Category Archives: Insulin Resistance and Hyperinsulinism

The Diabetes Question

Majid Ali, M.D.

Does Diabetes Begin As a Rising Blood Sugar Disease Or As a Rising blood Insulin Disease?

We Will Let Call It  

The Diabetes Question.


If the answer to the diabetes question is that it begins with rising blood insulin levels,  not with rising blood glucose levels, then the following new questions arise?

Question: Is excess insulin (hyperinsulinism) toxic to the body organs?

Answer, Yes, Excess insulin is fattening, fermentiing, and inflaming. It swells the liver and shrinks the brain. It is pro-cancer, pro-inflammation, and pro-degenerative diseases. In damages endo cells which lines the inside of the entire cardiovascular system and affects blood circulation everywhere in the body. Simply stated, excess insulin (insulin toxicity) is “pro-accelerated pro-aging.” 

Question: Can insulin toxicity be assessed with blood sugar tests?

Answer. No.

Question: In most people, how long does insulin toxicity go on undetected before blood sugar levels rise enough to make diabetes diagnosable with blood sugar tests?

Answer, for five, ten, or more years?

Question: Do doctors usually always test for blood insulin level before they test for blood sugar level?

Answer, No.


 

What Must Be Known About Crucial Diabetes and Its Complications

(In this article the terms diabetes and Type 2 dabetes are used interchangeably)

Diabetes (Type 2 Diabetes,T2D) Cannot Be Diagnosed In Time Without Insulin Tests, Diabetes Cannot Be Reversed Without Insulin Intelligence. Nor Can Diabetes Complications Be Prevented or Reversed Without Insulin Intelligence.


 

Summary

Diabetes Is Not a Sugar Problem,

It Is a Problem of Insulin Toxicity (Hyperinsulinism).

Insulin Toxicity Predates Diabetes by Five, Ten, or more Years, and Directly Leads to the Disease.


 

The Cost of Neglected Insulin Testing 

Hyperinsulinism (insulin toxicity) inflicts cellular injury in nearly all cellular populations in the body.  During the  years insulin toxicity remains ,undetected and untreated, simply because insulin testing is neglected by practitioners. Why?

Blood insulin testing is not considered a standard of care by those who control $1.3 trillion yearly spending for medical care in the United States. After considering the evidence I present in this and other articles in my “Diabetes Question Series,” the readers will decide for themselves as to the real reason for neglected insulin testing.  

I Leave the answer to readers.    


What Is Insulin Intelligence?

Simply stated, excess insulin (insulin toxicity and hyperinsulinism by other names)  is a fire which burns all parts of the body. It may start in different places and spread differently but the end result is always shortened life span with different diseases.

A practitioner who answers this questions with the “diabetes-hyperinsulinism” prevailing view does not, in my opinion, serve his patients well. Anyone who answers the question with one-liners recognizing insulin as the “life-span” hormone without does not deserve anyone’s time. As for me, I want to invite you to consider these questions by taking my free-of-cost course at this web site. A library of my selected article, published papers, and short videos is included in this post. Readers interested in my book on reversing diabetes and video seminar downloads can access these materials at http://www.aliacademy.org.


 

The Diabetes Question:

Can insulin regulation be assesses with sugar tests?

Specifically, can diabetes be detected in time with fasting blood sugar test, A1c blood tests, two-hour post prandial (after a meal) blood sugar level?

The answer: Categorically not.


 

What Is Optimal Insulin Homeostasis?

First, when the blood insulin levels after a glucose challenge are quite low;

Second, blood glucose after a glucose challenge are within low physiologic range.

Third, when there is no history of diabetes in parents and grandparents.

Fourth, when there is no insulin toxicity.

Fifth, when the immune system is robust and there is no chronic . immune-inflammatory disease.

Question: Can one optimize one’s insulin homeostasis? One can only answer this question for oneself.


 

One can tell oneself lies, but nature does not grant permission to believe one’s own lies. 


