VA Antibiotics studies on increased Blood Sugar and Weight Gain

https://www.breathewellbeing.in/blog/do-antibiotics-raise-blood-sugar-levels-in-diabetics/

History:
After struggling with increased A1C, BMI and Weight Gain I went through several supervised and controlled Weight Loss Programs. My continued A1C levels and lack of Weight Loss regardless of lower caloric intake and exercise lead me to begin researching possible medical/drug related causes.

After a conference of sports Doctors and Special Forces Medical Personnel it was suggested I review all medications I had taken just prior to the onset of the condition. After a full nutritional work up with detailed blood panels I disclosed I was on Doxycycline for a year every day twice as an antiMalarial protocol while deployed to Iraq during River Operations and in Afghanistan while living next to the Helmand River the entire deployment.

Three separate medical professionals mentioned a known reaction in some people that a disturbance of gut bacteria has led to permanent changes which impact increased blood sugar levels, higher BMI and Weight-gain.

A medication several, at least 3 Doctors, have suggested to me is Wegovy/Semaglutide. The drugs original use was for type 2 diabetes but it also has been approved by the FDA for Weight Loss. I am curious if this medication works on the same portions of the brain as the article implies.

Wegovy/semaglutide 2.4 mg weekly

Thesis:
My current belief is the long term use of Doxycycline has in some people permanently altered their gut microbes in a way they were artificially suppressed so long the body adjusted the blood sugar levels naturally occurring to set its new baseline. This bodily action would be similar to the adjustment of dopamine from narcotic drug use.

I believe a medical treatment, either drug related or surgical, which lowers the body’s blood sugar levels and choleric absorption rate is needed for individuals whose bodies reacted to the antibiotics/doxycycline altering their baseline levels.

Below I have attached several Medical Research articles as well as peer reviewed studies. I am currently finishing the narrative and proper citing to bolster my thesis.

https://www.aarp.org/health/drugs-supplements/info-2021/semaglutide-weight-loss-drug.html

Doxycycline Side Effects

Medically reviewed by Drugs.com. Last updated on Dec 4, 2021.

Metabolic
Hypoglycemia in a nondiabetic patient has been reported.[Ref]
Common (1% to 10%): Increased blood LDH, increased blood glucose
Rare (0.01% to 0.1%): Decreased appetite, porphyria
Frequency not reported: Hypoglycemia, anorexia[Ref]

https://www.drugs.com/sfx/doxycycline-side-effects.html

Doxycycline Induced Hypoglycemia in an Adult without Diabetes

Abstract
Hypoglycemia in adults without diabetes is rare and finding the cause can be challenging. We report a case of 91 year old male who developed severe and persistent hypoglycemia after treatment with doxycycline (DOXY). He was admitted with fatigue and weakness after failed outpatient treatment for pneumonia with amoxicillin/clavulanic acid. He was started on DOXY and piperacillin/tazobactam. On day 6 of hospitalization, patient had a change in mental status, shortness of breath, and rapid AF. Serum glucose was 13 mg/dl. He was given boluses of dextrose 50%, and infusion of dextrose 10% started. However, the patient’s blood glucose dropped as low as 30 mg/dl. 72 hours after DOXY and lisinopril were discontinued the patient’s blood glucose returned to normal, and remained stable for the remainder of admission. ACE-I are reported to cause hypoglycemia, however, this was less likely as this patient had been on lisinopril prior to hospitalization and didn’t develop hypoglycemia on restarting it outpatient. Tetracyclines have been described as a cause of hypoglycemia in few case reports. The proposed mechanisms for tetracycline induced hypoglycemia include increase insulin sensitivity, increased half-life of insulin, interference with epinephrine induced hyperglycemia and tetracycline induced hepatotoxicity. Awareness for this potential adverse event should be considered as this medication is commonly prescribed.

Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, SUNY Upstate Medical University, 3229 East Genesee Street, Syracuse, NY, USA
2 Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave. Farmington, CT 06030-1235, USA

https://www.jbclinpharm.org/articles/doxycycline-induced-hypoglycemia-in-an-adult-without-diabetes-4725.html

NEWSLETTERS – CLINICIAN SITE – NEWS AND RESEARCH
Antibiotic Use Linked to Increased Incidence of Type 2 Diabetes

Apr 13, 2018
Laurie Tarkan with commentary by Kristian Hallundbæk Mikkelsen

Abstract
The new study, conducted in Denmark, looked at more than 170,500 Danes with type 2 diabetes and a control group of more than 1.3 million. The researchers examined the use of all systemic antibiotics between January 1, 1995, and July 1, 2012.

