Mitochondrial Dysfunction in Type 2 Diabetes

Majid Ali, M.D.

—————————————————————————-In the oxygen model of diabetes (T2D), mitochondrial dysfunction plays a central role in the pathogenesis of Type 2 diabetes. I proposed this model about twenty years ago. Links to  pertinent citations are included below.

—————————————————————————-The scholarly article by Peti-Peterdi cited below would be of especial interest for readers who wish to study the oxygen model of diabetes.

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Mitochondrial TCA cycle intermediates body fluid and acid-base balance

Journal of Clinical Investigation. 2013;123(7)2788-90
Intrarenal mechanisms play an important role in the maintenance of body fluid and electrolyte balance and pH homeostasis. Recent discoveries of new ion transport and regulatory pathways in the distal nephron and collecting duct system have helped to better our understanding of these critical kidney functions and identified new potential therapeutic targets and approaches. In this issue of the JCI, Tokonami et al. report on the function of an exciting new paracrine mediator, the mitochondrial the citric acid(TCA) cycle intermediate α-ketoglutarate (αKG), which via its OXGR1 receptor plays an unexpected, nontraditional role in the adaptive regulation of renal HCO(3⁻) secretion and salt reabsorption.

What Causes Type 2 Diabetes?

Contributed by Peter Holleb

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Type 2 diabetes is becoming a growing epidemic. “Its prevalence has been due to sedentary lifestyles, obesity, aging and cardiovascular disease” (Pratley et al. 2013). “From 2007 to 2012, the number of Americans affected with Type 2 diabetes has increased from 23.8 million to 25.8 million” (Pratley et al. 2013). “Based on the prevalence of this disease in the past twenty years, it is predicted that the number of affected individuals will increase to 552 million adults by 2030” (Pratley et al. 2013). “One of the main factors in the increase in diagnosis of Type 2 diabetes is the rise in overweight and obese individuals leading to insulin resistance” (Kahn et al. 2006). Insulin resistance has increased the need for understanding insulin homeostasis and how it can be used for reversing Type 2 diabetes” (Ali et al. 2017).

During normal conditions, beta-cells of the pancreas increase insulin release to maintain glucose homeostasis. For individuals with Type 2 diabetes, “dysfunction in beta-cells make them unable to compensate for the decrease in insulin sensitivity” (Kahn et al. 2006). “With the dysfunction of beta-cells, there will be decreased uptake of liver and muscle glucose” (Khan et al. 2006). “One factor contributing to the malfunction of beta-cells would be the release of Non-Esterified Fatty Acids (NEFA)” (Kahn et al. 2006). Studies have suggested that the release of these fatty acids contribute to insulin response. “Insulin resistance will develop within hours of the release of Non-Esterified Fatty Acids” (Kahn et al. 2006). “It has been hypothesized that the release of Non-Esterified Fatty Acids inhibits pyruvate dehydrogenase, phosphofructokinase and hexokinase II activity by competing with glucose for oxidation” (Kahn et al. 2006). “Even though Non-Esterified Fatty Acids are important for insulin release, chronic exposure can drastically decrease insulin synthesis thus inhibiting its function” (Khan et al. 2006).

Type 2 diabetes is a rapidly spreading epidemic in the United States. Insulin resistance is a common aspect for predicting the onset of diabetes. ‘Hyperinsulinism can be described in the oxidative stress model focusing on a dysfunction of the insulin receptor as well as the disruptions in the Krebs cycle” (Ali et al. 2017).” According to the model, Insulin resistance accumulates inflammatory immune products disrupting oxygen homeostasis causing mitochondrial dysfunction” (Ali et al. 2017). “Through disruption of oxygen homeostasis, changes in gut microbiota will increase the rise in inflammatory markers making insulin receptors unresponsive leading to increased insulin resistance” (Festi et al. 2014). “The specific markers interleukin-6 (IL-6) and C-reactive protein (CRP) have been positively associated with an increased risk for type 2 diabetes and serve as a common target for treatments” (Wang et al. 2013). When treating type 2 diabetes, further research into inflammatory markers needs to be done due to elevations of blood glucose during inflammation.

When treating diabetes, it is important to examine the role of gut microbiota. These gut microbiotas can affect lipid metabolism as well as glucose storage. “Gut microbiota contributes to immune system maturation as well as T-cell differentiation” (Festi et al. 2014). “Disruption of the function of these microbiotas can lead to inflammation leading to insulin resistance” (Festi et al. 2014). Typically in individuals with hyperinsulinism, “there is a release of glycerol, non-esterified fatty acids as well as proinflammatory cytokines” (Ali et al. 2017). In 2014, a similar theory was purposed when the author noticed gram negative gut bacteria increased absorption of lipopolysaccharides (LPS) leading to a condition known as bacterial endotoxemia (Festi et al. 2014). The end result will disrupt oxygen homeostasis by accumulating oxidized lipids creating excess debris to create insulin receptor resistance (Festi et al. 2014).

