Category Archives: Diabetes Reversal With Insulin Detox

Is Diabetes A Sugar Problem? No.

Majid Ali, M.D.

Suite 3 C, 344 Prospect Avenue

Hackensack, New Jersey 07601



Is diabetes mellitus (Type 2 Diabetes) a sugar problem? No. The abnormalities of blood sugar seen in diabetes are the consequences of the derangements of cellular energetics and toxicity that collectively create what is commonly called diabetes. Is diabetes an insulin problem? No. The abnormalities of insulin functions are the consequences of plasticized (chemicalized) and hardened cell membranes that immobilize the insulin receptors embedded in them. Is diabetes a problem of blood vessels that causes blindness, kidney failure, stroke, heart attacks, and neuropathy? No. The abnormalities of blood vessels are the consequences of oxidizing and deoxygenizing influences in diabetes.

In this column, I marshal evidence for my view that the state of insulin resistance should be regarded as a “hardened cell membrane state.” The so-called metabolic syndrome should be visualized as a “gummed-up matrix state.” Prediabetes should be seen as a “mitochondrial dysfunction state.” The strategies for the prevention and reversal of diabetes yield better long-term clinical results if diabetes is recognized as a “dysfunction oxygen signaling,” or dysox, state.

In type 1 diabetes, insulin itself becomes a potent autoantigen and initiates autoimmune injury to pancreatic islet cells.1-3 I will show how this recently documented role of insulin in the pathogenesis of diabetes fits in the dysox model of diabetes presented here. In type 2 diabetes, insulin cannot function – insulin resistance, in the common jargon – and hyperinsulinemia develops, which triggers and amplifies the inflammatory response.4-6 In all types of diabetes, the endothelial cells produce nitric oxide and other bioactive factors in abnormal quantities and proportions.7,8 Diabetes causes neuropathy, retinopathy, nephropathy, dementia, stroke, and heart attacks. I will describe how those complications of diabetes can be better understood when the problems are seen through the prism of oxygen signaling.


Clinical, Epidemiologic, and Experimental Evidence Links Obesity With Insulin Toxicity

The link is supported by known metabolic roles of nonesterified fatty acids (NEFAs) and altered paracrine and endocrine functions of fat cells (adipocytes) in the energy economy of the body. For example, in a healthy state, NEFAs serve as substrates for adenosine triphosphate (ATP) generation. In obesity, these fatty acids are retained in excess in biomembranes of all cell populations of the body and within adipocytes. NEFAs, along with trans fats and oxidized lipids, then “harden” the cell membranes to clamp down on insulin receptors – rusting and impacting the crank, so to speak – to cause insulin resistance.12 Those lipids also “gum up” the matrix, blocking molecular cross-talk there. Eventually, those elements, along with other toxins, uncouple respiration from oxidative phosphorylation and impede mitochondrial electron transfer events.


In obesity, output of fattening hormones in adipocytes (fat cells) is chaotic in the ways in which it further increases cellular fat build-up and sets the stage for the development of diabetes.13,14 However, the obesity/diabetes link does not prevail in all populations of the world. For instance, in India, there is also an epidemic of low body-weight (LBW) diabetes15 – a phenomenon that clearly points to the existence of environmental factors unrelated to obesity that are involved in the pathogenicity of diabetes, and supports the dysox model of diabetes.

A growing number of free radicals, transcription factors, enzymes, and proteins has been – and continues to be – implicated in the pathogenesis of diabetes, including:
· nitric oxide16,17
· inducible nitric oxide synthase (iNOS)18
· mitochondrial uncoupling proteins (UCPs)19-21
· proinflammatory cytokines22-24
· resistin25,26
· leptin27,28
· adipokines29
· adiponectin30
· tumor necrosis factor-alpha (TNF-a)31
· peroxisome proliferator-activated receptor gamma (PPARgamma)32-34
· nuclear respiratory factor-1 (NRF-1)35
· suppression of cytokine signaling (SOCS) proteins36
· retinol-binding protein-4 (RBP4)37
· antibodies against glutamic acid decarboxylase38
· prothrombotic species, including fibrinogen, von Willebrand factor, and plasminogen activator inhibitor (PAI-1), adipsin (complement D), and acylation-stimulating protein (ASP) 39-42
· heat shock protein 60, voltage-dependent anion channel 1 (VDAC-1), and Grp7543
· hypercoagulable platelets44

