BuddyLeesWife

I can't comment on the ANS symptoms but I can tell you that I experienced hot flashes and confusion or what I think brain-fog must be with my injections. When I took the injections, they were to put your body into a "false menopause". So, if it works, you will get the hot flashes which to me was annoying but tolerable. I remember telling the Dr. that the most discomforting side effect was that I could not concentrate or pay attention to things. I told him that I felt like a dog, just minding my own business until I heard my name called and then I would snap to attention. He said "welcome to menopause, the Lupron is working" and that it is the number one complaint he hears from women. Good news is that my mind cleared once the injections were stopped. Hopefully you won't have any problems or maybe your dose is lower (I don't recall mine).

I suffered from severe periods and anemia for years due to fibroids. They tried every kind of medication/hormone, D&C, laproscopy, etc but mine just kept growing and causing problems. In 1996, I had a Myomectomy to remove the fibroids and rebuild the uterus. It is actually a more difficult surgery than a hysterectomy but it would hopefully preserve fertility. I felt good for a few years following the surgery and my periods while still heavier than most returned to a normal cycle. I don't remember the percentages, I was one of the group that grew new fibroids and in 2000 I was back and even worse than before (my last period was 90 days and they were unable to stop it with even double injections of Lupron). Back then, Lupron was just used as a temporary measure to both shrink the fibroids and stop the period to build up the blood supply before surgery. Once stopped, the periods would return. I didn't like the Lupron and my body stopped responding to it. There were other treatment options for fibroids back then and I am sure there are newer procedures available but you need to research them. Treatment options depend on the type, size and location of the fibroids. I had a hysterectomy in 2001 and it has been wonderful. Fertility was no longer an issue and I had struggled for 9 years. With the Myomectomy, recovery was I believe 3 days in the hospital and 8 weeks off work (in actuality, I was back at work after 4 weeks). With my hysterectomy, I was supposed to go home the same day (kept overnight only because the surgery was delayed in the day) and I was back to work and feeling great in about 5 days. I kept my ovaries and so far they must be working because I am 46 and still feeling fine. I had what is called a LAVH (laproscopic assisted vaginal hysterectomy) - just my uterus was removed, both ovaries were healthy so I choose to keep them and I also choose to keep my cervix. The surgery was done with three small cuts, not the bikini line cut that I had with the Myomectomy. I just wanted to write this so that you know there are options out there but it really is up to you to find a specialist and research them. Otherwise they will just recommend hysterectomy but even with that there are options availalbe. Also, the anemia made me feel awful and I don't suffer from ANS issues so I can just imagine what it would be like on top of that. Hopefully you will find something to get rid of the and get your energy back.

Rite-Aid has some sort of dispute with the manufacturer of Cerefolin so they no longer carry the product. It took months before we learned the real reason they weren't able to complete our refill. Our insurance uses MEDCO mail order and we were able to obtain it there.

Just as I thought something that seemed to be helping was safe, a new study warning of folic acid supplements. Also, our new neurologist cautioned that my husband not exceed 50mg of B6 per day as it can cause nerve damage (1 tablet of Cerefolin has 50mg of B6). For now he is going to continue to take it as we still believe it is helping. High Folate Intake Associated With More Rapid Cognitive Decline in Elderly http://www.medscape.com/viewarticle/502855?src=search By Amy Norton NEW YORK (Reuters Health) Apr 11 - Older adults with high intakes of the B vitamin folate may have a faster rate of mental decline than others their age, researchers report in the April issue of the Archives of Neurology. The finding is unexpected, and it's not completely clear that folate per se caused the cognitive deterioration seen in some study participants, according to the investigators. However, the study's lead author told Reuters Health, the results do suggest that older men and women should "use caution" in taking folic acid supplements.

My husband had to switch from Zoloft to Effexor XR and he also took a reduced dosage of Zoloft while increasing the Effexor. He really didn't have any problems with the transition other than he would have some gastro problems for the first couple of days when he increased the Effexor. So, we slowed the transition schedule down so that he always increased on a Friday which meant that by Monday everything was settled down. It stretched out the transition by a couple of weeks but it went fairly smooth. He was also on a higher dosage of Xanax than he is now. Once the transition was complete, his Xanax was reduced to .25mg once or twice a day and he has maintained at that dose for about a year.