Another possible mechanism for treatment of diabetes are drugs that act on the G-protein coupled receptors. More specifically, the “GPR91 which acts as a ligand for α-ketoglutarate and succinate” (Peterdi et al. 2010). “Succinate and α-ketoglutarate have been recognized as important signaling molecules involved in the hypoxic and hyperglycemic response in diabetic kidneys” (Peterdi et al. 2010). “This response has been associated with lower oxygen tensions further reducing mitochondrial function” (Peterdi et al. 2010). Over the years, studies have shown a link in the hypoxic response of GPR91 in diabetic nephropathy.

“The distal collecting duct system conveys the highest level of GPR91 expression as well as a key activator in the RAS system in a diabetic state “(Peterdi et al. 2010). “A possible theory in early diabetes for RAS activation is GPR91 renin release at the juxtaglomerular apparatus” (Peterdi et al. 2010). “This type of paracrine signaling mechanism is usually found after succinate administration or periods of high glucose” (Peterdi et al. 2010). When GPR91 expression is increased to activate RAS, Prostaglandin E2 and Nitric Oxide production occur to vasodilate the afferent arterioles thus triggering the hyperfiltration in early diabetes. Due to GPR91’s role in diabetes, more treatments need to target this G protein for success.

References:

Prately, Richard. The Early Treatment of Type 2 Diabetes. Am J Med. 2013 Sep;126(9 Suppl 1):S2-9. doi: 10.1016/j.amjmed.2013.06.007.

Khan, Steven. Mechanisms Linking Obesity to Insulin Resistance and Type 2 diabetes. Nature. 2006 Dec 14;444(7121):840-6.

Peti-Peterdi, Janos. High glucose and renin release: the role of succinate and GPR91. Kidney International (2010) 78, 1214–121.

Festi, Davide. Gut Microbiota and Metabolic Syndrome. World J Gastroenterol 2014 November 21; 20(43): 16079-16094.

Ali, Majid. Shifting Focus Glycemic Status to Insulin Homeostasis for stemming Global Tides of Hyperinsulinism and Type 2 Diabetes. Journal Townsend Letters 2017;402:91-96.

Wang, Xia. Inflammatory Markers and Risk of Type 2 Diabetes. Diabetes Care 2013; 36:166–175.

Corkey, Barbara. Hyperinsulinemia: Cause or Consequence?. Diabetes 2012; 61:4–13.

Glaser, Benjamin. Type 2 Diabetes: Hypoinsulinism, Hyperinsulinism, or Both? PLoS Med 2007; 4(4): e148. doi:10.1371/journal.pmed.0040148.

Hurrle, Samantha. The Etiology of Oxidative Stress in Insulin Resistance. Biomedical Journal 2017; 40: 257-262.

Liesie, Angela. Dietary Glycemic Index and Glycemic Load, Carbohydrate and Fiber Intake, and Measures of Insulin Sensitivity, Secretion, and Adiposity in the Insulin Resistance Atherosclerosis Study. Diabetes Care 2005; 28:2832–2838.

 

Is Diabetes A Sugar Problem? No.

Majid Ali, M.D.

Suite 3 C, 344 Prospect Avenue

Hackensack, New Jersey 07601

201-966-0027


 

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

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

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


 

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

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


 

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

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


Oxygen, Diabetes, Insulin References 


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What Can Appna Contribute to Stemming Global Tides of Hyperinsulinism and Diabetes

 

What Might APPNA Contribute for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes?


Shifting Focus From Glycemic Status to Insulin Homeostasis
Majid Ali, M.D.  FRCS (Eng), FACP  5.14.2017. 11 AM

The author is available for personal communication concerning this paper with interested APPNA clinicians by phone at 212-873-2444 or by e-mail at askipm@aol.com.

Download a pdf version of this paper.

The author’s work in molecular biology of oxygen1-6and molecular biology of insulin7-12 led him to recognize a need for a shift of focus from glycemic status to insulin homeostasis (the “Shift”).13,14 Here he marshals strong basic science and epidemiological lines of evidence for the Shift (Tables 1-3), and  presents robust reasons for suggesting that  APPNA,  a dedicated physician community, consider a long-term organizational  initiative to contribute efforts to stem global tides of hyperinsulinism which predates Type 2 diabetes (T2D) by five,  ten, or more years.

During the years of hyperinsulinism-to-T2D progression, cellular populations in nearly all body organs suffer diffuse and incremental damage inflicted by undetected and unmanaged non-metabolic toxicity of insulin dysregulation. Notable among them are disorders of neurodevelopment (autism and dysautonomia15,16), blindness from insulin-induced optic neuritis,13 mitochondrial dysfunction,1,13 immune-inflammatory entities,13 endothelial dysfunction,17 vagus nerve dysfunction,18 persistent cellular repair response (after chemotherapy for cancer,19 for instance), and hepatic lesions (such as steatosis). In his broader oxygen-insulin perspective of hyperinsulinism8 the author recognizes hyperinsulinism as chronic energetic response to increased energy requirements of cellular repair processes.

