Diabetes

[Jhanananda]

FMD Promotes a Gene Expression Profile in Adult Mice Similar to that Observed during Embryonic and Fetal Development

To identify the genes that may mediate the FMD-induced pancreatic regeneration, we measured gene expression in pancreatic islets at the end of the FMD and post-FMD re-feeding. At both time points, we observed a transient upregulation of Foxo1 (6.9-fold at FMD, 5.3-fold at RF1d, ∗p < 0.05 comparing to AL) and of a set of genes that have been previously identified as dual regulators for both fat metabolism and fate determination in mammalian cells (Cook et al., 2015, Haeusler et al., 2014, Johnson et al., 2004, Kim-Muller et al., 2014, Mu et al., 2006, Stanger, 2008, Talchai et al., 2012, Talchai and Accili, 2015, Tonne et al., 2013) (Figure 4A), in agreement with the metabolic changes found in mice receiving the FMD (Figure S1). We further examined whether the metabolic reprogramming caused by the FMD affects lineage determination in pancreatic islets. In Figure 4B, the expression of lineage markers was determined by the mRNA expression of purified islets from mice fed ad libitum (AL) or the FMD. Results from the qPCR array indicate that upregulation of the following genes was statistically significant (∗p < 0.05 comparing to AL, Figure 4B; see also Figure S5): (1) pluripotency markers (e.g., Lefty1, 3.0-fold during FMD, 7.0-fold at RF1d; Podx1, 3.9-fold during FMD, 9.8-fold at RF1d; Nanog, 2.6-fold during FMD and 5.4-fold RF1d, and Dnmt3b, 31.6-fold during FMD and 18.3-fold RF1d), (2) embryonic development markers (e.g., Sox17, 3.4-fold during FMD and Gata6 3.1-fold during FMD and 2.7-fold at RF1d), (3) pancreatic fetal-stage markers, and (4) β-cell reprogramming markers (e.g., Mafa, 4.7-fold at RF1d; Pdx-1 3-fold during FMD, 5.07-fold at RF1d; and Ngn3, 21.5-fold during FMD, 45.6-fold at RF1d) (Figure 4B; Zhou et al., 2008). These changes in gene expression suggest that the FMD causes either: (1) a de-differentiation of pancreatic cells toward pluripotency at the end of the diet followed by re-differentiation to pancreatic β-cell lineage during early re-feeding (RF1d) or (2) recruitment of cells with these features from outside of the pancreatic islets. The assessment of protein expression of cells within the islets was also carried out by immunostaining for key proteins associated with pancreatic development (Figures 4C and 4D). In agreement with the results of qPCR array (Figure 4B), we found that protein levels of Sox17, as the early lineage marker, were elevated at the end of the FMD (FMD-4d) and protein levels of Ngn3, a marker for endocrine progenitors, were transiently upregulated during early re-feeding (FMD-4d to RF1d) (Figure 4C).

To determine whether stepwise β-cell conversion from the dedifferentiated cells occurs during early refeeding, we performed double-staining for the targeted developmental markers (i.e., Sox17, Pdx-1, Ngn3) across the time points of FMD treatment. We also measured the expression of Oct4 (Pou5f1), which has been previously reported to be expressed in the nucleus of adult pancreatic islets in association with Foxo-1-related diabetic β-cell dedifferentiation (Talchai et al., 2012, Xiao et al., 2013). Oct4 (Pou5f1) mRNA expression showed a trend for an increase in mice on the FMD, which is not significant (Figure 4C, p > 0.05). Results of immunostaining indicate that Oct4 (Pou5f1) and Sox17 may only be co-expressed very transiently after overnight re-feeding (Figure S5B, RF12hr) followed by robust expansion of Sox17+Pdx1+ and then Pdx1+Ngn3+ cells at RF1d (Figure 4D and see also Figure S5B for all time points). Although Ngn3+ cells were also detectable in AL mice, they were mainly located outside or on the edge of the islets, in agreement with what was reported in previous studies (Baeyens et al., 2014, Gomez et al., 2015; Figure 4D). The number of Ngn3+ cells was increased both inside and outside of the islets during the FMD and re-feeding (Figure 4D).

These results suggest that, as a result of the FMD and re-feeding cycle, the pancreatic islets contain an elevated number of cells with features of progenitor cells, which may differentiate and generate insulin-producing cells.