A new study on sleep duration and Impaired Glucose Tolerance (IGT). I posted this because many on this site have problems with sleep and also problems with sugar. Looks like the range is really narrow - 7-8 hours is just right. Long or Short Sleep Time May Be Associated With Diabetes http://www.medscape.com/viewarticle/503847?src=search Adults at the extremes of sleep duration have been demonstrated to be at increased risk of developing IGT. This includes individuals who sleep too much as well as those who sleep too little. A reduced amount of sleep may exert a negative effect on glucose tolerance through increased sympathetic nervous system activity, a shorter period of quiescent secretion of cortisol along with slower cortisol excretion, or an increase in the release of growth hormone prior to sleep. Although the cause of IGT associated with oversleep is less clear, it may be due to the direct effect of less physical activity as well as an increase in visceral adiposity.

My husband also had an early April appointment that has not yet been rescheduled.

Another relevant article. http://www.medscape.com/viewarticle/484814_1 Conference Report Unraveling the Origin of Alzheimer's Disease 9th International Conference on Alzheimer's Disease and Related Disorders; July 17-22, 2004; Philadelphia, Pennsylvania Posted 09/08/2004 Sara M. Mariani, MD, PhD ONE OF THE PARADOXES LISTED IN THE ARTICLE For example, increased blood pressure was expected to be associated with poor cognitive function in older individuals. Some studies have, however, reported an inverse association: Very high blood pressure was found to play an apparently protective role from AD, and a very low blood pressure to predispose to AD. In prospective association studies, the increased risk for very low blood pressure appeared to be approximately 4.7. What to do? The Alzheimer's Association is calling for a campaign called "Maintain your brain" aimed at introducing changes in lifestyle that can help to reduce, whenever possible, the prevalence of these risk factors and thus delay or prevent the onset of AD.[12] Among them: Weight loss and healthy food diet; Reduction of cholesterol levels and high blood pressure; and Complex leisure activities with physical, mental, and social interactivity components.

One last study summary that is again inconclusive. I hope I'm not scaring anyone but I too am concerned about permanent damage to my husband and brother-in-law. My husband has been struggling with Brain Fog a.k.a. Cognitive Impairment and has been taking Cerefolin with some noticeable improvement and no side effects. This summary article is only 3 paragraphs in length. Journal Watch (General) January 23, 2004 An Association Between Low BP and Alzheimer Disease? People with low diastolic BP (</=70 mm Hg) had a significant doubling of risk for subsequent Alzheimer disease (relative risk, 1.91) compared with those who had normal diastolic BP (71-89 mm Hg). Results of this study, along with those from a recently published study from Sweden (Arch Neurol 2003; 60:223), suggest that low diastolic BP is associated with increased risk for Alzheimer disease in elders. If this relation indeed can be verified, several questions remain: Does hypotension contribute to dementia via decreased cerebral perfusion? Alternatively, does hypotension result from BP dysregulation that might accompany dementia? Or, is the association not causal but, instead, mediated by unknown confounding factors? Until these questions are answered, it seems prudent to avoid excessive diastolic BP lowering in older patients. http://www.medscape.com/viewarticle/468549?src=search

There isn't really any more to the Reuters article - it is a study abstract, less than one page in length and what I copied is all that is mentioned about low blood pressure. Here is another relevant article http://www.medscape.com/viewarticle/480720?src=search This article is about 1 page in length. Diastolic Blood Pressure Control: How Low Is Too Low? Posted 06/21/2004 Ari Mosenkis, MD; Raymond R. Townsend, MD Here are a couple of comments from the article: It is well established that controlling hypertension through the use of antihypertensive agents reduces morbidity and mortality. It has been further demonstrated that lowering systolic blood pressure (SBP) as well diastolic blood pressure (DBP) confers benefit.[1] In the late 1970s, reexamination of Framingham data revealed that whereas there is no level of SBP lowering that does not incrementally improve outcomes, such may not be the case for DBP They found a higher incidence of cardiovascular disease events in those patients with isolated systolic hypertension whose DBPs were lowered to <70 mm Hg. In those patients whose DBPs were reduced to below 55 mm Hg, the relative risk of cardiovascular events nearly doubled. There are some problems with these data because, again, the numbers of patients who achieved DBP <55 mm Hg were small and a careful reading of this study suggests that levels of 45 mm Hg were not deleterious Caution should reign when DBP hovers around 56-60 mm Hg because (as far as we can currently tell) that is the point at which risk may approach benefit. As always, it remains prudent to offer such patients aggressive control of their other cardiovascular risk factors. These articles are found on using Medscape Search (www.medscape.com) hopefully you can access them. I always use the Advanced Search feature because you can sort by publish date and avoid sifting through old information.