It is noteworthy that all clinical and laboratory work done for the above-cited publications was completed without any private or government funding. The same held for author’s related works in molecular and cellular pathology, as well as in therapeutics in the fields of environmental medicine, clinical nutrition, and immune-inflammatory disorders in the holistic-integrative models presented in the 10th, 11th, and 12th volumes of The Principles and Practice of Integrative Medicine.20-22

Insulin Homeostasis Protocol

The central goal of the proposed “Insulin Homeostasis Protocol” (the “Protocol”) is for APPNA to develop and implement a long-term organizational plan for shifting focus from glycemic status to insulin homeostasis in order to: (1) improve clinical outcome of individual patients with integrative treatments: (2) simplify patient education for superior compliance; (3) build an organizational insulin database for ongoing studies of the non-metabolic and metabolic consequences of disrupted insulin homeostasis; (4) document the prevalence and patterns of progression of hyperinsulinism co-morbidities, including T2D; (5) gather clinical data for examining the efficacy of indigenous therapies; and (6) foster the science and philosophy of holism in healing.

The Protocol is designed to be an all-voluntary distance-learning (internet-based) program. No need for significant outside funding is anticipated for APPNA participating clinicians; the initial time commitment of the APPNA administrative staff is expected to be modest.

Notable Strengths of the Protocol

The Protocol has some especial strength.   Notable among them are: (1) enhanced clinical results for individual patients (extensively documented in the author’s Darwin and Dysox Trilogy20-22 and multiple case studies presented in this article); (2) no-cost internet-based distance learning for participating APPNA clinicians; (3) no clinical restrictions on the participants in the integrative model  of the dietary, detox, and lifestyle Protocol guidelines; (4) no restrictions on concurrent use of pharmacologic regimens; (5) simplicity and uniformity of record keeping format for the insulin database for publications (illustrated in Tables used for presenting ; (6) no need for contractual obligations for APPNA, nor for APPNA clinicians; and (7) no additional uncovered cost of initial post-glucose challenge insulin and glucose profiles, and limited follow-up yearly insulin tests  (as has been the case for the author and his colleagues).

Type 2 diabetes is a spreading pandemic. In 2013, China in a large national study reported a prevalence rate of prediabetes and Type 2 diabetes (T2D) (50.1% of adults).1 In 2017, the author and his colleagues reported a prevalence rate of hyperinsulinism of 75.1% in  a survey of post-glucose challenge insulin and glucose profiles in 684 subjects in New York metropolitan area.13 This, to the authors’ knowledge, was the first statistical documentation of hyperinsulinism-to-T2D progression with direct measurements of blood insulin and glucose concentrations with multiple timed blood samples following a 75-gram glucose challenge.  The much higher rate of hyperinsulinism (75.1%) in New York population than the prevalence of prediabetes and T2D among the Chinese (50.1%) is not surprising since tests for the glycemic status provide only indirect information concerning the underlying insulin dysregulation.

In the 201713 and earlier reports,7-12 the author and his colleagues explored the following questions: (1) How does insulin resistance begin; (2) What is optimal insulin homeostasis; (3)  What is the prevalence of hyperinsulinism in a general population of New York metropolitan area; (4) What are the patterns of progression and/or arrest of hyperinsulinism-to-T2D continuum; (5) What are the non-metabolic developmental, differentiative, immune-inflammatory, degenerative, and metabolic effects of undetected incremental degrees of insulin dysfunction; (6) How do the diagnostic efficiencies for T2D of post-glucose challenge and insulin responses compare with those of the standard glucose tolerance; (7) How does insulin-based hyperinsulinism modification and T2D reversal plan compare with those based on glycemic criteria, especially in the cases of gestational diabetes and large-sized babies; and (8) What might be the crucial clinical entities in which unmasked hyperinsulinism poses special hazards, i.e., autism, Asperger’s syndrome, pediatric dysautonomia, childhood weight gain and obesity, pediatric fatty liver, peripheral neuropathy,  drug-induced tissue repair responses (during chemotherapy for cancer, for instance), polycystic ovarian syndrome, pustular  acne, and diverse allergic and chronic immune-inflammatory disorders.

Insulin Dysregulation in Chronic Cellular Repair Responses

All repair mechanisms in the body have  expanded energy requirement demands. Insulin can be rightfully considered the master energy hormone of the body. From an evolutionary energetic perspective, the lowest blood insulin concentrations accompanied by unimpaired glucose tolerance have been designated optimal insulin homeostasis  (Table 1).  Table 2 showing the correlation of incremental glycemic changes sheds light on the hyperinsulinism-T2D continuum. Our article entitled “Shifting Focus From Glycemic Status to Insulin Homeostasis is posted in full at www.alidiabetes.org, and furnishes a large body of original observations, including many of the above-cited forms of toxicity of hyperinsulinism fully referenced.