FMD Induces Ngn3 Expression to Generate Insulin-Producing β Cells

Ngn3+ cells within the pancreatic islets have been previously described as progenitor cells able to generate all lineages of endocrine cells, including the insulin-producing β cells, although the role of Ngn3 in adult β-cell regeneration remains unclear (Baeyens et al., 2014, Van de Casteele et al., 2013, Xu et al., 2008). To investigate whether the FMD causes de novo expression of Ngn3 and whether Ngn3+ cells may contribute to FMD-induced β-cell regeneration, we generated Ngn3-CreER;tdTomatoLSL-reporter mice to trace the lineage of putative Ngn3-expressing cells and their progeny in the adult mice treated with the FMD (Figure 5A). To initiate the loxP recombination for lineage tracing, low-dose tamoxifen injections (2 mg per day for 3 days) inducing the recombination (maximized at 48 hr and minimized within a week) were given to mice before or after the FMD and to mice fed ad libitum (AL control) (Figure 5A). Tissue collection time points are relative to the time of injection and to that of FMD treatments (Figure 5A). Results indicate that the FMD induces the expansion of the Ngn3-derived lineages (Figure 5B and 5C). Characterization of tdTomato+ cells by immunostaining indicates that tdTomato+ cells contributed 50.8% ± 8.3% of the overall β-cell pool following the FMD (Figure 5C, group C).

To confirm the contribution of FMD-induced Ngn3 lineages in reconstituting insulin-secreting β cells, we generated another mouse model (Ngn3-CreER/LSL-R26RDTA) and performed lineage-ablation experiments in both wild-type non-diabetic mice and STZ-treated mice (Figure 5D). The results indicate that ablation of Ngn3+ lineage reverses FMD-induced β-cell regeneration and its effects on fasting glucose levels (Figures 5E and 5F and S5) and glucose clearance capacities (IPGTT assay) in STZ-treated diabetic mice (Figure 5G), confirming that the FMD-induced β-cell regeneration is Ngn3 dependent and suggesting a critical role for this in glucose homeostasis.

Fasting Conditions or Inhibition of Nutrient-Signaling Pathways Promote Ngn3 Expression and Insulin Production in Human Pancreatic Cells

In both mouse and humans, Ngn3 expression occurs right before and during endocrine cell generation. Ngn3 mRNA expression in the developing mouse pancreas peaks around E15.5, which is roughly equivalent to week 7–8 (Carnegie stages 21–22) in human development. Expression of Ngn3 in adult mouse islets, although rare, has been demonstrated by rigorous lineage reporter analysis (Wang et al., 2009). In agreement with results from others, our data (Figures 5 and S5) indicate that Ngn3+ cells in adult pancreas islets are important for β-cell regeneration in mice. On the other hand, the role of Ngn3 in human islet development and β-cell regeneration in adulthood remains poorly understood (McKnight et al., 2010).

To investigate how the fasting mimicking conditions affect Ngn3 expression and β-cell function in human pancreatic cells, we performed ex vivo experiments using primary human pancreatic islets (Figure 6A). Briefly, the pancreatic islets from healthy and T1D subjects (HI and T1DI, respectively) were cultured according to the manufacturer’s instructions. The cultured islets were then treated with serum from subjects enrolled in a clinical trial testing the effects of a low-protein and low-calorie FMD lasting 5 days (NCT02158897). Serum samples were collected at baseline and at day 5 of the fasting mimicking diet in five subjects. We then measured IGF-1, glucose, and ketone bodies and treated human pancreatic islets with the subject-derived serum (Figure 6B and Table S1). In both healthy islets and T1D islets exposed to the serum of FMD-treated subjects, we observed a trend for glucose-dependent induction in the expression of Sox2 and Ngn3 (Figure S6A).