Here's a Reuters Health Information Article. It mostly mentions high blood pressure but I copied the paragraphs below that mention low BP. The article is short and basically leaves the question unresolved and needing further study. Too many variables come into play. http://www.medscape.com/viewarticle/501235_print Study Links Blood Pressure With Cognitive Decline Both high and low diastolic pressures were linked with poorer performance on tests of executive function and confrontation naming by less-educated subjects; poorer performance on tests of perceptuo-motor speed and confrontation naming in subjects not receiving treatment with antihypertensive drugs; and poorer performance on measures of executive function in older subjects. "Cross-sectional and longitudinal relations of blood pressure to cognitive function are predominantly nonlinear and moderated by age, education, and antihypertensive medications," the authors conclude. Monitoring and treatment of elevated or lower-than-normal blood pressure, they add, "may be critical to the preservation of cognitive function." Hypertension 2005;45:374-379. --------------------------------------------------------------------------------

A new research article (March 2005) - I've copied the Objectives and Conclusions of the study and provided the link to the article. Homocysteine and Cognitive Function in a Population-based Study of Older Adults Jyme H. Schafer, MD, MPH; Thomas A. Glass, PhD; Karen I. Bolla, PhD; Margaret Mintz, MS; Anne E. Jedlicka, MS; Brian S. Schwartz, MD, MS Objectives: To assess the relations between homocysteine levels and neurobehavioral test scores representing a broad range of cognitive domains in a population-based study of older adults. Conclusion: Higher homocysteine levels were associated with worse function across a broad range of cognitive domains, and the magnitude of the associations was large. The data suggest that homocysteine may be a potentially important modifiable cause of cognitive dysfunction. Link: http://www.medscape.com/viewarticle/501018?src=search

Below is my post from March 6th. I know it doesn't have as much credibility since I do not take it myself but can only comment on what I notice in my husband. When he first started Cerefolin, I recall that others on the NDRF site experienced headaches so I kept checking with him but fortunately he did not get them. He did have some gastro issues when he first started but I don't know if it was coincidental or not as he did not have any problems when he restarted with the supplement. I hope it helps you. Regarding the cost, it isn't as bad as I had previously mentioned (I'm still not used to buying in bulk). He takes 1 tablet a day and with our insurance the cost was $93.00 for a 6 month supply. My husband began taking the prescription vitamin supplement Cerefolin about 6 months ago to help with fatigue and brain fog. I read a post on the product from another member of this forum (or maybe NDRF) and our family doctor prescribed it. I noticed an improvement in his thinking (actually a lessening of his forgetfulness) and he noticed an improvement in his level of fatigue and a reduction in nap time. After about 3 months, we experienced difficulty in obtaining the supplement and finally learned that Rite-Aid is involved with a lawsuit with the manufacturer and will not carry the product. As a result, he did not take it for a couple of months. In the meantime he took regular folic acid and B-12 supplements. Now he has been taking Cerefolin for about 3 weeks and we have both noticed improvements again, me on the mental sharpness and he has commented on the improvement in his fatigue and also that he is thinking clearer (YEAH!). So, I don't know if this is just wishfull thinking on our part but this is the second time the product has resulted in noticeable improvements. There is a lot of research on the benefits of folic acid and vitamins B-6 and B-12 on cognition. The supplement is marketed for dementia and Alzheimers patients. It's not cheap. He takes 1 tablet in the morning and has not had any side effects. I'd be interested to hear an update from anyone else using this supplement. www.cerefolin.com

My husband and I also have Health Care Declarations (I think that's what they now call a Living Will) and Durable Power of Attorney for each other as well. You need to make sure that someone else in the family has a copy of the Health Care Declaration and also they suggest that you take a copy with you when you travel (I keep ours with the passports). My parents were vacationing down South and my Dad had an Abdominal Aoretic Aneurysm (sp?) and went into a vegetative state. The rules get really tricky because once you insert life support elements it is difficult to remove them but you need to insert them to make sure you are giving the person every chance to recover. That's why it is so important to document your wishes. In our case, the siblings were not in agreement as to what to do but we did agree that it was my Mom's decision. It has caused a rift in the family that still simmers 7 years later. So please, for your family's sake and so that they don't have to wonder if they are doing the right thing, put your wishes (whatever they are) in writing. It is difficult enough without having to second guess your actions.