Oxygen, Diabetes, Insulin References 

1.Nakayama M, Norio Abiru N, Moriyama H, et al. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice.
Nature. 2005;435,220-223.
2.Kent SC, Chen Y, Bregoli L, et al. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.
Nature. 2005;435:224-228.
3.von Herrath M. Insulin trigger for diabetes.
Nature. 2005;435:151-152.
4.Eisenbarth GS, et al. Insulin autoimmunity: Prediction/precipitation/prevention type 1A diabetes.
Autoimmun. Rev. 2002;1:139-145.
5.Todd JA, Bell JI, McDevitt HO. HLA antigens and insulin-dependent diabetes.
Nature. 1988;333,710-712.
6.Ali M. Hypothesis: obesity is adipomyocytic dysoxygenosis.
J Integrative Medicine. 2004;9:19-38.
7.Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes.
J. Clin. Invest. 2005;115:1111–1119.
8.Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance.
J. Clin. Invest. 2006;116:1793–1801.
9.World Health Organization Consultation on Obesity 1–253 (World Health Organization, Geneva, 2000).
10.Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030.
Diabetes Care. 2004;27:1047–1053.
11.Hedley AA. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002.
JAMA. 2004;291:2847–2850.
12.Leung, et al. Prolonged increase of plasma non-esterified fatty acids fully abolishes the stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity and pancreatic beta-cell function in obese men.
Diabetologia. 2004;247:204–213.
13.Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis.
Nature. 2006;444:847-853.
14.Nath D, Heemels M-T, Lesley Anson L Obesity and diabetes.
Nature. 2006;444, 839.
15.Das S. Identity of Lean-NIDDM: Clinical, metabolic and hormonal status. In: Kochupillai N, ed.
Advances in Endocrinology, Metabolism, and Diabetes. Vol. 2. Delhi, India: Macmillian; 1994:42-53.
16.Farmer SR. Transcriptional control of adipocyte formation.
Cell Metab. 2006;4:263–273.
17.Trayhurn P. Endocrine and signalling role of adipose tissue: New perspectives on fat.
Acta Physiol. Scand. 2005;184: 285–293.
18.Perreault M, Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle.
Nature Med. 2001;7:1138–1143.
19.Suh YH, Kim SY, Lee H, et al. Overexpression of short heterodimer partner recovers impaired glucose-stimulated insulin secretion of pancreatic beta-cells overexpressing UCP2.
J Endocrinol. 2004;183:133-44.
20.Ceddia1 RB, William WN, FB, et al. Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes.
Eur. J. Biochem. 2000;267:5952-5958.
21.Enerback S et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese.
Nature. 1997;387:90–94.
22.Xu H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.
J. Clin. Invest. 2003;112:1821–1830.
23.Shoelson, SE, Lee J. Goldfine AB. Inflammation and insulin resistance.
J. Clin. Invest. 2006;116: 1793–1801.
24.Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis.
Nature. 2006;444:854-859.
25.Stepphan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes.
Nature. 2001:409;307-312.
26.Berti L, Kellerer M, Capp E, et al. Leptin stimulates glucose transport and glycogen synthesis is in C2C12 myotubes: Evidence for a P3-kinase mediated effect.
27.Minokoshi Y et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase.
Nature. 2002; 415: 339–343.
28.Farooqi IS, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency.
J. Clin. Invest. 2002;110:1093–1103.
29.Shimomura I, Hammer RE, Ikemoto S, et al. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.
Nature. 1999;401:73–76.
30.Fain JN, Madan AK, Hiler ML, et al. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans.
Endocrinology. 2004;145:2273–2282.
31.Scherer PE. Adipose tissue: From lipid storage compartment to endocrine organ.
Diabetes. 2006;55:1537–1545.
32.Atherton HJ, Bailey NJ, Zhang W, et al. A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome.
Physiol Genomics. 2006;27:178-186.
33.Kadowaki T et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
J. Clin. Invest. 2006;116:1784–1792.
34.Farmer SR. Transcriptional control of adipocyte formation.
Cell Metab. 2006;4:263–273.
35.Yang Q, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.
Nature. 2005;436:356–362.
36.Mooney RA, et al. Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance.
J. Biol. Chem. 2001;276:25889–25893.
37.Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1.
Proc Natl Acad Sci U S A. 2003;100:8466-8471.
38.von Boehmer H, Sarukhan A. DAG, a single autoantigen for diabetes.
Science. 1999;284:1135-1136.
39. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease.
Nature. 2006;444:875-880.
40.Matsuzawa Y. The metabolic syndrome and adipocytokines.
FEBS Lett. 2006;580:2917–2921.
41.Konstantinides S, Schafer K, Koschnick S, et al. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity.
J. Clin. Invest. 2001;108:1533–1540.
42.Bernal-Mizrachi E, Wen W, Stahlhut S, et al. Islet cell expression of constitutively active Akt1/PKB induces striking hypertrophy, hyperplasia, and hyperinsulinemia.
J. Clin. Invest. 2001;108:1631–1638.
43.Turko IV, Murad F. Quantitative protein profiling in heart mitochondria from diabetic rats.
J Biol Chem. 2003;278(37):35844-35849.
44.Lillioja S, Mott DM, Spraul M, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependant diabetes mellitus: Prospective studies of Pima Indians.
N Engl J Med. 1993;329:1988-1992.
45.Sakaue M, Fuke Y, Katsuyama T, et al. Austronesian-speaking people in Papua New Guinea have susceptibility to obesity and type 2 diabetes.
Diabetes Care. 2003 26: 955-956.
46.Katulanda P, Sheriff MH, Matthews DR. The diabetes epidemic in Sri Lanka – a growing problem.
Ceylon Med J. 2006;51:26-28.
47.Landau BR, Chandramouli V, Schumann WC, et al. Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients.
Diabetologia. 1995;38:831-838.
48.Tian J, Zekzer D, Lu Y, et. al. B cells are crucial for determinant spreading of T cell autoimmunity among b-cell antigens in diabetes-prone NOD mice.
Journal of Immunology. 2006; 176: 2654-2661.
49.Jaeckel E, Lipes MA, von Boehmer H. Antigen-specific foxp3-transduced t-cells can control established type 1 diabetes.
Nature Immunol. 2004;5:1028-1035.
50.Lieberman SM, Evans AM, Han B, et al. Identification of the beta cell antigen.
Proc Natl Acad Sci U S A. 2003; 100:8384-8388.
51.Arif S, Timothy I. Tree1 TI, , Thomas P. Astill TP, et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health.
J. Clin. Invest. 2004;113:451-463.
52.Kent SC, Chen Y, et al. Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.
Nature. 2005;435:224-228.
53.Rotimi CN, Chen G, Adeyemo AA. A genome-wide search for type 2 diabetes susceptibility genes in West Africans: the Africa America Diabetes Mellitus (AADM) study.
Diabetes. 2004:53:1404.
54.Memon RA, Bessman SP, Mohan C. Impaired mitochondrial metabolism and reduced amphibolic Krebs cycle activity in diabetic rat hepatocytes.
Biochem Mol Biol Int. 1995;6:1079-1089.
55.Hotta K et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys.
Diabetes. 2001;50:1126–1133.
56.Giroix MH, Rasschaert J, Sener A, et al. Study of hexose transport, glycerol phosphate shuttle and Krebs cycle in islets of adult rats injected with streptozotocin during the neonatal period.
Mol Cell Endocrinol. 1992;83:95-104.
57.Rosen, E. D. et al. PPAR is required for the differentiation of adipose tissue in vivo and in vitro.
Mol. Cell. 1999;4:611–617.
58.La Selva M, Beltramo E, Pagnozzi F, et al. Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions.
Diabetologia. 1997;40:741-742.
59.Sullivan KA, Feldman EL. New developments in diabetic neuropathy.
Curr Opin Neurol. 2005;18:586-590.
60.Xie XM, Yang ZW, Chen MF. Effects of advanced glycation endproducts on the activity of NF-kappaB and the expression of fibronectin mRNA in the endothelial cells in aged rats.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006;31:883-887.
61.Després J-P, Lemieux I. Abdominal obesity and metabolic syndrome.
Nature. 2006;444: 881-887.
62.Ali M. Integrative Cardiology and Chelation Therapies: The Oxidative-Dysoxygenative Model and Chelation Therapies.
Principles and Practice of Integrative Medicine 6. 2nd ed. New York: Canary 21 Press; 2006.
63.Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts.
Townsend Letter for Doctors and Patients. 2005;262:98-103.
64.Ali M. Under Darwin’s Glow [editorial].
J Integrative Medicine. 1999. 3:1
65. Ali M. Darwin, fatigue, and fibromyalgia.
J Integrative Medicine. 1999;3:5-10.
66.Ali M. Darwin, oxidosis, dysoxygenosis, and integration.
J Integrative Medicine. 1999;3:11-16.
67.Ali M.
The Ghoraa and Limbic Exercise. Denville, New Jersey: Life Span Books; 1993.
68.Turnbaugh.PJ, Ley RU, Mahowald MA, et al. An obesity-related gut microbiome with increased capacity for energy harvest.
Nature. 2006;444:1027-1031.
69.Ley RE, Turnbaugh PJ, Klein S, et al. Human gut microbes associated with obesity.
Nature. 2006;444:1022.
70.Bajzer M, Seeley RJ. Obesity and gut flora.
Nature. 2006;444:1009-1010.
71.Ali M. Hurt human habitat and energy deficit – healing through the restoration of krebs cycle chemistry.
Townsend Letter. October 2006:112-116.
72.Ali M. Integrative Nutritional Medicine: Nutrition Seen Through the Prism of Oxygen Homeostasis.
Principles and Practice of Integrative Medicine 5. 2nd ed. New York: Canary 21 Press; 2005.
73.Ali M. Darwin, Dysox, and Disease.
The Principles and Practice of Integrative Medicine 11. New York: Canary 21 Press; 2002.