We then applied the low-glucose and low-serum fasting mimicking medium (STS) to the cultured pancreatic islets and found that it significantly stimulated the secretion of insulin in both HI and T1DI (Figure 6C). We further investigated the expression of lineage-reprogramming markers, which we found to be upregulated in mice as a result of the FMD-treatment (i.e., Nanog, Sox17, Sox2, Ngn3, and Ins). The results indicate that the fasting mimicking conditions had strong effects in inducing the expression of Sox2, Ngn3, and insulin in human pancreatic islets from healthy (healthy islets, HI) and T1D subjects (T1D islets, T1DI) (Figures 6D–6F). In cells from normal human subjects, these effects were reversed by IGF-1 treatment (Figure 6G). Notably, in human T1D cells, IGF-1 reversed the increased insulin and Sox 2 gene expression, but not that of Ngn3 expression caused by the STS medium (Figure 6G versus Figures 6D and 6E). Future studies are warranted to further investigate the role of circulating IGF-1 in the expression of lineage-reprogramming markers and pancreatic islet cells regeneration in vivo.

In both healthy and T1D human islets, STS medium significantly reduced the activity of PKA, an effect reversed by IGF-1 treatment (Figure 6H). It also dampened the activity of mTOR, which is a key mediator of amino acid signaling (Figure 6I). To further investigate the role of these nutrient-sensing signaling pathways in regulating the expression of lineage markers (i.e., Sox2 and Ngn3), we tested the role of the mTOR-S6K and PKA pathways, which function downstream of IGF-1, in the reprogramming of pancreatic cells. Human pancreatic islets cultured in standard medium were treated with rapamycin, which inhibits mTOR, and H89, which inhibits PKA. mTOR and PKA were implicated by our group and others in the regeneration of other cell types (Cheng et al., 2014, Yilmaz et al., 2012). We found that, in human islets from T1D subjects (T1DI), expression of the essential lineage markers Sox2 and Ngn3 was not induced by inhibition of either mTOR or PKA but was significantly induced when both mTOR and PKA were inhibited (Figures 6J and 6K). Interestingly, the constitutive mTOR, but not PKA, activity is trending higher in HI compared to T1D1 cells (Figure 6I, lane 1 for both sets for mTOR activity and Figure 6H for PKA activity), which may explain the overall differences between HI and T1DI in Sox2 and Ngn3 expression shown in Figure 6J. Taken together, these results indicate that fasting cycles may be effective in promoting lineage reprogramming and insulin generation in pancreatic islet cells, in part by reducing IGF-1 and inhibiting both mTOR and PKA signaling. Pancreatic cells from T1D subjects displayed constitutively elevated activity of mTOR-S6K and PKA, which points to the potential for inhibitors of both pathways in the induction of Ngn3-mediated lineage reprogramming. These results raise the possibility that the effect of the FMD on pancreatic regeneration in T1D subjects could be mimicked or enhanced by pharmacological inhibition of these pathways.

Discussion

During mouse development, at embryonic day E8.5, pancreatic progenitor cells co-express the SRY-related HMG-box transcription factor Sox17 and the homeodomain transcription factor Pdx1. These multipotent pancreatic progenitors are then converted into bipotent epithelial cells that generate duct cells or a transient population of endocrine precursor cells expressing the bHLH factor Neurogenin3 (Ngn3). Ngn3+ endocrine precursors give rise to all of the principal islet endocrine cells, including glucagon+ α cells and insulin+ β cells (Arnes et al., 2012). In mice, expression of Ngn3 in the developing pancreas is transient, detectable between E11.5 and E18 (Arnes et al., 2012). Whether developmental genes, including Sox17, Pdx-1, and Ngn3, could be activated to generate functional β cells in adults was previously unknown.

Both cell-based therapy and the use of cytokines and hormones that stimulate β-cell self-replication have the potential to restore insulin-producing β cells in diabetic patients (Dirice et al., 2014). However, despite some success with transplantation-based therapy, the short supply of donor pancreata plus the inefficient conversion of stem cells into specialized derivatives have represented obstacles for clinical application, suggesting that a successful β-cell regeneration might depend on the coordinated activation and re-programming of endogenous progenitors (Blum et al., 2014, Sneddon et al., 2012, Wang et al., 2009, Xiao et al., 2013). Recently, this in vivo lineage reprogramming or trans-differentiation has become an emerging strategy to regenerate β cells (Cohen and Melton, 2011, Heinrich et al., 2015, Abad et al., 2013, Xu et al., 2015).

