Insulin: The Life Span Hormone for Healthful Aging

Majid Ali, M.D.

140 West End Avenue, New York, NY 10023

212-873-2444


 

Article First Published in 2017

Outline

  1. Introduction: Insulin – the Life Span Hormone
  2. What Is Optimal Insulin Homeostasis?
  • Examples of Optimal Insulin Homeostasis?
  1. Hyperinsulinism As Pancreatic Response to Cellular Injury
  2. Hyperinsulinism Begets Hyperinsulinism
  3. The Oxygen-Insulin Matrix Model of Health and Disease
  • Four Dimensions of Insulin Dysregulation
  • Insulin Dysregulation Neglected In Unwell Individuals
  1. Insulin Dysregulation Associated With Unrelenting Stress, Mood Disorders and Weight Gain
  2. Hyperinsulinism Modification With Insulin Detox
  3. Polycystic Ovarian Syndrome Is Rooted In Insulin Dysregulation
  • Insulin-Monitored Long-Term Hyperinsulinism Modification and Reversal of Type 2 Diabetes
  • Insulin Profiling – Testing and Interpretation
  • Discussion
  1. Closing Comments

 

  1. Introduction : Insulin – the Life Span Hormone

The core message of this article is: Insulin is the life span hormone of human biology. To make his case for it succinctly with simple words, here the author introduces three terms: (1)  “oxygen-insulin signaling matrix”; and (2) “Oxygen-insulin matrix model of health and disease”; and (3) insulin as the “life-span hormone.” The term oxygen-insulin signaling matrix refers to a complete bioenergetics and clinical integration of molecular biology of oxygen and insulin homeostasis. The term disrupted oxygen-insulin matrix model of health and disease refers to unifying model of health/dis-ease/disease continuum, which, , has a strong explanatory power for understanding the pathogenesis and mechanism of healing for treating chronic diseases. The term insulin as the life-span hormone is intended to meaningfully counter the wholly inadequate “diabetes view of hyperinsulinism,” which, in the author’s view, is the principle folly in treating metabolic disorders in the prevailing medical model. It completely ignores the core issue of insulin dysregulation and allows hyperinsulinism-to-Type 2 diabetes (T2D) transition to occur undetected and untreated. Unmasked hyperinsulinism is permitted to inflict cellular damage of varying degrees in all cellular populations of the body for five to ten or more years before the diagnosis of T2D is made by the prevailing glycemic criteria. To underscore this crucial issue, a series of sets of insulin and glucose profiles obtained with five timed blood samples (fasting, ½-hour, 1-hour, 2-hour, and 3-hour) obtained after a 75-gram glucose challenge, are presented. For children, the glucose challenge is reduced to 50 grams. Brief clinical notes concerning individual patients are included to provide clinical context for interpreting sets of insulin and glucose  the stage for explanatory notes concerning these sets of three-hour insulin and glucose profiles.

  1. II. What Is Optimal Insulin Homeostasis?

What is optimal insulin homeostasis? Most regrettably, this crucial question has been almost totally ignored in endocrinology, diabetology, bariatrics, internal medicine, and family practice. On September 11, 2017, a Google search for optimal insulin homeostasis revealed only seven entries which listed the three words in that order; all of them by the author Notably missing were websites of the American Diabetes Association, the European Foundation for the Study of Diabetes, Diabetes Ca (Canada),  The American Congress of Obstetricians  and Gynecologists, and the World Health Organization.

In the context of healthful aging and life span, an  evolutionary bioenergetic optimum of human metabolism requires that:  (1) the lower the blood insulin concentrations following a glucose challenge accompanied by unimpaired glucose tolerance, the greater the efficiency of insulin; (2) the greater the efficiency of insulin, the closer the insulin homeostasis to its ideal; (3) hypoinsulinism by itself is of no clinical consequence since there are no known adverse effects of very low blood insulin concentrations when accompanied by unimpaired glucose tolerance; (4) hyperinsulinism sets the stage of metabolic overdrive in all cellular populations of the body; (5) insulin in excess has hepatic, endothelial, myocardial, neural, ovarian, renal, and other adverse effects; (6) the growth factor roles of insulin intensify and perpetuate inflammatory, autoimmune, and neoplastic processes. Table 1 and 2  display two sets of insulin and glucose profiles  which meet the criteria for optimal insulin homeostasis by criteria outlined here.