Cerefolin has helped my husband with fatigue and brain fog - it is a prescription nutritional supplement containing vitamins B2, B6, B12 and some sort of special Folic Acid that is more readily absorbed. We tried it over one of the other prescriptions for fatigue because it is vitamin based. www.cerefolin.com

I will forward this to my brother and sister-in-law and see if they respond back to you. My brother-in-law also has seizure activity with his syncope and has been unable to drive or work for about 2 years.

My husband has been diagnosed with NCS and for the most part his syncope is under control with periodic episodes of IBS and pre-syncope - he did not have seizure activity. His identical twin brother experiences more frequent and uncontrolled syncope and also has seizure-like activity during them - some lasting for quite some time and then he is pretty much "out of it" for a couple of hours. His current diagnosis is "non-epileptic seizures". You can also read the following article - I've copied part of it here. Unfortunately they haven't yet figured out the treatment to stop his syncope/seizures - I'll definately be watching to see if you have any success. My husband takes Effexor XR and now a small dose of Xanax when needed (.25mg) up to 2 times/day. Before he was treated by specialists the Xanax dose was 1 mg up to 6 times a day - way too much, it was like he was tranquilized (which is exactly what he was). The dosage increase was per the doctor's recommendation and we had no understanding of it so we along and then he had to work to taper off what his body had become addicted to. Now that he is on a small dose of Xanax his personality is back to normal. A beneficial medication if prescribed and used correctly. Neurologic Events Common During Neurocardiogenic Syncope http://www.medscape.com/viewarticle/461242?src=search Sept. 10, 2003 ? Neurologic events are common during episodes of neurocardiogenic syncope, according to the results of a study of tilt table testing published in the Sept. 8 issue of the Archives of Internal Medicine. The authors suggest that this diagnosis should be considered for unexplained seizure-like activity. "Failure to identify the cause of clinical seizures is not uncommon and may lead to therapies that are ineffective and potentially harmful," write Rod Passman, MD, MSCE, from Northwestern University in Chicago, Illinois, and colleagues. "Misdiagnosis may result in a failure to prescribe appropriate therapy and could expose the patient to the risks of recurrent syncope and possible sudden cardiac death." Of 694 consecutive patients undergoing tilt table testing for the evaluation of syncope, 222 had positive results, defined as reproduction of clinical symptoms associated with reduction in blood pressure. The tilt table protocol consisted of a 70 degree upright tilt for 40 minutes, followed by a 20-minute tilt while receiving isoproterenol. During tilt table testing, 18 patients (8%) had apparent neurologic events, including 11 patients (5%) with apparent tonic-clonic seizure-like activity and seven patients (3%) with non-tonic-clonic neurologic events. The latter group included three patients with focal seizures, two with dysarthria or aphasia, and one with symptoms of temporal lobe epilepsy. Systolic blood pressure after tilt table testing was significantly lower in the patients with apparent neurologic events than in those with positive tilt table results without provoked neurologic events (P < .01), and asystole was also more common in the former group (P = .03). Study limitations include retrospective design and applicability of the findings only to adults. "Vasodepressor syncope should be considered as a possible cause of unexplained seizurelike activity of all varieties, and tilt table testing should be considered early in the evaluation of such patients," the authors write.

We were just turned down for a study at Vanderbilt after sending both my husband's and his twin brother's medical files at their request. Again, no explanation, just a sorry but we don't think we can help you with your problems.