In this study, we discovered that a low-protein and low-sugar fasting mimicking diet (FMD) causes a temporary reduction in β-cell number followed by its return to normal levels after re-feeding, suggesting an in vivo lineage reprogramming. We show that the severe hyperglycemia and insulinemia in both the late-stage Leprdb/db T2 and the STZ-treated T1 mouse diabetes models were associated with severe β-cell deficiency in pancreatic islets. Six to eight cycles of the FMD and re-feeding were required to restore the β-cell mass and insulin secretion function and to return the 6-hr-fasting blood glucose to nearly normal levels. In non-diabetic wild-type mice, the portion of β cells per islet, as well as the total number of β cells per pancreas, were reduced at the end of a 4-day FMD, but their normal level was completely restored within 3–5 days post re-feeding. Also, insulin and blood glucose levels were reduced by 70% or more at the end of the FMD period but returned to normal levels within 24–36 hr of re-feeding. Interestingly, in diabetic mice, the majority of cells residing in the islets expressed neither insulin nor glucagon (i.e., non-α/β). This phenotype was also found in non-diabetic wild-type mice during the FMD and was accompanied by an increase of other transitional cell types (i.e., Pdx1+Glucagon+ cells and Insulin+glucagon+) followed by significant β-cell regeneration upon re-feeding. This suggests that the FMD alters the gene expression profile that normally suppresses the generation of β cells. More importantly, these results suggest that dietary-induced lineage conversion occurring prior to the β-cell proliferation may play an important role in β-cell regeneration across the diabetic and non-diabetic mouse models. One possibility is that glucagon and insulin expression are transiently suppressed in α and β cells during the FMD, followed by lineage reprograming in committed cells. Another possibility is that the FMD may cause cell death and then stimulate progenitor or other cells to regenerate β cells.

The FMD reversed the dedifferentiated expression profile for a number of genes associated with maturity-onset diabetes of the young (MODY) and regulated by Foxo1 (Kim-Muller et al., 2014). The FMD appears to cause pancreatic islets to first increase the expression of Foxo1 and its transcriptional targets, then induce transitionally the expression of the progenitor cell marker Ngn3+ upon re-feeding, leading to β-cell regeneration. We conclude that, together with the changes in a wide range of cytokines associated with β-cell regeneration, FMD and post-FMD re-feeding generate the complex and highly coordinated conditions that promote the generation of stable insulin-producing β-cells to reverse severe β-cell depletion. The key changes priming pancreatic islet cells for regeneration during the FMD appear to be the reduction of IGF-1 levels and the consequent downregulation of PKA and mTor activity, in agreement with the role for these pathways in hematopoietic (Cheng et al., 2014) and intestinal stem-cell self-renewal (Yilmaz et al., 2012). It was proposed that transient de-differentiation of β cells may play a role in their in vivo dynamics (Kim-Muller et al., 2014, Weinberg et al., 2007). The capacity of these de-differentiated cells to re-differentiate fundamentally changes the therapeutic potential of existing cells in promoting β-cell regeneration and reversing T1D symptoms (Blum et al., 2014, Wang et al., 2014). Thus, our study provides an example of a potent and coordinated dietary regulation of cell-fate determination with the potential to serve as a therapeutic intervention to treat diabetes and other degenerative diseases. Our preliminary results from a pilot clinical trial also indicate that the use of periodic cycles of a prolonged FMD is feasible and ready to be tested in large randomized clinical trials for effects on both insulin resistance and pancreatic β-cell regeneration for the treatment of both T1D and T2D.

[Jhanananda]

What I get from the above research report is regular fasting is good for people, especially diabetics.  So, I plan to start water fasting for 24 hours once a week to see if it helps bring down my daily blood sugar levels.

[Jhanananda]

I fasted for 36 hours and only saw my blood sugar continuing to rise.  So, while fasting might work for some diabetics, it does not seem to work for me.

[Jhanananda]

I have been exploring antihistamines, and I have successfully brought my blood sugar down to normal levels by using both benedryl, and certazine.  I am now getting 2 normal blood sugar readings each day out of 3 readings; and it is peak allergy season here, where it is the worst city in the nation for allergies and pollen.

A Brand New Type of Insulin-Producing Cell Has Been Discovered Hiding in the Pancreas

According to Huising, there are three main reasons to get excited about the result: firstly, it represents a new beta cell population in both humans and mice that we had no idea about before, and secondly, it also provides a potential new source of beta cells that could be used to treat diabetics.