The study, published in the Journal of Clinical Endocriniology & Metabolism, found that patients treated for type 2 diabetes filled on average 0.8 antibiotic prescriptions per year compared to 0.5 prescriptions per year among controls. The more antibiotics someone took, the more likely they were to have diabetes. Those that filled 2 to 4 prescriptions of antibiotics of any type had a 53% increased risk of having type 2 diabetes than those who filled 0 to 1 prescriptions of antibiotics. Slightly higher risks were found for narrow-spectrum antibiotics (like penicillin) compared with broad-spectrum antibiotics, such as fluorquinolones or tetracyclines.

https://www.endocrineweb.com/news/diabetes/16474-antibiotic-use-linked-increased-incidence-type-2-diabetes

Doxycycline Alters Metabolism and Proliferation of Human Cell Lines
* Ethan Ahler ,
* William J. Sullivan ,
* Ashley Cass,
* Daniel Braas,
* Autumn G. York,
* Steven J. Bensinger,
* Thomas G. Graeber,
* Heather R. Christofk
Published: May 31, 2013

Results
Doxycycline Induces Metabolic Gene Expression Changes in Human Cells

To look in an unbiased way at the effects of Dox on cells in culture, we performed gene expression analysis on MCF12A cells–an untransformed breast epithelial line–treated with the drug at 1 µg/mL or with a vehicle control. Metabolic pathway enrichment analysis (using Gene Set Enrichment Analysis (GSEA)) revealed several pathways, including oxidative phosphorylation and glycolysis, to be significantly enriched in the Dox-treated cells (Figure 1A; for enrichment plots, see Figure S1). Many of the constituent genes in these pathways show a robust change in expression in response to treatment (Figure 1B; for annotated gene sets, see Figure S2), including key enzymes in glycolysis and its major carbon shunts (Figure 1C). These results demonstrate that Dox, at a concentration commonly used in inducible systems, can alter the metabolic gene expression profile of cells.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064561

New study suggests that repeated antibiotic use could lead to higher BMI long term.
Johns Hopkins Bloomberg School of Public Health

The findings, published online Oct. 21 in the International Journal of Obesity, suggest that antibiotics may have a compounding effect throughout childhood on body mass index (BMI), a measure often used to determine whether someone is at a healthy weight.

“Your BMI may be forever altered by the antibiotics you take as a child,” says study leader Brian S. Schwartz, MD, MS, a professor in the Department of Environmental Health Sciences at the Bloomberg School. “Our data suggest that every time we give an antibiotic to kids they gain weight faster over time.”

https://publichealth.jhu.edu/2015/children-who-take-antibiotics-gain-weight-faster-than-kids-who-dont.t#:~:text=Antibiotics%20kill%20off%20harmful%20bacteria,turn%2C%20can%20increase%20weight%20gain

Chronic antibiotic use during adulthood and weight change in the Sister Study

Conclusions:
Chronic use of antibiotics during adulthood may have long-lasting impacts on BMI. Associations may differ by antibiotic class, and confounding by indication may be important for someantibiotic classes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522121/

Antibiotic exposure and risk of weight gain and obesity: protocol for a systematic review

Discussion
This systematic review will summarize the existing evidence evaluating the association between antibiotic use, weight gain, and obesity and facilitate the identification of important gaps and uncertainties in the literature.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571496/

Antibiotic Use and Obesity—Is There a Link?

Research published ahead of print in the journal Antimicrobial Agents and Chemotherapy suggests that patients on long-term antibiotic treatment gained weight and had significant changes in their gut microbiota.

Doxycycline and hydroxychloroquine treatment exhibited a reproducible effect on the community structure of the gastrointestinal microbiota, with treated patients presenting significantly lower concentrations of beneficial bacteria, Bacteroidetes, Firmicutes, and Lactobacilli,” says coauthor Angelakis Emmanouil, of Unite de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), CNRS, Marseille.

https://www.medindia.net/news/long-term-antibiotic-treatment-causes-weight-gain-134749-1.htm

Antibiotics-Induced Obesity: A Mitochondrial Perspective
Andrade M.J.a · Jayaprakash C.a · Bhat S.a · Evangelatos N.b, c · Brand A.b,d,e · Satyamoorthy K.a, e
Public Health Genomics 2017;20:257–273
https://doi.org/10.1159/000485095

ABSTRACT
Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity. Apart from the involvement of biosocial causes influencing diet, physical activity, and antibiotic use, pathogenesis of obesity is linked to interconnected functional alterations in cells, tissues and organs due to biochemical, epigenetic and genetic factors. Mitochondrial dysfunction is one such factor, which is becoming the primary focus of various aspects of research on multifactorial complex diseases and is providing new perspectives on etiology, biomarker-based diagnosis, and drug sensitivity. Through this review, we have made an attempt to present the interplay between use of antibiotics, obesity, and associated mitochondrial dysfunction. This may provide insights into the molecular basis, genetic predisposition and environmental triggers, which in turn may have potential clinical applications in the management of antibiotic use.