Majid Ali, M.D.

New York  212-873-2444

New Jersey . 201-996-0027


Unless specified otherwise,

the word at this web site is used for Type 2 diabetes.



  1. If you think, diabetes is a sugar problem, tests done for blood sugar levels for screening for diabetes will be misleading most of the time.
  2. The diagnosis of diabetes will be delayed for five, ten, or more years.
  3. If you are overweight, it will be much more difficult to lose weight. 
  4. Unless you are at your optimal weight, undetected insulin toxicity will injure all your body organs to varying degrees until diabetes is diagnosed and treated for years, usually five to ten or more years.


References for Insulin Toxicity and Diabetes 

  1. Ali M. Fayemi AO, Ali O, Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes. Townsend Letter. 2017; 402:91-96.
  2. Ali M. Importance of Subtyping Type 2 Diabetes Into Subtype A and Subtype 2A and Subtype 2B.  Townsend Letter. 2014; 369:56-58.
  3. Ali M, Dasoju S, Karim N, et al. Study of responses to carbhydrate and non-carbohydratechallenges in insulin-based care of metabolic disorders. Townsend Letter. 2016; 391: 48-51.


What IS Insulin Toxicity

Blood insulin test should be done for the following conditions since there is high probability that the underlying fires of these conditions are fed by insulin toxicity.


·       Loss of Vigor

·       Weight gain

·       Course skin

·       Acne in teenager

        Skin pigmentation changes

·       Facial hour for young women

·       Tingling and numbness in toes and fingers

·       Brain fog

·       Cognitive difficulties

·       Memory loss

·       Any infections that do not heal

·       Any inflammation that does not heal

·       Colitis of immune-inflammatory disorders

·       Arthritis of immune-inflammatory disorders

·       Connective tissue diseases

·       Any skin conditions that do not heal

·       Neurodermatitis

·       Brain atrophy

·       Brain degenerative conditions

·       Rising blood creatinine level

·       Rising liver enzyme levels

·       Rising CRP test results

·       Liver ultrasound with fatty liver disease, steatosis, or steatonecrosis.


Blood Cells Tell The Insulin Toxicity Story

Healthy Blood Cells for Comparative Study. Figure 1

Early Stress on Red Blood Cells (lower picture) . Figure 2

Red Blood Cells in a Micro-clot In Uncontrolled Diabetes (upper Picture) Figure 3

Red Blood Cell Clot Breaking Up (lower Picture) Figure 4

Micro-plaque Formation In Uncontrolled Diabetes (both pictures) Figures 5-6


Figure 7 (top) illustrates severely damaged erythrocytes in a 52-year-old man with persistent atrial fibrillation. Close examination shows some zones of congealing surrounding many damaged red blood cells.

Figure 8 (bottom) illustrates a zone of plasma congealing unaccompanied by any cellular elements of the blood (seemingly a “spontaneous” phenomenon) in a diabetic with IHD. In our view, such congealing represents accelerated oxidative stress on plasma.


Figure 9 (top) shows some needle-like and amorphous granular microclots in a patient with unstable angina.

Figure 10 (bottom) shows a “dirty” blood smear of a man with severe peripheral vascular disease and extensive bilateral leg ulcerations, showing zones of plasma congealing and lumpiness, platelet clumping, and some other zones of plasma congealing unaccompanied by any blood corpuscular elements, representing diffuse changes of AA oxidopathy.


Figure 11 (top) shows a microclot formed by a large aggregate of platelets and congealed plasma in a patient five days after angioplasty.

Figure 12 (bottom) shows another field from the same smear and illustrates how microclots in oxidative coagulopathy grow in size when oxidative stress persists.


Figure 13 (top) and figure 14 (bottom) show two microplaques in a patient who had received three unsuccessful angioplasties for advanced IHD. Photomicrographs were taken the day after a major nosebleed. Note the compaction of necrotic debris and blood elements in microplaques as contrasted with loose structure of microclots in figure 11.


References for Oxygen, Inflammation, Insulin, and Diverse Diseases


1.    Ali M. Spontaneity of Oxidation in Nature and Aging, (monograph). Teaneck, NJ, 1983.

2.    Ali M. Leaky Cell Membrane Disorder (monograph). Teaneck, NJ, 1987.

3.    Ali M. The agony and death of a cell. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine. Denver, Colorado, 1985.

4.    Ali M. Molecular medicine. In: The Cortical Monkey and Healing. Institute of Preventive Medicine, Bloomfield, NJ, 1990.

5.    Ali M. Ascorbic acid reverses abnormal erythrocyte morphology in chronic fatigue syndrome, Am J Clin Pathol. I990;94:5I5.

6.    Ali M. Ascorbic acid prevents platelet aggregations by norepinephrinc, collagen, ADP and ristocetin. Am J Clin Pathol 1991;95:281.

7.    Ali M. The basic equation of life. In: The Butterfly and Life Span Nutrition. The Institute of Preventive Medicine Press, Denville, New Jersey. pp 225-236, 1992,

8.    Ali M. Oxidative theory of cell membrane and plasma damage. In Rats, Drugs and Assumptions. 1995. Life Span, Denville, New Jersey. pp 281-302, 1995.

9.    Ali M, Ali O. AA oxidopathy: the core pathogenetic mechanism of ischemic heart disease. J Integrative Medicine 1997;1:1-112.

10.  Ali M. Ali O. Oxidative coagulopathy in fibromyalgia and chronic fatigue syndrome. Am J Clin Pathol 1999; 112:566-7.

11.  Ali M, Ali O. Fibromyalgia: An oxidative-dysoxygenative disorder (ODD) J Integrative Medicine, 1999;1:1717.

12.  Ali M. Syllabus of capital University of Integrative Medicine, 1997 Washington, DC.

13.  Ali M. Oxidative regression to primordial cellular ecology (ORPEC): Evidence for the hypothesis and its clinical significance. J Integrative Medicine 1988;2:4-55.

14.  Ali M. Primacy of the erythrocyte in vascular ecology. J Integrative Medicine. 2000;3:5-18.

15.  Ali M. The Oxidative-dysoxygenative perspective of apoptosis. J Integ Medicine. 2000;4:5-45.

16.  Ali M, Ali 0, Fayemi A, et al: Improved myocardial perfusion in patients with advanced ischemic heart disease with an integrative management program including EDTA chelation therapy. J Integrative Medicine. 1997;1:113-145.