"Finally, understanding how these cells mature into functioning beta cells could help in developing stem cell therapies for diabetes," a press release explains.

The research could also have benefits for type 2 diabetes, which occurs when beta cells become inactive and stop releasing or secreting insulin.

[Frederick]

Wow! Great find.

I'm so happy to hear this both from your health point of view and in the interest of science.

[bodhimind]

I'm finally studying about diabetes in my course, and this statement is not very accurate: "The research could also have benefits for type 2 diabetes, which occurs when beta cells become inactive and stop releasing or secreting insulin."

Type 2 diabetes (adult-onset) is mainly because of the unresponsiveness of cells to insulin, therefore any secretion of insulin will have a dampened response. Also, it can be accompanied with a decrease of insulin production, but not in everyone.

The main thing to worry about is hyperlipidemia, where too much fats and bad cholesterol can lead to atherosclerosis, arteriosclerosis or arteriolosclerosis. Therefore cardiovascular disease is a HUGE risk increase in diabetes mellitus. As a side measure because nearly 80% of diabetic patients die from CVD, perhaps Jhanananda can make sure to take foods with HDL (high density lipoprotein or good cholesterol) content as compared to LDL.

Also the complications of diabetes such retinopathy, nephropathy, neuropathy, etc. Normally these happen from high blood sugar causing damage of the vessels in these areas.

Very glad to hear that your blood sugar level is down from the use of antihistamines. I would just add on, to avoid antihistamines with steroids in them, because they stimulate the liver to send more glucose into the bloodstream.

Benadryl causes drowsiness/sleepiness, so perhaps the lack of inflammatory response decreases the need for the body to release sugar for energy. But just a caution in the case that it falls into hypoglycemic emergency.

[Jhanananda]

Thanks, bodhimind and Frederick for your kind comments.  I just had a difference of opinion with a medical dr. who told me that my findings are just a coincidence.  Oddly, the coincidence of consistently higher blood sugar during allergy season for the last 7 years; whereas, during this allergy season, which has been said to be record high, my blood sugar has been consistently lower than it has ever been during the allergy seasons of the last 7 years, is something that he cannot believe.  Oh, well.  What is knew about me coming into conflict with authority figures?

bodhimind, thanks for your comments.  I am well aware of the side effects of diabetes, and I have avoided most of them through living on an ultra-low carb diet, and now taking antihistamines.

[Frederick]

According to this article, anti-histamines affect blood sugar indirectly by affecting cortisol:

http://www.diabetesforums.com/forum/topic/49176-can-allergies-raise-glucose-level/

[Jhanananda]

Thanks, Frederick, for digging up this thread on a diabetes forum.  It certainly supports my findings.  I have noticed for over a year now that my blood sugar tends to be lower outside of Prescott, AZ.  So, I plan to at least spend a few months away from Prescott as soon as I get a more reliable vehicle running, to test this hypothesis.

Here are more links on this subject:

Allergies and blood glucose?

Seasonal Allergies May Irritate Your Blood Sugars

There’s not much research available on this topic, so we took our question to the community and posted a poll on Facebook: Do seasonal allergies affect your blood sugars?
 
A quarter of those who responded said seasonal allergies raise their blood sugars, one per cent said they lower their blood sugars, 43 per cent said their allergies have no impact and 31 per cent said they don’t have season allergies.

[Jhanananda]

http://www.diabetesforums.com/forum/topic/49176-can-allergies-raise-glucose-level/
Oh holy heck yes

Part of the body's natural allergic response is to produce cortisol (which is a steroid). The intent in the body is to reduce inflamation, but it has the unfortunate effect of causing elevated BG.. the effect varies. The last time I dealt with this I was having scary high numbers.

Antihistamines don't treat the symptoms, they actually do help to reduce the response. My CDE recently turned me on to using flonase to reduce my nasal symptoms, which seems to be the source of the typical seasonal allergy cascade for me.. I was skeptical about adding a steroid into the mix, but since it's localized it does seem to help without a huge impact on my BG. If I am having more systemic allergy issues, nothing really helps... I have to bump up the insulin a LOT.

