I would not deny that there are benefits in having lower iron levels with ferritin on an uninflamed basis below 100. However, it is more complex below that and particularly below 75 and it may require a form of cycling.
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Noted John.
As I’ve said before I think I have an iron absorption problem (maybe allied to gluten sensitivity, based on SNPs I have).
That said, my HsCRP remains low so not too concerned
I don’t think we really know exactly where things should lie. It is obvious that there is a point at which it is too low and a point at which it is too high. The level for brain iron looks to be higher than that for anemia. Questions that are hard to answer are the speed to which the reduction in brain levels occurs. Hence you could have a sufficiency in the brain and take ferritin below the maintenance level, but it will take a while before that will affect the brain negatively.
I can understand neurologists wanting higher ferritin, but probably this should guide GPs as well.
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For purely iron-related discussions, I recommend we continue in one of those threads:
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The Role of Glucagon in the Acute Therapeutic Effects of SGLT2 Inhibition
And then there is this freaky paper:
Uncoupling Insulin Sensitivity From Longevity: A Sex-Dependent Effect of Hepatic Glucagon Signaling
https://onlinelibrary.wiley.com/doi/10.1111/acel.70349
“ Glucagon, a key hormone in maintaining euglycemia during fasting, also exerts broad metabolic effects, including regulation of lipid oxidation, adiposity, insulin sensitivity, and metabolic rate. However, its role in aging and longevity remains largely unexplored, a significant omission given the extensive research on dietary restriction and insulin signaling in lifespan modulation. Here, we investigated the impact of hepatic glucagon receptor (GCGR) signaling on lifespan using a liver-specific GCGR knockout (LKO) mouse model. While male LKO mice exhibited normal lifespan, female LKO mice displayed a significant reduction in survival. Strikingly, and in contrast to prevailing expectations based on metabolic improvements, this shortened lifespan in females occurred despite marked enhancements in metabolic health, including reduced body weight and adiposity, preferential glucose oxidation, elevated metabolic rate, and enhanced glucose tolerance and insulin sensitivity throughout adulthood.”
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In patients with type 2 diabetes (T2D) treated with ICDs, the arrhythmic effect of empagliflozin appears more pronounced in men than in women, according to a subanalysis of the EMPA-ICD trial published Jan. 22 in JACC: Asia.
The randomized, double-blind EMPA-ICD study evaluated 150 patients across 31 centers in Japan. The study included men and women aged ≥20 years with T2D and cardiovascular disease who were being treated with an ICD or cardiac resynchronization therapy defibrillator (CRT-D). The patients (83% men) were randomized 1:1 to receive either empagliflozin 10 mg daily or placebo between April 2019 and April 2021. Patients were evaluated for adverse events and clinical status every three months.
The primary endpoint, detected by ICDs/CRT-D over 24 weeks, was the change in the number of ventricular arrhythmias (VA), including nonsustained ventricular tachycardia, as well as sustained ventricular tachycardia and ventricular fibrillation.
Looking at the primary outcome in men, there was a significant reduction in the number of VA events in the treatment group while they increased in the placebo group (–2.10 events vs. +2.25 events; p<0.001). In contrast, in women there was a slight increase in VAs in the empagliflozin group while there was a slight decrease in placebo group (+0.55 vs. –0.08 events; p=0.35). This translated to a rate ratio in men of 0.33 for empagliflozin vs. placebo (p<0.001), a 67% reduction in arrhythmia events. In women, there was no significant difference between groups, with a rate ratio of 1.78 (p=0.35). Moreover, a significant interaction between sex and treatment was observed, suggesting a sex-specific treatment response (p=0.006).
Miyo Nakano, MD, et al., note several limitations to their analysis, including the small number of female participants, the short follow-up period and the lack of diversity within the patient population. Despite limitations, they write “these results suggest that sex-related differences in arrhythmic substrate, comorbidities and pharmacokinetic properties of SGLT2 inhibitors may influence treatment response.” Furthermore, research is needed to understand these sex-differences in treatment and pharmacokinetics to develop appropriate treatment strategies in women.
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Zydus Lifesciences announced tentative approval from the US FDA for its Dapagliflozin Tablets (5mg and 10mg). This SGLT2 inhibitor, used for type 2 diabetes, targets a significant US market segment where the reference drug (Farxiga) reported annual sales of USD 10,486.9 million. The approval signifies Zydus’s expanding product portfolio in the crucial US market and adds to its 430 US FDA approvals. Zydus Lifesciences Secures Tentative USFDA Approval for Key Diabetes Drug
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Among study subjects, 1563 (7.8%) experienced recurrent cerebrovascular events. SGLT2 inhibitor users showed lower recurrence of cerebral infarction compared to metformin users (adjusted hazard ratio=0.84, p=0.010). Among the types of cerebrovascular diseases, ischemic stroke was associated with a significantly lower risk of recurrence in SGLT2 inhibitor users than metformin users (aHR=0.70, p=0.020). In the SGLT2 inhibitor group, concurrent use of DPP4 inhibitors was associated with a reduced risk of cerebrovascular event recurrence (aHR=0.69, p=0.011).
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