Expert Blog

Can Current Drug Therapy Prevent Beta Cell Failure and Bring Treatment Durability in T2DM?

John L. Leahy, MD
Endocrinologist

A hot topic in the type 2 diabetes world is whether we have in hand the tools to stop the decline in beta cell function that typifies this disease and, consequently, a therapy or therapies that successfully control blood glucose for many years – so-called treatment durability. Actually this is three topics. What are the specific mechanisms for the beta cell failure? Do any of our existing therapies, or those on the drawing board, reverse these mechanisms to slow or stop the beta cell failure? Do any of our current or potential therapies have treatment durability regardless of how they do it?

I spoke on this subject at the annual meeting of The Endocrine Society this past June. A couple of weeks later there was a multi-speaker symposium at the annual meeting of The American Diabetes Association–Chris Rhodes discussed basic beta cell biology, Stefano Del Prato argued that it was defective beta-function that caused the beta cell failure in type 2 diabetes, while Michael Nauck (standing in for Juris Meier) argued for a lowered mass of functional beta cells and David D’Alessio reviewed whether any of the existing therapies are beta cell protective. To summarize, a large number of cellular mechanisms for the beta cell failure in type 2 diabetes have been proposed, and we have therapies that at least theoretically could be protective. But are they? I’ll structure my remarks around that issue.

Improved glucose control

Many primary providers would probably consider reversal of glucose toxicity as a strategy to protect beta cells, in part because this is a well-known concept, and most providers have patients who responded incredibly well, almost magically, to early therapy. This became a hotly discussed topic in 2008 based on a study from China that intensively treated new onset patients with type 2 diabetes (A1c 9.5-9.8%) with oral agents or insulin to normalize blood glucose values, with therapy stopped two weeks later.[1] Amazingly, a year later half of the insulin-treated patients still required no pharmacologic therapy (i.e., they had fasting blood glucose less than 126 mg/dL and 2-hour postprandial glucose less than 180 mg/dL). The one-year remission rate was lower in the oral agent-treated group—27%. Whether these findings mean that insulin has superior protective potential or were a quirk of the protocol is unknown. More important to this discussion, however, was the fact that these results were paralleled by sustained improvements in beta cell function in the remission groups–prompting an ongoing discussion in the specialty diabetes world about whether early intensive therapy, especially with insulin, can alter the natural course of the beta cell dysfunction in type 2 diabetes. Additional insight will hopefully come when the ORIGIN trial finishes later this year. This trial used basal insulin versus standard oral agent therapy over eight years in more than 10,000 subjects with prediabetes or early-onset type 2 diabetes, with the primary outcome cardiovascular events but also including measures of beta cell function.[2] Whatever these findings might be, however, it’s important to remember that we’re only talking about treating early stage disease: everyone’s clinical experience with later stage type 2 diabetes is disappointing in terms of aggressive blood glucose control, stabilizing beta cell function, and reducing the need for therapy.

My Take: On balance intensive blood glucose control has little to no beta cell protective effect in the average patient with type 2 diabetes of more than a few years duration. It does have a role, but for prevention of microvascular and possibly macrovascular complications.

TZDs

I’ve written on this subject in the past.[3] Several TZD treatment studies have shown incredible success (best we have) at preventing conversion of prediabetes to overt type 2 diabetes through stabilizing beta cell function. The latest is the ACT NOW trial with a 72% success rate.[4] It's worth restating that no other therapy, lifestyle or pharmaceutical, comes close to that result. Also the ADOPT trial, performed in person with recent onset type 2 diabetes, reported better durability of rosiglitazone versus metformin or glyburide as first-drug therapy[5] because of stabilized beta cell function and improvements in insulin sensitivity.[6] The mechanism is thought to be “resting” of the beta cell – the lowered work load from the improved insulin sensitivity stops the beta cell excess drive or metabolic stress, thereby protecting the beta cell mass and/or function.

My Take: TZDs might be the best we have. Also, a lot could be learned about beta cell protection from finding out exactly how TZDS do what they do. Unfortunately, it's a moot point. These drugs are disappearing from the marketplace – the latest scare is bladder cancer with pioglitazone – and with them interest in better understanding PPARg physiology and pharmacology.

Incretin therapy

Many had hoped that incretin therapy – GLP-1 receptor agonists or DPP-4 inhibitors – would bring treatment durability. This is because of the current buzz over the importance of the incretin system in post-meal blood glucose control generally, how it’s broken in type 2 diabetes, and the ability of these agents to raise beta cell mass and function in preclinical rodent studies. Patricia Brubaker discussed this in a prior blog on this website. So what about human beings? The first answer is that it’s too early to say anything definitive. Second, we’re learning that it’s really hard to design a clinical trial to know if beta cell function is in fact stabilized or improved. It must be done after the drug is stopped to eliminate a “treatment effect” – but how long is too long to guard against a benefit being lost through recurrence of the disease? What is a meaningful effect? Test against an active comparator or no treatment? And how do we know whether a benefit is due to the drug itself and not more generally from improved blood glucose control during treatment? Such questions go on and on. A group from Amsterdam has taken on the challenge, but so far the findings are not particularly encouraging. They showed one year of vildaglipitin (a DPP-4 inhibitor available outside the U.S.) followed by a 12-week washout did not induce an improvement in beta cell function.[7] Also, exenatide for one year caused a sustained improvement in beta cell function when on therapy, but not after four weeks off the drug.[8] In contrast, an abstract at the 2010 American Diabetes Association annual meeting reported that three years of exenatide therapy was associated with improved beta cell function after a four-week washout, but the effect was so modest as to be clinically meaningless from my perspective.

