Saipan doing well with COVID-19 infection.

Compared to the rest of the world, Saipan and the CNMI are faring quite well.  COVID-19 testing levels here are higher, while disease rates and death rates are lower than most other parts of the world.  As I have previously blogged, Saipan is especially vulnerable to COVID complications, as they occur at much higher rates in those with diabetes.  Since Saipan has one of the highest rates of diabetes in the world, we need to be especially careful here.  In the following paragraphs I will outline how the CNMI compares to other parts of the world in terms of COVID-19 testing rates, rates of disease, and of course death.

COVID-19 Testing

So far the CNMI has tested 1480 people for COVID-19 infection.   Directly comparing this to other parts of the world can be difficult.  Most studies will list findings in tests per million population.  Maybe my epidemiology skills just aren’t strong enough, but I have trouble picturing what a gathering of a million people would look like.  I can, however, easily picture 1000 people.  Therefore, most of the numbers I discuss will be in cases per thousand population.  As the estimate of our CNMI population is 56,682, doing the math tells us we have done 26 COVID tests for every thousand people living here.

Most countries have done FAR less than this.  I will list a few below, again this is per thousand people.

1. CNMI                         26
2. Italy                           34
3. USA                            21
4. Turkey                      12
5. South Korea             12
6. India                           4
7. California                   1.9
8. Japan                          1.4
9. Philippines                1.0

Only a handful of countries have done more testing per capita than the CNMI.  These include Iceland, Estonia, and Italy.

Another interesting comparison is to other US territories.  Guam has done comparatively well, but lags behind the CNMI.  In order of the number of tests per thousand population.

1. CNMI                         26
2. Guam                        19
3. US Virgin Islands    10
4. American Samoa 1
5. Puerto Rico 0.4

The CNMI has done more COVID testing per person than almost anywhere else in the world.  Guam is not too far behind, but CNMI has tested 26 times more than American Samoa, thirteen times more than California, and 60 times more than Puerto Rico.

I consider the level of testing done in the CNMI thus far to be quite remarkable.  We should all be very proud of our first responders, the leadership of CHCC as well as the Governor’s COVID-19 task force.  They had very limited resources to work with, and clearly maximized them.  This accomplishment is even more extraordinary when you consider that other parts of the world all had a significant head start.   Our first COVID case was announced on March 28.  The US as a whole had its first case in early January.  Many, many other countries had a very slow start to their testing, not the CNMI.  It is also important to consider that the Virgin Islands, Puerto Rico, and Guam are much wealthier than the CNMI.

COVID PREVALENCE

So far 14 people have been diagnosed with COVID-19 in the CNMI.  This is less than one person per thousand (0.25).  About 1 of every 4,000 people in the CNMI has been diagnosed.  Most parts of the world are much worse than this, here is a partial listing of cases per thousand population.

1. CNMI                         0.25
2. Spain                         5.3
3. USA                            3.7       
4. Italy                           3.5
5. Great Britain            2.8
6. South Korea              0.21
7. Japan                         0.12    

From the above you can see that most major countries in Europe, as well as the United States have between 15 to 20 times more cases per thousand than the CNMI.  Among major countries only South Korea (barely) and Japan have a lower prevalence than Saipan.

Now a comparison to other US Territories:  COVID cases per thousand population.

1. CNMI                         0.25
2. Puerto Rico               0.60
3. Virgin Islands           0.62
4. Guam                        0.89
5. American Samoa      No cases yet

In other words, the other territories have 2.5 to 3.5 times more cases per thousand than us in the CNMI.

Deaths from COVID

So far two people have died from COVID-19 infection in the CNMI.  With so few cases, statistical analysis is difficult, and even one more case can dramatically change the numbers.  I will list a few anyway.  2 deaths in the CNMI is equivalent to 1 in 28,000 or (0.04).   Because the numbers are so small I will use deaths per 100,00 for comparison purposes. 

 Below is a listing:  Deaths per one hundred thousand population

1. CNMI                         3.5
2. Guam                        3.6
3. Spain                         54
4. Italy                           48
5. Great Britain            43
6. United States           21
7. South Korea              0.5
8. Japan                         0.4

Most countries have a death rate from COVID-19 between 7 and 17 times higher than the CNMI.  Guam and Saipan are very similar to each other, while South Korea and Japan have extraordinarily low death rates compared to virtually anywhere else.