17.  Ali M: Hypothesis: Chronic fatigue is a state of accelerated oxidative molecular injury. J Advancement in Medicine, 1993;6:83-96.

18.  Efficacy of ecologic-integrative management protocols for reversal of fibromyalgia: an open prospective study of 150 patients. J Integrative Med 1999:3:48-64.

19.  Ali M. Oxidative coagulopathy In environmental illness. Environmental Management and Health. 2000;11:175-191.

20.  All Recent advances in integrative allergy care. Current Opinion in Otolaryngology & Head and Neck Surgery 2000:8:260-266.

21.  Ali M. The agony and death of a cell. Syllabus of the instructional course of the American Academy of Environmental Medicine Denver, Co. 1985.

22.  Ali M. Intravenous Nutrient protocols in Nutritional Medicine, (monograph). Institute of Preventive Medicine. Denville, New Jersey 1991.

23.  Ali M. Oxidative theory of cancer. In: Rats, Drugs and Assumptions. 1995. Life Span, Denville, New Jersey. pp 1995:281-302

24.  Ali M. Amenorrhea, oligomenorrhea, and polymenorrhea in CFS and fibromyalgia are caused by oxidative menstrual dysfunction. J Integrative Medicine 1998;3:101-124.

25.  Ali M, Ali 0, Fayemi A, et al: Efficacy of an integrative program including intravenous and intramuscular nutrient therapies for arrested growth. J Integrative Medicine 1998:2:56-69.

26.  Ali M. Oxidative theory of cell membrane and plasma damage. In: Rats, Drugs and Assumptions. Life Span, Denville, New Jersey, 1995:281-302.

27.  Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine l999;1:11-16

28.  Ali M. Darwin, Oxidosis, Dysoxygenosis, and Integration. J Integrative Medicine. 1999;3:11-16.


Coronary Heart Disease Is Not a Plumbing Problem

Majid Ali, M.D.

New York  212-873-2444

New Jersey . 201-996-0027


Endo Health for Vascular Health

Oxygen-Insulin Signaling Matrix

Insulin-Endotoxicity and Cardiovascular Diseases

Two Enemies of the Heart: Conflict and Anger

Conflict cannot be cleared by letting the steam out.

Anger sometimes can be cleared by letting the steam out.

Clearer the Knowledge,

Better the Cardiovascular Health

Two Critical Links: the More the Coronary Plaques, Fewer the Heart Deaths 

The More-Coronary-Plaques-Fewer-Deaths Paradox

Conviction Concerning the Oxygen-Insulin Signaling Matrix

What Is Endothelium?

What Are Good Endo Spices?

What Are Good Endo Herbs


What Hurts Endos Most?

Perverted Oxygen-Insulin Signaling Matrix.


Crucial Endo Factors

Endothelium Maintains the Vasodilation and Vasoconstriction Balance

inhibition and promotion of the migration and proliferation of smooth muscle cells, fibrinolysis and thrombogenesis as well as prevention and stimulation of the adhesion and aggregation of platelets.


What Are Endos?

The vascular endothelium is a multifunctional organ and is critically involved in modulating vascular tone and structure. Endothelial cells produce a wide range of factors that also regulate cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. Thus, endothelial function is important for the homeostasis of the body and its dysfunction is associated with several pathophysiological conditions, including atherosclerosis, hypertension and diabetes. Patients with diabetes invariably show an impairment of endothelium-dependent vasodilation.

Endo Workers

  1.  Reactive Oxygen Species
  2.  Nitric Oxide
  3. Angiotensin II
  4.  EDHF      Endothelium-derived Hyperpolarization Factor
  5. .  Prostacyclin (PGI2
  6.    Antithrombotic (NO and PGI2 both inhibit platelet aggregation) 
  7.   Prothrombotic molecules [von Willebrand factor,
  8.   Plasminogen activator inhibitor-1 (PAI-1)


Nitric oxide

NO is a crucial player in vascular homeostasis. NO is synthesized within endothelial cells during conversion of l-arginine to l-citrulline by endothelial nitric oxide synthase (eNOS) [15]. It is released from endothelial cells mainly in response to shear stress elicited by the circulating blood or receptor-operated substances such as acetylcholine, bradykinin, or serotonin [16]. NO diffuses to vascular smooth muscle cells (VSMC) and activates soluble guanylate cyclase (sGC), yielding increased levels of cyclic guanosine-3,5-monophosphate (cGMP) and relaxation of VSMC [1,17]. Additionally, NO also prevents leukocyte adhesion and migration, smooth muscle cell proliferation, platelet adhesion and aggregation, and opposes apoptosis and inflammation having an overall antiatherogenic effect (Fig. 3) [18].

 Therefore, understanding and treating endothelial dysfunction is a major focus in the prevention of vascular complications associated with all forms of diabetes mellitus. The mechanisms of endothelial dysfunction in diabetes may point to new management strategies for the prevention of cardiovascular disease in diabetes. This review will focus on the mechanisms and therapeutics that specifically target endothelial dysfunction in the context of a diabetic setting. Mechanisms including altered glucose metabolism, impaired insulin signaling, low-grade inflammatory state, and increased reactive oxygen species generation will be discussed. The importance of developing new pharmacological approaches that upregulate endothelium-derived nitric oxide synthesis and target key vascular ROS-producing enzymes will be highlighted and new strategies that might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated vascular complications.

Decreased formation of NO

eNOS is a dimeric enzyme depending on multiple cofactors for its physiological activity and optimal function. eNOS resides in the caveolae and is bound to the caveolar protein, caveolin-1 that inhibits its activity. Elevations in cytoplasmic Ca2 + promote binding of calmodulin to eNOS that subsequently displaces caveolin and activates eNOS


Vascular Function and Endothelium

The endothelium is a monolayer of cells covering the vascular lumen. For many years this cell layer was thought to be relatively inert, a mere physical barrier between circulating blood and the underlying tissues. It is now recognized, however, that endothelial cells are metabolically active with important paracrine, endocrine and autocrine functions, indispensable for the maintenance of vascular homeostasis under physiological conditions [1,2]. The multiple functions of vascular endothelium are summarized in Fig. 1 and include regulation of vessel integrity, vascular growth and remodeling, tissue growth and metabolism, immune responses, cell adhesion, angiogenesis, hemostasis and vascular permeability. The endothelium plays a pivotal role in the regulation of vascular tone, controlling tissue blood flow and inflammatory responses and maintaining blood fluidity.


Crucial Endo Factors

Endothelium Maintains the Vasodilation and Vasoconstriction Balance

, inhibition and promotion of the migration and proliferation of smooth muscle cells, fibrinolysis and thrombogenesis as well as prevention and stimulation of the adhesion and aggregation of platelets.