My Take: We don’t have evidence for incretin therapy inducing a sustained rise in beta cell mass and/or function after stopping the drugs, at least after four weeks. Given the hope and excitement that came with these drugs based on the rodent findings, that’s a big disappointment for many. However, what has been lost in this discussion is that the studies DO show a continued improvement in beta cell function when on drug. So the million dollar question (many billions is probably more correct) is how long does that treatment benefit last, and will it bring a durability that exceeds what we currently have and is clinically meaningful? That’s the information we are really waiting for.

Interleukin-1 receptor antagonists

An example of a therapy possibly on the drawing board is interleukin-1 receptor antagonists. Of course, these drugs already exist and are used in various arthritis conditions. Trying them for type 2 diabetes results from basic science, which uncovered that islet inflammation may be a pathogenic mechanism for the beta cell pathology in type 2 diabetes.[9] So the next step was trying interleukin-1 receptor antagonists in type 2 diabetes. The first high profile study was a 13-week pilot trial with anakinra in 70 persons with type 2 diabetes that showed a 0.4% lowering of A1c along with a modest improvement in stimulated c-peptide secretion.[10] However the same patients studied 39 weeks after anakinra withdrawal showed a loss of the improved c-peptide secretion in the overall group, although the proinsulin to insulin ratio was still modestly improved.[11]

My Take: Sexy and timely research topic. However the clinical results so far (admittedly very early) seem a bit underwhelming.

Conclusions

I finished my talk at the Endocrine Society with the following summary slide:

- Many existing diabetes therapies improve beta cell function:

  • Direct
  • Indirect effects -- Beta cell rest or reversal of glucose toxicity. Thus, existing therapies may be useful for prevention of diabetes

- Durability or beta cell protection REQUIRES proof of a reduction in the progressive decline in beta cell function in type 2 diabetes by proving all of the following:

  • Long-term drug response and attenuation of the progressive beta cell failure -- proof requires at least a five-year study
  • Meaningful sustained improvement in beta cell function after discontinuing the drug
  • Plausible biological mechanism for the beta cell protection
  • No current therapy meets these criteria

 

References:


Comments

Submitted by Jeff Unger MD on

Jack: What about insulin therapy? Several studies have suggested that intensive insulin therapy in newly diagnosed patients with T2DM may result in beta cell rest over a prolonged, yet uncertain period of time.
Intensive insulin pump therapy has also been demonstrated to restore B-cell function. A study recruited 138 newly diagnosed patients with type 2 diabetes having fasting glucose levels > 200 mg/dL. (Li Y, Xu W, Liao Z, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of -cell function. Diabetes Care 2004. 27:2597-2602). All patients were hospitalized for two weeks and place on intensive insulin pump therapy. Optimal glycemic control was attained within 6.3  3.9 days in 126 patients. The remission rates (percentage of participants maintaining near-normal glucose levels) at the 3rd, 6th, 12th, and 24th months were 72.6, 67.0, 47.1, and 42.3%, respectively. Those patients in remission for > 1 year had greater recovery of B-cell function compared with the non-remission group as demonstrated by favorable proinsulin:insulin ratios in the long-term remission group. Under normal circumstances, small amounts of proinsulin are secreted concurrently with insulin; the result is a plasma proinsulin:insulin ratio of approximately 0.1. Conditions characterized by inflammation or dysfunction of B-cells are associated with increased levels of proinsulin, resulting in increased ratio of proinsulin to insulin (Mykkanen L, Haffner SM, Kuusisto J, et al. Serum proinsulin levels are disproportionately increased in elderly prediabetic subjects. Diabetologia. 1995;38:1176-1182).

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Submitted by Dr. Gauranga C. Dhar on

Can not we add phlorizin derivatives e.g. dapagliflozin (SGLT-2 receptor inhibitor) to this list? With main action in renal tubules , this group of drugs in addition to reduction of hyperglycemia may prevent progressive loss of beta cells (Ref: Diabetes, Obesity and Metabolism Volume 12, Issue 11, Pages 1004-1012, November 2010).

Submitted by Dr. Gauranga C.... on

It is very unfortunate that on the 19th of this month FDA has declined its approval to dapagliflozin due to increased risk of bladder cancer. Of course same thing applies to TZD; pioglitazone as due to red alert on pioglitazone for its adverse effects in bladder, most of the physicians including me have restricted their new prescription for pioglitazone.

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All these post about HERBAL MEDICINE and spell caster are scammer and fake
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occupation and when you have given them all the information, they will be
asking for money. my name is Blessing,a woman of 39years I was once suffering from herpes for good 3years and i spent a
lot of money going from one herbal doctor to another but they all scam and
take my money away until i told my friend the problems am facing in life he quickly introduce me to this powerful herbal man called
Dr.LUCK who cured me from Herpes with his herbal medication , after
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send him my residential address, so that he will send the herbal medicine
to me via D.H.L so i did. 2days later, i received the herbal medicine and i
had to follow the instructions he gave to me on how i will apply it. After using if for a week and few days and I noticed that all the symptoms, pain, itch and blisters are gone. 2weeks
later i went to hospital for test and according to the test done by the
Medical doctor called Steven it stated that i was herpes negative.
So viewers be wise and beware of fake people and fake herbal
doctors, they are all over the internet trying to steal from poor people. I
will drop the email of this powerful herbal doctor just in case you
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1. HERPES
2. LASSA FEVER
3. GONORRHEA
4. HIV/AIDS
5. LOW SPERM COUNT
6. MENOPAUSE DISEASE
7. EPILEPSY
8. ASEPSIS
9. CANCER
10. ANXIETY DEPRESSION
11. PREGNANCY PROBLEM
12. SHORT SIGHTEDNESS PROBLEM
13. ALS
14. PTSD
15 ADHD