III. Examples of Optimal Insulin Homeostasis

 

 Table 1. Insulin and Glucose Profiles Of A 51-Yr-Old 5’ 1” Female Weighing 160 Lbs. Indicating Optimal Insulin Homeostasis.  The Patient Presented With Chronic Constipation.
Patient Fasting 1-Hr 2-Hr 3-Hr
Insulin uIU/mL <2 17 15 6
Glucose mg/mL 75 61 72 71
Table  2.  Insulin and Glucose Profiles Of A 58-Yr-Old 5’ 11” Male Weighing 218 Lbs. He Had Undergone Radical Prostatectomy for Prostate Cancer Two Years Earlier When He Weighed 300 Lbs.
Insulin uIU/mL 3.0 22.0 13.0 <2
Glucose mg/mL 82 75 63 60

In a survey of insulin homeostasis in 684 patients (506 of them with known T2D, (Table 3) in the general New York metropolitan area,  the authors and colleagues reported a prevalence rate of hyperinsulinism in 75.1%.1 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 in old age had prediabetes. This subgroup appears to reflect ideal metabolic efficiency of insulin in the larger evolutionary context.

 

Table 3. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes .1
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, 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 hyperinsulinism,  peak insulin between 40 and <80; (4) moderate  hyperinsulinism,  peak insulin between 80 and <160; and (5) severe hyperinsulinism,  peak insulin 160 and over.

 

  1. Hyperinsulinism As Pancreatic Response to Cellular Injury

In the author’s oxygen-insulin view of insulin dysregulation-to-diabetes continuum, hyperinsulinism results from the response of the pancreas to meet increased energy needs of stressed and injured cells anywhere in the body during the repair processes. This perspective does not challenge the established knowledge of dynamics of hyperglycemia and hyperinsulinism, nor does it abandon any of the regulatory roles of pro-insulin and anti-insulin hormones like glucagon, glucagon-like peptides, and others. The explanatory power of the model, however, reaches far beyond the prevailing understanding of insulin functions and their clinical significance.

The inferences drawn from the author’s large personal database and presented here form the scientific basis and rationale for his view that incremental hyperinsulinism develops as a result of growing pancreatic-bioenergetic response for meeting increasing cellular demands for energy, except in cases of ectopic insulin production in hormone-producing neoplasms.2-5 Additional evidence for this view is drawn from an extensive body of clinical observations concerning improved clinical results of treatment of diverse disorders when hyperinsulinism accompanying them was detected  and duly addressed with integrative hyperinsulinism modification plans. It is anticipated that readers, who diligently study the diverse case studies presented here and critically examine the included insulin and glucose data will find them compelling and  convincing.

  1. Hyperinsulism Begets Hyperinsulinism

 As put forth here, hyperinsulinism developing as pancreatic insulin response to increased tissue demands for energy comes at a cost: a “hyper-insulin” state – so to speak – which results from metabolic and non-metabolic insulin overdrive. This insulin state is fattening, fermenting, inflaming, and self-perpetuating.6-9 Simply stated, excess insulin begets excess insulinism.  From these aspects of pathophysiology of insulin dysfunction and overdrive,  abundantly documented by case studies included here and published previously,10-13 hyperinsulinism is expected to play central roles in the pathogenesis and progression of most, if not all chronic metabolic, developmental, inflammatory, infectious, autoimmune, degenerative, and malignant diseases.  This, indeed, is observed when insulin homeostasis is assessed in individual patients with appropriate carbohydrate challenges. This is what the author and his colleagues observed in a large survey of hyperinsulinism in a general population in metropolitan New York area.1 Insulin dysfunction with varying levels of hyperinsulinism was found and documented in all chronic diseases so investigated – acne to dermatitis, psoriasis to sarcoidosis, autism to Alzheimer’s disease, liver steatosis to heart amyloidosis,  bronchiectasis to pulmonary fibrosis, lupus to scleroderma, rheumatoid arthritis to Lyme polyarthralgia, interstitial cystitis to recurrent prostatitis, and malignant tumors.4-18   

Tables 2 and 3 present insulin and glucose profiles of a survey subject which meet the numerical criteria of optimal insulin homeostasis. Specifically, the peak blood insulin concentration accompanied by unimpaired glucose tolerance in a female adult is below 20 uIU/mL and a male subject is below 25 uIU/mL..

