Statins Are Associated With Increased Insulin Resistance and Secretion

[AspiringSage]

I suspect that readers of this forum are already suspicious of statins. It is always handy to have more evidence for discussion. In this study, they administered atorvastatin 40mg daily to adults without known atherosclerotic cardiovascular disease or type 2 diabetes for ten weeks. The primary outcomes were measured insulin resistance and insulin secretion at baseline, two week intervals and conclusion of the study. The secondary outcomes were measured fasting glucose and glucose tolerance tests.

Statins Are Associated With Increased Insulin Resistance and Secretion

“Effect of Atorvastatin on Body Weight and Concentrations of Lipids, Glucose, and Insulin

Statin therapy reduced total cholesterol by 37%, LDL-C by 53%, and triglycerides by 28% (Table IV in the Data Supplement). There was no change in body weight.

Effect of Atorvastatin on Insulin Resistance

Statin treatment significantly increased insulin resistance, a co-primary outcome. Across the entire study population, the median insulin resistance (ie, SSPG) increased from 130 to 139 mg/dL (P=0.01) while the median percent increase in insulin resistance was 8% (IQR, −10% to 32%; Table; Figure 2A, Figure I in the Data Supplement). Steady-state plasma insulin decreased by 5%, but there was no significant correlation between the change in steady-state plasma insulin and the change in insulin resistance”

“Conclusions:
In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.”

Citation:

Fahim Abbasi, Cindy Lamendola, et all. Statins Are Associated With Increased Insulin Resistance and Secretion, Arteriosclerosis, Thrombosis, and Vascular Biology, 2021;41:2786–2797, Originally Published 26 Aug 2021

 

[AspiringSage]

About a year and a half ago a friend of mine (mid 30’s male, sedentary, prediabetic, obese, celiac disease, high cholesterol, low testosterone) ended up tossed between providers and conflicting approaches.

His NP/DN (a naturopath with prescriptive authority) advised radical change from the typical American diet. She pushed him towards low carb (primarily starch avoidance), moderate protein, low PUFA, calorie counting, etc. She advised rigorous cardio and weightlifting. She prescribed K2, B vitamins, niacinamide, enclomiphene, anastrozole, low dose ozympec 2.5mg/week, 500mg metformin/day.

He essentially ended up eating chicken, steak, non starchy veggies, carrots, fruit and occasional brown rice with no fast food/limited PUFAs. He cooked with organic extra-virgin olive or coconut oil. He made improvements on essentially every health metric. Unfortunately, his insurance wouldn’t cover the enclomiphene or ozympec and he ended up seeing a mainstream/on insurance endocrine.

The mainstream/on insurance endocrine an MD declined to treat his low testosterone (e.g. discontinued enclomiphene/anastrozole), pushed a continuous glucose monitor, prescribed atorvastatin 40mg/day, increased his metformin from 500mg to 2grams/day, increased his ozympec to 5mg/week (which made him feel ill). And advised less meat more brown rice and slow starches (because she was concerned about his natural pre waking glucose spike). She pushed him to cook with vegetable oil. She emphasized long walks over weightlifting. He has since put on weight, become depressed (ended up on an SSRI), been diagnosed with type 2 diabetes, generally declined and is headed straight towards insulin therapy.

In light of this study, I am left to wonder what role atorvastatin played in this progression.

 

[Grapelander]

Statins More Than Double The Risk Of Diabetes Compared To Non-users

Spacedoc.com

Spacedoc

spacedoc.com

Cholesterol, longevity, intelligence, and health.

Ray Peat

raypeat.com

 

[J.R.K]

About a year and a half ago a friend of mine (mid 30’s male, sedentary, prediabetic, obese, celiac disease, high cholesterol, low testosterone) ended up tossed between providers and conflicting approaches.

His NP/DN (a naturopath with prescriptive authority) advised radical change from the typical American diet. She pushed him towards low carb (primarily starch avoidance), moderate protein, low PUFA, calorie counting, etc. She advised rigorous cardio and weightlifting. She prescribed K2, B vitamins, niacinamide, enclomiphene, anastrozole, low dose ozympec 2.5mg/week, 500mg metformin/day.

He essentially ended up eating chicken, steak, non starchy veggies, carrots, fruit and occasional brown rice with no fast food/limited PUFAs. He cooked with organic extra-virgin olive or coconut oil. He made improvements on essentially every health metric. Unfortunately, his insurance wouldn’t cover the enclomiphene or ozympec and he ended up seeing a mainstream/on insurance endocrine.