Submitted by Blessing on

All these post about HERBAL MEDICINE and spell caster are scammer and fake
trying to collect money all in the name of HERPES cure and when you contact
them, they will be asking for your name, pictures, country, phone number,
occupation and when you have given them all the information, they will be
asking for money. my name is Blessing,a woman of 39years I was once suffering from herpes for good 3years and i spent a
lot of money going from one herbal doctor to another but they all scam and
take my money away until i told my friend the problems am facing in life he quickly introduce me to this powerful herbal man called
Dr.LUCK who cured me from Herpes with his herbal medication , after
Doctor Luck has finished preparing the herbal medicine, he asked me to
send him my residential address, so that he will send the herbal medicine
to me via D.H.L so i did. 2days later, i received the herbal medicine and i
had to follow the instructions he gave to me on how i will apply it. After using if for a week and few days and I noticed that all the symptoms, pain, itch and blisters are gone. 2weeks
later i went to hospital for test and according to the test done by the
Medical doctor called Steven it stated that i was herpes negative.
So viewers be wise and beware of fake people and fake herbal
doctors, they are all over the internet trying to steal from poor people. I
will drop the email of this powerful herbal doctor just in case you
want to contact him for help,EMAIL ON :{dr.luckspelltemple@gmail.com}
Dr LUCK CAN AS WELL CURE THE FOLLOWING DISEASE:-

1. HERPES
2. LASSA FEVER
3. GONORRHEA
4. HIV/AIDS
5. LOW SPERM COUNT
6. MENOPAUSE DISEASE
7. EPILEPSY
8. ASEPSIS
9. CANCER
10. ANXIETY DEPRESSION
11. PREGNANCY PROBLEM
12. SHORT SIGHTEDNESS PROBLEM
13. ALS
14. PTSD
15 ADHD

Submitted by Blessing on

All these post about HERBAL MEDICINE and spell caster are scammer and fake
trying to collect money all in the name of HERPES cure and when you contact
them, they will be asking for your name, pictures, country, phone number,
occupation and when you have given them all the information, they will be
asking for money. my name is Blessing,a woman of 39years I was once suffering from herpes for good 3years and i spent a
lot of money going from one herbal doctor to another but they all scam and
take my money away until i told my friend the problems am facing in life he quickly introduce me to this powerful herbal man called
Dr.LUCK who cured me from Herpes with his herbal medication , after
Doctor Luck has finished preparing the herbal medicine, he asked me to
send him my residential address, so that he will send the herbal medicine
to me via D.H.L so i did. 2days later, i received the herbal medicine and i
had to follow the instructions he gave to me on how i will apply it. After using if for a week and few days and I noticed that all the symptoms, pain, itch and blisters are gone. 2weeks
later i went to hospital for test and according to the test done by the
Medical doctor called Steven it stated that i was herpes negative.
So viewers be wise and beware of fake people and fake herbal
doctors, they are all over the internet trying to steal from poor people. I
will drop the email of this powerful herbal doctor just in case you
want to contact him for help,EMAIL ON :{dr.luckspelltemple@gmail.com}
Dr LUCK CAN AS WELL CURE THE FOLLOWING DISEASE:-

1. HERPES
2. LASSA FEVER
3. GONORRHEA
4. HIV/AIDS
5. LOW SPERM COUNT
6. MENOPAUSE DISEASE
7. EPILEPSY
8. ASEPSIS
9. CANCER
10. ANXIETY DEPRESSION
11. PREGNANCY PROBLEM
12. SHORT SIGHTEDNESS PROBLEM
13. ALS
14. PTSD
15 ADHD

Submitted by Jazmine Davis on

Am here to testify of the miraculous work of a great traditional doctor called DR.ZUKU ..I have been suffering from Herpes since last 2 years with my Husband but today I am happy that am cure from it with the herbal medicine made by Dr.ZUKU the great healer, I was browsing the internet searching for help when I came across a testimony shared by someone on how Dr.ZUKU cure her from Herpes Disease. I quickly contacted him to get the cure and today i am now free from the Virus, I am so much happy today that we have someone like this great healer out there, so' people out there kindly contact this great doctor on his email address please sir keep your good work cause there are people out there who is in need of your healing medicine .once more contact him now drzukuspelltemple@gmail.com or call or text +16177296273 Dr.Zuku can prepare Herbal medicine for all kind of disease. HIV. CANCER. HEPATITIS B.DIABETES.COLD SORES. Syphilis. HBV, HPV, STD's And many more.contact Dr.Zuku to get your healing.Email drzukuspelltemple@gmail.com

Submitted by GREG LEONARD on

I was diagnose by DIABETES dew to that my Wife left me and and i was all left with out a family non friend, one day i was searching for help on net and i

came across a testimony of CHRIST EDWARD how DR JATTO help him Cure his wife but i said in my mind if it will work and the second thought was it will work so

i decide to give a try, on the testimony of CHRIST EDWARD i saw an email and a phone number= jattospiritualtemple@gmail.com +2349056539383. I email him and

give him a call that same time then he ask for my details and i send it to him immediately and said he will make the spell done in the next 6 hours when he

is done he will call me back. In the next six hours he called me that he his done with it and he have give the DHL Service to deliver the parcel to me in the

next day that i will see it. The next day i was at home watching evening news when i hard a knock on the door and i went and open it to found out the person

was from the DHL Service and i sign and collect it. Then i called him to ask him how will i use it and he told me off which i did after i did in the next two

hour i called and ask him how will it go next and he said to me that i should keep on taking it for three days and i DID. In the next three days i called him

and he said after today i should go for check up. When i get to the hospital i was told i have been cured and i thought it was a joke i went to another

hospital the same thing i called him and told him that i have been cure and he said my people will now start looking for me include my Wife and i was happy

at that time when i got home preparing food to eat my phone ring it was my Wife he ask me were i am and i answer her, in few time she came and ask for

forgiveness for everything that i past through and i did now we are both together happily with the help of DR JATTO.
His details is as below if you need his help.