  1.  Reactive Oxygen Species
  2. Nitric Oxide
  3. Angiotensin II
  4.  EDHF      Endothelium-derived Hyperpolarization Factor
  5. .  Prostacyclin (PGI2
  6.    Antithrombotic (NO and PGI2 both inhibit platelet aggregation) 
  7.   Prothrombotic molecules [von Willebrand factor,
  8.   Plasminogen activator inhibitor-1 (PAI-1)

Endothelium-derived factors with vasodilatory and antiproliferative effects include endothelium-derived hyperpolarization factor (EDHF) [], nitric oxide (NO) [8,9] and prostacyclin (PGI2) [10], while endothelin-1 (ET-1) [11], angiotensin II and reactive oxygen species (ROS) are among the mediators that exert vasoconstrictor effects [12,13]. Endothelial cells also produce antithrombotic (NO and PGI2 both inhibit platelet aggregation) and prothrombotic molecules [von Willebrand factor, which promotes platelet aggregation, and plasminogen activator inhibitor-1 (PAI-1), which inhibits fibrinolysis] [5].

As a major regulator of vascular homeostasis, the endothelium maintains the balance between vasodilation and vasoconstriction, inhibition and promotion of the migration and proliferation of smooth muscle cells, fibrinolysis and thrombogenesis as well as prevention and stimulation of the adhesion and aggregation of platelets (Fig. 2) [5]. Disturbing this tightly regulated equilibrium leads to endothelial dysfunction.


Many Faces of Endothelium

Fig. 1. Multiple functions of endothelium.


Spices and Herbs For Endo Health









Citations for the Diabetes Question Series


Free Access Library of Articles for Reversing Hyperinsulinism and Type 2 Diabetes

(Part of the Diabetes Question Series)

1.     M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004;253:64-65.
2.     Ali M. Oxygen and Aging. Book Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000. .
3.     Ali M. Succinate Retention. In: Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435.
4.     Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.
5.     Ali M. Epidemic of Dysoxygenosis and the Metabolic Syndrome. In: The Principles and Practice of Integrative Medicine. Volume 5. Pp 246-256. Canary 21 Press. New York. 2005.
6.     Ali M. Dysox and Climatic Chaos –  The primacy of oxygen issues over carbon issues. Part I. Townsend Letter-The examiner of Alternative Medicine. 2008;299:125-132.
7.     Ali M. Oxygen, Insulin Toxicity, Inflammation, And  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.
8.     Ali M. Insulin Reduction and EDTA Chelation: Two Potent and Complementary Approaches For Preventing and Reversing Coronary Disease. Oxygen, Insulin Toxicity, Inflammation, and the  Clinical Benefits of Chelation – Part II. Townsend Letter-The examiner of Alternative Medicine. 2010;323:74-79. June 2010.
9.     Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
10. Ali M. Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
11. Ali M. Importance of Subtyping Diabetes Type 2 Into Diabetes Type 2A and Diabetes Type 2B. Townsend Letter-The Examiner of Alternative Medicine. 2014; 369:56-58.
12. Ali M. Dasoju S, Karim N, Amin J, Chaudary D. Study of Responses to Carbohydrates and Non-carbohydrate Challenges In Insulin-Based Care of Metabolic Disorders.  Townsend Letter-The Examiner of Alternative Medicine. 2016; 391:48-51.
13. Ali M, Fayemi AO, Ali O. Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Homeostasis. .  Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.
14. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic Description: eta cells through GPR40Nature;422:173–176.
15. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
16. Reaven GM, Hollenbeck C, Jeng CY, et al. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDMDiabetes. 1988;371020–1024.
17. Sako, Y. & Grill, V. E. A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidationEndocrinology 127, 1580–1589 (1990). |
18. Rhodes, C. J. Type 2 diabetes — a matter of Description: eta-cell life and death? Science. 2005;307:380–384.
19. Kahn, S. E., Bergman, R. N., Schwartz, M. W., Taborsky, G. J. & Porte, D. Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humansAm. J. Physiol.1992;262:E518–E523.
20. Ali  M. Molecular Basis of Autism and Dysuatonomia – The Impeded Progenitor Cell Progression (IPCP) model of ASD and Dysautonomia.  Townsend Letter for Doctors and Patients. 2017 (In press)
21. Ali  M.  Insulin Laboratory Ranges.
22. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
23. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.
24. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition.
25. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
26. Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very-Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiologic Changes in Responders and Nonresponders. Diabetes Care. 2016 Mar 21. pii: dc151942.
27. Tilman D, Clark M. Global diets link environmental sustainability and human health. Nature. 2014;515, 518B522.
28. Hu, F. B. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 2011; 34:1249B1257.
29. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
30. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.
31. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition.
32. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
33. Ali M. The Principles and Practice of Integrative Medicine Volume X: Darwin, Oxygen Homeostasis, and  Oxystatic Therapies.  3 rd. Edi. (2009) New York. Institute of Integrative Medicine Press.
34. Ali M. The Principles and Practice of Integrative Medicine Volume  XI: Darwin, Dysox, and Disease. 2000. 3rd. Edi. 2008. New York.  (2009) Institute of Integrative Medicine Press.
35. Ali M. The Principles and Practice of Integrative Medicine Volume  XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.
36. Ali M. Oxygen, Inflammation, and Castor-Cise Liver Detox. Hormones. Townsend Letter-The examiner of Alternative Medicine. 2007. Published online.
37. Ali  M. Philosophy and Science of holism in healing. APPNA Journal. 2015.
38. Ali M. Hyperinsulinism Associated With Breast and Prostate Cancer. Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.
39. Kamada N, Seo S-U, Zhiming C, et al. Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology. 2013;12:321-335.
40. Grocott M, Richardson A, Montgomery H, et a. Caudwell Xtreme Everest: a field study of human adaptation to hypoxia. Critical care 2007;11:151.
41. Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.
42. Stanley SA, Kelly L, Kaasmashri N, et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature. 2016  531:647–650.
43. Murphy KG, Bloom SR. Gut hormones and the regulation of energy bhomeostasis. Nature. 2006;444:854-859.


Link to Am Important Article

Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes

Majid Ali, MD, FRCS (Eng), FACP; Alfred O. Fayemi, MD, MSc (Path), FCAP; Omar Ali, MD, FACC; Sabitha Dasoju, MB, BS; Daawar Chaudhary; Sophia Hameedi; Jai Amin; Kadin Ali; Benjamin Svoboda


Optimal and Inappropriate Laboratory Testing For Assessing Insulin Homeostasis

Majid Ali, M.D.

Grievous Errors in Insulin Testing


What Is Optimal Laboratory Insulin Testing?

What Are Commonly Made Grievous Insulun Testing Errors?

 Optimal laboratory testing for assessing insulin homeostasis is to use tests that directly and specifically assess various aspects of insulin homeostasis. Inappropriate laboratory testing for assessing insulin homeostasis is to use tests that do not directly and specifically assess various aspects of insulin homeostasis.
Examples of optimal laboratory tests for insulin homeostasis are measurement of blood insulin concentration with fasting blood samples and timed samples obtained after a standard glucose challenge. Examples of inappropriate insulin tests are fasting blood glucose level, two-hours post-prandial blood glucose level, and A1c since these tests are test for glycemic status and not for assessing insulin homeostasis. 