The mainstream/on insurance endocrine an MD declined to treat his low testosterone (e.g. discontinued enclomiphene/anastrozole), pushed a continuous glucose monitor, prescribed atorvastatin 40mg/day, increased his metformin from 500mg to 2grams/day, increased his ozympec to 5mg/week (which made him feel ill). And advised less meat more brown rice and slow starches (because she was concerned about his natural pre waking glucose spike). She pushed him to cook with vegetable oil. She emphasized long walks over weightlifting. He has since put on weight, become depressed (ended up on an SSRI), been diagnosed with type 2 diabetes, generally declined and is headed straight towards insulin therapy.

In light of this study, I am left to wonder what role atorvastatin played in this progression.

I have a friend that has type two diabetes and she changed her diet similar to the mainstream doctor in your description but also included salmon three times a week with similar results. So the doctor prescribed a statin as well, her health has declined further since the prescription.
Your query is echoed on the roll the statin played in this further decline.
I am trying to understand the method of action of Metformin, as to whether it removes the sugar from the blood, or if it forces the cell to take up the sugar, which in a person with lypolysis and therefore low metabolic rate would cause the black box warning regarding lactic acidosis.Any light on this would be greatly appreciated. @AspiringSage, @Grapelander @haidut @Regina @boris @yerrag @Drareg @tankasnowgod

 

[Grapelander]

method of action of Metformin

This is the methods of action for type-2 medications:

Several classes of type 2 diabetes medicines exist. Each class of medicine works in different ways to lower blood sugar.
A drug may work by:

• Stimulating the pancreas to produce and release more insulin
• Inhibiting the production and release of glucose from the liver
• Blocking the action of stomach enzymes that break down carbohydrates
• Improving the sensitivity of cells to insulin
• Inhibiting the reabsorption of glucose in the kidneys
• Slowing how quickly food moves through the stomach

Each class of medicine has one or more drugs. Some of these drugs are taken orally, while others must be injected.

Metformin method of action:
It works by decreasing glucose production by the liver,
by increasing the insulin sensitivity of body tissues,
and by increasing GDF15 secretion.

Looks like metformin started off as antiviral class - synthetic of Goat's Rue. It is in the bean family (Fabaceae).
Metformin is a synthetic derivative of guanidine, a natural product found in the herbal medicine Galega officinalis used in medieval Europe.
In 1950 Filipino physician Eusebio Y. Garcia used metformin (he named it Fluamine) to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic. Garcia believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic, and analgesic actions. In a series of articles in 1954, Polish pharmacologist Janusz Supniewski was unable to confirm most of these effects, including lowered blood sugar. Instead he observed antiviral effects in humans. <wiki>

I'd be concerned about long-term use.
Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. <wiki>
Associated with increased homocysteine levels and malabsorption of vitamin B12. <wiki>
Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. Common causes include alcoholism (due to depletion of NAD+ stores), heart failure, and respiratory disease (due to inadequate tissue oxygenation); the most common cause is kidney disease. <wiki>

 

[tankasnowgod]

I have a friend that has type two diabetes and she changed her diet similar to the mainstream doctor in your description but also included salmon three times a week with similar results. So the doctor prescribed a statin as well, her health has declined further since the prescription.
Your query is echoed on the roll the statin played in this further decline.
I am trying to understand the method of action of Metformin, as to whether it removes the sugar from the blood, or if it forces the cell to take up the sugar, which in a person with lypolysis and therefore low metabolic rate would cause the black box warning regarding lactic acidosis.Any light on this would be greatly appreciated. @AspiringSage, @Grapelander @haidut @Regina @boris @yerrag @Drareg @tankasnowgod

I would think she would want to do a full iron panel. High body iron stores are known to impair carbohydrate metabolism, and lowering them (through both phlebotomy and diet) have been shown to improve carbohydrate tolerance, and can also improve mood and energy.

Here are two studies from Dr. Facchini that show this-

DEFINE_ME

A Low-Iron-Available, Polyphenol-Enriched, Carbohydrate-Restricted Diet to Slow Progression of Diabetic Nephropathy

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial

diabetesjournals.org

The second link shows improvement even in patients with later stage renal disease.

Note, the improvements came from induction of near iron deficiency, so just being "in range" can still be problematic. The ferritin range can go from 30-400. The average baseline for the patients in the second study was 300-350, meaning that many of them would be considered "normal" by many lab ranges. Near Deficiency should have ferritin closer to about 30-50, certainly under 100.

While I'm not a doctor, I wouldn't think the statin or metformin are doing her any good.

 

[J.R.K]

I would think she would want to do a full iron panel. High body iron stores are known to impair carbohydrate metabolism, and lowering them (through both phlebotomy and diet) have been shown to improve carbohydrate tolerance, and can also improve mood and energy.