Email him= jattospiritualtemple@gmail.com
WhatsApp= +2349056539383
Call= +2349056539383
THANK YOU.

Submitted by Jazmine Davis on

I am so glad to be cured from my ALS Disease, that i have suffered for 4years and ever since i have gone to many places to seek a cure but all to no avail. until one beautiful morning when i was checking out possible remedy for my ALS Disease, then i stumbled on a testifier talking about how Dr.Zuku cure him from ALS Disease after reading through the comment, i went ahead and contacted Dr.Zuku and asked for his medicine to cure my ALS Disease, after providing the materials to prepare my cure, he sent it to me through courier service and i received it within 4days and when he instructed me about how to use it and i did, 2 weeks of usage Dr.Zuku told me to go to check my self again, and behold i was negative. Dr .Zuku email drzukuspelltemple@gmail.com Or CALL/Number:+16177296273

Submitted by Tammy Lisa Donna on

Herpes cure with the help of herbal medication for herpes and hpv cure should contact Dr Oz

Herpes and HPV being Sexually Transmitted Diseases (STDs) can severely restrict one’s social and love life. Many people suffering from these conditions choose to remain silent, thus living a life filled completely with loneliness and frustration. But life isn’t over yet. You can not only find support with millions of other people with the same condition. I bring to you good news that can get you a permanent cure through real and effective herbal cure.He cured me and could cure you too, here is Dr Oz contact:Email

Ozremedycure@gmail.com

Phone Him on +2348056391583

Submitted by Jazmine Davis on

I am very happy to share this amazing testimony Dr.Zuku herbs help me to cure my Herpes Simplex Disease and i have this Herpes 3 months ago.. i had unprotected with man i met and he did tell me he had Herpes disease after some weeks later i started seeing bump and sore on my vaginal, and i was so scared so i went to my doctor and did some test and behold i was confirmed Herpes positive, i went home so confuse and frustrated about this, especially when i was told there was no permanent cure for it, i said to myself i need to research about this, maybe there might be a herbal help for me, and so i did and when i was researching about herbal herbs, i keep seeing Dr.Zuku on every blog and guestbook, so i immediately wrote to Dr.Zuku, after we discuss he prepared my medicine and sent it to me, within few days i received my medicine and started applying it as instructed within 2weeks Dr.Zuku told me to go and check up, and i did, shocking my result came out negative, i am so thanks to you sir,
contacthis email address,

drzukuspelltemple@gmail.com

more information Number :+16177296273

by Dr.Zuku Blogs

https://drzukuspelltemple.blogspot.co.ke/

Submitted by Jazmine Davis on

Am here to testify of the miraculous work of a great traditional doctor called DR.ZUKU ..I have been suffering from Herpes since last 2 years with my Husband but today I am happy that am cure from it with the herbal medicine made by Dr.ZUKU the great healer, I was browsing the internet searching for help when I came across a testimony shared by someone on how Dr.ZUKU cure her from Herpes Disease. I quickly contacted him to get the cure and today i am now free from the Virus, I am so much happy today that we have someone like this great healer out there, so' people out there kindly contact this great doctor on his email address please sir keep your good work cause there are people out there who is in need of your healing medicine .once more contact him now drzukuspelltemple@gmail.com or contact Dr Zuku Blogs https://drzukuspelltemple.blogspot.co.ke/ call or text +16177296273 Dr.Zuku can prepare Herbal medicine for all kind of disease. HIV. CANCER. HEPATITIS B.DIABETES.COLD SORES. Syphilis. HBV, HPV, STD's And many more.contact Dr.Zuku to get your healing.True Website https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

Submitted by Ashley Balton on

IT IS REAL!!! HOW I COMPLETELY GOT RID OF 4 YEARS GENITAL HERPES WITHIN 7 DAYS... GOD IS AWESOME,I AM A LIVING TESTIMONY!!!!....

HIS WEBSITE: http://draramideherbalcure.wordpress.com/contact/

I have been dating for almost 7 years until i contracted GENITAL HERPES VIRUS from my Ex-boyfriend who never told me he was having it.Ever since then i have been searching for cure everywhere because i was feeling so uncomfortable having so many outbreaks, Most people have herpes in one form or another, i was first taking Antiviral medicines such as acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex), which are recommended for treating primary genital herpes outbreaks..But i needed to get rid of it completely, I came across so many testimonies online speaking about cure to herpes. i was so eager to be completely cured, I became a victim of fraud after contacting several so-called herbal doctors i was referred to. I lost a lot of money but i didn't stop searching for a cure.
Then one faithful day,i came across a testimony of a lady saying that she got her Genital herpes cured by a GREAT HERBAL DOCTOR she called Dr. Aramide by contacting him through his email address. And she advised anyone with GENITAL HERPES or SIMPLEX HERPES to contact him for HERBAL CURE. I contemplated for about 4 hours whether or not to contact him. Then something inside of me told me to give a try. I then contacted him through his email and told my problems to him. He told me all the things I needed to do and also gave me instructions to follow, Which i did properly. Just within the 7 days of drinking and applying the herbal medication he sent to me through DHL delivery service, I started feeling changes in my body i went to my medical doctor for check-up, I was so happy when he told me i was no more having GENITAL HERPES VIRUS and that i was free, It was all tears of Joy from that moment, I never thought ROOTS & HERBS could cure HERPES and if i could ever meet a GENUINELY GREAT HERBAL DOCTOR. I'm so grateful to him. i am completely free from GENITAL HERPES VIRUS,i recommended him to a family friend having Simplex Herpes virus, He called me and told me he is also cured completely. I promised to share my own testimony like that of the lady on the internet. If you are also having
*GENITAL & SIMPLEX HERPES... or need cure to diseases/viruses like..
*EPSTEIN-BARR VIRUS
*PREDIABETES/DIABETES/DIABETES MELLITUS...
*MENINGITIS...
*MERS-CoV...
*HIV...
*LEISHMANIASIS...
*LOW SPERM COUNT...
*SHIGELLA INFECTION...
*SYPHILLIS
*CANCER...
*LOWER RESPIRATORY INFECTION...
*STAPHYLOCOCCUS AUREUS...
*HEPATITIS...
*SHINGLES...
*YELLOW FEVER...
*POLIO...
*LUPUS...
*STROKE...
*FIBROID...
*EPILEPSY...
*TUBERCULOSIS...
*LEUKAEMIA...
*SICKLE CELL...
*ASTHMA.. Etc..
Without Hesitation Contact him Today for a testimony through his Email _ dr.aramideherbalcure@gmail.com & Website: http://draramideherbalcure.wordpress.com/contact/