In addition, intense antibiotic use causes mutations in the mitochondrial DNA, which could also lead to mitochondrial dysfunction and thereby, obesity. Antibiotics also exert their influence on cytokines, causing a decrease in energy production and increased ROS production, and alter the mitochondrial biogenesis pathways. Similarly, MMPs are affected by antibiotics such that they damage the structure and integrity of the mitochondria, activate the apoptotic machinery, and disturb ETC functionality. Moreover, MMPs are involved in adipose tissue remodeling, and control proteolysis and adipogenesis in obese individuals.

https://www.karger.com/Article/Fulltext/485095#

Doxycycline in Extremely Low Dose Improves Glycemic Control and Islet Morphology in Mice Fed a High-Fat Diet
Authors Chen Y, Chen Y, Wang N, Gu S, Wang M, Fu Y, Wei C, Xu W
Received 20 November 2020
Accepted for publication 15 January 2021
Published 11 February 2021 Volume 2021:14 Pages 637—646
DOI https://doi.org/10.2147/DMSO.S292264
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Juei-Tang Cheng

Results:
Doxycycline at 200 μg/mL tended to increase body weight, islet mass, and the percentage of large islets (diameter > 350 μm). At 20 μg/mL, doxycycline significantly improved glucose tolerance and decreased fasting blood glucose. At 2 μg/mL, doxycycline increased the percentage of small islets (diameter < 80 μm). Serum C-reactive protein and lipopolysaccharide levels significantly decreased while the beta-cell ratio increased in all doxycycline-administered mice.

Conclusion:
Our results suggest that doxycycline, even at an extremely low {dose, could improve glycemic control and islet morphology via its anti-inflammatory activities.

https://www.dovepress.com/doxycycline-in-extremely-low-dose-improves-glycemic-control-and-islet–peer-reviewed-fulltext-article-DMSO

Decoding a Direct Dialog Between the Gut Microbiota and the Brain
FeaturedNeuroscience·April 15, 2022

Summary:
Hypothalamic neurons directly detect variations in bacterial activity and adapt appetite and body temperature accordingly. The findings demonstrate a direct dialog occurs between the brain and the gut microbiota.

Source: Pasteur Institute
Gut microbiota by-products circulate in the bloodstream, regulating host physiological processes including immunity, metabolism and brain functions.

https://neurosciencenews.com/gut-brain-dialog-20383/?fbclid=IwAR3As7KFezkMbXzM91BwzFvNW6vVQO9KqVJD8_oXXLT97n7BnwhkpZt7Dcw

Long-term Antibiotic Use Tied to Higher CVD Risk
Batya Swift Yasgur MA, LSW
May 09, 2019

Women in middle or late life who use antibiotics on a long-term basis have a higher risk for cardiovascular disease (CVD) events, new research suggests.
Investigators followed close to 36,500 female participants in the Nurses’ Health Study (NSH) who were free of CVD at baseline over an 8-year period.

https://www.medscape.com/viewarticle/912793

Changes in the microbiota due to prolonged antibiotic treatment may lead to weight gain

The study has analysed for the first time the metabolic activity of gut bacteria enzymes present in stool samples of obese and lean individuals, as well as antibiotic-treated and non-antibiotic-treated persons. According to CSIC researcher and lead author Ester Hernández, “the study has allowed us to observe that obese people or those with a high body mass index and people treated with antibiotics show similar metabolic behaviour, with consequences for their ability to assimilate sugars from their diet.

Prolonged antibiotics treatment modifies the gut microbiota, increasing the activity of its enzymes and leading to swifter and more unbalanced absorption of carbohydrates, which may lead to obesity, food-related disorders and, in the last resort, diabetes.

The study’s conclusions open doors to future research that may lead to the development of personalised diets adjusted to the activity of the enzymes found in each individual’s intestine. Work could also be done in this respect on designing probiotic and prebiotic treatment that may be given along with antibiotics to minimise collateral effects, thus maintaining the diversity and composition of the gut microbiota.

https://www.gutmicrobiotaforhealth.com/changes-in-the-microbiota-due-to-prolonged-antibiotic-treatment-may-lead-to-weight-gain/#:~:text=Prolonged%20antibiotics%20treatment%20modifies%20the,in%20the%20last%20resort%2C%20diabetes

Some antibiotic treatments alter gut microbiota

If you took a microscope and zoomed on your intestine, you would find tens of trillions of bacteria that make up your gut microbiota. This community of microorganisms plays a key role in your health and wellbeing, as already reported on this blog, but it can also be affected by a range of external factors, including what we eat and the medical treatments we sometimes need to undergo.