Here are two studies from Dr. Facchini that show this-

DEFINE_ME

A Low-Iron-Available, Polyphenol-Enriched, Carbohydrate-Restricted Diet to Slow Progression of Diabetic Nephropathy

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial

diabetesjournals.org

The second link shows improvement even in patients with later stage renal disease.

Note, the improvements came from induction of near iron deficiency, so just being "in range" can still be problematic. The ferritin range can go from 30-400. The average baseline for the patients in the second study was 300-350, meaning that many of them would be considered "normal" by many lab ranges. Near Deficiency should have ferritin closer to about 30-50, certainly under 100.

While I'm not a doctor, I wouldn't think the statin or metformin are doing her any good.

An interesting thought and thank you the input @tankasnowgod.
This is a part that gets a little odd, she has actually been diagnosed as being anemic and is on iron pills, (yikes I know it sent a chill down my spine when she told me that).
She had been on them for over a year and there is no improvement, so it might very well be possible that this extra iron is being locked up in her tissues, as extra weight which has her classified as obese which is often seen, to accompany usually precede type 2 diabetes.

 

[J.R.K]

This is the methods of action for type-2 medications:

Several classes of type 2 diabetes medicines exist. Each class of medicine works in different ways to lower blood sugar.
A drug may work by:

• Stimulating the pancreas to produce and release more insulin
• Inhibiting the production and release of glucose from the liver
• Blocking the action of stomach enzymes that break down carbohydrates
• Improving the sensitivity of cells to insulin
• Inhibiting the reabsorption of glucose in the kidneys
• Slowing how quickly food moves through the stomach

Each class of medicine has one or more drugs. Some of these drugs are taken orally, while others must be injected.

Metformin method of action:
It works by decreasing glucose production by the liver,
by increasing the insulin sensitivity of body tissues,
and by increasing GDF15 secretion.

Looks like metformin started off as antiviral class - synthetic of Goat's Rue. It is in the bean family (Fabaceae).
Metformin is a synthetic derivative of guanidine, a natural product found in the herbal medicine Galega officinalis used in medieval Europe.
In 1950 Filipino physician Eusebio Y. Garcia used metformin (he named it Fluamine) to treat influenza; he noted the medication "lowered the blood sugar to minimum physiological limit" and was not toxic. Garcia believed metformin to have bacteriostatic, antiviral, antimalarial, antipyretic, and analgesic actions. In a series of articles in 1954, Polish pharmacologist Janusz Supniewski was unable to confirm most of these effects, including lowered blood sugar. Instead he observed antiviral effects in humans. <wiki>

I'd be concerned about long-term use.
Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. <wiki>
Associated with increased homocysteine levels and malabsorption of vitamin B12. <wiki>
Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. Common causes include alcoholism (due to depletion of NAD+ stores), heart failure, and respiratory disease (due to inadequate tissue oxygenation); the most common cause is kidney disease. <wiki>

Thank you for expanding my knowledge once again @Grapelander, I was aware of the lactic acidosis being a concern.
I had recently read a study from that had indicated that the long term use of ACE inhibitors seen an increased risk of developing pancreatitis. This made me question if this condition would lead potentially to the development of diabetes.
With metformin being the go to drug of choice to control diabetes, I would be inclined to believe that a preexisting inflammatory condition combined with an increased risk of lactic acidosis might expedite the development of cancer within the most inflamed area.

ACE inhibitors and the risk of acute pancreatitis-a population-based case-control study - PubMed

Angiotensin converting enzyme inhibitor use seems to be associated with a moderately increased risk of acute pancreatitis. Copyright © 2017 John Wiley & Sons, Ltd.

pubmed.ncbi.nlm.nih.gov

 

[Peatness]

Angiotensin Receptor Blockers also increase the risk of pancreatitis

Acute pancreatitis associated with angiotensin II receptor antagonists - PubMed

Clinicians should be aware that irbesartan/HCTZ or losartan may cause acute pancreatitis. If abdominal pain develops, the medication should be discontinued and the patient investigated for acute pancreatitis.

pubmed.ncbi.nlm.nih.gov

 

[tankasnowgod]

An interesting thought and thank you the input @tankasnowgod.
This is a part that gets a little odd, she has actually been diagnosed as being anemic and is on iron pills, (yikes I know it sent a chill down my spine when she told me that).

There are plenty of types of anemia that can happen even in the face of high iron...... from serious ones like sickle cell and thalassemia, to ones related to various B vitamin deficiencies like pernicious anemia, which are fairly easily treated. If they just diagnosed anemia based on hemoglobin (which wouldn't be surprising), it's likely they know nothing about total body iron stores. Even so, if she's been on iron supps for over a year, she should demand a full iron panel with ferritin. Or, she could always get one on direct labs, they are fairly inexpensive.