Last year, Dr. Grubb told us that EVERYONE should be taking folic acid for a healthy heart. Take a multi-vitamin with B12 and B6 and an additional 1-2mg of folic acid daily. He said that there is OVERWHELMING evidence that folic acid needs to be added to our diets. It provides something like a 25% decrease in colon cancer and also a decent decrease in breast cancer. The B12 + B6 are needed to make use of the folic acid. My husband was taking 800 mcg of folic acid, 2500 mcg of B12 plus multi-vitamin but he only took 1/3 of the daily dose of the multi-vitamin. He no longer takes the separate folic acid and B12. Several months after of appointment with Dr. Grubb I saw the post by another member about the Cerefolin and we decided to try that over the Provigil for fatigue because it contains vitamins that were already recommended. Also, if you read up on B-12 deficiency and pernicious anemia the symptoms overlap with many of NCS and POTS. Regarding the cost, I guess it isn't as bad as I thought. Our co-pay was $93.00 for 180 tablets - a 6 month dose. I'm still not used to having to buy in bulk via mail order. Regarding why it is supposed to work, I can only forward what I have read. "Elevated levels of homocysteine have been found to be associated with cognitive impairment and folic acid, B-12 and B-6 are the nutritional supplements used to lower homocysteine" (from the manufacturer's literature). Another article from Medscape Cardiology (august 2004) can be found at http://www.medscape.com/viewarticle/483204?src=search High Homocysteine Levels Contribute to Cognitive Dysfunction Interest in homocysteine as a risk factor for CVD has mounted during the last few years. It has been suggested that high levels of this sulphur-containing amino acid can elevate the risk of dementia and depression and can confer significant morbidity and mortality. With the advent of simple assays, homocysteine measurement has become accepted as a standard and routine clinical test.[15] During the past 15 years, it has been thoroughly documented that moderate elevation of homocysteine levels in serum or plasma is a strong and independent risk factor for occlusive arterial disease and venous thrombosis, and is a predictor of vascular and all-cause mortality. As many as 50% of patients with stroke and other atherothrombotic diseases have high homocysteine levels (> 15 micromol/L).[15] An association between elevated homocysteine levels and impaired cognitive performance and dementia has also been documented. Several prospective studies have demonstrated that folate and/or vitamin B12 status and elevated levels of homocysteine are predisposing factors for the development of dementia or contribute to an accelerated rate of progression of the disease.[15] Reduction of homocysteine levels has been shown to increase regional cerebral blood flow and to have a positive impact on cognitive performance in elderly individuals with mild cognitive impairment. However, early intervention appears to be crucial, because severe underlying neuronal and vascular damage is irreversible (although studies in animals suggest the possibility of reversibility of neuronal damage). Vitamin therapy has also been demonstrated to influence the rate of progression of atherosclerosis and to increase endothelium-dependent blood flow.[15]

My husband began taking the prescription vitamin supplement Cerefolin about 6 months ago to help with fatigue and brain fog. I read a post on the product from another member of this forum (or maybe NDRF) and our family doctor prescribed it. I noticed an improvement in his thinking (actually a lessening of his forgetfulness) and he noticed an improvement in his level of fatigue and a reduction in nap time. After about 3 months, we experienced difficulty in obtaining the supplement and finally learned that Rite-Aid is involved with a lawsuit with the manufacturer and will not carry the product. As a result, he did not take it for a couple of months. In the meantime he took regular folic acid and B-12 supplements. Now he has been taking Cerefolin for about 3 weeks and we have both noticed improvements again, me on the mental sharpness and he has commented on the improvement in his fatigue and also that he is thinking clearer (YEAH!). So, I don't know if this is just wishfull thinking on our part but this is the second time the product has resulted in noticeable improvements. There is a lot of research on the benefits of folic acid and vitamins B-6 and B-12 on cognition. The supplement is marketed for dementia and Alzheimers patients. It's not cheap. He takes 1 tablet in the morning and has not had any side effects. I'd be interested to hear an update from anyone else using this supplement. www.cerefolin.com

I found this on a search of the National Osteoporosis Foundation website. I did not find the full article because it is part of a 153 page set of abstracts. ...Departments of Medicine and Public Health Sciences, St George's Hospital Medical School, London, UK Background. Hypertension is associated with increased urinary calcium (UCa) excretion. A high sodium intake increases both UCa and... http://www.nof.org/events/world_congress/abstracts.pdf http://search.atomz.com/search/?sp-q=hyper...00001&x=13&y=21

Welcome from a kinda-sorta member of the group. My husband has NCS so I frequent this forum to increase my own understanding of what he might be experiencing. I was trying to find something to help you explain your limitations to your daughter and the best idea I came up with is using the stories from younger kids with dysautonomia on the dynakids website ( www.dynakids.org ). I frequently use the Dysautonomia for Dummies article from the August 2001 newsletter to explain to friends and family members but even that is too complicated for a 7 year old. Maybe the words of those closer to her age will help her understand what you are going through. Just a thought.