In relation to this, a study led by group of researchers at the Spanish National Research Council (CSIC – Consejo Superior de Investigaciones Científicas), has confirmed that antibiotic treatment alters gut microbiota. For the first time, the bacteria, genes, enzymes and molecules that characterise the gut microbiota of a patient treated with antibiotics have been analysed. Results have shown that antibiotics lead to changes in our microbial and metabolic patterns, even during the initial phases of the treatment.

The study mentions damage to the biodiversity of gut microbiota, which can reach its minimum levels after 11 days of treatment. On completing the treatment, however, the situation can revert as the study showed that there was a general tendency towards the restoration of the original (day 0) untreated total and active bacterial composition of gut microbiota 40 days after cessation of the antibiotic treatment.

Nevertheless, researchers highlight that the study “shows for the first time that, as a result of an antibiotic treatment, gut bacteria present a reduced capacity for protein production and deficiencies in terms of other key metabolic functions, during and after treatment.” A notable finding in this study was that protein expression appeared to decrease as a consequence of antibiotic treatment in the analysed patient.

https://www.gutmicrobiotaforhealth.com/some-antibiotic-treatments-alter-gut-microbiota/

7 Common Meds That May Make It Harder to Control Your Blood Sugar
Take care when using these common medicines, and work with your doctor to minimize the effects.
By Alice Callahan
Medically Reviewed by Kacy Church, MD

Certain Antibiotics to Address Infections, Such as UTIs and Pneumonia
A class of antibiotics called fluoroquinolones, used to treat illnesses like pneumonia and urinary tract infections (UTIs), has been shown to cause both very low and high blood sugar, a study published in October 2013 in the journal Clinical Infectious Diseases found. In addition, pentamidine, an antimicrobial drug used to treat a certain kind of pneumonia, can also cause a rise in blood sugar.

https://www.everydayhealth.com/type-2-diabetes/treatment/medications-may-affect-blood-sugar-control-diabetes/

PMCID: PMC7124920PMID: 32043448
Impact of Doxycycline as Malaria Prophylaxis on Risk of Influenza-Like Illness among International Travelers
2004-5 Iraq Deployment

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124920/

Brief Report
January 12, 2005
An Outbreak of Malaria in US Army Rangers Returning From Afghanistan

https://jamanetwork.com/journals/jama/fullarticle/200113

When Severe Infection Causes Long-Term Mood Disorders
FeaturedNeurosciencePsychology·April 20, 2022
Summary: The activation of a neural circuit comprising of the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the first hours following sepsis infection induced anxiety behaviors in mice two weeks after the infection cleared. The behaviors mimicked the PTSD symptoms patients experience following sepsis infection.
Source: Intitute Pastuer

https://neurosciencenews.com/infection-mood-disorder-20422/?fbclid=IwAR34bhtL9z8H3N0TYidJm89uq2GBntTmRqSUEsGRFofKcqmADWaENDxXQsQ

Certain Antibiotics Tied to Blood Sugar Swings in Diabetics

https://www.medicinenet.com/script/main/art.asp?articlekey=172680

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This article is from the archives of the UB Reporter.
ARCHIVES
Treatment aids glucose level
Regimen for gum disease in diabetics improves glucose status
Published: March 20, 2003

https://www.buffalo.edu/ubreporter/archive/vol34/vol34n17/articles/diabetes.html

The Effect of Topical Doxycycline Gel on HbA1c in Patients With Type 2 Diabetes Mellitus(DM) ®

ClinicalTrials.gov Identifier: NCT0273583

https://www.clinicaltrials.gov/ct2/show/NCT02735837

Does doxycycline affect blood sugar?
16th June 2020nih21

https://answersdrive.com/does-doxycycline-affect-blood-sugar-13903811

A Common Medication with an Uncommon Adverse Event: A Case of Doxycycline-induced Pancreatitis
Shweta Paulraj , Prashanth Ashok Kumar, Dinesh Subedi

Published: April 01, 2020 (see history)
DOI: 10.7759/cureus.7496

https://www.cureus.com/articles/27240-a-common-medication-with-an-uncommon-adverse-event-a-case-of-doxycycline-induced-pancreatitis

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