Can insulin homeostasis (insulin regulation as a whole) be assessed with blood sugar tolerance  test, A1c blood tests, two-hour post prandial (after a meal) blood glucose tests, as for instance the tolerance test done for gestational diabetes?

The answer: Categorically not.


To provide a broader context for due deliberation of the above questions, please consider sets of blood insulin and glucose profiles below which were prepared with fasting and timed post-glucose challenge.
       Table  1  Control Profiles
       Table 2,3 Blood glicose tests are inappropriate for assessing insulin homestasis
       Table 4.  Hyperinsulinism in Autism Spectrum Disorder 

Table 1. Two Sets of Control Insulin and Glucose Profiles

1.Healthy control subject:. Case 1.

                 INSULIN :    <2 uIU/mL, 18, uIU/mL, 4,       and <2;    

                 GLUCOSE:    77, 168, 109, 74, 52.

2. Healthy Control Subject: Case 2  

               INSULIN :    3 uIU/mL, 11, uIU/mL, 7,   and <2;    

               GLUCOSE:    81  157, 98, 63, 52.


The Challenge in Reversing Diabetes

is not to know what any doctor thinks about diabetes and drugs used to treat diabetes but how to learn to think for yourself about insulin, health, and healing.

I suggest you spend time at http://www.alidiabetes.org 


The Most Important Question in the Prevention and Reversal of Diabetes (Type 2)

No question is more important for stemming the global tides of insulin toxicity and diabetes than the question in the title of this post.


The Answer:

Insulin levels rise first, usually by five, ten, or more years before blood sugars level rise.
Why is this important?
Because insulin toxicity continues to cause cellular damage in the liver, kidneys, heart, brain, eyes and other organs unknown to the patient and the doctor if insulin tests are not done. For more info, go to http://www.Ali Diabetes.Org for the author’s free-access course at
http://www.Ali Diabetes.Org.

https://wordpress.com/post/alidiabetes.org/2966


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     (6.12)
14.3
Optimal Insulin Homeostasis N =126
24.9 %
121.2     (6.73)
26.7
Hyperinsulinism, Mild                N =197
38.9 %
136.5   (7.58)
58.5
Hyperinsulinism,  Moderate       N =134
26.5 %
147.0    (8.16)
109.1
Hyperinsulinism,  Severe             N =  49
9.7 %
150.0    (8.33)
(less than time and a half higher) 
231.0
(nearly 17 times higher)
#   Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.
  *Criteria for classification: (1) Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild insulin homeostasis, peak insulin  between <40 and 80 uU/mL;  accompanied by unimpaired glucose tolerance; ; (3) moderate insulin homeostasis, peak insulin  between <80 uU/mL and 160 uIU/mL accompanied by unimpaired glucose tolerance;  and (4) severe insulin homeostasis, peak insulin  > 160 uU/mL accompanied by unimpaired glucose tolerance.

Why Do Diabetics Need Insulin Shots?

Because Their Pancreas Has Exhausted Its Lifetime Capacity of Produce Sufficient Insulin

Note the extremely high blood insulin level (298 uIU/mL) still cannot keep the blood glucose level in the normal non-diabetic level.
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

What Is Optimal Insulin Homeostasis?

It is the lowest blood insulin levels that can keep the blood glucose levels in the normal range.
In other words, It is ideal state of insulin utilization, in which insulin toxicity does not exist, nor is insulin wasted because there is too much of it in the blood.
is not wasted .
In 2017, in a large survey of insulin and glucose profiles in the general New York metropolitan population, my colleagues and I reported a hyperinsulinism prevalence of 75.1%. Below is the link to get free access to the full text of this report:

http://www.townsendletter.com/Jan2017/insulin0117.html

Or, you may get the report on this website by entering , please use the the following words on the search box of the site:  “Shifting Focus from Glycemic Status.”