For more info;
Phone No: +1(786)581-7266

*GOD IS TRULY FAITHFUL*

I so much appreciate the great Dr Akuna for his marvelous work done for my life and of my partner, we were both HERPES SIMPLEX VIRUS(HSV2) Positive, and this went on for more than 4years and 5month, but when i stumbled on Dr Akuna herbal healing herbs my life was changed for the better, so i am writing to inform the whole world of this wonderful man, Dr Akuna is very trusted and 100% guarantee to offer you the help of your choice, at first i thought this was a scam, but after taking Dr Akuna herbal healing herbs my life and of my partner was turnaround, i cant say more but to say well done sir, and more blessing to you and your handwork. Dr Akuna also cure all types of disease, EPILEPSY.CANCER.HIV.DIABETES.SHINGLES.HPV.HEPATITIS A.B.C AND MANY MORE. Just email Dr Akuna: drakunasolutiontemple@gmail.com or What app/Call: +2348154625070 or his website: http://drakunasolutiontemple.com

Submitted by Jazmine Davis on

Thank to Dr.ZUKU i will forever continuously testify Dr.Zuku for changing my life with your herbs Remedy, i have be Suffering from HEPATITIS B over Three years ago i have battled with this virus and was about to ruin my entire body,I have been living with this virus and it has been giving me challenges,one morning i was browsing through the internet then i saw several testimonies about Dr.Zuku curing people from HEPATITIS B and immediately i contacted Dr.Zuku on his email and he assure me that will prepared herbal medicine and when after drinking for 2 weeks i went back to my doctor and my result came out HEPATITIS B negative.Viewers i am so glad, email Dr.Zuku and get your cure. Email: drzukuspelltemple@gmail.com call or text for more information +16177296273 contact Dr Zuku Blogs https://drzukuspelltemple.blogspot.co.ke/ or contact Web/Site https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

I so much appreciate the great Dr Akuna for his marvelous work done for my life and of my partner, we were both HERPES SIMPLEX VIRUS(HSV2) Positive, and this went on for more than 4years and 5month, but when i stumbled on Dr Akuna herbal healing herbs my life was changed for the better, so i am writing to inform the whole world of this wonderful man, Dr Akuna is very trusted and 100% guarantee to offer you the help of your choice, at first i thought this was a scam, but after taking Dr Akuna herbal healing herbs my life and of my partner was turnaround, i cant say more but to say well done sir, and more blessing to you and your handwork. Dr Akuna also cure all types of disease, EPILEPSY.CANCER.HIV.DIABETES.SHINGLES.HPV.HEPATITIS A.B.C AND MANY MORE. Just email Dr Akuna: drakunasolutiontemple@gmail.com or What app/Call: +2348154625070 or his website: http://drakunasolutiontemple.com

Submitted by James Panny on

I want to say a big thank you to Dr Akuna for giving me unspeakable joy, 13years ago i had Hepatitis B disease and it was a headache to me as my eyes turn yellow and after giving several tries in church and mosques and traditional homes and nothing worked out, i decide to surf online for possible cure for my ailment and to my great surprise i saw lots of people speaking of how Dr Akuna is using his herbal medicine to cure their diseases namely, HIV,CANCER,DIABETES,SARS,HEART DISEASE,BRONCHITIS AND MORE that cannot be wrote mentioned, and i also visited his website and i found out truly Dr Akuna has been helping a lot of people online, and i sent email to him and he replied back to me and i told me what and what is needed to get my herbal medicine and i gave him and without any delays i received my herbal medicine after using for 2weeks i went to test myself again and there was no trace of Hepatitis B disease in my blood again. to reach Dr Akuna Email:drakunasolutiontemple@gmail.com or Visit his web page :drakunasolutiontemple.com or Call him:+2348154625070 I'm sure he will be of help to your situation.