Grievous Errors In Insulin Laboratory Tests
I recognize the following commonly made grievous errors in laboratory assessment of insulin homeostasis. Regrettably, these errors are deemed optimal standards for many doctors. 
1.   Blood insulin tests are done on randomly drawn blood tests (Results of such tests                              simply cannot be interpreted).
2.   The epidemic prevalences of hyperinsulinism of varying degrees are near-completely                     ignored in clinical medicine and insulin tests are simply not done (Table 2). 
3.   Tests for blood  sugar levels are done as substitutes for insulin tests. Glucose tests                            and others for glycemic status simply are not insulin tests.
4.   Laboratories use wholly inappropriate references ranges for blood insulin concentrations (See Table 2 for specifics). 
5.   Cut-off points for blood insulin concentrations determined with timed, post-glucose-                   challenge are not based on real insulin testing data.
6.   Insulin is the primary pro-weight gain and pro-obesity hormone, and yet insulin tests                 are done in weight loss and obesity programs. 
7.  Gestational diabetes is an insulin disorder before it becomes a glucose (sugar)                                 disorder. Insulin tests are not done for gestational diabetes.
8.  Insulin in excess is a potent the primary pro-weight gain and pro-obesity hormone,                       and yet insulin tests are done in weight loss and obesity programs. 
9. Insulin in excess is proinflammatory, pro-infections, pro-cancer, pro-premature aging,                 and pro-degenerative disorders and yet insulin tests are seldom, if ever, done by                 most doctors. 
10. Indeed, insulin in excess increases the risk of and fans the fires of all nearly chronic                  diseases 

Two Subtypes of Type 2 Diabetes: T2D Subtype A and T2D Subtype B
In 2014, I recognized the need to subtype Type 2 diabetes (T2D) into two T2D subtypes:
                              T2D subtype A
                               T2D subtype B
Diabetes is a two-faced disease, one with insulin toxicity and the other with insulin depletion: this diabetes duality in itself is most revealing. Below we present five sets of illustrative insulin and glucose profile taken from our original communication to make and illustrate our main points, which are presented and its full clinical implications considered in a separate chapter For the first five, ten or more years, the disease is characterized by rising blood sugar levels accompanied by increasing blood concentrations of insulin (hyperinsulinism aptly designated insulin toxicity). In the later years, T2D is characterized by rising blood sugar levels accompanied by falling insulin levels, this is the stage of insulin depletion (see Tables 1.1 and 1.2 for details).
Table 1. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes
Insulin Category*
Percentage of Subgroup
Mean Peak Glucose  mg/dL
Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis.N 12**
110.2     (6.12)
Optimal Insulin Homeostasis N =126
24.9 %
121.2     (6.73)
Hyperinsulinism, Mild                N =197
38.9 %
136.5   (7.58)
Hyperinsulinism,  Moderate       N =134
26.5 %
147.0    (8.16)
Hyperinsulinism,  Severe             N =  49
9.7 %
150.0    (8.33)
(less than time and a half higher) 
(nearly 17 times higher)
#   Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.
*Criteria for classification: (1) Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild

Table 2.  Insulin Reference Ranges  in uIU/mL of Six Laboratories in New York Metropolitan Area*
 1 Hr
 2 Hr
 3 Hr
 Laboratory 1
1.9 – 23
8  –  112
 5 – 35
 Not Reported
 Laboratory 2
 2.6 – 24.9
 0.0  – 121.9
 0.0 – 163.5
 Not Reported
 Laboratory 3 
 2.6 – 24.9
 8  –  112
 5  –  55
 3  –  20
 Laboratory 4
 6  – 27
 20  –  120
 18  –  56
 8  –  22
 Laboratory  5
 00  – 30
 30  –  200
 40  – 300
 50  – 150
 Laboratory 6
 Does not include insulin ranges in the report. Instead it includes the following note: Insulin analogues may demonstrate non-linear cross-reactivity in this essay. Interpret results accordingly.**
*Upper and lower limits of laboratory reference ranges for blood insulin concentration determined following a Standard 75-gram glucose challenge.
**Personal communications with clinicians revealed that they do not find this laboratory note to be satisfactory in their clinical decision-making.

Grievous Errors in Insulin Testing

First Grievous Error: Believing That Diabetes (T2D) Is a Sugar (Glucose) Problem 
The first grievous error of considering insulin insufficiency as the cause of T2D has misled generations of doctors, leading to the mistreatment of hundreds of millions of people with prediabetes and T2D. In reality, hyperinsulinism predates T2D for five to ten or more years, although the study of insulin homeostasis is not deemed a standard of care for health preservation and disease prevention and/or control. Indeed, it is not taught in medical schools or on hospital wards, even where there are patients with suspected or diagnosed diabetes. The neglect of this core aspect of insulin dysregulation results in: (1) delayed diagnosis of T2D, and (2) as we document conclusively, the failure to detect and address long-established metabolic, inflammatory, immune, cardiovascular, and neurological consequences of insulin hyperinsulinism (Bahi-Buisson et al., 2008; Dandona, Aljada and Bandyopadhyay, 2004; IDFDA, 2016; Khan, Hull and Utzschneider, 2006; Shoelson, Lee and Goldfine, 2006; Shulman, 2014; Wellen and Hotamisligil, Shargill and Spiegelman,2005). Notable in this context is the recent documentation of hyperinsulinism in autism and pediatric dysautonomia (Ali, 2017a), which is discussed in chapter 6.
During the years of excess insulin – hyperinsulinism, or more appropriately insulin toxicity – widespread damage is inflicted in nearly all cell populations in the body. There is a profound irony here.  The very definitions of T1D and T2D lays bare the falsehood of the prevailing belief, the former being a state of near-complete absence of insulin in the blood while the latter for years is accompanied by raised blood insulin concentrations (as documented in Table 1.2). To add to the irony of this, consider the definition of insulin from the website of Merriam Webster Dictionary (March 15, 2017) reproduced verbatim here:
a protein pancreatic hormone secreted by the beta cells of the islets of Langerhans that is essential especially for the metabolism of carbohydrates and the regulation of glucose levels in the blood and that when insufficiently  produced results in diabetes mellitus …and that when insufficiently  produced [insulin] results in diabetes mellitus!
Consequently, it is not surprising that this utterly false notion of T2D caused by insulin insufficiency has become so deeply entrenched in public consciousness? The enduring belief of medical and nursing communities in this misleading dogma is of great concern. The key question is why has this definition not been previously challenged by the medical community?
To bring this grievous error into yet sharper focus, T1D is an acute-onset type disease usually occurring in children, characterized by near-complete absence of insulin-producing capacity of the pancreas gland. By contrast, T2D develops insidiously and, until recently, nearly always developed in adults. The blood insulin concentrations begin to fall after decades of insulin waste that occurs during the hyperinsulinism phase of the disease: this is what medical students learn in classrooms and on medical wards and  what nurses learn in nursing schools. Then the medical tragedy happens. Simple blood tests, for determining blood insulin concentrations to assess the state of insulin homeostasis of individual patients, is not considered a standard of care in any medical specialty or general practice. This disturbing notion of T2D being rooted in insulin insufficiency persists and so the hazards of insulin toxicity go unrecognized.