Examples of Insulin and Glucose Profiles of Individuals With Perfect Insulin Regulation

Table 1. Post-Glucose Load Insulin and Glucose Profiles of Seven Individuals With Optimal Insulin Homeostasis as Defined Above.
Fasting
½-Hr
1-Hr
2-Hr
3-hr
Insulin Profile 1. Insulin And Glucose Profiles of a 47-yr-old 5′ 5″ Male Runner Weighing 130 lbs. Who Presented With Inhalant Allergy and Hemorrhoids.
Insulin uIU/mL
1.5
9.7
9.0
4.6
<1.0
Glucose mg/dL
72
148
134
108
54
Insulin Profile 2. Insulin and Glucose Profiles of a  45-Yr-Old  5’9″Man Weighing 125 lbs. Presenting With Allergy and Dry Skin.
Insulin uIU/mL
1.0
2.7
9.8
2.7
<1.0
Glucose mg/dL
85
110
75
70
52
Insulin Profile 3. Insulin and Glucose Profiles of a 51-year-old 5’6″ Man Weighing 120 lbs. He Consulted Me for Cardiac Rhythm Disorder, Hypothyroidism and  Allergy.
Insulin uIU/mL
2.9
6.0
11.5
2.5
Glucose mg/dL
89
103
134
110
59
Insulin Profile 4. Insulin and Glucose Profiles of a 52-Yr-Old 5’1″ Woman Weighing 120 lbs. Presenting With Constipation and  Allergy.
Insulin uIU/mL
<2
17
15
6
Glucose mg/dL
78
61
72
71
Insulin Profile 5. Insulin and Glucose Profiles of a  52-Yr-Old 5’ 7″ Man Weighing 155 lbs. Presenting With Anxiety, Depression, and Diarrhea. A1c. 5.3%
Insulin uIU/mL
2.0
8.1
19.6
17.7
4
Glucose mg/dL
94
140
158
91
73
Insulin Profile 6. Insulin and Glucose Profiles of a  62-Yr-Old  5’3″ Woman Weighing 114 lbs. Presenting With Allergy and Hand Arthralgia.
Insulin uIU/mL
1.8
17.8
11.0
10.0
Glucose mg/dL
80
159
76
75
68
Insulin Profile 7. Insulin and Glucose Profiles of a 51-year-old 5’2″ Woman Weighing 120 lbs. She Consulted Me for Hypothyroidism and  Allergy
Insulin uIU/mL
3.2
11.8
2.4
1.9
Glucose mg/dL
86
110
75
70
52
Insulin Lab Reference Ranges Not  Fit for Use
In a previous report the author and his colleagues have highlighted the serious problem of inappropriate prevailing reference ranges for blood insulin concentrations.13 The data in Table 2 reproduced from that publication dramatically illustrates the dimension of this problem with findings of a survey of major laboratories in the New York City metropolitan area. The study data also calls into question the clinical value of single and random blood insulin test results. Photographs of illustrative lab reports are posted online.14

Absurd Laboratory Reference Ranges

Table 2. Upper and Lower Limits of Laboratory Insulin Reference  Ranges Expressed In uIU/mL Following a Standard Glucose Load From Six Major Clinical Laboratories in the New York Metropolitan Area.2
Laboratory
Fasting
1 Hr
2 Hr
3 Hr
Laboratory 1
1.9 – 23
8  –  112
5 – 35
Laboratory  2
2.6 – 24.9
0.0  – 121.9
0.0 – 163.5
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. Personal communications with clinicians revealed that they do not find this laboratory note to be helpful.
 