Overall, these findings have been highly reassuring to me.  Of course great caution and care is still needed, things could easily get worse. Also, there are currently 110 pending tests, if many are positive, these numbers will change. I had, however, feared it would be far worse at this point.  I will encourage my friends at CHCC and the Governor’s task force to keep up the good work.  What has been accomplished so far with testing is simply amazing.

Good blood sugar control in those with the COVID-19 infection appears to be highly protective in the latest study released yesterday.  Here in Saipan, I have been especially concerned about my patients with diabetes.  Previous studies such as this one from the Journal of the American Medical Association have shown that people with diabetes who develop COVID infection are around three times more likely to die than others.  With the incredibly high rate of diabetes seen in the CNMI our population would be especially vulnerable.

The latest study presented in the journal Cell Metabolism looked at a cross section of 7337 positive cases of COVID-19 across 19 hospitals in Hubei province, China.  952 had diabetes.   282 where well controlled, 528 showed poorly control blood sugar.  Like other studies, those with diabetes were about three times more likely to die (7.8 percent, compared to 2.7% of the non-diabetic control group).  However, researchers where surprised to see vary favorable outcomes in those whose diabetes was controlled.  Patients with well controlled diabetes died at a lower rate than the overall rate of death in the non-diabetes cohort.   The comparison grew more startling when comparing those with the best and worst diabetes control.  The patients with the worst diabetes control where 10 times more likely to die than diabetes patients with excellent control.

The studies authors had three takeaway points:

1.  People with diabetes are at increased risk to die if they develop COVID-19, also suffering more complications when compared to the non-diabetic population.  Therefore, those with diabetes should do more to prevent infection,
2. Patients with diabetes should take extra care to fully control their blood sugar during this pandemic.
3. If infected it is extremely important to maintain good diabetes control in addition to other needed treatments.

 Yesterday the Centers for Disease Control  released their 2020 National Diabetes Statistics Report.  I will list some of the findings I find especially pertinent to the CNMI below:

Last year I wrote a diabetes newsletter to the Physicians and other medical providers on Saipan, Rota & Tinian.   It detailed new treatments for diabetic retinopathy with Fenofibrate.  Also updates on diabetes medications Metformin and Jardiance.  I will be writing more on these topics soon.  Till then here is last years update:

Diabetes Update  
Diabetes information for health care professionals  

Highlights
 -Metformin safe to a GFR of 30, see FDA announcement.
     -Jardiance lowers death and heart disease from diabetes
     -Fenofibrate proven effective to treat worsening retinopathy

Metformin Safe for most patients with renal disease

On April 8, the FDA announced changes in its guidelines for Metformin. They no longer recommend using creatinine readings to restrict its usage.  The American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists(AACE) have long called for this change. When metformin was approved in 1995, it was not initially approved for patients with kidney disease. This restriction was based on experience with phenformin, which was removed from the market in 1976 after it induced severe lactic acidosis in many patients with kidney disease. Metformin, in numerous studies over the years, has not been associated with this problem. In fact, most studies have shown a lower rate of lactic acidosis with metformin, compared to patients taking other diabetes medications.

The new guidelines from the FDA call for the use of Metformin down to a glomerular filtration rate (GFR) of 30. The ADA is slightly more conservative.  Their standards,  call for the use of Metformin in nearly every patient for the entire course of their diabetes, first as monotherapy, then in combination with other oral medications and/or insulin. The ADA recommends using maximal dose Metformin until stage 3b kidney disease, when the GFR goes to 44 or lower. If the GFR falls between 30 and 44, limiting the dosage to 1000 mg/day is recommended. If the GFR drops below 30, then Metformin should be discontinued. These are similar to the clinical guidelines being used in most developed nations.

This decision from the FDA has been widely praised by diabetes experts, here is one example:                           Silvio Inzucchi, MD, of Yale Diabetes Center, New Haven, Connecticut,” I am very pleased that the FDA has made their decision to expand the potential use of metformin to more patients. Evidence has emerged over the past 2 decades that the prior guidelines as related to renal function were overly restrictive and, essentially, prevented the use of this important, effective, and inexpensive generic medicine to hundreds of thousands of patients in the US.”

