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Archive for the ‘lipids lipid metabolism’ Category

This is not a breaking news story. It’s the same old secret that was exposed in JUPITER  trial with Rosuvostatin 14 years ago. Yes, I am talking about the relationship between the usage of statin and the occurrence of diabetes. Now, we have this huge study on possible diabetes progression with statins. It’s not from a small journal to ignore. 

83 thousand patients data, the world’s largest series on link between statin therapy and diabetes.

 

This study has this to conclude

Diabetogenic statins

Something* happens as the statins antagonize the HMG COA  enzyme that resides within the delicate membranes of the endoplasmic reticulum inside the most specialized cells in our human body, called hepatocytes.

*What is that something?

Image source Umme Aiman et al Journal of Pharmacology and Pharmacotherapeutics 5(3):181-5DOI: 10.4103/0976-500X.136097

How to go about this issue?

With-holding statin in as many as possible is the best thing for such diabetic  (non-diabetic?) patients. But, the more pragmatic option is to ignore these negative studies, and instead intensify diabetes management if it worsens. After all, we can’t afford to lose the prodigious evidence-based cardio-vascular protective effects of statins and earn the wrath of our patients and peers you know!

Further Interest

1.Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of Statin Therapy Initiation With Diabetes ProgressionA Retrospective Matched-Cohort StudyJAMA Intern Med. Published online October 04, 2021. doi:10.1001/jamainternmed.2021.5714

2.Aiman U, Najmi A, Khan RA. Statin induced diabetes and its clinical implications. J Pharmacol Pharmacother. 2014 Jul;5(3):181-5. doi: 10.4103/0976-500X.136097. PMID: 25210397; PMCID: PMC4156828.

 

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Sharing a presentation on lipid control done in 2020. This talks about newer strategies beyond statins.

 

 

 

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Caution: Please don’t expect much scientific content in this post. I Hope, you can spare a minute to answer this hypothetical question.

What will be the shape of the curve,  If you plot BMI in the X-axis and LDL/ total cholesterol in Y-axis from a thousand normal adult populations?

  1. It will be linear for sure.
  2. Maybe a little curvilinear.
  3. Its likely J shaped with age 
  4. I think it is U shaped
  5. No, it is Inverted U
  6. Sorry, I don’t know.
  7. No one knows.
Answer: Though linear relation is the one we expect, all sorts of shapes are reported in various correlation studies, making the response 7 likely to be correct.

Why BMI refuse to go along linearly with LDL (Cholesterol)?

Only an ultra-fraction of total body fat is represented as cholesterol within the vascular system. It’s worthwhile to note, total body fat store is about 8-10 kg,  the amount of cholesterol in circulating blood is hardly 10 grams. It is presumed another 30 grams is present in cells. Body synthesise 1 gram /day.I don’t know whether I can make this statement. It may appear total body fat and cholesterol are almost unrelated things in spite of the dynamism of Intermediary metabolism exogenous and endogenous cholesterol levels are modulated to keep the intravascular cholesterol within an amazingly narrow range

How justified are we to expect a good correlation between BMI and Cholesterol? 

Apart from the presumed logic, there are other dynamic factors that dictate how any person deals with excess lipids/cholesterol. 

  • Genetics profile(Hereditary dyslipidemia)
  • Dietary habits 
  • Various hormone sensitivity to cells.
  • Physical activity 
  • Age /Gender 
  • Ethnicity

Most excess fat gets deposited within adipocytes. So it is scientifically impossible to guess the serum cholesterol level by just looking at overweight people. 

Final message

Even after 50 years of vigorous research, we are clearly ignorant about this fundamental question in lipidology and clinical cardiology. This is directly reflected in myriad dietary guidelines that flooding in the academic and public domain. Let us be transparent to our patients about our knowledge or lack of it. At the minimum, we should stop confusing all those healthy, active people with borderline obesity.

Further, we need to come out of our villainous portrait of fat in general. Let us respect the fat as an essential building block of every cell and hence the whole body. We still need to pursue a long journey to identify &  target only the high-risk population who have atherogenic dyslipidemia that impacts the cardiovascular outcome.

Counterpoint

There is indeed a correlation between body weight and serum lipid. Don’t be dogmatic with limited research and knowledge and confuse the academics. Go through the literature right from Framingham /MRFIT/Monica to Interheart study. There is scattered evidence to show BMI do have a reasonable correlation with blood lipids. 

Yes, scattered is the right word, it can mean anything.

Reference

This well-conducted study suggests, within the normal BMI range there could be a correlation with LDL. I don’t know how useful is this data in clinical practice. 


Coming next 

There is one more question, which has not clearly answered. What is the relationship between seum cholesterol and Intra plaque cholesterol?

For lighter reading , Ruben Meerman is able to kindle the hidden science.

When you lose weight , Where does the fat go ?

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