tananth
#41
That just means the cutoff for being classified as pre-Diabetic is 5.7 or more and anyone with A1C 5.6 or less (while not taking diabetes medications) is considered non-Diabetic. It does NOT mean that a non-diabetic with an A1C of 5.0 to 5.6 is normal or healthy.
It looks like the 5.7 cutoff is based on the 97.5 percentile of A1C for those not previously diagnosed as diabetic AND having fasting BG < 127 and 2-hour post meal BG < 140.
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Neo
#42
Iām doing an experiment to budge mine down a bit per
But that is mostly to see if I feel different / if has an effect on my strength training. From a pure longevity perspective it may not be bad and even good
In human and rodent CR individuals SHBG is higher
Perhaps higher SHBG is actually consistent with multiple longevity dimensionsā¦. see eg below.
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I have a hypothesis that megadosing melatonin drives up SHBG. I am not particularly stressed about it though.
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It does NOT mean that a non-diabetic with an A1C of 5.0 to 5.6 is normal or healthy.
That is what the CDC website explicitly says - āA normal A1C level is below 5.7%ā
Never seen anywhere that says, āAll non-diabetics are supposed to have A1C 4.9 or less.ā
Thatās what I found interesting about the video that an HbA1c above 5 is possibly better than say 4 (from the perspective of ACM.). However, lower HbA1cs are probably linked to alcohol consumption to some extent.
In early 2022 I was binge drinking intermittently, but also had peaks of over 10 mmol/L in serum glucose. According to the CGM my peaks are now (then because it was some months ago) under 8 mmol/L, but I am still intermittently binge drinking.
What I should probably do is review the week before my measurement of 4.18% and see if there is an obvious cause.
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Higher alcohol intake was associated with lower HbA1c levels
Wow, if that explains it in the population, then maybe lower levels, like 4.8 (or even ~4.5) are ideal, not 5.
4.8 still does not mean hypoglycemia.
I almost never drink alcohol and my levels have consistently been 4.8-4.9 irrespective of diet (even though my glucose spikes heavily in response to carbs (and are thick), esp fruit, so mine could be lower)
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You may be right, but it is difficult to isolate the effect of alcohol.
what if your level is real low because you are non prediabetic and taking life extension drugs like sglt2 and acarbose?
How low is real low? Are you suffering the effects of hypoglycemia?
scta123
#50
Neither acarbose or SGLT2i have much potential for hypoglycemia.
Acarbose just slows the absorption of glucose, thus no postprandial spike and SLGT2 inhibitors start working at around 140 mg/dl and just flattens the spike above that level.
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no, just potentially (havenāt measured) lower than what would be optimal for some on all cause mortality
Good to hear. I want to ramp up on the acarbose too for possible life extension. It would seem a little precarious for a non prediabetic taking a high or solid dosage of both jardiance and acarbose. On the initial glucose readings though I didnāt notice any hypoglycemia taking jardiance 25 and acarbose 50 once a day (didnāt see hba1c yet)
If your blood sugar is too low, your body will tell you by giving you side effects such as nausea, dizziness, etcā¦ This is typically a sign of hypoglycemia. So, if these side effects manifest, then your blood sugar is too low.
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AnUser
#54
Iām trying to find studies how much oral melatonin affects CSF concentrations? I couldnāt find any.
Bicep
#55
Thank you for this information. I had not heard this at all. Are you saying the SGLT2 does nothing until blood sugar gets up to 140? So a guy on keto using it overnight and it does nothing? I really have trouble believing this. I thought it was draining 500 grams of glucose per day. Where did you get this ?
tananth
#56
That is not quite correct : SGLT2i will lower fasting BG, well below 140 mg/dl, though its effect is stronger when BG is above 140mg/dl. It is indeed unlikely to cause hypoglycemia unless you are also taking insulin (in which case you will need need to lower your basal insulin dosage to keep your fasting BG at your target level).