 

Spectrum of Insulin Dysfunction and Hyperinsulinism in Autism

Table 4 presents insulin and glucose profiles of 10 patients with dysautonomia. Note that all patients suffered from allergic disorders.
Table 4. Insulin and Glucose Profiles of Individuals With Autism.
The Blood Insulin and Glucose Levels Are Expressed in uIU/mL and mg/dL respectively.
Fasting
½ Hr
1 Hr
2 Hr
3 Hr
Autism Case 1. Insulin and Glucose Profiles of 14-Yr-Old 5’ 9” Boy Weighing 115 lbs.Who Presented Without Expressive Speech Since Birth.
Insulin uIU/mL
24
300
235
211
83
Glucose mg/dL
83
129
98
95
61
Autism Case 2. Insulin Profile and Glucose Profiles of 15-Yr-Old Boy With  Autism, Allergy, and Fatigue.
Insulin uIU/mL
10.4
43.7
37.6
33.7
7.8
Glucose mg/dL
79
104
86
82
53
Autism Case 3. Insulin and Glucose Profiles of 17-Yr-Old-Boy With Autism, Eczema, And Anxiety.
Insulin uIU/mL
24.4
N/A
73.8
71.6
28.0
Glucose mg/dL
95
N/A
79
79
69
Autism Case 4.  Insulin and Glucose Profiles of 8-Yr-Old Boy Presenting With Autism, Sudden Mood Shifts, and Inhalant Allergy.
Insulin uIU/mL
6.2
40.36
41.5
24.8
3.9
Glucose mg/dL
96
192
131
109
57
Autism Case 5. Insulin and Glucose Profiles of A Three-Year-Old  Boy With Asperger’s Syndrome, Temper Tantrums, Eczema, And Inhalant Allergy.
Insulin uIU/mL
1.28
14.3
0.33
Glucose mg/dL
71
126
88
Autism Case  6. Insulin and Glucose Profiles Of A Four-Year-Old Boy Weighing 35 lbs. Limited expressive speech, Often in non-communicative trance. Mother’s Words: “Very Intelligent In Things That Interest Him.”
Insulin uIU/mL
2.3
24.2
20.2
17.8
0.8
Glucose mg/dL
89
151
102
98
79
Autism Case 7 .  Insulin and Glucose Profiles of A 5-yr-old Boy With Autism Focus Disorder. No Expressive Speech Until Age 30 Months, Single Words 10-15 Words. No Voluntary Sentences. Eczema, Recurrent Ear Infections.
Insulin uIU/mL
1.31
47.16
43.99
Glucose mg/dL
64
127
150
Autism Case 8 . Insulin And Glucose Profiles  of  A 7-Yr-Old Boy Presenting With Diagnoses of Autism, Inhalant Eczema, Food Allergy, and History of Multiple Courses of Antibiotics for Sore Throats.
Insulin uIU/mL
11.0
Glucose mg/dL
73
Autism Case 9. Insulin And Glucose Profiles  of A Six-Yr-Old Boy Presented With Autism, Hypothyroidism, Food and Inhalant Allergy.
Insulin uIU/mL
13.0
Glucose mg/dL
85
The staff of a university hospital mishandled the blood samples on two different occasions.
Autism Case 10. Insulin and Glucose Profile of A 28-yr-old Man Who Was Diagnosed With Autism with complete Absence of Expressive Speech Until Age 4 And Then Transitioned to Asperger’s Syndrome. At Age 21, He Was An Excellent Athlete But Could Speak Only To His Mother.
Insulin uIU/mL
7
174
365
71.9
7.9
Glucose mg/dL
81
178
160
85
56
Follow-Up Testing One Year Later
Insulin uIU/mL
8.2
139.9
152.0
40.82
2.82
Glucose mg/dL
88
128
125
100
47

Free-Access Library for Reversing Diabetes.

First things first: Only you can reverse your diabetes, not anyone else.

Insulin Toxicity of the Unborn

Majid Ali, M.D.

The incidence of pregnancy-associated insulin resistance is rising worldwide, I think it is appropriately designated as insulin toxicity of the unborn.