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, 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 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)
T2D With Hyperinsulinism, Mild          N =  53 29.0% 252.0   (14.00) 55.4
T2D With Hyperinsulinism, Moderate N =  42   24.0% 242.1   (13.45) 112.4
T2D With Hyperinsulinism, Severe       N =  24 13.9% 224.6   (12.47) 298.0
T2DF With Low Insulin Levels               N =  59 33.1% 294.0    (16.33) 22.9

Reading Insulin/Glucose Profiles As Examining Surgical Pathology Slides

Within some months of beginning my study of insulin homeostasis with 3-hour post-glucose-challenge insulin and glucose profiles, I found myself reading the profiles as I read microscopic slides as a hospital surgical pathologist. One might expect that individual subjects will display wide variations in their insulin and glucose profiles in most instances. This, indeed, is the case . This point is amply demonstrated in case studies shown in Tables 3-7. Table 3 shows what is usually dismissed as an error of omitting the glucose challenge by the patient or the  lab staff since the “flat” post-glucose-challenge tolerance pattern is not a generally recognized entity. It is caused by a brisk initial insulin spike which masks the expected initial glucose spike. This can be readily proved by taking measurements at 1/2-hour post-challenge blood sample. Tables 7 documents insulin dysregulation in autism and pediatric dysautonomia.

Table 3. Optimal Insulin Homeostasis With Very Low Blood Insulin Concentrations and Unimpaired “Flat” Glucose Tolerance Curve* of A 52-Yr-Old 5’1” Woman With Constipation and Osteoarthritis.
Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL <2 17 15 6
Glucose mg/mL 75 61 72 71

 

Table 4. Insulin and Glucose Profiles of 75-Yr-Old 5’7” Woman Weighing 192 lbs. Who Presented Following A Coronary Bypass Procedure With Fatigue, Sinusitis, and Without Known Type 2 Diabetes (Not An Uncommon Case In the Author’s Integrative Clinical Practice). A1c 5.6%.
6.3.2010 Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL 9.8 25 92.4 2.2
 Glucose mg/mL 112 170 241 273
7.23.2013. Insulin Tests Not Ordered By Her Primary Physician. A1c 5.8%
Insulin uIUi/mL
Glucose mg/mL 97 159 219 247
5.11.2014. ”Mostly Good Compliance” By  Patient’s Account.  A1c  5.7
Insulin uIUi/mL 6.43 58.2 33.87 6.4
Glucose mg/mL 99 182 139 81
2016 Hospitalized for Angina. A1c 5.7. No Diabetic Drugs Prescribed By the Attendning Cardiologist.

 

Table 5. Reversal of Type 2 Diabetes in a 78-Yr-Old 5’2” Woman Weighing 162 Lbs. Achieved By Dramatic Hyperinsulinism Modification (Reduction of 3-Hr Insulin from 152 uIU/mL in 2013 to 75.2 in 2014 to 39.7 in 2015, indicating  restoration of Insulin Homeostasis.
4.30.2013 Fasting 1-Hr 2-Hr 3-Hr
Insulin uIUi/mL 16 59 113 152
 Glucose mg/mL 112 214 241 155
10.17.2014,   A1c  6.3%
Insulin uIUi/mL 23.8 36.9 114.7 75.2
 Glucose mg/mL 116 253 297 172
4.14.2015,  A1c 5.9%
Insulin uIUi/mL 6.2 42.9 51.2 39.7
 Glucose mg/mL 96 193 112 105

 

Table 6. Severe Hyperinsulinism In A Previously Health 13-Yr-Old Girl With Multiple Hospitalizations for Recurrent Pneumonia, Thrombocytopenia, Polyarthralgia, Polymyalgia , and Severe Optic Neuritis With Complete Loss of Vision in Right Eye. Her Final Diagnosis in the Hospital was Systemic Lupus Erythematosus*
Fasting 1Hr 2Hr 3Hr
Insulin uIU/mL 27.9 424.0 718.2 571.7
Glucose mg/mL 70 157 150 111
Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Parenteral Nutritional and Detox Therapies With Focus on Restoration of Gut Flora.
Insulin uIU/mL 7.2 238.5 208.0 132.0
Glucose mg/mL 81 181 130 97
*The patient showed dramatic improvement  in all areas except in right eye blindness. Follow-up questioning revealed a history of massive exposure to mold overgrowth while playing in an abandoned building.

Information Sources

I consider the journal Nature to be the supreme source of information in the world of science. Since 2015, Nature frequently e-published my comments expressing holistic-integrative perspective on health and healing concerning major articles published by the journal. Below are excerpts from five of those pieces on the subject of this proposal for APPNA (citations within the text are originals from e-publications):

  1. Shifting Focus From Glycemic Status to Insulin Homeostasis14

 Type 2 Diabetes (T2D) is rapidly eclipsing other chronic diseases in becoming the preeminent threat to human health worldwide…. The work of Yamaguchi and colleagues must be celebrated in this larger context. Their previous work involved generation of whole organs from donor pluripotent stem cells using their chimaera-forming ability to complement organogenesis-disabled host animals in vivo. They now report generation of autologous functional islets with interspecies organogenesis through interspecies blastocyst complementation. This stellar work advances the goal of treating diabetes with islet transplantation. Here, Yamaguchi  et al. also put forth a serious challenge to physician community: How to protect transplanted islet cells from the host elements that caused hyperinsulinism leading to Type 2 diabetes in the first place?