In fact, SGLT2iās are probably the only safe medication to lower fasting BG (the other medication, basal insulin, is more effective but comes with a serious risk of hypoglycemia due to accidentally injecting into a small vein, which happens about 1-2 times per year by accident). Bill Faloon, the president of Life Extension Foundation is a great advocate for non-diabetics using SGLT2iās to lower their fasting BG to youthful levels of 70-75 (along with lowering sodium levels to reduce hypertension). Association studies, similar to the one that started this thread, seem to show a J shaped curve with minimum ACM at fasting BG of 85 for those over age 60 : This could be misleading and caused by reverse causation so optimal levels of fasting BG may indeed be closer to youthful levels of 70-75 as suggested by Bill Faloon, or alternately, it is possible that aging brains need more BG for optimal functioning (for example, to avoid the risk of death from slip & fall due to slower reaction times).
More generally, targeting optimal fasting BG makes more sense than targeting optimal A1C : The risk of hypoglycemia and possible suboptimal brain function depends mainly on fasting BG (the lowest level of BG you are likely to encounter if NOT taking Insulin), and since A1C levels are directly proportional to the level of AGE formation, the lower the better, for a given value of fasting BG.
With fasting BG=70, the lowest achievable A1C = 4.1 (if you avoid all refined carbs and sugar, or load up on Acarbose and avoid all sugar), so your BG is 70 at all times. With fasting BG=85, the lowest achievable A1C = 4.6.
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scta123
#57
My husband who is a MD explained it to me. It is a simplified model, as @tananth describes the effect is more pronounced above this threshold. The action of SGLT2i is more complex and yes there is certain level of glucose excretion even below this level. Reabsorption of glucose happens via SGLT2 and SGLT2 and other mechanism. And taking SGLT2i (or combined SGLT1i) does not completely block SGLTs and approximation model is that renal threshold (180-200 mg/dl) is lowered 30-50% in dose dependent manner.
My question was whether it makes sense to take Acarbose and SLGT2i together for a non diabetic and the takeaway was that it would not make much sense for sugar control but since there might be other benefits I might take it for that.
Even diabetics drain just around 90 grams per day on average from what I remember. 500 grams would mean 2000 kcal daily deficit.
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J0hn
#58
Thatās what I 
love about this forum, I learn so much from it.
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One would assume it gets into the CSF via the choroid plexus. In any event the key is the question as to what concentrations of melatonin are good for brain cells be they getting there from the pineal injecting into the third ventricle or from blood serum.
What I can tell you is that they definitely get to the brain from serum as well as from the CSF. Whether that is mainly directly from serum or indirectly I cannot necessarily say, but I would make a stab at direct supply probably predominating (I thought previously it was indirect that was key, but that was a timing thing and the timing thing that matters is the ultradian cycle).
It is difficult to measure CSF levels and I would expect concentration of melatonin to vary depending upon where in the CSF (I would be surprised if it did not).
Hence I am not surprised that there are no studies.
However, it obviously is a mistake to be guided merely by serum levels when we know that the CSF concentration is multiples of serum. (particularly from experiments with sheep).
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I have not written for a long time, but have been reading the blog regularly. I am very impressed with the level of education, knowledge, intentions to share personal experiences and help others! I am also impressed with how well the RapAdmin manages the forum and how many great new members joined during last couple of years.
I have learned an interesting, but disturbing new information from 23&me through Dr.Rhonda Patrickās genetic program. I have a variant rs12506228A, which is situated close to melatonin receptor type 1A gene (MTNR1A). This genotype is associated with an increased risk for late-onset Alzheimerās disease (usually older than 85) and intolerance to shift work. (Talking about shift work, I was on call every third night during my neurology residency and survived and even functioned reasonably well!).
melatonin is decreased in CSF of patients with Alzheimerās disease, especially in patients with more severe forms. Most studies on using melatonin in animal models or in people with Alzheimerās disease used only small doses and results were negative.
Theoretically a high dose of melatonin may help to prevent Alzheimerās disease in patients with this genetic variant, but I canāt find any supporting information.
Hope smart people on the forum have some ideas!
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