 

The insulin and glucose profiles presented in Table 3 provide a rare insight into the dynamics  of insulin homeostasis. The patient, a 58-Yr-Old 5’ 11” man weighing 218 Lbs. presented in December 2012 with neuropathy  involving legs and an A1c value of 5.3%. The insulin profile of this patient meets the numerical criteria of optimal insulin homeostasis; specifically, the peak blood insulin concentration accompanied by unimpaired glucose tolerance is below 25uIU/mL. Most notably, this patient weighed 300 Lbs. two years earlier when he underwent radical prostatectomy for prostate cancer. Postoperatively he lost 82 Lbs. in weight (which would be expected to be associated with lower insulin levels) and experienced persistent and incremental family stresses (which would be expected to raise insulin levels). The insulin and glucose profiles of the case, then, reveal the sum total of these diverse influences. The blood insulin concentrations in all four post-glucose challenge samples were raised, with a near-fourfold rise in the 1-hr post glucose challenge blood sample (22 rising to 86 iIU/mL). The matter of hyperinsulinism associated with prostate and breast cancer breast has been discussed in the author’s two reports.17,18

  1. The Oxygen-Insulin Matrix Model of Health and Disease

Human life span is put in jeopardy by disruptions of molecular biology of oxygen and insulin homeostasis; life expectancy of an individual is shortened by diminished signaling of the former1-8 as well as by excessive signaling of the latter.9-14 Oxygen is the organizing principle of human biology and orchestrates all aging processes. In service of oxygen, insulin governs the energy economy of the body. Injured cells need more energy for repairing themselves. Glucose is the primary readily useable fuel for ATP energy generation. Insulin activates glucose transporters, drives glucose into the cells, initiates pathways of ATP energy generation, as well as energy utilization for life functions, and regulates energy transformations, producing proteins for cellular structural needs and fats for energy storage.13 It can be rightfully designated as the “master energy hormone” for the life span.

Oxygen signaling and insulin signaling are so inextricably intertwined throughout the kaleidoscopic bioenergetics mosaic of human biology that these two primary signaling systems of the body cannot be considered as discrete entities. In integrative medicine, clinical imperatives are commonly compelling and the scientific basis for the use of time-tested indigenous therapies with empirical benefits are not forthcoming.  Under these conditions, the unifying oxygen-insulin signaling matrix model of health/dis-ease/disease continuum provides valuable and reassuring scientific rationale for integrating indigenous therapies with others for which clear “scientific basis” has not been established.

 

Some readers may be interested in the author’s prior clinical and research work that led to the conceptualization of oxygen-insulin signaling matrix, disrupted oxygen-insulin matrix model of health/dis-ease/disease continuum , and insulin as the life-span hormone.” The author points out his core clinical and research work in chronic disease ranged widely and was the subject of his Townsend Letter columns on oxygen homeostasis (from 2004 to 2015 and columns on insulin homeostasis from 2016 to the present. The web site of Townsend Letter offers full details of specific subjects covered in addition to the work cited among citations in this column.

VII. Four Dimensions of Insulin Dysregulation

The author recognizes four dimensions of insulin dysregulation: (1) the first dimension of rising blood insulin concentrations (hyperinsulinism) without raised glucose levels (hyperglycemia) that meet criteria of pre-diabetes or diabetic criteria (Table 4); (2) the second dimension of hyperinsulinism with sharp glucose and/or insulin shifts but without meeting the criteria for pre-diabetes or diabetes (Table 5); (3) the third dimension of hyperinsulinism associated with hyperglycemia that meets the criteria of Type 2 diabetes (Table 6); and (4) the fourth dimension of insulin-depletion Type 2 diabetes (T2D Subtype B15 ) is shown in  Table 7.

