Category Archives: Shifting Fcus From Glycemic Status to Insulin Homeostasis

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
(mmol/mL)
Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis.N 12**
1.7%
110.2     (6.12)
14.3
Optimal Insulin Homeostasis N =126
24.9 %
121.2     (6.73)
26.7
Hyperinsulinism, Mild                N =197
38.9 %
136.5   (7.58)
58.5
Hyperinsulinism,  Moderate       N =134
26.5 %
147.0    (8.16)
109.1
Hyperinsulinism,  Severe             N =  49
9.7 %
150.0    (8.33)
(less than time and a half higher) 
231.0
(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*
 Laboratory
 Fasting
 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 (www.alidiabetes.org). 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
(mmol/mL)
Mean Peak Insulin (uIU/mL)
Diabetic Hyperinsulinism, Mild              N =  53
29.0%
252.0   (14.00)
55.4
Diabetic Hyperinsulinism, Moderate    N =  42
24.0%
242.1   (13.45)
112.4
Diabetic Hyperinsulinism, Severe          N =  24
13.9%
224.6   (12.47)
298.0
Diabetic  Insulin Deficit                             N =  59
33.1%
294.0    (16.33)
22.9
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*
 
Fasting
½ Hr
1 Hr
2 Hr
3 Hr
Insulin uIU/mL
<2
18
14
4
<2
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*
 
Fasting
½ Hr
1 Hr
2 Hr
3 Hr
Insulin uIU/mL
23.8
19.3
36.9
114.7
75.2
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*
Fasting
½ Hr
1Hr
2Hr
3Hr
Insulin uIU/mL
  12.9
27.2
29.2
36.2
25.4
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*
Fasting
½ Hr
1Hr
2Hr
3Hr
Insulin uIU/mL
3
23
22
8
<2
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*
Fasting
½  Hr
1Hr
2Hr
3Hr
Insulin uIU/mL
27.9
362.5
424.0
718.2
571.7
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
7.2
125.1
238.5
208.0
132.0
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.
 

References For Insulin Homeostasis and Diabetes

Majid Ali, M.,D.

Selected References Reversing Diabetes D3 Series


References

1.   Ali. M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004.

2.   Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine. 1999;3:11-16.

3.   Darwin, Dysox, and Disease. Volume 11. The Principles and Practice of Integrative Medicine 11. New York: Canary 21 Press; 2002.

4.   Ali M. The Principles and Practice of Integrative Medicine Volume I: Nature’s Preoccupation With Complementarity and Contrariety. New York. Canary 21 Press. 1998. 2nd edition 2005.

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. Insulin Toxicity, Inflammation, And  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.

7.   Ali M. Hypothesis: obesity is adipomyocytic dysoxygenosis. J Integrative Medicine. 2004;9:19-38.

8.   Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.

9.   Shoelson, SE, Lee J. Goldfine AB. Inflammation and insulin resistance. J. Clin. Invest. 2006;116: 1793–1801.
2

10.                  Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854-859.

11.                 .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.

12.                 International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. www.diabetesatlas.org.

13.                 Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.

14.                 Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.

15.                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.

16.                Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000.

17.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

18.                Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

19.                 Ali M. Fayemy 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.

20.                 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.

21.                 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.

22.                 Ali M. The Principles and Practice of Integrative Medicine Volume XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.

23. Ali M. The Philosophy and Science of Healing. APPNA Journal. 2015;25:18-19.

24.                Nath D, Heemels M-T, Lesley Anson L Obesity and diabetes. Nature. 2006;444, 839.

25.                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.

26.                 Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

27.                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.

28.                 von Herrath M. Insulin trigger for diabetes. Nature. 2005;435:151-152.

29.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

30.                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.

31.                 Stanley SA, Kelly L, Kaasmashri N, et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature. 2016  531:647–650.

32.                Ali M. Autism. Nature

33.                Ali M. Ali M. Molecular basis of autism and dysautonomia. Townsend Letter-The examiner of Alternative Medicine. 2017 (in press).