  1. Obesity, Energetics, Environment, and Hyperinsulinism23

Just how error-prone and self-correcting is science? Allison and colleagues raise a question that physicians often raise – in hospitals, clinics, and laboratories. A more compelling question for those interested in obesity, energetics, and inflammation, and insulin homeostasis is: How can the subjects of obesity and energetics be investigated and/or discussed without considering the tedious and disconcerting matter of environmental and inflammatory toxins that impair mitochondrial function and oxygen signaling? Automobile mechanics know well how their engines get clogged and lose efficiency and mileage. In 2004, the author published data concerning impaired mitochondrial function in chronic immune-inflammatory and metabolic disorders.1  His observations were validated by the work of others as well as his follow-up studies.23

  1. Osteocrin, Making Connections, and Autism16

Ataman et al. linked osteocrin, a gene expressed in muscles and bones, to a new primate-specific enhancer sequence that binds to a myocyte enhancer factor 2 (MEF2.) (ref. 1). MEF2C mutations resulting in haploinsufficiency represent a form of intellectual disability in humans. (ref.2,3). MEF2A- and MEF2C-binding sites are enriched in genes associated with idiopathic autism spectrum disorder (ref. 4).

This new osteocrin work is especially important for integrative clinicians who care for autism and other disorders of developmental neurobiology. No pharmacologic agents to treat autism spectrum are available at this time. However, it is well established that neuronal activity triggers distinct transcriptional responses in different neuronal subtypes (ref. 5) This offers an opening for integrative clinicians to investigate the potential benefits of non-pharmacologic approaches to enhance neuronal activity to evoke desirable neurological responses for improved clinical outcomes. Notable among these are dietary, nutritional, metabolic, and gut mircobiota-directed therapies, as well as educational and behavioral programs. Specifically, the use of injectable and oral glutathione, methylcobalamine, taurine, calcium, magnesium, vitamin B complex usually yield gratifying results in treating atism (ref. 6,7).

The work of Ataman et al inspires this writer to pursue his impeded progenitor cell progression model of autism (ref. 6). He put forth this unifying model as a frame of reference for establishing clinical priorities to improve clinical results by identifying and addressing all prenatal and postnatal challenges to developmental neurobiology which seem relevant to the pathogenesis of ASD. The core tenet of this model is impeded neuronal progenitor cell progression to mature neurons during antenatal and postnatal lives caused in autism is disrupted oxygen signaling (ref. 6,8,9) resulting from: (1) Krebs cycle dysfunction (ref. 10); (2) overdriven immune-inflammatory dynamics (ref. 11); and (3) disruptions of insulin homeostasis and IGF1-dynamics (ref. 12,13). The members of this trio amplify challenges to progenitor cell progression posed by one another, and impede progenitor cell progression during antenatal and postnatal lives.

  1. Insulin.Autism.Hypothalamus24

The work of Stanley et al. points out how their constructs targeting glucose-sensing neurons will also be applicable to other areas, including insulin signaling. I have two specific reasons for celebrating this work. First, my work with hyperinsulnism and diabetes led me to recognize a clear need for a shift of focus from glycemic status to insulin homeostasis for stemming the tide of Type 2 diabetes in children (ref. 2-4). Second, I have special interest in the subject of hyperinsulinism in children with neurological challenges, such as autism and dysautonomia. (ref.5) Readers might find the following data concerning four children with hyperinsulinism, two with autism and two with dysautonomina, interesting. The insulin and glucose profiles were obtained with blood samples drawn at fasting and 1-hour, 2-hour, and 3-hour after a 75-gram challenge. I also include an insulin profile of a healthy subject with unimpaired glucose tolerance as a control. Insulin and glucose concentrations in 3-hour insulin and glucose profiles of  four children given below are expressed in uIU/ml and mg/mL respectively.

Table 7. Insulin and Glucose Profiles of Two Children each With Autism, and Dysautonomia, and One Control Child .
Fasting 1-Hr 2-Hr 3-Hr
Autism Case 1
 Insulin uIU/mL 24.4 73.8 71.6 28
Glucose mg/mL 95 79 79 69
Autism Case  2
Insulin uIU/mL 6.2 40.3 41.5 24.8
Glucose mg/mL 96 131 109 57
Pediatric Dysautonomia Case 1
Insulin uIU/mL 9.3 90.7 119.9 53.8
Glucose mg/mL 78 165 141 99
Pediatric Dysautonomia Case 1
 Insulin uIUi/mL 3.9 49.59 13.1 7.8
Glucose mg/mL 84 96 71 77
Control Subject Without Any Neurologic Disorder
Insulin uIU/mL <2 18 4 <2
Glucose mg/mL 77 109 74 52

 

  1. Darwin Moms, Nursing Milk, and Antibiotic Resistance25

Darwin moms have much to teach clinicians like me. To cite one example, women in Punjab diligently follow the family tradition of mustard oil rubs over their bellies daily for forty days after delivering a baby. I recommend this simple remedy to my American patients who nearly always find it beneficial in improving bowel health and reducing abdominal fat. They also report good results with castor oil rubs for their colicky babies.

Darwin moms have taught me much about many other remedies for controlling pregnancy-related digestive-absorptive disruptions and for improving their nutritional,  metabolic, and immune status, as well as of their children. Such measures profoundly affect the nourishing quality and safety of nursing milk, a crucially important immune booster. This approach can be expected not only to reduce the need for antibiotics but also diminish the frequency and intensity of their adverse effects when antibiotics cannot be avoided.