 

Table  4.  Insulin and Glucose Profiles of a 67-Yr-Old 5’3” Woman Weighing 215 Lbs.Presenting With Polymyalgia, Osteoarthritis of Right Knee, Allergy, Sinusitis, And Chronic Fatigue.
6.15.2017 Fasting ½ Hr 1-Hr 2-hr 3-Hr
Insulin uIU/mL 12 83.8 64.3 35.3 4.6
Glucose mg/ mL 105 173 144 93 56
Table 5.     Insulin and Glucose Profiles of a 50 Year Old 5’ 2” Woman Weighing 141 Lbs. Presented With Mold Allergy, Sinusitis, Headache, and a History of Multiple Antibiotic Courses.
Insulin uIU/mL 3.5 55.7 68.5 71.5 26.5
Glucose mg/ mL 87 137 136 86 73
 Table  6.  Insulin and Glucose Profiles of a 61 Yr-Old  Man Weighing 173 Lbs.  With Type 2 Diabetes of Six Years Duration, Hypertension, and Osteoarthritis.
6.15.2017 Fasting ½ Hr 1-Hr 2-hr 3-Hr
Insulin uIU/mL 8.4 52.6 94.9 117.7 46.9
Glucose mg/ mL 82 147 215 201 157
Table 7. Insulin and Glucose Profiles of a 55-Yr-Old 5’ 3” Woman Weighing 145 Lbs . With Type 2 Diabetes Associated Insulin-depletion (T2D, subtype B).15  Hashimoto’s Disease, Polyarthralgia, and Inhalant Allergy.
Insulin uIU/mL <2 11 7 6
Glucose mg/ mL 221 448 399 287

 

 

 

VIII. Insulin Dysregulation Neglected In Unwell Individuals

Unwellness is epidemic now in the United States and generally spreading worldwide. It is not attributed to insulin dysregulation and assessment of insulin homeostasis is not included in the prevailing standards of care. A recent survey of prevalence of hyperinsulinism, as established by the survey criteria, in the general population of New York metropolitan area conducted by the author and his colleagues was 75.1%.1  This rate was not surprising since they used insulin criteria by contrast to the Chinese who employed blood glucose-based diagnostic criteria and reported a prevalence rate of 50.1% for prediabetes and diabetes among the Chinese adults.19

Tables 8 and 9 present two case studies of hyperinsulinism associated with chronic symptom-complexes of unwellness, such as lack of interest and vigor, anxiety, fatigue, mood disorders, cognitive difficulties, brain fog, allergy, abdominal bloating, and digestive symptoms. These symptom-complexes were not relieved by commonly prescribed symptom-suppressive pharmacologic agents. Note the sharp drop  of one-hour Insulin Level from 183.5 to 57.4 uIU/mL. in Table 8,  which was accompanied by good clinical response.

 

Table 8. Insulin and Glucose Profiles of a 41-Yr-Old 6’ Man Weighing 260 Lbs. Who Presented With Fatigue, Light-headedness, Anxiety, Facial Numbness, and Abdominal Bloating. He Responded Well to Eight Weeks of Successful Hyperinsulinism Modification (“Insulin Detox”) Program described at www.alidiabetes.org. Note A Sharp Drop of one-hour Insulin Level from 183.5 to 57.4 uIU/mL.
9.15.2016 Fasting ½ Hr 1 Hr 2 Hr 3 Hr
Insulin uIU/mL 10.9 148.84 183.5 25.55 9.1
Glucose mg/ mL 83 141 159 91 60
11.17.2016
Insulin uIU/mL 5.9 38.9 57.4 28.8 6.6
Glucose mg/ mL 76 124 178 136 82
 Table 9. A 60-Yr-Old 5’8” Woman Weighing 180 Lbs. Presented With Concern About A1c value of 6%. Past History Included A Prior Weight of 190 Lbs. Episodes of Anxiety, Bronchospastic Disorder, Facial Rashes. Weight Gain With Three Pregnancies Were: 40, 35 LBs, and 50 Lbs. Respectively.
Insulin uIU/mL Fasting ½ Hour 1 Hr 2 Hr 3 Hr
Insulin uIU/mL 5.1 93.1 58.8 45.8 3.4
Glucose mg/ mL 92 128 111 88 53

 

  1. Insulin Dysregulation Associated With Unrelenting Stress, Mood Disorders, and Weight Gain

 Hyperinsulinism in patients with anxiety-depression complex,  unrelenting stress, and weight gain often goes unrecognized even though hyperinsulinism is widely recognized as fattening and inflaming. Tables10 and 11 present two such patients.