34.                Ali M. Lab ranges www.alidiabetes.org

35.                 Kaveeshwar SA, Cornwell J. The current state of diabetes mellitus in India. Australas Med J. 2014;7:45-48.

36.                 Lesley J, Manning LA, Ogle GD. A survey of diabetes services in hospitals in Ali Papua New Guinea. P N G Med J. 2001: 44:88-95.))

37.                 Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults. JAMA. 2013; 310: 948-59.

38.                 Ali M.  Oxygen model of hyperinsulinism.  xxxx

39.                 Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.

40.                 Ali M. Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.

41.                 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.

42.                 Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515, 431–435.

43.                 Ali M. Succinate Retention. In: Chouchani ET. Pel VR,  Gaude E, et al.Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature;2014;515:431. (commentary after references).

44.                 185. Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.  

Reversing Prediabetes and Diabetes With 3D Plan: Insulin-Wise and Insulin-Unwise Foods and Meals

Majid Ali, M.D.

A Question-Answer Learning Exercise of Great Importance for Reversing Hyperinsulinism (Prediabetes) and Reversing Diabetes


 

Reversing Prediabetes and Diabetes 3D Plan

 

Three prongs of the Reversing Diabetes D3 are:

                                     D  for diet

                                     D  for Detox

                                     D  for Dysox

I use the term dysox in the context of controlling hyperinsulinism and reversing Type 2 diabetes (T2D) for oxygen-related co-morbidities of both hyperinsulinism and T2D.


 

Questions Exercise

For Losing Weight and Reversing Prediabetes (Hyperinsulinism) and Diabetes

with Diabetes 3D

I suggest that you print these questions and circle your answer in light of materials presented at this website. Specifically, which one of the following food/meal options are insulin-wise compared with others. The answers and explanatory comments appear at the end of questions.

  1. Popcorn in the movie house or a slice of pizza before the movie.
  2. Popcorn with butter or popcorn without butter
  3. Whole milk yogurt or fat-free milk
  4. Yogurt or kefer for snack
  5. Fruit juice or protein shake
  6. Egg omelette or scrambled egg
  7. Fish meal or beef meal
  8. Whole milk or 2% milk
  9. Toast with olive oil or with it
  10. Blueberries snack with or without cheese
  11. Peanut butter snack or an apple
  12. Foods that cause sugar spikes or foods that trigger insulin spikes
  13. Salad with olive or salad with salad dressing
  14. Flaxseed oil or freshly ground flaxseeds
  15. An apple in the afternoon at work or two teaspoons of almond butter
  16. Breakfast Protein Shake with or without Spices
  17. White rice of brown rice for dinner
  18. For high morning blood sugar levels due to diabetes, four ounces of protein shake in the morning before breakfast or at bed time
  19.  Carrots or radishes in equal weight  
  20. Total gluten abstinence for GERD-gastritis complex or for colitis
  21. Aspartame or saccharine as sweeteners 

 

Essentials of Relationships Between Food Spikes and Insulin Spikes

  1. Every food that causes a sugar spike triggers an insulin spike.
  2. Every insulin spike causes a sharp drop in blood sugar level (hypoglycemia).
  3. Every sharp drop in blood sugar level creates a craving for foods that produce sugar spikes.
  4. Every sharp insulin spike sets the stage for secondary, albeit lower, insulin spikes.
  5. The larger the number of insulin spikes, higher the chance of developing hyperinsulinism (insulin toxicity by its more appropriate name)  

 

Plant Remedies and Supplements

for Reversing Hyperinsulinism (Prediabetes) and Diabetes

Phytofactors (Plant Remedies) 

  1. Aloe Vera
  2. Bitter melon
  3. Cinnamon
  4. Fenugreek
  5. Flaxseed
  6. Garlic
  7. Ginseng (Panax ginseng)
  8. Gymnema sylvestre
  9. Huckelberry
  10. Neem
  11. Nopal (prickly pear cactus)

