High Insulin, IR and ? Harm Before Diabetes

There is growing concern that people

  • who do not meet the diagnostic test cut-off points for a diagnosis of diabetes
  • may, none the less, be suffering substantial harm during the many years in which the metabolic state that leads to type 2 diabetes is present and slowly becomes worse and worse.

So, there is a question:

  • do we regard pre-diabetes as of concern mostly because it indicates a risk for progressing to T2 diabetes, and thus the harm of being diabetic (being a marker for risk of later development of diabetes and/or the pre-diabetic state affecting the body in a way that promotes the development of type 2 diabetes
  • do we regard the state of pre-diabetes as causing harm during that time, not just as to whether it is a risk marker for later developing diabetes or is a state that promotes the development of diabetes
  • if pre-diabetes is a state that causes harm in itself, beyond being associated with or promoting the development of T2 diabetes, then at what point in the change from normal metabolism to T2 diabetes does the harm start?

Below, I have listed some examples of evidence suggesting harm from, or associated with:

  • elevated insulin and/or glucose,
  • or simply being in the state of insulin resistance
  • or meeting the criteria for Metabolic Syndrome

in people who do not meet the criteria for diabetes as used by the researchers.

Related to this is a video posted below, which goes into this in more detail.

First, a brief video intro to the topic

Presentation by Catherine Croft (PhD student) regarding insulin resistance:


(1) Right Ventricle Dysfunction and Metabolic Syndrome

“Right ventricle free wall mechanics in metabolic syndrome without type-2 diabetes: effects of a 3-month lifestyle intervention program.” Cardiovasc Diabetol. 2014 Aug 3;13:116. doi: 10.1186/s12933-014-0116-9.  LINK  to full text

Meaning and Importance of the Study Findings (Quotes): 

  • With prevalence reaching alarming proportions worldwide, MetS is now considered to be the driving force for a cardiovascular disease epidemic.
  • In this context, the present study underlines the necessity for a close clinical RV monitoring in MetS patients even when type 2 diabetes is not associated.
  • Moreover, this study underlines the importance of central obesity and its associated inflammation as independent factors explaining RV mechanical abnormalities,
  • highlighting the need for treatment of central fat and inflammation to decrease or prevent the deleterious impact of MetS on RV function.
  • Finally, the present work emphasizes the importance of lifestyle changes since the RV dysfunction can be corrected even only three months after an exercise and nutrition intervention.

Further, from the paper (MetS is Metabolic Syndrome, RV is right ventricle of the heart):

  • “The metabolic syndrome (MetS) is a cluster of cardio-metabolic risk factors predisposing the development of cardiovascular pathologies [1]. It is a low grade inflammatory disease [2] associated with potentially adverse effects on cardiac remodeling and function [3],[4].”
  • “Thirty-nine MetS adults free of diabetes were enrolled in a three month lifestyle intervention program including diet and physical exercise, and compared with forty healthy controls.”
  • “Conclusions: MetS is associated with subtle impairments in both RV free wall diastolic and systolic myocardial function which could be partly related to central-obesity induced changes in pro- and anti-inflammatory cytokines and left ventricular remodeling. The favorable impact of healthy dieting and physical activity on RV free wall mechanics indicates that cellular and sub-cellular alterations responsible for the RV myocardial abnormalities are probably not permanent and modifiable throughout adequate interventional strategies.”
  • “Special attention should be paid to this specific population in clinics, as earlier identification of asymptomatic patients at high risk of evolution to RV failure is of primary importance because it may facilitate timely and more effective intervention.”

(2) Left Ventricular Diastolic Dysfunction and Insulin Resistance

Cardiovasc Diabetol. 2015; 14: 4. doi: 10.1186/s12933-014-0168-x
PMCID: PMC4298953
Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes
Ricardo Fontes-Carvalho, Ricardo Ladeiras-Lopes, et. al.

Image tweeted by Dr Aseem Malhotra, British Cardiologist, August 31, 2015. As he was attending a conference at the time, I believe this is a poster presentation from that conference.
Image tweeted by Dr Aseem Malhotra, British cardiologist, August 31, 2015. As he was attending a conference at the time, I believe this is a poster presentation from that conference. @DrAseemMalhotra

Quoted from the paper:

  • Diabetes increases the risk of heart failure but the underlying mechanisms leading to diabetic cardiomyopathy are poorly understood. Left ventricle diastolic dysfunction (LVDD) is one of the earliest cardiac changes in these patients.
  • Subclinical left ventricle diastolic dysfunction (LVDD) is
    • common in the community [1] and
    • is recognized as an important predictor of heart failure [2] and long-term mortality [3].
    • Current heart failure guidelines [4] give special emphasis to the early detection of these asymptomatic changes of left ventricle function and the identification of its main risk factors
  • Several studies have suggested that LVDD is one of the earliest signs of myocardial involvement in type 2 diabetes mellitus (T2DM) [10], being a key component of diabetic cardiomyopathy [11].
  • More recently, it was suggested that changes in diastolic function precede the onset of diabetes, being already present in pre-diabetic patients [12,13], which could be associated with the state of insulin resistance.
  • Indeed, patients with metabolic syndrome also have an increased prevalence of LVDD [15,16], frequently with a subclinical course [17].
  • Conclusion:
    • Insulin resistance and metabolic syndrome are associated with diastolic dysfunction independently of age, blood pressure and body mass index.
    • These data suggest that subclinical changes in myocardial diastolic function are already present before the onset of diabetes, being associated mainly with the state of insulin resistance and not only to sustained hyperglycemia.
    • Future research will determine if improving insulin resistance using insulin-sensitizers or lifestyle changes can improve diastolic function.

Interview with Dr. Kraft, Pathologist and Author of “Diabetes Epidemic and You”

Dr. Richard K. Kraft, now age 95, became interested in the topic of diabetes many decades ago. Being a pathologist, he was most concerned with studying the damage caused to body tissues by diabetes. He did a great many autopsies and thousands of 5-hour glucose tolerance tests where both blood glucose and blood insulin levels were measured. Over time, he has become convinced that the damage to the body starts in the stages before the blood glucose levels show as elevated in the standard tests.

This is well-explained in his book and in this interview conducted July 31, 2015.

Dr. Kraft’s work has been under-recognized but fortunately recently came to the attention of Professor Grant Schofield, of New Zealand.  LINK  Prof. Schofield and Catherine Croft, one of his research team, are currently looking into Dr. Kraft’s data and concepts and seeing how this translates to clinical and research implications today. Others have taken up the task of bringing Dr. Kraft’s body of work and concepts to greater awareness – so the ideas can be considered, discussed and explored in research as warranted.

Ivor Cummins, an engineer who has over some years developed a keen interest in  metabolism and nutrition, has played a prominent role in getting out the word that Dr. Kraft has some very interesting ideas that warrant attention and discussion, and that Dr. Kraft’s ideas were built on a truly remarkable body of work and data.

For more information and a number of blog posts on the topic, please see Mr. Cummins blog The Fat Emperor.  LINK

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