Two Dimensions of Insulin Dysregulation
Majid Ali, M.D., FRCS (Eng), FCAP (Path)
Type 2 Diabetes (TD2) Is Rooted In the First Dimension of Insulin Dysregulation. Type 2 diabetes does not occur when the first dimension of insulin dysregulation is detected and reversed.
Treatment plans for reversing prediabetes (hyperinsulinism) and diabetes are presented at this site under the titles of
Reversing Prediabetes and Diabetes With 3D Plan
Links to important related articles are included at the end of this article.
Two Dimensions of Insulin Dysregulation
The author recognizes two primary dimensions of insulin dysregulation: (1) the first dimension is of excess insulin accompanied by a multitude of adverse effects of hyperinsulinism without associated glycemic disruptions characteristic of Type 2 diabetes; and (2) the second dimension of excess insulin accompanied by glycemic disruptions that meet the numerical criteria of Type 2 diabetes (T2D). The first dimension is rooted in the toxicities of food, environment and thought, while the second dimension is rooted in the first dimension. The first dimension is optimally detected by measuring timed blood insulin concentrations following an oral glucose load as shown in Tables used for case studies. The core message of this short article is this: If the first dimension of insulin dysregulation can be reversed, the problem of the second dimension (T2D) simply does not arise.
The Oxygen-Insulin View of Insulin Dysfunction, Diabetes Type 2, and Reversing Diabetes 3D
Oxygen is the organizing principal of biology and governs the aging process. The author began his book Oxygen and Aging (2000) with those words. This simple statement was the essence of his interest and study of molecular biology of oxygen for twenty years.1-4 His interest in molecular biology of insulin5-8 arose from his work in oxygen. The “oxygen-insulin perspective” of the two dimensions of insulin dysfunction and its scientific underpinnings was comprehensively discussed in his book entitled Dr. Ali’s Plan for Reversing Diabetes (2011)9 as well as in a series of follow-up publications.10-18
Life is an injury-repair-injury cycle. Cellular injury is intertwined with cellular repair by diverse mechanisms. Patterns of repair change with varying types of injury and the prevailing tissue condition. The constant in all this is expanded energy requirement of cells in the repair processes. Whether cellular repair is in acne or psoriasis, in polycystic ovarian syndrome in young women or recurrent prostatitis in young men, in chronic GERD-gastritis complex or Crohn’s colitis, inflammatory arthritis or pulmonary interstitial fibrosis, steatosis of the liver or chronic renal failure, systemic lupus erythematosus (see illustrative case study in Table 4) or scleroderma, the core requisite of cellular repair is the same: increased energy demands. Hyperinsulinism, in this context, is pancreatic response to increased energy needs for repair of injured tissues. The author has documented the presence of the first dimension of insulin dysregulation in all of the above-mentioned pathologic entities.
Three Crucial Aspects of Two Dimensions of Insuloin Dysregulation
From a clinical standpoint, three other aspects of the two dimensions of insulin dysfunction are:
- Epigenetics play greater roles than genetics in both dimensions;
- Understanding the pathophysiology, clinical courses, and optimal management of both dimensions of insulin dysregulation calls for a shift of focus from glycemic status to insulin homeostasis;
- Since first dimension is not accompanied by glycemic disruptions, the lab tests for glycemic status (fasting and 2-hour postprandial blood sugar levels, and A1c test) are not suitable in the detection and reversal of the first dimension.
Neglect of the First Dimension Deepens the Suffering of the Second Dimension
The data in Tables 1 and 2 summarizes the core statistical relationships between the two dimensions of insulin dysfunction. The two columns presenting mean peaks of blood glucose and post-glucose-load insulin concentrations in Table 1 dramatically document how far the prevailing practices of neglecting the first dimension go to deepening the problems caused by the second dimension.
Table 1. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes
|Insulin Category*||Percentage of Subgroup||Mean Peak Glucose mg/dL(mmol/mL)||Mean Peak Insulin (uIU/mL)|
Exceptional Insulin Homeostasis N = 12**
Optimal Insulin Homeostasis N = 126
|24.9 %||121.2 (6.73)||26.7|
Hyperinsulinism, Mild N = 197
|38.9 %||136.5 (7.58)||58.5|
Hyperinsulinism, Moderate N = 134
|26.5 %||147.0 (8.16)||109.1|
Hyperinsulinism, Severe N = 49
|9.7 %||150.0 (8.33)||231.0|
|Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.|
*Criteria for classification: (1) Exceptional insulin homeostasis, with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild hyperinsulinism, peak insulin <80 accompanied by unimpaired glucose tolerance; (4) moderate hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance; (5) severe hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance.
** Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis.
|Table 2 Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes|
|Insulin Category||Percentage of Subgroup||Mean Peak Glucose, mg/dL
|Mean Peak Insulin (uIU/mL)|
Diabetic Hyperinsulinism, Mild N = 53
Diabetic Hyperinsulinism, Moderat N = 42
Diabetic Hyperinsulinism, Seve N = 24
Diabetic Insulin Deficit N = 59
Neglect of the First Dimension By Laboratory Professionals
The neglect of first dimension by the laboratory professionals is one of the most disturbing aspects of the sordid story of the two dimensions of insulin dysregulation. For instance, the reference range for the 2-hr post challenge blood insulin concentration of laboratory 2 (Table 3) is an astonishingly and utterly clinically unusable 0.0 to 163.5.
Table 3. Insulin Reference Ranges in uIU/mL of Six Laboratories in New York Metropolitan Area*
|Laboratory||Fasting||1 Hr||2 Hr||3 Hr|
|Laboratory 1||1.9 – 23||8 – 112||5 – 35||Not Reported|
|Laboratory 2||2.6 – 24.9||0.0 – 121.9||0.0 – 163.5||Not Reported|
|Laboratory 3||6 – 24.9||8 – 112||5 – 55||3 – 20|
|Laboratory 4||6 – 27||20 – 120||18 – 56||8 – 22|
|Laboratory 5||00 – 30||30 – 200||40 – 300||50 – 150|
|Does not include insulin ranges in the report. Instead it includes the following note: Insulin analogues may demonstrate non-linear cross-reactivity in this essay. Interpret results accordingly.**|
*Upper and lower limits of laboratory reference ranges for blood insulin concentration determined following a Standard 75-gram glucose challenge.
**Personal communications with clinicians revealed that they do not find this laboratory note to be satisfactory in their clinical decision-making.
Mechanisms of Insulin Regulation and Two Dimensions of Insulin Dysregulation
The following is text on the subject from the author’s comments e-published in June, 2017 by the journal Nature. “The work of Zhang and colleagues is important for physicians who treat diabetes because class B G- protein-coupled receptors (GPCRs) are important therapeutic targets. Beyond that, this work invites all physicians to a deeper study of the inner mechanisms of insulin homeostasis, a subject that is seldom duly considered in clinical medicine. Specifically, insulin dysregulation has two distinct dimensions: (1) the first dimension of pathophysiology of hyperinsulinism which predates Type 2 diabetes (T2D) and is not accompanied by glycemic abnormalities detectable by the laboratory tests in current use; and (2) the dimension of T2D accompanied by hyperglycemia and its biochemical consequences. This author has long recognized the need for a shift of clinical focus from glycemic status to insulin homeostasis for detecting and optimally managing adverse metabolic, proinflammatory, endothelial, developmental, and neurologic effects of hyperinsulinism (ref. 2-6).”
Table 4. Severe Hyperinsulinism In A 13-Yr-Old With SLE, ITP, Recurrent Pneumonia, and Optic Neuritis With Right Eye Blindness.
The Peak Insulin Fell from 718 to 238.5 In Four Months of Robust Integrative Treatment.
|Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Therapies|
Table 5. Control of Hyperinsulinism With Reversal of Type 2 Diabetes In A 75-Yr-Old 5’ 2” Female Weighing 162 Lbs. With Hypertension and Chronic Sinusitis.
|4.30.2013||Fasting||½ hr||1 hr||2 Hr||3 Hr|
Glucose mg/mL (mmol/L)
Glucose mg/mL (mmol/L)
Glucose mg/mL /L)
* A1c, 6.3%; ** A1c, 5.9%
Reversing Prediabetes (Hyperinsulinism) and Diabetes With 3D Plan
The insulin homeostasis protocol (the “Protocol”) evolved as a three-prong approach comprising: (1) diet; (2) detox; and (3) dysoxic comorbidities (oxygen-related coexisting pathologic entities) including disrupted hypothalamic and related neural pathways which regulate the energy economy of the body. The three “diabetes 3D” subjects are vast and clearly beyond the scope of this brief outline. A comprehensive discussion of all above subjects is presented at free access www.alidiabetes.org. Google search words are: majid ali, shifting focus from glycemic status to insulin homeostasis.
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