Nutritional Supplements

  1. Coenzyme Q10
  2. Chromium
  3. Lipoic acid (alpha lipoic) 
  4. Magnesium, potassium, Taurine
  5. Cinnamon                    
  6. Chromium                   
  7. Vanadyl sulfate           
  8. Multivitamin
  9. Multimineral

 


Highly recommended readings at this website

  1. Reversing diabetes 3D
  2. Shifting Focus from Glycemic Status to Insulin Homeostasis for stemming Global tides of hyperinsulinism and Type 2 Diabetes
  3. Free Access Dr. Ali’s Insulin Course
  4. Free Access Dr. Ali’s Library of Videos and Articles

 

Video and Article Library

Majid Ali, M.D. * Insulin Toxicity De-mystifies the Metabolic Syndrome …

Jun 28, 2012 – Uploaded by majid ali

The true mature of the metabolic syndrome is insulin toxicity. The term metabolic syndrome creates creates …

Majid Ali MD, Dr. Ali’s Book on Reversing Diabetes – Dr. Ali’s Plan for …

https://vimeo.com › Majid Ali › Videos
Nov 6, 2014

I outline the contents of this book on reversing diabetes Type 2. I explain how it begins with insulin toxicity …

How Do You Reverse Diabetes Majid Ali MD on Vimeo

https://vimeo.com › Majid Ali › Videos
May 24, 2014

Professor Majid Ali shares information about “How Do You Reverse Diabetes

Majid Ali MD, Castor Oil Rubs for Insulin Detox for Weight Loss and …

https://vimeo.com › Majid Ali › Videos
Jan 24, 2015

Type 2 diabetes is an insulin-toxicity state for years before the body reserves ofinsulin are depleted and the …

Dr. Ali’s Insulin Reduction Protocol

Majid Ali, M.D. … For individuals with pre-diabetes with insulin toxicity but without high blood sugar levels, my … I present this subject at length in my book entitled “Dr. Ali’s Plan for Reversing Diabetes” and in a 40-minute video seminar that can …

Dr. Ali’s Diabetes Reversal program – Dr. Ali’s Virtual Medical Library

drali1.org/dr__ali’s_diabetes_reversal_guidelines.htm

Majid Ali, M.D.. The science and philosophy of reversing diabetes Type 2 associated with excess insulinis simple to understand. On this website and in my video …

Reversing Diabetes – Majid Ali

aliacademy.org/reversing_diabetes.htm

Simply stated, diabetes Type 2A is a state of insulin toxicity created by insulin … 1 of a video seminar on reversing diabetes, Professor Majid Ali, M.D. presents a …

Dr. Ali’s Insulin-Based Diabetes Reversal | – alihealing.org

Jan 11, 2017 – Majid Ali, M.D. Workable Simplicity to Understand Maddening Complexity of Three Scourges of Our Time Dr. Ali’s InsulinDiabetes Video and …

 

Diabetes Reversal With Insulin Profiling : Dr Majid Ali : Free Download …

May 5, 2014 – For more information on the subject , please consider Prof.Ali`s Video seminars and courses available as downloads at www.aliacademy.org.

Insulin Toxicity | Childrens Health Corps

Jul 15, 2014 – Insulin Toxicity Video Series … Insulin-Wise Eating Majid Ali, M.D. To reverse pre-diabetesand diabetes (completely or partially), my primary …

Majid Ali MD – Home | Facebook

… about this. Majid Ali, MD has compiled a free video library of thousands of videos pertaining to health. … Ozone | Diabetic or Insulin Neuropathy. Ozone by …

18006336226.com

THESE ARE VIDEO DOWNLOADS from ALIACADEMY.org … Instant Seminars with Majid Ali, M.D.. ThevideosInsulin Toxicity and Reversal of Diabetes. Skin.

Reversing Diabetes With Diabetes Reversing Plan D3

Majid Ali, M.D.