APPNA and Global Challenges of Disrupted Oxygen and Insulin Signaling

In closingAPPNA has an impressive world-class “clinician capital.” What might it contribute to the daunting challenge of stemming global tides of diabetes? Hyperinsulinism is recognized not only as the primary pathogenetic  mechanism for Typ2 diabetes but also as playing central roles in  diverse developmental, diffferentiative,  immune-inflammatory,  cardiovascular, neurologic, hepatic, endocrine, and cellular repair-related pathologies. Within the broader evolutionary context, the incremental “non-metabolic effects” of disrupted insulin homeostasis inflict diffuse cellular injury in nearly all organ systems of the body. The case of a 13-yr-old with total loss of vision in one eye presented in Table 6 and those of children with autism and dysautonomia in Table 7 offer intellectual and clinical challenges worthy of APPNA physicians. The integrative clinical Protocol guidelines proposed here also harness myriad low-cost indigenous therapies. The oxygen-insulin dimensions of the Protocol provide the scientific underpinning and rationale for gauging and engaging therapeutic aspects of molecular biology of oxygen and insulin.

In this light, APPNA clinicians considering the Protocol may look forward to exploring rewarding new dimensions of the new global realities of health and healing. Excerpts from the writer’s comments published online by the journal Nature provide windows to some of these dimensions. I add here that I consider publications in Nature analogous to the U.S Supreme Court admitting cases – to be presented, argued for and against, and then to be ruled on.

References

  1. M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit States. Townsend Letter for Doctors and Patients. 2004;253:64-65.
  2. 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.
  3. Ali M. Succinate Retention. In: Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014;515:431–435. Data after references).
  4. Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000.
  5. Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
  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. Ai M. Ali’s Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.
  8. Ali M. Oxidative regression to primordial cellular ecology. J Integrative Medicine 1998; 2:4-55.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Ali M. Ali Fayemi AO, Shifting Focus From Glycemic Statsu to Insulin Homeostasis. Ali M, Fayemi AO, Ali O, Dasoju S, Chaudhary D, Hameedi S, Amin J, Ali K, and Svoboda B. Shifting focus from glycemic status to insulin homeostasis for stemming global tides of hyperinsulinism and Type 2 diabetes. Townsend Letter – The examiner of Alternative Medicine. 2017;402:91-96.
  14. Ali M. Shifting Focus From Glycemic Status to Insulin Homeostasis. E-comments In Nature. 2017;542:191.Re: Kobayashi T, Yamaguchi T, Hamanaka S, et al. Generation of rat pancreas in mouse by interspecies blastocyt injection of pluripotent stem cells. Cell. 2010;142:787-799.
  15. Ali M. Ali M. Molecular basis of Autism and Dysautonomia. Townsend Letter – The examiner of Alternative Medicine . In Press.
  16. Ali M. Osteocrin, Making Connections, and Autism. 2016;539:242.
  17. Arcaro G, Cretti A, Balzano S, et al. Insulin Causes Endothelial Dysfunction in Humans: Sites and Mechanisms. Circulation. 2002;105:576-582.
  18. Lustig RH, Rose SR, Burghen GA, et al. Hypothalamic obesity caused by cranial insult in children: Altered glucose and insulin dynamics and reversal by a somatostatin agonist. The Journal of Pediatrics. 1999;135:162-168.
  19. Ali M. Cancer,-Endothelium Dynamics, and DR6-Based Anti-Metaststic Therapies. Comments e-published in: 2016;536:215-218.
  20. Ali M. Darwin, Oxygen Homeostasis, and  Oxystatic Therapies. Volume X, 3 rd. Edi The Principles and Practice of Integrative Medicine (2009) New York. Institute of Integrative Medicine Press.
  21. Ali M. The Principles and Practice of Integrative Medicine Volume  XI: 3rd. Edi. 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. Obesity, Energetics, Environment, and Hyperinsulinism. e-comments. In: Nature. 2016;530:27.
  24. Ali M. Autism.Hypothalamus. e-published at www.Nature.com. In: Nature. 2016;531:647-650.
  25. Ali M. Darwin Moms , Nursing Milk, and Antibiotic Resistance. E-published at Nature.com. 533:212.

 

d.
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, 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

Dr. Ali’s Nutrient and Herbal Protocols for Preventing and Reversing Diabetes

Majid Ali, M.D.

201-996-0027

Suite 1 C, 344 Prospect Ave, Hackensack, NJ 07601


Below are the nutrient, herbal, and spice protocols  formulated by Dr. Ali and prescribed for his patients  for over 30 years. Dr. Ali for the prevention, reversal, or control of diabetes. He highly recommends that they be used under a clinician’s supervision. A special precaution suggested for the clinicians is to consider blood creatinine level of the patient as an indicator of kidney function when prescribing protocols containing potassium, although the potassium doses included are modest.

Two Most Important Questions

Is Diabetes a Sugar Problem?

The Answer: NO.

Is Diabetes An Insulin Problem?

The Answer: Yes. Yes.