The incidence of pregnancy-associated insulin resistance is rising worldwide, and is commonly associated with many physiological bioenergetic, biochemical, metabolic, physiological, hematological and immunological alterations.  Many of the factors involved with these alterations render cell membranes resistant to the action of insulin.  At the end of healthy pregnancy, these changes are  reversible after delivery [1]. Healthy women pregnancy can be associated with resistance to the action of insulin on glucose uptake and utilization.


 

Here is an important link for expecting moms and dads

https://wordpress.com/post/alidiabetes.org/2730

 

The Crank-Crank-Shaft Model

of Insulin Resistance Insulin Toxicity

Insulin resistance as the resistance of cells, most notably of the muscles, liver, and fatty tissue to the action of insulin. In 2000, I offered the analogy of a crank and crank-shaft to explain how insulin resistance develops. 

I proposed The Crank-Crank-Shaft Model of Insulin Toxicity to offer a simple and visual model to explain insulin resistance, excess insulin activity (hyperinsulinemia), and insulin toxicity. In simple words, the “crank of insulin” fails to turn the “crank-shaft of insulin receptor” protein embedded in the cell membrane. This happens when the cell membrane is covered with grease—the crank-shaft is rusted, turned, and twisted, so to speak—so rendering insulin ineffective. I point out that the insulin receptor crankshaft is roughly 70 times larger than the insulin crank.

To illustrate injury to the cell membrane, I proposed The Grease and Detergent Model in which the cell innards, the cell membrane, and the cement that holds the cells together (the matrix) accumulate “cellular grease” due to insufficient detergents in the body. Cellular grease is composed of cellular waste, molecular debris, rancid fats, sticky sugars, and pulped proteins. The primary detergent in the body is oxygen, with secondary “oxy-detergents,” such as hydrogen peroxide, nitric oxide, hydroxyl radicals, oxygen-activated enzymes, and grease-eating phagocytes

In cellular grease, in scientific terms, rancid fats are oxidized and peroxidized lipids, sticky sugars are glycosylated proteins and lipids, and pulped proteins are cross-linked peptides (chains of amino acids that make up proteins). This is a vast subject which I address in several articles in my Insulin Toxicity Series. Here I point out that cellular grease buildup is caused by toxic foods, toxic environment, and toxic thoughts.

In The Crank-Crank-Shaft Model of Insulin Toxicity, the blood sugar level rises when insulin fails to drive sugar into the cells to be metabolized (“burned”) to produce energy. The pancreas senses the rising blood sugar levels and responds with overproduction of insulin hormone in order to overcome the resistance of cellular grease. This works for sometime. However, excess insulin is fattening, inflaming, and grease-building. So begins the vicious cycle of:

*  More grease,

*  More insulin resistance,

*  Higher blood sugar,

*  More insulin production,

*  Yet more grease,

*  Yet higher blood glucose level,

*  Yet more insulin production, and

*  Yet more grease.

Pregnant women require an additional energy of 300 kcal/day over routine energy intake [2] while the average glucose utilized by a growing fetus at the 3rd trimester reaches approximately to 33 μmol/kg/min [4]. Maternal IR leads to more use of fats than carbohydrates for energy by mother and spares carbohydrates for fetus. Thus, the development of IR serves as a physiological adaptation of the mother to ensure adequate carbohydrate supply for the rapidly growing fetus [4].

As the pregnancy advances to third trimester, insulin sensitivity may gradually decline to 50% of the normal expected value [5]. This decline is reported to be mediated by a number of factors such as increase in the levels of estrogen, progesterone, human placental lactogen (hPL), among other factors [6].

Normally, insulin binding to insulin receptor causes phosphorylation of β-subunit of receptor and it further leads to phosphorylation of Insulin Receptor Substrate-I (IRS-I) at tyrosine residue which act as docking site for further signal transduction molecules [7].