Introduction and Outline of Dr. Ali’s Reversing Diabetes 3D Plan for Reversing Hyperinsulinism and Reversing Diabetes 3D

Unless specified otherwise, the term diabetes in this article is used for Type 2 Diabetes (T2D) which is the main type of diabetes. 


 

The 3D Plan

  1. D    for Insulin Diet Plan for Reversing Diabetes
  2. D    for Insulin Detox for Reversing Diabetes
  3. D    for Insulin Dysox for Reversing Oxygen-Related Co-morbidities of Prediabetes and Diabetes 

 

Nine Essentials

of 3D Plan for Reversing Prediabetes and Diabetes

 

  1. Diabetes is not a sugar problem. It is a type of insulin dysregulation caused by toxicities of food, environment, and thought which collectively create dysfunctional oxygen metabolism and signaling.
  2. Insulin dysregulation has two dimensions: (A) the first dimension of insulin toxicity (hyperinsulinism) without raised blood glucose levels diagnostic of diabetes; and (B) the second dimension of insulin toxicity accompanied by raised blood sugar levels diagnostic of diabetes.
  3. In the writer’s oxygen-insulin perspective of human biology, insulin serves as the primal energy hormone of the body serving at the pleasure of oxygen. Homeostatic pathways of oxygen and insulin are intricately intertwined. 
  4. Insulin dysfunction can be reliably diagnosed only with blood insulin tests, not by tests for blood sugar levels (fasting blood sugar level, A1C level, two-hours post-prandial blood glucose test, or glucose tolerance test).
  5. Insulin toxicity (hyperinsilinism always predates diabetes by five, ten, or more years.
  6. So the only right way to prevent diabetes is to detect insulin toxicity and reverse it. No insulin toxicity, no diabetes. It is really that simple.
  7. Hyperinsulinism is eclipsing all chronic diseases worlwide. This writer and his colleagues documented a hyperinsulinism prevalence rate of 75.1% in the general population of New York Metropolitan area.
  8. Hyperinsulinism-to-diabetes continuum begins withe increased production and release of insulin by the pancreas gland in order to meet increased energy demands of injured tissues as they strive to repair their injuries.
  9. Reversing of hyperinsulinism and diabetes requires philosophy and science of holism in healing.

 

A Crucial Message From My Patients – My True Teachers

 

Hyperinsulinism cannot be controlled and diabetes cannot be reversed with denial of dieting or euphoria of eating. These objectives can be achieved and maintained by an informed focus on

                           1. Divine Love 

                           2. Oxygen

                           3. Prayer

                           4. Insulin


 

High-priority Reading Materials for Reversing Prediabetes and Diabetes D3 Plan

From Dr. Ali’s Insulin and Diabetes Library Posted At This Site

  1. Oxidative Model of Diabetes (1994) 
  2. Respiratory-to-fermentative Shift in ATP Production (1997) 
  3. Beyond Insulin Resistance (2001)
  4. Darwin, Dysox, and Disease, 10th Volume of The Principles and Practice of Integrative Medicine (2002)
  5. Respiratory-to-fermentative Shift in ATP Production (2004) 
  6. Obesity Is An Oxygen Dysfunction State (2004) 
  7. Insulin-Wise and Insulin-Unwise Foods and Meals (2005) 
  8. The Dysox Model of Hyperinsulinism and Diabetes (2007)
  9. Dr. Ali’s Plan for Reversing Diabetes Book (2011)
  10. Insulin-Wise and Insulin-Unwise Foods and Meals (2012) 
  11. Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes (2017) . (full article posted on this website)

 

Here are two important facts concerning hyperinsulinism-diabetes continuum in a question form:

First, according to a report of Global Burden of Disease Obesity Collaborators concerning 195 countries published in The New England Journal of Medicine on July 6, 2017, since the prevalence of obesity doubled in:

  1. More than 20 countries

  2. More than 30 countries

  3. More than 50 countries

  4. More than 70 countries

  5. More than 90 countries.

Second, insulin in excess is fattening, fermenting, and inflaming.