Jardiance (Empagliflozin) and Cardiac Death

Dramatic decreases in heart failure and cardiovascular death surprised researchers studying diabetes patients taking Jardiance (empagliflozin). The study: EMPA-REG or Empagliflozin, Cardiovascular Outcomes & Mortality in Type 2 diabetes, was released in the New England Journal of Medicine in Sept. 2015.   It was a randomized, double blind, placebo controlled study of just over 6,000 patients followed for a period of 3.1 years. Patients had an entering A1C of 7.0 to 9.0, the majority had pre-existing cardiac disease.
In the study Jardiance showed a 38% reduction in cardiovascular mortality, and a 32% reduction in all-cause mortality. This was a surprise to researchers as studies of other medicines have shown limited to no improvements in cardiovascular disease deaths. Metformin is the only other diabetes medication that has been proven to lower cardiovascular mortality.

These results have shifted the treatment strategies for many physicians. Please see this discussion from Anne Peters M.D., an endocrinologist and director of the USC Westside Center for Diabetes.   Many leading diabetes specialists are now placing Jardiance as second line therapy to add when Metformin fails to achieve glycemic targets, especially in patients at higher risk for heart disease.

Jardiance is a Sodium Glucose Transport (SGLT- 2) inhibitor, first approved by the FDA in 2013. Other medications in the same class include Invokana and Farxiga. SGLT-2 inhibitors work by decreasing renal glucose re-absorption in the proximal tubule, thus increasing urinary glucose excretion. This extra excretion of glucose averages about 100 g of sugar in the urine per day, leading to weight loss. In most studies including EMPA-REG, the weight loss averaged about 8 pounds over the first 26 weeks. In EMPA-REG the weight loss was maintained throughout the three-year study period.

Studies have shown a low rate of side effects. The most common has been termed a “nuisance” as opposed to serious side effect. Between 5-10% of women experienced genital mycosis infection, a smaller percentage occurred in uncircumcised males. These infections usually occurred just once, early in the treatment course, with very few recurrences. More serious side effects have proven rare. The largest studies showed a similar rate of ketoacidosis in Jardiance and placebo treated patients. Other, smaller studies have raised a concern about rare, but increased rates of ketoacidosis with Jardiance treatment, ongoing trials are in place.

Jardiance is on the Formulary for every major insurance in the CNMI including Calvos, Staywell,
Netcare/Moylan’s and Aetna. It is covered by Medicaid, but would require a prior authorization form to be filled out. Jardiance is an expensive medication, the average retail price in the U.S. is $371.00 per month, slightly lower than the cost of Januvia. In most studies it lowers the A1C an additional 0.7-1.0 when added to Metformin. It is available in dosages of 10 and 25 mg, with the 25 mg dose having slightly higher efficacy, but also a slighter higher risk of side effects.

Fenofibrate dramatically reduces diabetic retinopathy progression

Several large placebo controlled, double blind studies have demonstrated dramatic reductions in diabetic retinopathy with fenofibrate. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was centered in Australia. 10,000 patients were randomized to Fenofibrate or placebo. Over a five-year period, those in the Fenofibrate group were 79% less likely to have worsening retinopathy, and 31% less likely to require laser surgery. The ACCORD Eye Study randomized 5518 diabetes patients to either statin & placebo, or statin with fenofibrate. Both groups were followed for four years. The fenofibrate group had a 36% decrease in retinopathy progression and was also 31% less likely to need laser surgery, See this link for expert discussion of these study findings.

There have been growing calls for wider use of fenofibrate to treat retinopathy. In 2013 it was approved for treatment of retinopathy in Australia. See this editorial printed in Ophthalmology last year, Ophthalmology is the official journal of the American Academy of Ophthalmology.

The editorial calls for the use of fenofibrate in those with worsening retinopathy. Studies indicate that the beneficial effects seen for retinopathy are independent of any changes in cholesterol levels. The particular mechanism is not fully understood, but fenofibrate seems to protect against the breakdown of the blood-retinal barrier. In these large studies significant side effects were rare.

Kidney function is monitored when prescribing, as studies indicate fenofibrate should be stopped if GFR goes below 30. We will monitor liver enzymes, as this has been an issue in rare cases. Fenofibrate is contraindicated in those with gallbladder disease, and has not been tested in pregnancy, so should be avoided in women of childbearing years. It is relatively inexpensive, with an average US retail price under $30.00 per month, and is covered by every insurance in the CNMI.

Don Hardt is a Board Certified Optometrist and Certified Diabetes Educator, (C.D.E.). He and his partner, his brother David, are two of only ten eye doctors in the United States who have become C.D.E.’s. Their clinic has the first, and the only Diabetes Education program to be officially recognized by the American Diabetes Association in any of the US Pacific territories.