shown to improve insulin action.97,98 At the same time, common lipid-lowering drugs used by diabetics further deplete magnesium levels.99 Experts are therefore deeply interested in these nutrients as beneficial supplements for diabetics and obese pre-diabetics.100

Summary

The combination of diabetes and obesity—now termed “diabesity” by some experts—is the largest epidemic in human history, estimated to escalate to 380 million victims worldwide by 2025. The harbingers of diabesity can go undetected for years, as conventional medicine focuses on antiquated blood references ranges while ignoring the key factor that links obesity and diabetes: inflammation.

Curcumin has been shown to impose an anti-inflammatory blockade across multiple systems ravaged by “diabesity.” Curcumin increases glucose metabolism in the liver, while simultaneously reducing expression of glucose-producing genes. It intervenes at nearly every stage in the process of diabetic progress, enhancing the endothelial and multi-organ function, providing optimal cardiac defense, and boosting levels of primary antioxidants while suppressing pro-inflammatory cytokines generated by fatty tissue.

Carnitine helps promote healthy blood sugar and blood lipid levels, while vitamin E and magnesium improve insulin sensitivity, reduce oxidative stress, and support healthy blood pressure. Together, these nutrients synergize to provide powerful defense against the epidemic of diabesity.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.

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