 


A large number of videos on the above subjects are posted on this website

For information on Dr. Ali’s Library of Videos and DVDs, please go to:

 

WWW.ALIACADEMY.ORG


 

 

Two Dimensions of Insulin Dysregulation

Majid Ali, M.D., FRCS (Eng), FCAP (Path)

Type 2 Diabetes (TD2) Is Rooted In the First Dimension of Insulin Dysregulation. Type 2 diabetes does not occur when the first dimension of insulin dysregulation is detected and reversed.


SPECIAL NOTES

Treatment plans for reversing prediabetes (hyperinsulinism) and diabetes are presented at this site under the titles of

Reversing Prediabetes and Diabetes With 3D Plan 

 Links to important related articles are included at the end of this article.


Two Dimensions of Insulin Dysregulation

The author recognizes two primary dimensions of insulin dysregulation: (1) the first dimension is of excess insulin accompanied by a multitude of adverse effects of hyperinsulinism without associated glycemic disruptions characteristic of Type 2 diabetes; and (2) the second dimension of excess insulin accompanied by glycemic disruptions that meet the numerical criteria of Type 2 diabetes (T2D). The first dimension is rooted in the toxicities of food, environment and thought, while the second dimension is rooted in the first dimension. The first dimension is optimally detected by measuring timed blood insulin concentrations following an oral glucose load as shown in Tables used for case studies. The core message of this short article is this: If the first dimension of insulin dysregulation can be reversed, the problem of the second dimension (T2D) simply does not arise.


The Oxygen-Insulin View of Insulin Dysfunction, Diabetes Type 2, and Reversing Diabetes 3D

Oxygen is the organizing principal of biology and governs the aging process. The author began his book Oxygen and Aging (2000) with those words. This simple statement was the essence of his interest and study of molecular biology of oxygen for twenty years.1-4 His interest in molecular biology of insulin5-8 arose from his work in oxygen. The “oxygen-insulin perspective” of the two dimensions of insulin dysfunction and its scientific underpinnings was comprehensively discussed in his book entitled Dr. Ali’s Plan for Reversing Diabetes (2011)9 as well as in a series of follow-up publications.10-18

Life is an injury-repair-injury cycle. Cellular injury is intertwined with cellular repair by diverse mechanisms. Patterns of repair change with varying types of injury and the prevailing tissue condition. The constant in all this is expanded energy requirement of cells in the repair processes. Whether cellular repair is in acne or psoriasis, in polycystic ovarian syndrome in young women or recurrent prostatitis in young men, in chronic GERD-gastritis complex or Crohn’s colitis, inflammatory arthritis or pulmonary interstitial fibrosis, steatosis of the liver or chronic renal failure, systemic lupus erythematosus (see illustrative case study in Table 4) or scleroderma, the core requisite of cellular repair is the same: increased energy demands. Hyperinsulinism, in this context, is pancreatic response to increased energy needs for repair of injured tissues. The author has documented the presence of the first dimension of insulin dysregulation in all of the above-mentioned pathologic entities.


 

Three Crucial Aspects of Two Dimensions of Insuloin Dysregulation

From a clinical standpoint, three other aspects of the two dimensions of insulin dysfunction are:

  1. Epigenetics play greater roles than genetics in both dimensions;
  2. Understanding the pathophysiology, clinical courses, and optimal management of both dimensions of insulin dysregulation calls for a shift of focus from glycemic status to insulin homeostasis;
  3. Since first dimension is not accompanied by glycemic disruptions, the lab tests for glycemic status (fasting and 2-hour postprandial blood sugar levels, and A1c test) are not suitable in the detection and reversal of the first dimension.