Second Grievous Error
Neglect of a Specific Quantitative and Modifier Marker
 The Third Grievous Error: Absurd Laboratory Insulin References Ranges
The third grievous error concerns laboratory reference ranges for blood insulin concentrations reported by most university hospital and nationwide commercial laboratories. Rather than guide clinicians interested in the study of insulin dysregulation in their patients, clinical pathologists and laboratory professionals have for decades compounded the problem of neglected hyperinsulinism. Table 1.3 displays wide variations in the lower and upper limits in the reference ranges for fasting and post-glucose challenge blood insulin concentrations employed by six major laboratories in the New York City metropolitan area. The variation in insulin reference ranges invariable invites skepticism, with photographs of actual laboratory reports on the web ( Note that laboratory 1 reports a range of 5-35 for 2-hour blood insulin level while laboratory 5 reports of range of 40-300 for the sample blood sample: while laboratory 1 reports a range of 5-35 for 2-hour blood insulin level. Further, laboratory 5 reports of range of 40-300 for the sample blood sample, while laboratory 2 reports a range of 0.0 to 121.9 and laboratory 4 reports 20-120 for the same blood sample. It is difficult to imagine a parallel for this level of absurdity in the entire field of laboratory medicine.

Cut-off Points for Optimal Insulin Homeostasis and Degrees of Hyperinsulinism
Our selection of the peak insulin value of <40 mIU/mL as the cut-off point for optimal insulin homeostasis in our survey of prevalence of hyperinsulinism in New York (see Table 1.1), was based on a preliminary review of the first 50 sets of insulin and glucose profiles (Ali et al., 2017a). We opted for cut-off points for hyperinsulinism stratification based on doubling of the levels (to <80, <160, and >160 uIU/mL for mild, moderate, and severe hyperinsulinism) with two considerations: (1) are these cut-off points appropriate for this study, and (2) do they provide a frame of reference for future investigations of diverse aspects of insulin homeostasis and hyperinsulinism-to-T2D progression? There are a number of other issues that need to be considered in this context: (1) what constitutes optimal insulin homeostasis, (2) what should the insulin cut-off point be, as there is no agreement within the relevant literature, (3) no adverse effects of low insulin levels when accompanied by unimpaired glucose tolerance have been reported, and (4) Hyperinsulinism and the metabolic syndrome are commonly spoken in the same breath,  explicitly or implicitly referring to them as the two faces of the same coin. However, there is a crucial difference between the two, the peak insulin level and other features of three-hour insulin and glucose profiles provide clinicians with  specific and quantitative cut-off  points for detecting and stratifying hyperinsulinism but no such criteria have been established for the metabolic syndrome. In addition, three-hour insulin and glucose profiles shed light on other aspects of glycemic status and insulin homeostasis, some of which are presented later in this chapter.
A subgroup of twelve participants was designated ‘exceptional insulin homeostasis’ for two reasons: (1) they showed an extremely low fasting insulin value of <2 uIU/mL (mean 14.3 uIU/mL) and peak insulin concentrations <20 uIU/mL accompanied by unimpaired glucose tolerance, and (2) ten of the twelve had no family history of diabetes (parents, siblings, grandparents, children, uncles or aunts), while the mother of the eleventh subject developed T2D in the closing months of her life at age 74 and both parents of the twelfth subject had T2D. This subgroup appears to reflect ideal metabolic efficiency of insulin in the larger evolutionary context.

Shifting Focus from Glucose Testing to Insulin Testing
As reported in the preface, the much higher rate of hyperinsulinism observed in New York’s general population compared to rates of T2D in India (Kaveeshwar and Cornwell, 2014) and China (Xu et al., 2013), provides strong support for the view that there is a need to shift focus from glucose testing to insulin testing for stemming global tides of hyperinsulinism and T2D. A crucial point in this context is that the data published in the Indian and Chinese studies was derived from glucose testing, whereas our insulin database was derived exclusively from direct insulin testing, with measurements of post-glucose challenge blood insulin concentrations with sequential and timed blood samples.
Here we point out that the insulin and glucose profiles presented in this and other chapters shed light on the full spectra of insulin homeostasis, hyperinsulinism and related patterns of insulin dysfunction, for example insulin spikes followed by hypoglycemic episodes which create hunger for foods that create yet more sugar spike. Therefore the insulin and glucose profiles presented in Tables 1.4-1.8 in this (and numerous in other chapters) require that the data be considered in light of the clinical context as well as looking through the kaleidoscopic prisms of molecular biology of oxygen Ali, 2000, 2002, 2004a, 005a, 2007, 2009a, 2011), oxygen model of hyperinsulinism (Ali, 2014a) and oxygen model of T2D (Ali, 2001). As for co-morbidities of the hyperinsulinism-T2D continuum (metabolic, inflammatory, immune, infectious, cardiovascular, neurological, developmental, gut-microbiota-related, differentiative, and degenerative), we do not recognize any  inconsistencies between our observations and inferences and those of earlier workers (Nath, Heemels and Anson, 2006; Nichols, 2012; Patti et al., 2003; Saltiel and Kahn, 2001; Scherer, 2005; Stanley, 2016; Turnbaugh, 20