Submitted by Elizabeth on

I was diagnosed of Hepatitis B in 2016, I have tried all possible means to get cure but all my effort proved abortive, until a friend of mine introduced me to a herbal doctor from Africa called Dr.Ere, who prepare herbal medicine to cure all kind of diseases including Hepatitis B virus (Hepatitis B), when i contacted this herbal doctor via his email: dreremuselespell@yahoo.com, he sent me Hepatitis B herbal medicine via courier service, when i received the herbal medicine he gave me step by step instructions on how to apply it, when i applied it as instructed i was totally cured from the virus within 14 days of usage. Contact this great herbal doctor via (dreremuselespell@yahoo.com) or call him on his phone number +254728442268

Submitted by Sofia Maola on

I give this testimony to spread the good work of Dr Koba,when i gave birth to our first son,i was diagnosed with Diabetes and herpes virus and i have never been happy,my Spouse test himself and was also found herpes Positive,we suffered for many years, but i was optimistic that somewhere, someday there will be a way out of this horrible suffering, i went in searching of a way out, and i got jam on a page full of comment where they talked about a herbal doctor name Dr Koba. and i was certain he has solution for all ailment, so i contacted him and he advice me on how he can help me and i was happy after he assured me that 2weeks if i and my spouse is not cured i should know he is not a real herbal doctor, so i rely on his words and after 3days i received his medicine and i gave to my spouse and myself also took the medicine and after 2weeks i and my spouse went to test ourselves again, true to his words we both was confirm negative of herpes and my spouse diabetes was negative too, that is how my family was cured and free, do not waste anytime to contact this great man, on his
Email:drkobaherbalsolutionhome@gmail.com
Visit his website:https://drkobaherbalsolutionhome.wordpress.com/contact/

Submitted by Sofia Maola on

I give this testimony to spread the good work of Dr Koba,when i gave birth to our first son,i was diagnosed with Diabetes and herpes virus and i have never been happy,my Spouse test himself and was also found herpes Positive,we suffered for many years, but i was optimistic that somewhere, someday there will be a way out of this horrible suffering, i went in searching of a way out, and i got jam on a page full of comment where they talked about a herbal doctor name Dr Koba. and i was certain he has solution for all ailment, so i contacted him and he advice me on how he can help me and i was happy after he assured me that 2weeks if i and my spouse is not cured i should know he is not a real herbal doctor, so i rely on his words and after 3days i received his medicine and i gave to my spouse and myself also took the medicine and after 2weeks i and my spouse went to test ourselves again, true to his words we both was confirm negative of herpes and my spouse diabetes was negative too, that is how my family was cured and free, do not waste anytime to contact this great man, on his
Email:drkobaherbalsolutionhome@gmail.com
Visit his website:https://drkobaherbalsolutionhome.wordpress.com/contact/

Submitted by Eric Mark on

My name is Eric Mark from USA.. I was diagnosed with Herpes Genital Virus and i have been so unhappy everyday and depressed whenever i think that i have this virus in my body, and i had sore in my mouth and penis for the past 6 years, I have been dealing with this disease but I am thankful after seeing a comment on how Dr.Zuku has cured so many others, I email him and he sent me his natural herbs and when i used it within 2 week I was found negative after my Doctor tested me, i also found out that Dr.Zuku has remedy to other diseases such as, HSV 1&2, HEPATITIS B, CANCER,HIVAIDS,DIABETES,And GENITAL WARTS And many more,I am so surprise and happy thank you sir for curing my Herpes Genital Virus Dr.Zuku, you can write to him and get cured. email: drzukuspelltemple@gmail.com his Mobile number +16177296273 contact his Blogs https://drzukuspelltemple.blogspot.co.ke/ his website https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

Submitted by Thomas Kirkman on

Entirely grateful for the work Dr Akuna is doing to save lives around the whole globe, i was so happy to have witness his miracle in his herbs that he use to cure my HIV AIDS Disease,that i have suffered for 7years now, that many people are suffering from all around the world saying that there is no cure, i am writing to inform the whole world here is a cure for this deadly disease, you can get a maximum 100% guarantee cure with Dr Akuna Powerful herbs which save me from the disease that has killed so many. feel free to write him now and lay your complain, i know he has a solution for all ailment, you can visit his website:https://drakunasolutiontempleofallkindsofsicknessistreated.wordpress.com and also Call/ What app Dr Akuna:+2348154625070

Submitted by JOAN on

Indeed, this year 2017 is really mine, all thanks to chief priest of solution who help me in having my husband back after three years of separation, i have fallen a victim of scam on several occasion but i just felt having my husband back worth all the risk in the world' till I met DR.LOVESPELL who finally helped me. for this simple reason i am telling the world that DR.LOVESPELL is real and reliable, for help you can contact him on this email and te.+37060501930(lovespellpower@hotmail.com)from JOAN

Submitted by Jazmine Davis on

Am here to testify of the miraculous work of a great traditional doctor called DR.ZUKU ..I have been suffering from Herpes since last 2 years with my Husband but today I am happy that am cure from it with the herbal medicine made by Dr.ZUKU the great healer, I was browsing the internet searching for help when I came across a testimony shared by someone on how Dr.ZUKU cure her from Herpes Disease. I quickly contacted him to get the cure and today i am now free from the Virus, I am so much happy today that we have someone like this great healer out there, so' people out there kindly contact this great doctor on his email address please sir keep your good work cause there are people out there who is in need of your healing medicine .once more contact him now drzukuspelltemple@gmail.com or contact Dr Zuku Blogs https://drzukuspelltemple.blogspot.co.ke/ call or text +16177296273 Dr.Zuku can prepare Herbal medicine for all kind of disease. HIV. CANCER. HEPATITIS B.DIABETES.COLD SORES. Syphilis. HBV, HPV, STD's And many more.contact Dr.Zuku to get your healing.True Website https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

Submitted by Sylvia Bane on

I will always give thanks to Dr Mabuwa help on my family, i was the last born of my family, and it was said that we suffered from Hepatitis B disease, and it was very hilarious as my elderly brothers and sisters suffered from this disease, i was tired and decided to look for help for my family, and so i went online and i saw many blogs talking about Dr Mabuwa how he has helped some others person, and so surprisingly his herbs was so powerful, so i contacted him and asked for his help and that was how he prepared 4bottles for the 4 of us, and when we received it and started using it in 2weeks i was totally cured and that was how we went to test ourselves and we were found negative, i am so happy by your work Dr Mabuwa, why not contact his Email address:drmabuwasolutioncuretemple@gmail.com or What app him:+2348130714541 or website:https://drmabuwasolutioncuretemple.wordpress.com/contact/