Unless specified otherwise, the word at this web site is used for Type 2 diabetes.


BEWARE!

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

Important Links
to
Dr. Ali’s Free Diabetes Course
Diet for Preventing, reversing, and controlling diabetes
Special Recipes for Preventing, reversing, and controlling diabetes

Diabet Protocol

 for Prevention, Reversal, and Control of Diabetes
Two Capsules on Alternate Days
Component /Ingredient
Daily Dose
How It Works
Chromium
100 mcg
For regulating carbohydrate metabolism, and  controlling blood glucose, and blood pressure, One of diabetes mineral trio (with Selenium, and Molybdenum),  for carbohydrate metabolism, mineral trio, along with Selenium, and Molybdenum, 
Gymnema sylvestre
750 mg
Curbs appetite, Reduces craving for sweets, Increases Energy, Quick recovery after physical activity
Neem extract
50 mg
All-purpose diabetes prevention and reversal
Huckleberry leaf
100 mg
Preserves kidney health and for all-purpose diabetes prevention and reversal
Vanadyl sulfate
20 mg
Complements Gymnema sylvestre

Vascular Protocol

 for Prevention, Reversal, and Control of Vascular Complications of Diabetes. One capsule Twice Daily
Component /Ingredient
Dose
How It Works
Arginine
100 mg
Cardioprotective, enhances heart strenth
Carnitine
100 mg
Cardioprotective, enhances heart strenth
Selenium
50 mcg
Vascular health
Hawthorne Pyridoxine HCL
200 mg
4:1 Extract
For normalizing blood pressure, anxiety control
Allium
300 mg
For blood health and circulation
Pyridoxine HCL
 
For protein and amino acid metabolism
Vit B6 (as pyridoxine HCL)
100mg
Protein metabolism,
Folic acid
800 mcg
 
Vitamin B 12
1000 mcg
 
Bromlain
200 mg
Antinflammatory, precents microclot formation in circulating blood
 
For anxiety associated with prediabetes or diabetes, Howthorne can used as tincture and combined with tincture of assionflowert, seven drops each added to once of cold water and sipped dlowly. This combination can be repeated three times inn24 hours, if needed.
 

K-Mag-Tau Diabetes Protocol

 for Bowel Detox In Prevention, Reversal, and Control of Diabetes

One Tablet Twice daily

Component /Ingredient
Amount
In Mgs
How It Works
Potassium
50
Highly recommended for their complementary benefits of bowel-blood detox for diabetes, circulation, and heart health
Magnesium
150
Taurine
250
Oral Chelation Protocol for Diabetes and Heart
 for Prevention, Reversal, and Control of Diabetes, Stroke, and Diabetic Heart and Vascular Complications
One Tablet Twice daily
Component /Ingredient
Amount
In Mgs
How It Works
EDTA
1000 mg
All ingredient produce their benefits by their integrated roles in cleansing blood, preventing stickiness of blood cells, preserving endo cells (endothelial lining the inside of blood vessels. ner (endo cells)
Magnesium
250 mg
Potassium
25 mg
Taurine
250 mg
MSM
100
Glutathione
25
Vitamin C
500

Turmeric-Vitamin C Protocol

 for Prevention, Reversal, and Control of Diabetes
Twice Daily, Take three Times A Day If Any infection coexist
Component /Ingrediant
Amount
In Mgs
How It Works
Turmeric
1.3 teaspoon
Cleanses blood, improves circulation, reduces stickiness of blood cells
Vitamin C
1000 mg
Antioxidant, Improves Blood Circulation Blood cleanser
 

Blood Cells Tell The Insulin Toxicity Story

Healthy Blood Cells for Comparative Study. Figure 1
Early Stress on Red Blood Cells (lower picture) . Figure 2
Description: https://i0.wp.com/web.archive.org/web/20071019123118im_/http://www.jintmed.com/pg31.jpg
.

Microplaques in Circulating Blood

When Blood Glucose Level Rises Above 200 mg/dL

Description: https://i2.wp.com/www.drali1.org/13-14.jpg
Figure 13 (top) and figure 14 (bottom) show two microplaques in a patient who had received three unsuccessful angioplasties for advanced IHD. Photomicrographs were taken the day after a major nosebleed. Note the compaction of necrotic debris and blood elements in microplaques as contrasted with loose structure of microclots in figure 11.


Red Blood Cells in a Micro-clot In Uncontrolled Diabetes (upper Picture) Figure 3
Red Blood Cell Clot Breaking Up (lower Picture) Figure 4
Description: https://i1.wp.com/www.drali1.org/11-12.jpg

Micro-plaque Formation In Uncontrolled Diabetes (both pictures) Figures 5-6
Description: https://i2.wp.com/www.drali1.org/13-14.jpg

Description: https://i2.wp.com/www.drali1.org/7-8.jpg
Figure 7 (top) illustrates severely damaged erythrocytes in a 52-year-old man with persistent atrial fibrillation. Close examination shows some zones of congealing surrounding many damaged red blood cells.
Dr. Ali’s Video Library