The case study presented in Table 10 reveals the weight gain aspect of insulin toxicity (rising insulin levels) well. The patient, a 46-yr-old 5’2” woman weighing 160 Lbs. presented in 2011 with diagnoses of fibromyalgia, cognitive disorder, severe family stress, sleep disorder, constipation, cold sensitivity, and depression treated by a psycho-pharmacologist. In one 2014 office visit, she said, “Everybody at home is sick. I’m so angry, in such rage that I think I’m destroying my two daughters.”

 

Table  10. Insulin and Glucose Profiles of a 46-yr-old 5’2” woman weighing 160 Lbs. She presented in 2011 with diagnoses of fibromyalgia, cognitive disorder, severe family stress, sleep disorder, constipation, cold sensitivity, and depression treated by a psycho-pharmacologist
11.22.2011 Fasting ½ Hr 1 Hr 2 Hr 3 Hr
Insulin uIU/mL 2.2 37.7 44.2 28 29
Glucose mg/ mL 87 131 150 91 97
7.23.2014      Weight  150Lbs  ““Everybody at home is sick. I’m so angry, in such rage that I think I’m destroying  my two daughters.”
Insulin uIU/mL 6.3 30.8 61 25 10.9
Glucose mg/ mL 65 114 105 75 68
3.28.2016.    Weight , 145 Lbs
Insulin uIU/mL 9.3 39.5 47.0 35.4 7.0
Glucose mg/ mL 86 115 114 73 52
6.23.2017      Weight, 190 Lbs.
Insulin uIU/mL 10.5 37.9 77.0 99.4 17.8
Glucose mg/ mL 83 127 155 115 66
Table 11.  Severe Hyperinsulinism Caused By Severe Stress.

Insulin and Glucose Profiles  of an 81-Yr-Old 5’ 3”Female Weighing 172 Lbs. With Depression-Anxiety Complex, Hypertension, Fibromylagia, Mold and Food Allergy and Dizziness. Her 1-Hr and 2-Hr Insulin Levels More Than Doubled (From 105.6 to 213.5 and 92.9 to  243.9 Respectively) From 2014 to 2016 With Severe Emotional Stress of Family Betrayal .

Insulin uIU/mL 11.3 152.6 105.6 92.9 10.3
Glucose mg/ mL 81 152 76 116 56
27 Months Two Later With Severe Emotional Stress of Family Betrayal
Insulin uIU/mL 16.7 201.7 213.5 243.9 30.7
Glucose mg/ mL 95 156 180 116 56

 

  1. Hyperinsulinism Modification With Insulin Detox

Insulin in excess is potently pro-inflammatory. Chronic inflammation  causes incremental hyperinsulinism, which usually responds well to robust integrative management plans.  The case studies presented in Table 12, 13 illustrates these points well.  The full description of author’s hyperinsulinism modification  with insulin detox is offered as a part of his free access Diabetes Course at www.alidiabetes.org.  Insulin Detox are the search words for entry in the search bos of the web.

 

 

Table 12.  Insulin and Glucose Profile of A 59-Yr-Old 5” Female   Weighing 135 Lbs. Who Presented With Elevated Liver Enzyme, Paresthesia, Polyarthralgia, Myalgia, Chronic Diverticulitis, With Marked Reduction of Paresthesia.
Fasting 2 HR 1 HR 2 HRS 3 HRS
 Insulin uIU/mL 11.5 263.5 356.7 202.1 14.0
Glucose mg/mL 85 109 79 64
Insulin and Glucose Profiles Obtained 11 Months After Treatment
 Insulin uIU/mL 9.6 124.8 224.7 112.7 32.6
Glucose mg/mL 85 103 98 78 48

 

  1. Polycystic Ovarian Syndrome (PCOS) Is Rooted In Insulin Dysregulation

 

The rising prevalence of polycystic ovarian syndrome (PCOS) among young women in the U.S. (up to 20% in some studies) is disconcerting.20  Elevated blood concentrations of insulin and testosterone are two primary hormonal abnormalities of the syndrome. These disruptions with clinical symptom-complexes of PCOS generally respond to integrative treatment plans focus of the bowel-liver-blood ecosystem. Table 13 presents the changes in insulin and glucose profiles which accompanied a successful pregnancy.