Submitted by Rose Roxas on

I want use this opportunity to tell the world what has really happened to me for past few months, I have been married for two years without a child i was so worried, I have visited several hospitals and I was told i can't not conceive because i was having fibroid, I have been treated and even undergoes cloistral operation but still couldn't conceive until One day i came across Lillian Testimony on a guest book she was sharing the same problem exactly what is happening to me how Dr,,Miracle has cure his Fibroid, immediately i contacted him and told him about my Problem and he gave me hope that i should not be worried at all that he has cure more people already having same problem and said he can cure me under 8 weeks i was amaze. I Believe in him because he was the only hope and i followed him up he prepared me some herbs and send it to me in my state. I started using the herbs with his prescriptions, as i was taking the herbs i started noticing some changes in my body, to cut everything short i missed my period and today i have a child baby girl, My husband is so much happy and my mum too God. Thank you Dr,,Miracle I can't just keep this to my self i decided to share and post it here on-line for everyone to see that the work Of God In My Life True His Son Dr,,Miracle God Bless Doctor And More Grace To His Work,Here’s His Contact: Email Him At: ((Miraclespellhome@yahoo.com)) ,,,You Can Also Call Him Or Add Him On Whats-app: +2348071398555 ,,

Dr Koba is TRUE herbalist who helped my father to be cured from 10 years Diabetes disease which he suffered since when he was 33years old and he has done all clinical checkup but the disease was growing very strong and bad, but so thankful on the day i saw Dr Koba Email:drkobaherbalsolutionhome@gmail.com and also saw comment of him helping lot of people, i copied his email and wrote to him, within 4hours he replied back and i told him about my father health and he assured me that my father will be cured from his diabetes disease, i believed him, so i did all i had to do to get the medicine and when my father received it, he gave me instruction to take the medicine and that was how my father after 2weeks went to check up again and behold there was no trace of Diabetes disease on him, my father is so much happy and full of life now. get Dr Koba herbal super cure now. Call him/ What app:+2349037387574 or Visit his website:
https://drkobaherbalsolutionhome.wordpress.com/contact/

Submitted by Candy Wilson on

Thank to Dr.ZUKU i will forever continuously testify Dr.Zuku for changing my life with your herbs Remedy, i have be Suffering from HEPATITIS B over Three years ago i have battled with this virus and was about to ruin my entire body,I have been living with this virus and it has been giving me challenges,one morning i was browsing through the internet then i saw several testimonies about Dr.Zuku curing people from HEPATITIS B and immediately i contacted Dr.Zuku on his email and he assure me that will prepared herbal medicine and when after drinking for 2 weeks i went back to my doctor and my result came out HEPATITIS B negative.Viewers i am so glad, email Dr.Zuku and get your cure. Email: drzukuspelltemple@gmail.com call or text for more information +16177296273 contact Dr Zuku Blogs https://drzukuspelltemple.blogspot.co.ke/ or contact Web/Site https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

Submitted by Wells Cobes on

Grateful to Dr Akuna for all his help for my life, my partner was having Herpes Simplex Virus, and we were planing on getting married on early December, when we decided to get ourselves tested first and we found out that my fiancé was HSV 2 Positive, my fiancé was so unhappy, because this was a barrier for us to get married, so i went out to search out a remedy for my partner, and it was so surprising how Dr Akuna has been a blessing and healing to the masses, after reading about his work on a blog i immediately emailed him: drakunasolutiontemple@gmail.com and he wrote back to me that my fiancé will be OK and that we we get married this same year, i couldn't believe it, after doing all that is needed to be done, i was surprise that after 2weeks of using his medicine my fiancee went to the doc and was diagnose negative. For more info contact his email or What app:+2348154625070 or Website:https://drakunasolutiontempleofallkindsofsicknessistreated.wordpress.com/

Submitted by Tosha Parker on

I am very happy to share this amazing testimony Dr.Zuku herbs help me to cure my Herpes Simplex Disease and i have this Herpes 3 months ago.. i had unprotected with man i met and he did tell me he had Herpes disease after some weeks later i started seeing bump and sore on my vaginal, and i was so scared so i went to my doctor and did some test and behold i was confirmed Herpes positive, i went home so confuse and frustrated about this, especially when i was told there was no permanent cure for it, i said to myself i need to research about this, maybe there might be a herbal help for me, and so i did and when i was researching about herbal herbs, i keep seeing Dr.Zuku on every blog and guestbook, so i immediately wrote to Dr.Zuku, after we discuss he prepared my medicine and sent it to me, within few days i received my medicine and started applying it as instructed within 2weeks Dr.Zuku told me to go and check up, and i did, shocking my result came out negative, i am so thanks to you sir,
contacthis email address,

drzukuspelltemple@gmail.com

more information Number :+16177296273

contact Dr Zuku Blogs

https://drzukuspelltemple.blogspot.co.ke/

his website https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/c...