She had been on them for over a year and there is no improvement, so it might very well be possible that this extra iron is being locked up in her tissues, as extra weight which has her classified as obese which is often seen, to accompany usually precede type 2 diabetes.

There are many people with anemia who don't respond to iron pills that do respond to a B Complex (some continuing the iron supp, some discontinuing it). I know from personal experience, when I was getting de-ironed (via Blood Donation), that a B Complex can raise hemoglobin, even when ferritin (and whole body iron stores) are declining.

 

[J.R.K]

There are plenty of types of anemia that can happen even in the face of high iron...... from serious ones like sickle cell and thalassemia, to ones related to various B vitamin deficiencies like pernicious anemia, which are fairly easily treated. If they just diagnosed anemia based on hemoglobin (which wouldn't be surprising), it's likely they know nothing about total body iron stores. Even so, if she's been on iron supps for over a year, she should demand a full iron panel with ferritin. Or, she could always get one on direct labs, they are fairly inexpensive.

There are many people with anemia who don't respond to iron pills that do respond to a B Complex (some continuing the iron supp, some discontinuing it). I know from personal experience, when I was getting de-ironed (via Blood Donation), that a B Complex can raise hemoglobin, even when ferritin (and whole body iron stores) are declining.

Very interesting thank you for sharing your experience @tankasnowgod! The B vitamins seem to be playing an important role in the whole diabetes scheme thiamine, niacinamide, biotin and riboflavin as well as folate seem to be the main ones to lead the charge, with B12 bringing up the rear.
I am seeing increasingly the importance of iron management as well as the calcium to phosphorus ratio, as well as carbohydrate to protein being a recurring theme in the,”plague of diseases” that has descended upon the Earth, with stress, polluted environment and PUFA laden food supplies.

 

[tankasnowgod]

I am seeing increasingly the importance of iron management as well as the calcium to phosphorus ratio, as well as carbohydrate to protein being a recurring theme in the,”plague of diseases” that has descended upon the Earth, with stress, polluted environment and PUFA laden food supplies.

E.D. Weinberg and other researchers have pointed out that high iron is involved in many degenerative diseases. Especially the big ones, like diabetes, heart disease, and cancer. Many others as well.

On top of that Calcium and Iron are basically absorbed through the same channels. Additional Calcium is one way to lower iron absorption. E.D. Weinberg also stated that calcium channel blockers lower the absorption of iron, and was part of his iron lowering strategy he mentioned in this interview-

Eugene D. Weinberg on Iron Toxicity

A couple of my recent articles have been devoted to the topic of iron and its involvement in many disease states and in aging itself. (See […]

roguehealthandfitness.com

Since calcium can block iron absorption, it would also make sense that iron could block calcium absorption.

Here are two charts that show the PUFA and Iron Intake in recent decades.

 

[J.R.K]

E.D. Weinberg and other researchers have pointed out that high iron is involved in many degenerative diseases. Especially the big ones, like diabetes, heart disease, and cancer. Many others as well.

On top of that Calcium and Iron are basically absorbed through the same channels. Additional Calcium is one way to lower iron absorption. E.D. Weinberg also stated that calcium channel blockers lower the absorption of iron, and was part of his iron lowering strategy he mentioned in this interview-

Eugene D. Weinberg on Iron Toxicity

A couple of my recent articles have been devoted to the topic of iron and its involvement in many disease states and in aging itself. (See […]

roguehealthandfitness.com

Since calcium can block iron absorption, it would also make sense that iron could block calcium absorption.

Here are two charts that show the PUFA and Iron Intake in recent decades.

View attachment 38844

View attachment 38846

That was a great article. Thank you for posting it. I was unaware that iron was involved in bacterial infection, it brought my mind directly to the discussion about bacteria being involved with atherosclerosis and red meat. I know that saturated fats are preferably metabolized, but perhaps the real problem is the iron component in the red meat that is the issue.
I was never a coffee drinker prior to my introduction Dr Peats work, but when I consume red meat I always folllow it with a cup of coffee with milk and also some grape juice to block the iron and the methionine.
When you deironized did you find or notice any changes in how you felt?

 

[tankasnowgod]

When you deironized did you find or notice any changes in how you felt?

I had high ferritin (444), and when I got it down to the near deficiency range (roughly 50), I noticed improved mood and energy, plus I was able to eat fairly big carb meals without any sort of "carb crash." I realized after a time I have fewer electric shocks with metal/computer equipment. Ferritin has tested as low as 28 and even 18, and I didn't notice any negatives at those levels.