Aberdeen Int Prep Flashcards
Role of nitric oxide in the body
Cellular function
Vascular function - Vascular tone, blood flow (muscle relaxation and vasodilation)
Defects in nitric oxide production can cause?
Endothelial dysfunction
Cardiovascular problems - hypertension, atherosclerosis
Spiked blood sugar levels
Insulin resistance
Type 2 diabetes
How is nitric oxide produced?
Nitric oxide synthase (NOS) oxidises L-arginine to L-citrulline producing NO from this reaction
Nitrate-nitrate oxide pathway - diatary nitrate (NO3-) is absorbed by small intestine. Enters circulation and 75% is excreted by kidney 25% uptake into the salivary glands. Nitrate reducing oral bacteria then reduce the nitrate to nitrite (NO2-) (mainly in the cleft of the dorsum) and is swallowed. Swallowed nitrite is reduced to NO in the stomach acid and remainder is absorbed by intestine and enters circulation to be reduced to NO.
Describe how we have a symbiotic relationship with oral bacteria
We provide bacteria with the necessary nitrate at the termainal electron receptor for respiration in the absence of oxygen.
We receive nitrite which can then be converted into nitric oxide.
What did the studies prove about the connection between oral bacteria and general health?
15 people with hypertension used antibacterial mouthwash for 3 days experienced increased nitrate concentrations in saliva and decreased nitrite. This was accompanied by an elevation in systolic blood pressure.
19 patients with healthy bodies show if mouthwash was used 7 days a week that 90% reduction in oral nitrite and a 25% reduction in plasma nitrite. These levels were accompanied by increases in systolic and diastolic blood pressure.
A systematic review of human and animal studies concluded that dietary nitrates from vegetables can reduce blood pressure.
The connection between NO and diabetes?
Reduced NO bioavailability causes increased insulin resistance.
There is evidence of decreased NO in obese patients and those with insulin insensitivity.
Increased NOS3 causes
Incresed NO form L-arganine to L-citruline
Anti-obesogenic
Insulin-sensing effects
Mouthwash and diabetes
Using mouthwash 2 times or more a day causes a significantly increased risk of developing prediabetes/diabetes combined over the course of 3 years compared to those using mouthwash less than twice daily. these risks total 50% increased likelihood.
Using mouthwash once daily did not increase the risk of developing diabetes compared to baseline.
What are the limitations of the study?
There were many limitations to the study:
Type of mouthwash - There was no documentation of the type of mouthwash used or why it was being used (mouthwash for reducing gingivitis or just for freshening breath). Antibacterial (gingivitis) mouthwash can reduce oral bacteria and affect salivary nitrite and thus plasma nitrite concentrations.
Glycated hemoglobin- The only variable measured to determine the risk of diabetes was the measurement of glycated hemoglobin. There was no data collected o the nitrate-reducing bacteria on the dorsum of the tongue or anywhere else, salivary or plasma levels of nitrate or nitrite or NO bioavailability. This means that they have no real confirmation of the mechanism of action and only likely associations.
Bleeding from probing - Important statistical information was left out ralating to the bleeding from probing in peope with prediabetes vs normoglycemic. Study reported a difference but P values were missing and on review of the data it looks statistically insignificant.
Periodontitis as a confounding variable -There were surprisingly high levels of periodontitis levels in those assessed with normoglycemic and prediabetes. This is surprisingly high and the thresholds for the definition of moderate to severe periodontitis was not stated in the study.
There is a documented link between periodontitis and diabetes.
Obesity - A high percentage of the people in the study were obese 65.7% for mouthwash twice a day and 63.1% for mouthwash less than twice a day.
Prediabetes less in those who use mouthwash at baseline - A high percentage of the baseline already had prediabetes. Also baseline levels of prediabetes were less in those using mouthwash twice a day. This is counterintuitive considering the findings of the study over a three-year period.
Prediabetes and diabetes pooled - Progression to prediabetes and diabetes were pooled together and not separated. This was heavily miss reported in media as they suggested a 50% increase in developing diabetes regardless of starting point which is not true.
Mouthwash use self reported -The use of mouthwash was self-reported and the participants have an interest in suggesting they do use mouthwash as they believe the clinicians will like this. There was no validation to the truth of how many times it was used a day.
Use of mouthwash before study - There was no information about when the participants started using the mouthwash at baseline. This means prior to the start of the study people could have been using it for years. This can obviously this could mean that these individuals are already experiencing effects prior to the study.
How many uses a day -There was no indication of how many times people in the more than twice-a-day category used mouthwash at baseline or if this number changed over the course of the three years.
Not applicable to general populous - This information is not necessarily reflective of non obese people as it only assesses those with high risk of developing diabetes anyway.
Misrepresentation of study reports in lay news
The study stated that there was a 50% increased chance of developing prediabetes/diabetes combined if you ue mouthwash twice a day or more while the newspaper stated 50% increase for just diabetes.
What is the link between periodontitis and diabetes?
Periodontitis can cause infection to spread to bloodstream and can cause the body to release molecules that raise blood sugar.
The researchers from the study however contacted the author and confirmed that when adjusting for periodontitis there was little to no difference in the result.
What things did the researchers try to address and the limitations of this?
They performed an ancillary study to find out retrospectively what type of mouthwash was being used on 132 users however it is not confirmed if these people are the same ones involved in the first study. They also reported brand names not the specific type.
Periodontitis advise in this paper?
Mechanical plaque control is much more affective than chemical control. Only in special instances where people cannot brush mechanically will mouthwash be truly advised.
However, should we dissuade people from using mouthwash especially when it can help with periodontitis which has been proven to cause diabetes?
What are the factors that the Puerto Rico study accounts for?
- Income
- Education
- Oral hygiene
- Oral conditions
- Sleep breathing disorders
- Diet
- Medication
- Insulin resistance
- Fasting glucose
- Two-hour post load glucose
- C reactive protein
Authors’ conclusions about the Puerto Rico study and what this means for general health?
- That mouthwash may not cause diabetes
- Preventing people from using mouthwash might be doing more harm than good
- There need to be more studies conducted in this area to allow us to keep up with emerging information in dentistry