 

Neglect of the First Dimension Deepens the Suffering of the Second Dimension

The data in Tables 1 and 2 summarizes the core statistical relationships between the two dimensions of insulin dysfunction. The two columns presenting mean peaks of blood glucose and post-glucose-load insulin concentrations in Table 1 dramatically document how far the prevailing practices of neglecting the first dimension go to deepening the problems caused by the second dimension.

Table 1. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes

Insulin Category* Percentage of Subgroup Mean Peak Glucose mg/dL(mmol/mL) Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis   N =   12**
1.7% 110.2     (6.12) 14.3
Optimal Insulin Homeostasis         N =   126
24.9 % 121.2     (6.73) 26.7
Hyperinsulinism, Mild                       N = 197
38.9 % 136.5   (7.58) 58.5
Hyperinsulinism, Moderate           N = 134
26.5 % 147.0   (8.16) 109.1
Hyperinsulinism, Severe                 N = 49
9.7 % 150.0   (8.33) 231.0
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, 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 hyperinsulinism, peak insulin <80 accompanied by unimpaired glucose tolerance; (4) moderate hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance; (5) severe hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance.

** Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis.


 

Table 2 Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes
Insulin Category Percentage of Subgroup Mean Peak Glucose, mg/dL

(mmol/mL)
Mean Peak Insulin (uIU/mL)
Diabetic Hyperinsulinism, Mild       N =   53
29.0% 252.0   (14.00) 55.4
Diabetic Hyperinsulinism, Moderat N = 42
24.0% 242.1   (13.45) 112.4
Diabetic Hyperinsulinism, Seve       N =   24
13.9% 224.6   (12.47) 298.0
Diabetic Insulin Deficit                     N = 59
33.1% 294.0   (16.33) 22.9

 

Neglect of the First Dimension By Laboratory Professionals

 The neglect of first dimension by the laboratory professionals is one of the most disturbing aspects of the sordid story of the two dimensions of insulin dysregulation. For instance, the reference range for the 2-hr post challenge blood insulin concentration of laboratory 2 (Table 3) is an astonishingly and utterly clinically unusable 0.0 to 163.5.

Table 3. Insulin Reference Ranges in uIU/mL of Six Laboratories in New York Metropolitan Area*

 

Laboratory Fasting 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 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.


 

Mechanisms of Insulin Regulation and Two Dimensions of Insulin Dysregulation

 The following is text on the subject from the author’s comments e-published in June, 2017 by the journal Nature. “The work of Zhang and colleagues is important for physicians who treat diabetes because class B G- protein-coupled receptors (GPCRs) are important therapeutic targets. Beyond that, this work invites all physicians to a deeper study of the inner mechanisms of insulin homeostasis, a subject that is seldom duly considered in clinical medicine. Specifically, insulin dysregulation has two distinct dimensions: (1) the first dimension of pathophysiology of hyperinsulinism which predates Type 2 diabetes (T2D) and is not accompanied by glycemic abnormalities detectable by the laboratory tests in current use; and (2) the dimension of T2D accompanied by hyperglycemia and its biochemical consequences. This author has long recognized the need for a shift of clinical focus from glycemic status to insulin homeostasis for detecting and optimally managing adverse metabolic, proinflammatory, endothelial, developmental, and neurologic effects of hyperinsulinism (ref. 2-6).”

Table 4. Severe Hyperinsulinism In A 13-Yr-Old With SLE, ITP, Recurrent Pneumonia, and Optic Neuritis With Right Eye Blindness.

The Peak Insulin Fell from 718 to 238.5 In Four Months of Robust Integrative Treatment.

Fasting ½ Hr 1Hr 2Hr 3Hr
Insulin uIU/mL
27.9 362.5 424.0 718.2 571.7
Glucose mg/mL
      70 140 157 150 111
Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Therapies
Insulin uIU/mL
7.2 125.1 238.5 208.0 132.0
Glucose mg/mL
81 154 181 130 97
 

Table 5. Control of Hyperinsulinism With Reversal of Type 2 Diabetes In A 75-Yr-Old 5’ 2” Female Weighing 162 Lbs. With Hypertension and Chronic Sinusitis.