 

Table 13. Insulin and Glucose Profiles of 33-Yr-Old 5’ 7” Female Weighing 122 Lbs. With Polycystic Ovarian Syndrome (PCOS), IBS, GERD, Recurrent Vaginitis, and Mold Allergy.  Testosterone 49 mg/nL. Delivered A Baby on 8.9.2017.*
12.15.2017 Fasting ½ -Hr 1 –Hr 2- Hr 3- Hr
Insulin uIU/mL 5.2 80.4 69.6 83.9 22.6
Glucose mg/mL 72 152 128 90 54
7.17.2017
Insulin uIU/mL <2 44.9 60.9 66.5 10.5
Glucose mg/mL 75 153 132 86 31

*Note the lower blood insulin concentration in the 2017 profile in spite of third-trimester pregnancy status.

 

 

XII. Insulin-Monitored Plans for Long-Term Hyperinsulinism Modification  and Reversal of Type 2 Diabetes

 

Two insulin-based diet plans have been employed by the author for his patients with insulin dysregulation: (1) Insulin Diet Plan One for hyperinsulinism modification; and (2)  Insulin Diet Plan Two for Reversal of Type 2 Diabetes. The full details of these Insulin Diet Plans are posted at www.alidiabetes.org.  For free ready access to these diet plans, readers are invited to enter the following search words in the search box of the website: Insulin Diet Plans Majid Ali.

 

Tables 14 presents a pattern of hyperinsulinism modification and reversal of Type 2 diabetes achieved with an insulin reduction diet plan21  21 (fully described at free-access www.alidiabetes.org.)

 

 

 

Table 14. Control of Hyperinsulinism With Reversal of Type 2 Diabetes In A 75-Yr-Old 5’ 2” Femaile Weighing 162 Lbs. With Hypertension and Chronic Sinusitis. * A1c, 6.3%;  ** A1c, 5.9%

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              A1c, 6.3%
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               A1c, 5.9%
Insulin uIU/mL 6.2 22.1 42.9 51.2 39.7
Glucose mg/mL  /L) 96 130 193 112 105

XIII.  Insulin Profiling – Testing and Interpretation 

In a previous publication, the author recognized two subtypes of T2D: (1) T2D subtype A (insulin excess diabetes) and T2D subtype (insulin-depletion diabetes), and underscored the clinical imperatives for doing so.37 In companion publications, he explained why he now reads 3-hour insulin and glucose profiles of individual patients the same way he used to read diagnostic biopsy slides in his hospital based surgical pathology work, pattern recognitions fully mindful of the clinical context. 38,39 The results of insulin tests performed on randomly drawn blood samples in his opinion,  should not be interpreted.

Recently, the author and his colleagues reported hyperinsulinism prevalence of 75.1% in 684 patients from a general population in New York metropolitan area.1  1 The insulin database of this study permitted us to explore the following aspects of insulin homeostasis and insulin dysregulation: (1) pathogenesis of insulin resistance; (2) stratification of hyperinsulinism for optimal clinical use; (3) study of responses to carbohydrates and non-carbohydrate challenges in insulin-based care of hyperinsulinism and T2D12; (4) hyperinsulinism-to-T2D progression; (5) proinflammatory and immune-dysregulating roles of insulin dysregulation; (6) the central role of mitochondrial dysfunction in insulin dysregulation; (7) hyperinsulinism as an energetic response to chronic cellular injury; and (8) the profound therapeutic significance of insulin serving as the “minister of metabolism and energy” to “King Oxygen” of the human body.22-25 

The most disappointing aspect of the matter of insulin homeostasis in clinical practice is that, with very uncommon exceptions, hyperinsulinism is not detected with direct insulin testing. Insulin toxicity is allowed to inflict widespread cellular damage for years, sometimes for decades, until glycemic criteria for the diagnosis of Type 2 diabetes are met.  This has been amply documented in this and past communications on the subject. Below are some specific issues concerning improper insulin testing;