Cortisol is produced by your adrenal glands. They are little endocrine glands that look like dunce caps sitting upon your kidneys. Cortisol is a hormone that is required for life. It is also a fight or flight hormone (ie stress).
Cortisol does not suppress your immune system, it is Cortisone which is a glucocorticoid steroid that will supress your immune system (along with solumedrol, depomedrol, prednisone, ect).
With extra cortisol coursing throughout your body, your body is either under going stress, or some kind of fight/flight reaction and therefore more cortisol pumped out of your adrenals, the higher your sugars are going to go, and the more insulin resistant you will become (ie in response to allergies/allergic reactions).

I suspect that the 1% who notice that their blood sugar goes down during allergy season are most likely taking antihistamines.

The allergy causes diabetes argument resorts to the rising cortisol argument.  And, it turns out that my bone and joint pain is also down.  Here, the argument might be the same argument for 25% of the diabetic population, which is no small percentage.

Further using this argument to explain my observations, suggests that cortisol is being triggered by allergies, which raises blood sugar to combat the invasion of allergens, which requires the body to generate sugar for the energy to combat the invasion of allergens, which explains why type II diabetics have plenty of insulin, but it does not bring the blood sugar down.  Thus, using antihistamines to combat the allergens, gives the body a break on sugar production from glucogon. 

Further, the reason why I have bone and joint pain, is the body stores surplus glucogon in the bones, so when the body is extracting glucogon from the bones produces bone and joint pain. 

I found taking 10mg of clariton in the morning plus 25mg of benedryl, plus 10mg of certirizine plus 25mg of benedryl before bed, works for me to normalize my blood sugar.  Some other suite of antihistamines might work better for others.

Antihistamines: singular, Zyrtec (Certirizine HCl), Claritin (Loratadine HCl), benadryl (diphenhydromine HCl), Azestilin (Azestiline HCL..nasel spray), Optivar (Azestline HCL.. eye drops) plus prednisone; and possibly an anti-inflammatory.

Allergens: dust, dust mites, mold, mildew, pollens, cat dander, cat saliva, bird feathers, raspberries, strawberries, coconut, coconut oils, walnuts, dairy, eggs.

[Jhanananda]

My morning blood sugar is highest.  It is known as the Dawn Effect.  Now realizing that my high blood sugar seems to be the effect of allergies, and knowing that plants produce their pollen at night, then it is very possible that the Dawn Effect is due to night pollen production.

Why Is My Blood Sugar High in the Morning?

Do you take insulin for diabetes and have high blood sugar levels in the morning? It happens to a lot of people, and there are solutions -- once you know why it’s happening.

Doctors have narrowed down the reasons for this to two different causes.

The dawn phenomenon. This is the result of several natural body changes that happen while you’re asleep. Between 3 a.m. and 8 a.m., your body starts to ramp up the amounts of certain hormones that work against insulin's action to drop blood sugar levels. They enter your system just as your bedtime insulin is wearing out and sugar levels rise.

The Somogyi effect. Named after the doctor who first wrote about it, doctors also call this "rebound hyperglycemia." The term refers to pattern of your blood sugar being high in the morning, after having been low (hypoglycemia). Usually there are no symptoms, but night sweats can be a sign.

Your blood sugar may drop too low in the middle of the night. In response, your body releases hormones to raise it. This could happen if you took too much insulin earlier or if you didn’t have enough of a bedtime snack.

To learn the reason for your high morning blood sugar, your doctor will likely ask you to check your levels between 2 a.m. and 3 a.m. for a few nights in a row.

If it’s consistently low during this time, the Somogyi effect is probably the cause. If it’s normal or high during this time period, the dawn phenomenon is more likely the reason.
How Do I Treat It?

Once you and your doctor figure out how your blood sugar levels behave overnight, she may suggest changes like these:

    Change the type of insulin so it doesn’t peak at the wrong time or in the middle of the night.

    Take extra insulin overnight if your blood sugar goes up during the evening.

    Switch to an insulin pump, which can be programmed to the release the amount of insulin you need during the problem time periods.

Or, try taking anti-histamines before bed to see if your body is reacting to night time pollen production.

[rougeleader115]

This all sounds like a very reasonable argument. It makes sense the body using energy and inflaming in relation to allergens thus causing an increase in glucose production. I feel more stable physically and less ill in general since i began taking an almost daily dose of 25-100mg of dephinhydramine last spring for nausea. It is very possible my body reacts more deeply to allergens than i have been aware of. Very informative thanks!