Submitted by Roger on

I was diagnosed of hepatitis in 2016, I have tried all possible means to get cure but all my effort proved abortive, until a friend of mine introduced me to a herbal doctor from Africa, who prepare herbal medicine to cure all kind of diseases including hepatitis b virus (Hepatitis), when i contacted this herbal doctor via his email dreremuselespell@yahoo.com, he sent me hepatitis b herbal medicine via courier service, when i received the herbal medicine he gave me step by step instructions on how to apply it, when i applied it as instructed i was totally cured from the virus within 14 days of usage. Contact this great herbal doctor via dreremuselespell@yahoo.com or call him on his phone number +254728442268

Submitted by Dr otubo on

Am here to appreciate Dr otubo for using his herbal medicine to cure my /WARTS virus. since 5 years now I have been living with this virus and it has been giving me challenges, I was so perplexed cause i have been taking several drugs to be cured but all of my effort was in vain,one morning i was browsing through the internet then i saw several testimonies about Dr. Aba curing people from Herpes virus and immediately i contacted Dr. otubo on his email: drotubospellhome@gmail.com i told him about my troubles and he told me that i must be cured, gave me some instructions and which i rightly followed. so he prepared a herbal medicine for me and sent it to me which i used for 2 weeks and everything was like a dream to me and my Herpes virus was totally gone, why don't you contact him today and be free from your diseases because he is very good and honest Doctor. contact him via email. drotubospellhome@gmail.com or whatsApp him on +2348161532663 OR +2348115151940 HERPES / HPV ETC

Submitted by Roger on

I was diagnosed of hepatitis in 2016, I have tried all possible means to get cure but all my effort proved abortive, until a friend of mine introduced me to a herbal doctor from Africa, who prepare herbal medicine to cure all kind of diseases including hepatitis b virus (Hepatitis), when i contacted this herbal doctor via his email dreremuselespell@yahoo.com, he sent me hepatitis b herbal medicine via courier service, when i received the herbal medicine he gave me step by step instructions on how to apply it, when i applied it as instructed i was totally cured from the virus within 14 days of usage. Contact this great herbal doctor via dreremuselespell@yahoo.com or call him on his phone number +254728442268

Submitted by susan on

It’s obvious some patient with HIV/CANCER are been enslaved to the antiviral and other supplementary Orthodox medicine just to help suppress the virus and not a cure. I have been with the virus since 2012 until I was introduce by a blogger who also narrated Her story online on how she was cured of Hepatitis b after using Dr Ajayi Herbal Medicine. This is a year and 2 weeks since I was delivered from Hepatitis b. All thanks to God for using this Great herbalist to heal me. I have promise to keep telling good about this. Please fill free to share Your problems with him and don’t forget to tell him I did refer you to Him. Thanks. Write him on mail drajayiherbalhome@gmail.com or Ajayiherbalhome@hotmail.com or whatsapp him on +2349054914348

Submitted by lindacarter12 on

Do anyone still doubt natural herbs? I've seen the great importance of natural herbs and the wonderful work they have done in people's lives. I wonder why people still spent their hard earn money on injections and drugs each time they are sick. Natural herbs can cure herpes, diabetics, asthma, HIV, hepatitis, etc. I've seen it with my own eyes. I was cured of HIV and my aunt was cured of herpes by Dr. Baba Ogu natural herbs. Even Dr. Sebi prove to the whole world that natural herbs can cure all illness and he cured countless of people using natural herbs. Dr Baba Ogu is also a spell caster, he can cast a spell to bring back your ex lover, a life betterment spell, etc. i know is hard to believe but am a living testimony. If anyone here is sick or has problem, why not give him a try, there is no harm in trying. Contact Dr. Baba Ogu with the below details:
Email address: drbabaogu@gmail.com
phone/whatsap no: +2348137291215
Facebook: facebook.com/Dr.babaogucurecenter/

Submitted by Alex Eliana on

I'm here to testify about what DR. PEPOKO did for me. I have been suffering from (GENITAL HERPES VIRUS) disease for the past 2 years and had constant pain and inching, especially in my private part. During the first year, I had faith in God that i would be cured someday.This disease started circulating all over my body and I have been taking treatment from my doctor, few weeks ago I came across a testimony of Lolita Thompson on the internet testifying about a Man called DR. PEPOKO on how he cured her from 5 years HSV 2. And she also gave the email address of this man, advise anybody to contact him for help on any kind of diseases that he would be of help, so I emailed him telling him about my (HSV 2) he told me not to worry that I was going to be cured!! Well, I never doubted him I have faith he can cure me too,, DR. PEPOKO prepared and sent me Healing Oil, Soap, roots and herbs which I took. In the first one week, I started experiencing changes all over me, after Two weeks of using his Roots/ Herbs, Oil and Soap, I was totally cured. no more inching , pain on me anymore as DR. PEPOKO assured me. After some time I went to my doctor to do another test behold the result came out negative. So friends my advise is if you have such disease or know anyone who suffers from it or any other disease like HPV, HBV, HIV, ALS, HBP, CANCER etc. you can contact DR. PEPOKO for help via email} pepokoherbatemple@gmail.com or whatsaap him through his mobile} +2347053699933
You can also email me on alex.eliana4040@gmail.com I may not reply your mail immediately but at my leisure i will do so, Thanks once again DR.PEPOKO for making me a happy woman again

E-mail::: pepokoherbatemple@gmail.com

whatsapp Or Viber number::: +2347053699933

Here is my details also if you wish to contact me personal:::: alex.eliana4040@gmail.com

Submitted by don emily on

I have been suffering from (HERPES) disease since last year without hope for cure and i was miserable until this year i was checking on new developments about this virus then i saw how different persons talks about getting cure for herpes through a particular herbalist called Dr.Adodo so I Contacted him through his email (Adodospelltemple@gmail.com) and he responded with instructions about what he needs to prepare the herbal medication which i did and he sent it to me in LA and after taking the herbal medicine as he instructed i went back to the hospital few days later and the test result shows i,m negative and now i,m completely free of genital Herpes thanks to Dr.Adodo for his urgent response, you can call his personal cell phone +1 (661) 704 3225

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