  1. Insulin tests are performed on randomly drawn blood tests (Results of such tests  cannot be interpreted with confidence);
  2. Laboratories employ utterly unusable references ranges for blood insulin concentrations, as documented definitively in Table 1;
  3. Tests for glycemic status (fasting blood  glucose, two-hour postprandial glucose level, A1c levels) are performed as substitutes indicators of the insulin status;
  4. Cut-off points for post-glucose challenge blood insulin concentrations reported in laboratory reports are not based on actual post-glucose-challenge testing data; 39
  5. Gestational diabetes is a hyperinsulinism disorder before it becomes gestational diabetes by glycemic criteria;
  6. Pregnant women are unscientifically and improperly assured of their metabolic health simply because their glucose tolerance tests are considered negative for gestational diabetes;
  7. Insulin is the primary pro-weight gain and pro-obesity hormone, and yet insulin tests are not done in weight loss and obesity programs.
  8. Failure to assess insulin homeostasis with direct post-glucose challenge tests leaves patients and clinicians in the dark concerning the central roles of hyperinsulinism in the pathobiology of chronic inflammatory, infectious, autoimmune, metabolic, neoplastic, and degenerative disorders.

Two important concerns in this context are: (1) Study of Responses to Carbohydrates and Non-carbohydrate Challenges In Insulin-Based Care of hyperinsulinism and related Metabolic Disorders13; and (2) Importance of Subtyping Diabetes Type 2 Into Diabetes Type 2A and Diabetes Type 2B.14

It is lamentable that in the dominant medical thought, crucial health and healing aspects of chronically sluggish oxygen signaling and incrementally exaggerated insulin signaling are consistently neglected. How often is the centrality of dysoxygenosis (dysfunctional oxygen signaling) in chronic diseases recognized and effectively addressed in doctors’ offices and clinics? How often are the fattening, fermenting, and inflaming effects of simmering hyperinsulinism detected and controlled by restoring optimal insulin metabolism? Mention of mitochondrial malfunctions evokes tired yawns; the word insulin triggers Pavlovian mumbling about diabetes.

 

Table 14. Insulin and Glucose Profile of A 59-Yr-Old 5” Female   Weighing 135 Lbs. Which Show Marked Reductions In Blood Insulin Concentrations Achieved In Four Months of Implementation Of An Insulin Modification Plan. She Presented With Elevated Liver Enzyme, Paresthesia, Polyarthralgia, Myalgia, And Chronic Diverticulitis, Insulin Reduction Was Accompanied With Marked Reduction of Paresthesia.
8.27.2015 Fasting 2 HR 1 HR 2 HRS 3 HRS
 Insulin uIU/mL 11.5 263.5 356.7 202.1 14.0
Glucose mg/mL 85 109 79 64
1.13.2016
 Insulin uIU/mL 9.6 124.8 224.7 112.7 32.6
Glucose mg/mL 85 103 98 78 48

 

 

 

XIV.  Discussion 

 

Oxygen signaling and insulin signaling are so inextricably intertwined throughout the kaleidoscopic bioenergetics mosaic of human biology that, in the author’s view, they cannot be considered as discrete entities.  He recognized this first as an integrative clinician (finding sharp therapeutic focus on oxygen and insulin equally necessary for reversing and/or controlling chronic diseases) and as a researcher in basic bioenergetics of human biology.

 

The author was fortunate to have undertaken clinical, bioenergetic, and histpathogical  studies of broad range of chronic allergic, infectious, immune-inflammatory, gastrointestinal, reproductive, neurodevelopmental, degenerative, and neoplastic diseases. This work paved the way for his work in molecular biology of oxygen2-8 and aging,25-27and then to insulin homeostasis and insulin dysregulation,28-36 including the study of insulin dysregulation in metabolic syndromes, obesity, fatty liver disease, steatonecrosis, Type 2 diabetes, gestational diabetes, Type 1 diabetes, and the range of diabetic complications.

 

Insulin signaling has widespread established metabolic, developmental, and differentiative roles in human biology.37-42 When seen within the broader evolutionary  energetic perspective, the core tenet of the insulin being the life span hormone of human biology is logical, rational and completely consistent with the established aspects of the kaleidoscopic hormonal mosaic of human biology.