Table 3. Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes
Insulin Category
Percentage of Subgroup
Mean Peak Glucose, mg/dL
Mean Peak Insulin (uIU/mL)
Diabetic Hyperinsulinism, Mild              N =  53
252.0   (14.00)
Diabetic Hyperinsulinism, Moderate    N =  42
242.1   (13.45)
Diabetic Hyperinsulinism, Severe          N =  24
224.6   (12.47)
Diabetic  Insulin Deficit                             N =  59
294.0    (16.33)
Illustrative Case Studies of Insulin Responses to Glucose Challenge
Tables 4 to 8 present five illustrative sets of insulin and glucose profiles with brief clinical notes. The insulin profiles in Tables 4 and 8  represent the two extremes of insulin peaks (18 uIU/mL and 718.2 uIU/mL) encountered in this survey. The first of the two profiles (Table 4) is reflective of ideal metabolic efficiency of insulin in a larger evolutionary perspective of energy economy in the body. Notable findings here are: (1) a very low fasting insulin level of <2 uIU/mL reflecting efficient insulin conservation during the fasting state; (2) low insulin peak value (18 uIU/mL) indicating high insulin efficiency following a substantial glucose challenge; and (3) a very low insulin level in the 3-hour sample (<2 uIU/mL) reflects optimal beta cell response to glucose level falling below the fasting level.
Table 4. Example of Insulin and Glucose Profiles In Exceptional Insulin Homeostasis Category*
½ Hr
1 Hr
2 Hr
3 Hr
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
77     (4.27)
168   (9.33)
109      (6.05)
74       (4.11)
59    (2.88)
*The Patient,  A  60-Yr-Old 5’ 7” Man Weighing 138 lbs. Presented for a Wellness Assessment. He Was Considered to be in Excellent Health By Clinical and Laboratory Evaluation Criteria.
Table 5.  Severe Hyperinsulinemia in A Subject With Previously Undiagnosed Type 2 Diabetes*
½ Hr
1 Hr
2 Hr
3 Hr
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
112     (6.21)
158   (8.77)
214      (11.76)
241    (13.38)
129   (7.16)
* The Patient,  A 64-Yr-Old 5’ 4” Woman Weighing 164 lbs. Presented With Hypothyroidism, History of Coronary Artery Stent Insertions, Fatty Liver, Memory Concerns And Without Previous Diagnosis of Type 2 Diabetes.
Table 6. Hyperinsulinism 18 Years After the Diagnosis of Type 2 Diabetes*
½ Hr
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
128      (7.10)
224   (12.43)
278    (15.42)
297    (16.48)
249     (13.81)
*The Patient,  A 74-Yr-Old 5’ 6” Woman Weighing 155 Lbs. Presented With Bronchiectasis, Rheumatoid Arthritis, Prehypertension, and Inhalant Allergy.
Table 7. Brisk Insulin Response With A “Flat” Glucose Tolerance Profile*
½ Hr
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
72      (3.39)
44     (2.44)
63    (3.49)
58     (3.21)
65   (3.90)
*The Patient,  A 47-Yr.Old  5’ 5” Woman Weighing 170 Lbs. Presented With Polyarthralgia, Recurrent Sinusitis, and Fatigue.
Table 8. Severe Hyperinsulinism In A 13-Yr-Old Girl With Lupus Erythematosus*
½  Hr
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
      70   (3.88)
  140     (7.77)
   157     (8.71)
   150    (8.33)
   111   (6.16)
Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Therapies
Insulin uIU/mL
Glucose mg/mL  (mmol/L)
81     (4.49)
154   (8.54)
181     (10.04)
130     (7.21)
97      (5.38)
*The Patient,  A 13-Yr-Old Girl With a History of Three Hospitalizations In One Year for Systemic Lupus Erythematosus, Recurrent Pneumonia, Thrombocytopenia, and Severe Optic Neuritis Resulting In Complete Loss of Vision In Right Eye. The Peak Insulin Fell from 718 to 238.5 In Four Months of Robust Integrative Treatment.

Insulin Essentials

Majid Ali, M.D.

Very little of What I Learned About Diabetes In Medical School Has Been Validated by My Patients, My True Teachers.


Insulin Essentials

  1. Insulin is the master energy hormone of the body, for energy generation as well as energy expenditure.
  2. The energy demands of chronically-injured cells increase because repair of injured tissues needs more energy.
  3. Increased demands for cellular repair energy can be met only with increased supply of fuel (glucose) for producing more cellular energy.
  4. Higher demands for glucose require higher insulin activity.
  5. The validity of these statements can be tested only with direct blood insulin tests, not by doing blood tests for glucose (fasting blood glucose, A1c test, two-hour post-prandial blood sugar, or three-hour glucose tolerance test after a glucose load.
  6. other forms of sugar.
  7. Anyone can test the validity of the above statement with blood insulin tests.


What My Professors Did Not Tell Me About Insulin Essentials

  1. Newborn babies with birth weight larger than eight pounds are insulin toxic.
  2. Mothers of babies with birth weight larger than eight pounds are insulin toxic.
  3. Expecting moms with gestational diabetes are insulin-toxic and will remain so after delivering their babies for variable periods of time.
  4. Boys with widespread persistent acne are insulin-toxic.
  5.  Young girls with polycystic ovarian cystic syndrome are insulin-toxic.
  6. Nearly all obese children are insulin-toxic.
  7. Children and adults with fatty liver and steatosis are insulin-toxic.
  8. Most patients with pulmonary fibrosis, bronchiectasis, and active tuberculosis are insulin-toxic. 
  9. Most individuals with psoriasis and sarcoidosis are insulin-toxic.
  10. Most individuals with chronic autoimmune disorders (rheumatoid arthritis, lupus, scleroderma, and others) are insulin-toxic.
  11. Most patients with chronic renal failure are insulin-toxic.
  12. Most individuals with memory loss, dementia, Alzheimer’s disease, and diverse chronic diseases of the brain are insulin-toxic.
  13. Most individuals with cancer are insulin-toxic.
  14. Nearly all people become insulin-toxic after receiving chemotherapy.



  1. Individuals with psoriasis are insulin-toxic.
  2. babies with birth weight larger than eight pounds are insulin toxic.
  3. In


Dementia Is Rooted in Insulin Brain Toxicity

Majid Ali, M.D.

All Known risk factors of dementia are first known risk factors of hyperinsulinism (insulin toxicity and then of Dementia.

Dementia Is rooted in insulin toxicity. I support my view by showing here that all known risk factors of dementia are rooted in insulin toxicity excess – hyperinsulinism, by another name.


Insulin Toxicity Can Be Reliably Detected Only by Blood Insulin Tests

The only direct and reliable method of detecting insulin toxicity is timed measurements of blood insulin concentrations after a glucose challenge. Employing this insulin test, in 2017, my colleagues and I documented a prevalence rate of hyperinsulinism of 75.1% in the general population in New York metropolitan area.1 This was not surprising since four years earlier the Chinese, employing blood glucose tests had reported a combined prevalence rate of prediabetes and diabetes of 50.1%.2

The core message of this short article, I state at the beginning, is: find out if you are insulin-toxic with blood insulin tests, and if this be the case, and you and on the path to dementia, clear insulin toxicity. For this purpose, I suggest my 3D Insulin Protocol comprising diet, detox, and dysox plans, and are presented in detail at


Dementia Is rooted in insulin excess – hyperinsulinism, in the medical jargon is the term for it – which precedes Type 2 diabetes (T2D) by five, ten, or more years. This, succinctly stated, is the basic relationship between dementia, diabetes, insulin resistance and hyperinsulinism.


As for the cause of dementia, my assertion that insulin toxicity is the root cause of dementia was one of the prediction of both oxygen model of hyperinsulinism and the oxygen model of dementia. I put forth these models in 19951 as extensions of my oxygen model of aging proposed in 19802. These models were based on my studies of mitochondrial dysfunction and respiratory-to-fermentative shift in chronic immune-inflammatory and other disorders proposed on 1980.

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