Progesterone suppresses the phosphoinositol 3-kinase-mediated pathway by reducing the expression of IRS-1. Gradually increasing progesterone concentration with advancement of normal pregnancy is associated with increased inhibition insulin-induced GLUT4 translocation and glucose uptake [8]. Estrogen concentration is also high in pregnancy. 17β-estradiol diminishes insulin sensitivity at high concentrations [9].

hPL has both insulin-like and anti-insulin effects. In vitro, it has been shown to increase lipolysis and free fatty acids (FFAs) in adipocytes. Increased hPL level in pregnancy is found to increase glucose uptake, oxidation, and incorporation of glucose into glycogen, which may favor glycogen storage in the mother [10].

Human placental growth hormone (hPGH), a product of the human growth hormone variant gene, is not regulated by growth hormone- releasing hormone (GH-RH) and is secreted tonically rather than in a pulsatile fashion. hPGH has the same affinity for the growth hormone receptor as pituitary GH. The hPGH may also have the same diabetogenic effects as pituitary growth hormone such as hyperinsulinemia, decreased insulin-stimulated glucose uptake and glycogen synthesis, and impairment of the ability of insulin to suppress hepatic gluconeogenesis [10].

Other factors such as increased levels of serum cortisol, Tumor necrosis factor α ( TNF α, ILs etc., can interrupt the insulin signaling pathway and can lead to IR during normal pregnancy [11].

Available literature [1214] suggests that there is a rise in IR in 3rd trimester of pregnancy. However literature is less on the 1st and 2nd trimester. So the present study was undertaken to evaluate the status of IR in different phases of normal pregnancy.

Seven Stages of Hyperinsulinism

Majid Ali, M.D

An Article of Dr. Ali’s Free Course on Insulin Homeostasis


In matters of the life span, I summarize the lessons learned from my patients with the following simple word

*  Keep insulin low without drugs and live longer, or

*  keep blood sugar low with drugs and die young.

The pandemic of diabetes can be neither understood nor addressed without knowing the fundamentals of the molecular biology of insulin, a subject that is sadly and regularly neglected in the prevailing model of medicine. I wrote Insulin Toxicity Series to shed lights on the various faces of this pandemic.

My patients also helped me recognize seven stages of insulin toxicity:

.  The first stage of insulin toxicity is without apparent negative health effects recognized by the person.

.  The second stage of insulin toxicity is with negative health effects recognized by the person but unknown to the doctor.

.  The third stage of insulin toxicity is tissue injury (in the liver, kidneys, skin, and other organs) unrecognized by a doctor who is clueless about molecular biology of insulin.

.  The fourth stage of insulin toxicity is prediabetes without tests to detect insulin waste and damages.

.  The fifth stage of insulin toxicity is Type 2 diabetes with the use of diabetes drugs (that add to the insulin activity, hence its toxicity) (with the blessings of the American Diabetic Association).

.  The sixth stage of insulin toxicity is toxicity created by peaks of insulin caused by insulin injections (the end-stage of insulin depletion which is called insulin-dependent diabetes).

.  The seventh stage of insulin toxicity is loss of vision and blindness (diabetic retinopathy), dialysis (diabetic nephropathy), and increased risk of heart attacks, strokes, autoimmune diseases, inflammatory disorders, and all degenerative states.

I present evidence for all of the above in other 29 parts articles in my Insulin Toxicity Series:

The Take-home Message

of this article is: the use of diabetes drugs to lower blood sugar levels without non-drug plans to lower blood insulin levels to lower insulin levels is feeding pandemic of insulin toxicity and diabetes. The American Diabetic Association and The New England Journal of Medicine teach doctors to use only drugs to lower blood sugar when what the people really need are programs to de-grease the cell membranes, free up insulin receptor proteins embedded in the membranes, and lower blood insulin levels.

The last article entitled “Insulin Toxicity and Metformin Mania” reveals how many holistic doctors are now succumbing to the lure of easy answers with drugs as well.

Learning Materials for Insulin Intelligence

I suggest you continue your study of insulin with my three seminars on the subject included in my Insulin Toxicity Course, which can be downloaded by clicking the box below:

Insulin TOXICITY Course