4.30.2013 Fasting ½ hr 1 hr 2 Hr 3 Hr
Insulin uIU/mL
16 37 59 113 152
Glucose mg/mL (mmol/L)
112 158 214 241 155
10.17.2014*
Insulin uIU/mL
23.8 19.3 36.9 114.7 75.2
Glucose mg/mL (mmol/L)
116 167 253 297 172
4.14.2015**
Insulin uIU/mL
6.2 22.1 42.9 51.2 39.7
Glucose mg/mL /L)
96 130 193 112 105

* A1c, 6.3%; ** A1c, 5.9%

 

Reversing Prediabetes (Hyperinsulinism) and Diabetes With 3D Plan

The insulin homeostasis protocol (the “Protocol”) evolved as a three-prong approach comprising: (1) diet; (2) detox; and (3) dysoxic comorbidities (oxygen-related coexisting pathologic entities) including disrupted hypothalamic and related neural pathways which regulate the energy economy of the body. The three “diabetes 3D” subjects are vast and clearly beyond the scope of this brief outline. A comprehensive discussion of all above subjects is presented at free access www.alidiabetes.org. Google search words are: majid ali, shifting focus from glycemic status to insulin homeostasis.


 

References

1.   Ali. M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004.

2.   Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine. 1999;3:11-16.

3.   Darwin, Dysox, and Disease. Volume 11. The Principles and Practice of Integrative Medicine 11. New York: Canary 21 Press; 2002.

4.   Ali M. The Principles and Practice of Integrative Medicine Volume I: Nature’s Preoccupation With Complementarity and Contrariety. New York. Canary 21 Press. 1998. 2nd edition 2005.

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. Insulin Toxicity, Inflammation, And  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.

7.   Ali M. Hypothesis: obesity is adipomyocytic dysoxygenosis. J Integrative Medicine. 2004;9:19-38.

8.   Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.

9.   Shoelson, SE, Lee J. Goldfine AB. Inflammation and insulin resistance. J. Clin. Invest. 2006;116: 1793–1801.
2

10.                  Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854-859.

11.                 .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.

12.                 International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. www.diabetesatlas.org.

13.                 Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.

14.                 Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.

15.                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.

16.                Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000.

17.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

18.                Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

19.                 Ali M. Fayemy 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.

20.                 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.

21.                 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.

22.                 Ali M. The Principles and Practice of Integrative Medicine Volume XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.

23. Ali M. The Philosophy and Science of Healing. APPNA Journal. 2015;25:18-19.

24.                Nath D, Heemels M-T, Lesley Anson L Obesity and diabetes. Nature. 2006;444, 839.

25.                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.

26.                 Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

27.                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.

28.                 von Herrath M. Insulin trigger for diabetes. Nature. 2005;435:151-152.

29.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

30.                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.

31.                 Stanley SA, Kelly L, Kaasmashri N, et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature. 2016  531:647–650.

32.                Ali M. Autism. Nature

33.                Ali M. Ali M. Molecular basis of autism and dysautonomia. Townsend Letter-The examiner of Alternative Medicine. 2017 (in press).

34.                Ali M. Lab ranges www.alidiabetes.org

35.                 Kaveeshwar SA, Cornwell J. The current state of diabetes mellitus in India. Australas Med J. 2014;7:45-48.

36.                 Lesley J, Manning LA, Ogle GD. A survey of diabetes services in hospitals in Ali Papua New Guinea. P N G Med J. 2001: 44:88-95.))

37.                 Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults. JAMA. 2013; 310: 948-59.

38.                 Ali M.  Oxygen model of hyperinsulinism.  xxxx

39.                 Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.

40.                 Ali M. Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.

41.                 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.

42.                 Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515, 431–435.

43.                 Ali M. Succinate Retention. In: Chouchani ET. Pel VR,  Gaude E, et al.Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature;2014;515:431. (commentary after references).

44.                 185. Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.