When Francis Crick theorised the genetic dogma that DNA flowed in only one direction to RNA and protein assembly, it was maintained by those who were not aware of reverse transcriptase. Or by those who wanted to maintain the authoritarian stance and determinism, that genes were supposed to influence every level of function and inheritance. This bottom up approach, denies the top down approach that can often meet in the middle, encompassing the breadth of physiological function that can occur at molecular (gene expression) and supra molecular  (blood tests etc) levels.

The dogma of the low carb/keto/carnivore diet devotee, which includes many doctors. Is that carbohydrates (CHO) are bad/unnecessary/causative of diabetes and responsible for all of the woe on this planet. Unlike the work of scientist Barbara Mcclintock who showed that genetic dogma was an incomplete theory, and likely wrong due to the transcriptome, and that RNA can flow to DNA, reorganising chromosomes (Noble, 2022); a broad body of literature already exists detailing why CHO consumption is not at the heart of diabetes. At the same time, there exists a vast amount of literature on potential hormone and glucose disrupting agents (Diamanti-Kandarakis et al., 2009; Gore et al., 2015)

 I acknowledge that removal of CHO from the diet will lower hyperglycemia and often improve insulin sensitivity. However, it cannot be proclaimed that one has reversed type 2 diabetes melliitus (T2DM) by removing CHO, unless, upon return to consuming CHO that the often-championed tests of OGTT, HBA1C and HOMA-IR and blood glucose tests present as normal function. Obviously removing CHO from the diet will lower glucose values because the substrate is removed, and energy will be presented in the form of both fats and proteins to be used as a fuel.

The erroneous claim that CHO consumption is unnecessary because “the body makes its own carbohydrate” is shortsighted and ignores the basic premise of optimal biology. Gluconeogenesis is not supposed to be a permanent feature of metabolism.

So, if removing CHO to improve T2DM is not the primary mechanism to address. What are the key considerations? An important consideration should be the well-established idea that sub clinical hypothyroidism (SCH) is associated and causative of sub-optimal glucose responses. In a blog from 2021 I shared research on how hypothyroidism can cause HBA1c tests to be elevated, and how a diet rich in PUFA/HUFA can be responsible for excess lipid peroxides contributing to less capacity to allow glucose to progress to pyruvate for oxidation.

Vitamin E has been shown to improve markers of T2DM (Asbaghi et al., 2023). Its positive effects are shown to benefit insulin sensitivity, HBa1c, and HOMA-IR, the key medical evaluations alongside the oral glucose tolerance test (OGTT) for diagnosing type 2 diabetes. Where Vitamin E doesn’t benefit is a lack of response to blood glucose values. It shouldn’t necessarily. And much like the individual with poor glucose utilisation, who attempts to reintroduce CHO back into their diet, and then blames this event for hyperglycemia. Falling back on their demonization of those nasty carbs.

In reality there are a number of reasons why, upon reintroduction of carbohydrates, utility tests of glucose don’t look that great. The most obvious reason why being that the most important mechanisms for improving glucose use have not been addressed. In no particular order are the most pertinent considerations for optimising pancreatic, circulating and tissue uptake of glucose.

·      Optimal thyroid function beyond standard blood tests

·      Adequate light exposure

·      Adequate energy and cofactor intake

·      Excess calorie consumption

·      Excessive PUFA consumption

·      Inadequate movement

·      Pollutant exposure

People ask if I think thyroid is the most important factor. I’m biased of course as I’m an endocrine researcher, so I’ll present just some of the mechanisms associated with CHO transport and uptake.

Thyroid hormones and particularly triiodothyronine have been shown to improve pancreatic signaling (through phosphorylation of protein kinase b/pAkt) increase pyruvate progression to acetyl coA (ultimately increase oxidation of glucose), increase glucose 6 phosphate and 6-PG dehydrogenase, ultimately improving glucose tolerance (Mendez & Ortiz, 2021).

Multiple endocrine disrupting chemicals are associated with diabetes risk and progression (Song et al., 2016). The pathways of these chemicals having specific thyroid (and other endocrine pathways) disrupting pathways that can contribute to inhibition of glucose oxidation. The ubiquity of these EDCs are often overlooked as being implicated as a causative agent of disease.