 

The author’s work in insulin homeostasis cited in this report led him to the development of a completely integrated view of molecular biology of oxygen and insulin signaling, which culminated in   conceptualization of a clinico-pathologic “oxygen-insulin signaling matrix model.” This model has a strong explanatory power for diverse clinical and bioenergetics phenomena of the health/dis-ease/disease continuum, the primary strength being unrelenting focus on harnessing therapeutic benefits of all relevant oxygen-based and insulin-driven therapies in the treatment of all chronic diseases. From a didactic standpoint, this model helps in reducing many clinical complexities of human biology into workable simplicities, and facilitates presentation of a synthesis of clinical, microscopic, and bioenergetic findings concerning the essential roles of oxygen signaling and insulin homeostasis in the pathobiology of chronic diseases.

 

For patient education and robust patient compliance, the oxygen-insulin signaling matrix model markedly enhances understanding of the scientific underpinnings of diverse disease processes related to various patterns of impaired oxygen signaling (dysoxygenosis),  insulin dysregulation, and treatment options. Specifically, this model calls for deliberating and addressing all relevant oxygen and insulin issues for individual patients.

 

  1. Closing Comments

 

Treatment of chronic diseases that is confined to pharmacologic agents can be considered neither scientific nor ethical. Readers are invited to closely examine case studies presented in this column. They are drawn from the author’s personal insulin database of over 1100 post-glucose challenge insulin profiles. They can then determine if there is merit to his case for diligence in assessing insulin homeostasis with such laboratory tests.  The matters of keeping oxygen homeostasis at the therapeutic center stage for every patient with chronic disease with documentation of clinical outcomes have been covered at length in Darwin and Dysox Triology, the 10th, 11th, and 12th volumes of the Principles and Practice of Integrative Medicine. 44-46  

Here, the author sees a glaring clinical deficit: a near-complete neglect of relevant oxygen and insulin issues in patient care in doctor offices and clinics in the prevailing medical model in the U.S.  To assess the scope of this issue, he conducted an informal survey of his patients who had seen two or more physicians (primary physician, internists, endocrinologists, diabetologists, and others) during the year prior to visiting me. None of them recalled any visit in which relevant issues of insulin homeostasis or oxygen signaling in were discussed and appropriate tests were performed. Nearly of all them complied with my request to review their prior medical records. He did not find 3-hour post-glucose challenge insulin studies in any patients.

References 

 

  1. Ali M, Fayemi AO, AO, Ali O. Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Fayemi Homeostasis. .  Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.
  2. 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.
  3. Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
  4. Ali Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
  5. Ali M. Fayemi AO, Braun EV:  Malignant APUDoma of the liver with symptomatic intractable hypoglycemia.  Cancer, 1978; 42:686-692.
  6. 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.
  7. Ali M. Oxygen, Insulin Toxicity, Inflammation, and  the Clinical Benefits of Chelation. Part II. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.
  8. 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.
  9. Ali Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
  10. 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.
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  13. 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
  14. 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.
  15. Ali Dr. Ali’s Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
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  17. Ali M. Endothelial-Neoplastic -Dynamics, Death Receptor 6, and Ani-Metastatic Therapies. Commentary in: Nature 2016;536:215-218.
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  20. Orio F, Vuolo L, Palomba S, et al. Metabolic and cardiovascular consequences of polycystic ovary syndrome. Minerva Ginecologica. 2008;60:39-51.
  21. Ali 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.
  22. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
  23. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
  24. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑
  25. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. diabetesatlas.org.
  26. 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 oxidation. Endocrinology127, 1580–1589 (1990).|
  27. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004;253:64-65.
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  30. Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.
  31. Ali M: Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine 1999;3:11-16.
  32. 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.
  33. Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
  34. Ali Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
  35. 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.
  36. 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.
  37. 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.
  38. Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.
  39. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116 :1793B1801.
  40. Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑
  41. International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. diabetesatlas.org.
  42. Ali M. Oxidative Cell Membrane Disorder – Leaky Cell Membrane Disorder (monograph). Teaneck, NJ, 1987
  43. 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.
  44. 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.
  45. Ali M. The Principles and Practice of Integrative Medicine Volume  XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.
  46. Ali M. The Philosophy and Science of Holism in Healing. APPNA Journal. 2015;25:18-19.

 

 

 

END  END END

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