How Do You Reverse Diabetes Majid Ali MD on Vimeo

https://vimeo.com/96366665

 
https://vimeo.com › Majid Ali › Videos
May 24, 2014 – Uploaded by Majid Ali
Professor Majid Ali shares information about “How Do You Reverse Diabetes
 

How Do You Reverse Diabetes Majid Ali MD on Vimeo

 
https://vimeo.com › Majid Ali › Videos
May 24, 2014 – Uploaded by Majid Ali
Professor Majid Ali shares information about “How Do You Reverse Diabetes
You’ve visited this page 2 times. Last visit: 6/11/18

What Is Your Diabetes Subtype? Majid Ali MD on Vimeo

 
https://vimeo.com › Majid Ali › Videos
May 19, 2014 – Uploaded by Majid Ali
I recognize two subtypes of diabetes Type 2: diabetes Type 2A (high insulin) anddiabetes Type2 B (insulin …

Vegetarian Diet for Type 2 Diabetes Majid Ali MD on Vimeo

 
https://vimeo.com › Majid Ali › Videos
Apr 23, 2014 – Uploaded by Majid Ali
Professor Majid Ali shares information about “Vegetarian Diet for … Vegetarian Diet for Type 2 Diabetes Majid …
Can I Have Diabetes With Normal A1c Test Majid Ali MD

My Top Three Weight Loss and Anti-diabetes Omelettes Majid Ali MD

Two Most Important Questions After Diabetes Diagnosis Majid Ali MD

Diabetes and insulin Majid Ali MD

How Do I Reverse Diabetes Majid Ali MD

Is Diabetes Really A Sugar Problem? No.

 

Majid Ali, M.D.

New York  212-873-2444

New Jersey . 201-996-0027


 

No, Diabetes Is Not a Sugar Problem.

It is an insulin Problem.


Unless specified otherwise, the word at this web site is used for Type 2 diabetes.


 

BEWARE!

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

 

Large Scientific Claims Require Large Scientific Evidence

The Common Diabetes Is Not a Sugar Problem, But An Insulin Toxicity Problem.


Table 2. 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
14.3
Optimal Homeostasis,N=  126
24.9 %
121.2
26.7
Hyperinsulinism, Mild,       N =  197
38.9 %
136.5
58.5
Hyperinsulinism, Moderate,  N =  134
26.5 %
147.0 
109.1
Hyperinsulinism, 
Severe,  N =  49

9.7 %

150.0

1.3 – Fold Increase

231.0

17-Fold Increase

#   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

Large Scientific Claims Require Large Scientific Evidence

The Common Diabetes Is Not a Sugar Problem, But An Insulin Toxicity Problem. 

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


How Absurd Can the Lab Normal Ranges Become?

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.

Can I Have Diabetes With Normal A1c Test Majid Ali MD


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More free videos on Diabetes


References for Insulin Toxicity and Diabetes 

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

 

What IS Insulin Toxicity?

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

 

·       Loss of Vigor

·       Weight gain

·       Course skin

·       Acne in teenager

        Skin pigmentation changes

·       Facial hour for young women

·       Tingling and numbness in toes and fingers

·       Brain fog

·       Cognitive difficulties

·       Memory loss

·       Any infections that do not heal

·       Any inflammation that does not heal

·       Colitis of immune-inflammatory disorders

·       Arthritis of immune-inflammatory disorders

·       Connective tissue diseases

·       Any skin conditions that do not heal

·       Neurodermatitis

·       Brain atrophy

·       Brain degenerative conditions

·       Rising blood creatinine level

·       Rising liver enzyme levels

·       Rising CRP test results

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


 

Blood Cells Tell The Insulin Toxicity Story

Healthy Blood Cells for Comparative Study. Figure 1

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

.


 

Microplaques in Circulating Blood

When Blood Glucose Level Rises Above 200 mg/dL 

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


 

 

 


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

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


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


 

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

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


 

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

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


 

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

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


 

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

 


References for Oxygen, Inflammation, Insulin, and Diverse Diseases

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Majid Ali, M.D.

New York  212-873-2444

New Jersey . 201-996-0027


 

Unless specified otherwise,

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


 

BEWARE!

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

 

References for Insulin Toxicity and Diabetes 

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

 

What IS Insulin Toxicity

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

 

·       Loss of Vigor

·       Weight gain

·       Course skin

·       Acne in teenager

        Skin pigmentation changes

·       Facial hour for young women

·       Tingling and numbness in toes and fingers

·       Brain fog

·       Cognitive difficulties

·       Memory loss

·       Any infections that do not heal

·       Any inflammation that does not heal

·       Colitis of immune-inflammatory disorders

·       Arthritis of immune-inflammatory disorders

·       Connective tissue diseases

·       Any skin conditions that do not heal

·       Neurodermatitis

·       Brain atrophy

·       Brain degenerative conditions

·       Rising blood creatinine level

·       Rising liver enzyme levels

·       Rising CRP test results

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


 

Blood Cells Tell The Insulin Toxicity Story

Healthy Blood Cells for Comparative Study. Figure 1

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


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

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


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


 

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

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


 

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

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


 

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

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


 

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

 


References for Oxygen, Inflammation, Insulin, and Diverse Diseases

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


 

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