Many papers show the intimate link between hypothyroidism both overt and subclinical, and its relationship with both metabolic syndrome and diabetes (Gencer, Collet, Virgini, Auer, & Rodondi, 2013; Udovcic, Pena, Patham, Tabatabai, & Kansara, 2017; van Tienhoven-Wind & Dullaart, 2015). There are studies that also suggest minimal link and no clear association (Shin & Kim, 2021). However, understanding of the problems with TSH expression and feedback loops might provide more insights in this area.

Considerable research exists showing the fruit juice and other carbohydrates as minimal to no effect on glucose response tests (Wang, Liu, Mi, & Wang, 2014)(Murphy, Barrett, Bresnahan, & Barraj, 2017)

A low to normal thyroid stimulating hormone (TSH) value is associated with increased inflammation, persistent production of interleukin 37 (and many others) and likely present with low and chronic organ inflammation as aging progresses (Majnarić, Bosnić, Štefanić, & Wittlinger, 2022)

I have no problem with those who want to remove CHO to pass their blood sugar tests but the ultimate mark of metabolic flexibility is not simply keeping their “type 2 diabetes in remission.” It is, to reintegrate nutritious, tasty and often protective foods back into their diet with no problem. Suppression of biological function has some limited success but getting back to normal is where the real gains lie.

References

Asbaghi, O., Nazarian, B., Yousefi, M., Anjom-Shoae, J., Rasekhi, H., & Sadeghi, O. (2023). Effect of vitamin E intake on glycemic control and insulin resistance in diabetic patients: an updated systematic review and meta-analysis of randomized controlled trials. Nutrition Journal. https://doi.org/10.1186/s12937-023-00840-1

Diamanti-Kandarakis, E., Bourguignon, J. P., Giudice, L. C., Hauser, R., Prins, G. S., Soto, A. M., … Gore, A. C. (2009). Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocrine Reviews. https://doi.org/10.1210/er.2009-0002

Gencer, B., Collet, T.-H., Virgini, V., Auer, R., & Rodondi, N. (2013). Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies. Endocrine, Metabolic & Immune Disorders Drug Targets, 13(1), 4–12. https://doi.org/https://doi.org/10.2174/1871530311313010003

Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., … Zoeller, R. T. (2015). Executive Summary to EDC-2: The Endocrine Society’s second Scientific Statement on endocrine-disrupting chemicals. Endocrine Reviews. https://doi.org/10.1210/er.2015-1093

Majnarić, L. T., Bosnić, Z., Štefanić, M., & Wittlinger, T. (2022). Cross-Talk between the Cytokine IL-37 and Thyroid Hormones in Modulating Chronic Inflammation Associated with Target Organ Damage in Age-Related Metabolic and Vascular Conditions. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms23126456

Mendez, D. A., & Ortiz, R. M. (2021). Thyroid hormones and the potential for regulating glucose metabolism in cardiomyocytes during insulin resistance and T2DM. Physiological Reports, 9(16). https://doi.org/10.14814/phy2.14858

Murphy, M. M., Barrett, E. C., Bresnahan, K. A., & Barraj, L. M. (2017). 100 % Fruit juice and measures of glucose control and insulin sensitivity: a systematic review and meta-analysis of randomised controlled trials. Journal of Nutritional Science. https://doi.org/10.1017/jns.2017.63

Noble, D. (2022). Modern physiology vindicates Darwin’s dream. Experimental Physiology. https://doi.org/10.1113/EP090133

Shin, K. A., & Kim, E. J. (2021). Association between thyroid hormone and components of metabolic syndrome in euthyroid Korean adults: A population-based study. Medicine (United States), 100(51). https://doi.org/10.1097/MD.0000000000028409

Song, Y., Chou, E. L., Baecker, A., You, N. C. Y., Song, Y., Sun, Q., & Liu, S. (2016). Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: A systematic review and meta-analysis. Journal of Diabetes, 8(4). https://doi.org/10.1111/1753-0407.12325

Udovcic, M., Pena, R. H., Patham, B., Tabatabai, L., & Kansara, A. (2017). Hypothyroidism and the Heart. Methodist DeBakey Cardiovascular Journal, 13(2), 55–59. https://doi.org/10.14797/mdcj-13-2-55

van Tienhoven-Wind, L. J. N., & Dullaart, R. P. F. (2015). Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders. European Journal of Clinical Investigation. https://doi.org/10.1111/eci.12423

Wang, B., Liu, K., Mi, M., & Wang, J. (2014). Effect of fruit juice on glucose control and insulin sensitivity in adults: A meta-analysis of 12 randomized controlled trials. PLoS ONE, 9(4). https://doi.org/10.1371/journal.pone.0095323