Rougeleader

[Jhanananda]

Thanks, rougeleader115, for your contribution.  Yes, I am developing an hypothesis that allergies are far more influential in our life than most of us had here-to-for understood.

[Jhanananda]

So, here is an update:

I was diagnosed type 2 diabetic 6 months after arriving in Prescott, AZ, 7 years ago. I had had a physical in Tucson exactly 1 year earlier. Then the physician said that I had the cardio-vascular system of an athlete, and there were no problems to report. I happen to be a field archaeologist by profession, which is very physically demanding, and requires top fitness.

OK, so 7 years ago, after a bout of seasonal allergies, my Prescott physician reported to me, "You are full-on diabetic, with a blood sugar of 250 (150 over normal), you have high blood pressure, and you have very high cholesteral."

So, what changed in a year? I moved to Prescott.  I left his office severely depressed, went to the pharmacy to get the blood glucose test meter and blood glucose test strips.  I tested my blood sugar every morning, and found it normal every morning for a week, so I determined that the lab must have mixed up my sample with someone else’.  However, I had gained 50 pounds in my first 6 months here, which was unusual.

Six months later during another severe bout of seasonal allergies, I went back to my Prescott physician. 

He asked me, “Have you been testing your blood sugar?”

I said, “No,” and explained why.

He sent me back to the lab for another blood test.  It came back 150 over normal, the same as it was 6 months earlier.

I must also point out that since arriving in Prescott I had been dealing with sever joint and bone pain as well, which was not new, but episodic, and back again.

So, since then I have been doing a great deal of research on diabetes, to understand why I am the only member of my family that has it.  I have also scrutinized my health and environment rigorously.  There is clearly something about Prescott that causes my blood sugars to rise significantly.  I have since come to realize that my diabetes is due to allergies, and all I need to do to control my diabetes is to treat my allergies with antihistamines.

I recently told a doctor about my finding above, and he threw me out of his office, and on my way out I heard him tell his nurse not to treatment.

So, I happened to tell a friend of mine here about my findings. 

He said, “It sounds weird, but my sister is an expert in diabetes treatment, and she works for a pharmaceutical company as a consultant in diabetes for them.

He came back to me a few days later and said, “My sister said, ‘Sure, blood sugar can be effected by any stress, and since allergies are a stress on the body, then there is no reason why your friend would not have the results that he has found.’”

Since then my joint and bone pain is down, and I have lost 50lbs.

So, the conclusion is, we should not consider all doctors are experts in all fields of medicine; and we need to become our own advocates, and experts regarding our health; and, if we can develop a means of closely monitoring our health, fitness, and environment, then we may find improved health.

[bodhimind]

I remember an immunologist saying that food allergies have increased over 50 percent over just 5 years. Hygiene hypothesis says that we grew up with lack of exposure to third-party agents like infectious diseases or allergens and this probably makes our immune system oversensitive due to the lack of 'reference points'. For example, the immune system can 'prime' itself against viruses due to weak attacks from vaccines (dead/attenuated viruses). Bacteria, on the other hand, develop resistances very quickly and there's no way to actually 'prime' completely against it, so we use antibiotics.

If we understand that our body is mostly made out of flora, all over the skin and inner linings of our digestive system, then the use of antibiotics can significantly alter the composition of them. I would even say that the warming global climate pays a huge difference to the composition of gut flora.

Given that allergies are classified as a Type I hypersensitive reaction, alongside Type II (autoimmune), Type III (like rheumatoid arthritis), etc... It's all highly associated with the immune system's responding with inflammatory responses.

Perhaps we have an over-sensitive defense system. What was considered normal in the past, such as exposure to pollen or various other allergens like the big 8 food allergens (Milk, eggs, peanuts, tree nuts, soy, wheat, fish and shellfish), is probably toxic to the normal human. It is just that in some compromise of the bodily system, such as breakdown of pancreatic cells or loss of insulin response, the body becomes less able to cope. It could also explain why obesity is highly linked to type 2 diabetes as well.

Curiously, now Alzheimer's disease is also called Type 3 diabetes, which claims there is a huge link between diet itself and neurodegenerative diseases. I wonder if it has to do with hypersensitivity as well.