As the "currently healthy" one in my marriage I have a suggestion. In addition to finding things that we CAN do together, I also found a few things that I do on my own with friends BUT, I set a few ground rules: 1. The activities I do on my own are not exclusive - my husband can join in whenever he wants at whatever level of participation he is up to. I joined a health club (he hasn't visited yet), organized a book club (he has read several or viewed the movie) and have taken up hiking (he helps me train by going on shorter hikes). 2. My friends are female or mixed groups - never just me and the guys. I have many male friends but I think it would be unfair for me lets say to take off hiking for a weekend with another guy while my husband is willing but unable. 3. My activities still leave us with lots of together time - I exercise while he is on his way home from work and I read while he naps or heads to bed early. It's only the hiking that I have to plan for and so far we've worked it out. After a couple of years of decreased activity from his fatigue, I did start to get resentful when he couldn't do things we had previously. He kept encouraging me to do things on my own but I really do enjoy his company so I resisted and yes, I felt "sorry" for him (my problem not his). For me, this set of activities keeps us involved together but has given me the increased social and physical activity I needed. We celebrate our 10th anniversary this May PS - I was previously married to a healthy man but I would pick my current husband even if I knew of his illness when we first met.

I wish I had answers to your questions because it would mean I knew what I was talking about - I don't. I came across the article on DAN while searching for something that explained all of my husband's symptoms, not just some or most of them. Your post came up the next time I signed on so I thought I would include the article I read. My husband is diagnosed with NCS (he's a fainter) and his identical twin also faints but his diagnosis is "non-epileptic seizures", meaning they don't know what is wrong. So, I too keep searching and reading and taking stuff to the doctor, hoping that they will find something that responds more consistently to treatment but so far no luck here.

http://www.medscape.com/viewarticle/473205_1 I just read this article last night on Diabetic Autonomic Neuropathy, I've copied the introduction and the table of symptoms. Hopefully you can get to the article using the above link. Table 1. Clinical Manifestations of Autonomic Neuropathy Cardiovascular Tachycardia, exercise intolerance Cardiac denervation Orthostatic hypotension Gastrointestinal Esophageal dysfunction Gastroparesis diabeticorum Diarrhea Constipation Fecal incontinence Genitourinary Erectile dysfunction Retrograde ejaculation Cystopathy Neurogenic bladder Neurovascular Impaired skin blood flow Heat intolerance Gustatory sweating Dry skin Metabolic Hypoglycemia unawareness Hypoglycemia unresponsiveness Hypoglycemia-associated autonomic failure Pupillary Decreased diameter of dark adapted pupil Argyll-Robertson type pupil -------------------------------------------------------------------------------- Introduction Diabetic neuropathy is a heterogeneous disorder that encompasses a wide range of abnormalities affecting both proximal and distal peripheral sensory and motor nerves, as well as the autonomic nervous system (ANS). Diabetic autonomic neuropathy is among the least recognized and understood complications of diabetes despite its significant negative impact on survival and quality of life in people with diabetes.[1-3] Many organs are dually innervated, receiving fibers from the parasympathetic and sympathetic divisions of the ANS. Diabetic autonomic neuropathy typically occurs as a systemwide disorder affecting all parts of the ANS. Diabetic autonomic neuropathy manifests first in longer nerves. The vagus nerve (the longest of the ANS nerves) accounts for ~75% of all parasympathetic activity; as such, even early affects of diabetic autonomic neuropathy are widespread. The organ systems that most often exhibit prominent clinical autonomic signs and symptoms in diabetes include the pupil, sweat glands, genitourinary system, gastrointestinal tract system, adrenal medullary system, and the cardiovascular system (Table 1).[4] The availability of sensitive, specific, and reproducible noninvasive tests of autonomic function has enhanced our understanding of the prevalence, pathophysiology, and clinical manifestations of this disorder.[1,5-6] Clinical symptoms of autonomic neuropathy generally do not occur until long after the onset of diabetes. Subclinical autonomic dysfunction, however, can occur within a year of diagnosis in type 2 diabetic patients and within 2 years in type 1 diabetic patients.[7]