A new clinical study has shown that over half of COVID-19 patients developed diabetes in individuals who were not previously diagnosed with diabetes. In addition, the majority of intubated COVID-19 patients and those who died of the disease had high blood sugar.
To be clear, pre-existing diabetes is a significant risk factor for individuals who contract COVID-19, but this study provides evidence that COVID-19 itself can cause hyperglycemia. Of course, increased blood sugar caused by COVID-19 will put the patient at even higher risk of hospitalization and death, so it becomes a positive feedback loop.
I’ve written about this before — there is solid evidence that COVID-19 is linked to diabetes, but this study not only reinforces that claim but also researchers have proposed a biologically plausible mechanism for causing it.
Let’s take a look at this new research and the proposed mechanism.
What is diabetes?
Type 1 diabetes is an autoimmune disease that is characterized by autoreactive T lymphocytes (T-cells) that destroy pancreatic islet beta cells, which produce insulin. Essentially, these lymphocytes mistakenly attack the islet cells as if they were a foreign body, as they are supposed to do with a viral or bacterial infection.
In addition, regulatory T-cells (which are often called Tregs) modulate the immune system and would normally reduce the effect of an autoimmune attack. Tregs act like brakes that normally prevent mistaken attacks, like on the pancreatic islet cells, without affecting the whole immune system. A branch of diabetes research has suggested that abnormal Tregs could be the key to finding treatments to reverse type 1 diabetes.
Once the pancreatic islet cells are damaged, they no longer produce insulin, which is critical to regulating the levels of blood glucose. Without insulin, the blood glucose levels increase rapidly leading to long-term damage to eyesight, kidneys, limbs, heart, and other organs.
In fact, type 1 diabetes can be deadly if uncontrolled blood sugar leads to a life-threatening condition called diabetic ketoacidosis. Without regular insulin injections, a patient has little chance of living beyond a short period of time, and even then it could lead to a horrifically painful demise.
It is not known what causes this autoimmune disease, although there is strong evidence that genetics is the most important factor. However, other things may be implicated, like vaccine-preventable diseases, which could be important co-factors in the development of the disease. Just to be clear, vaccines are not linked to type 1 diabetes.
Currently, there are no known cures for type 1 diabetes. The only treatment for the disease is regular injections of human insulin, manufactured from genetically engineered E. coli cultures. In addition, careful diet and lifestyle management help regulate blood glucose levels, although it cannot replace insulin injections.
Type 2 diabetes is a substantially different disease from type 1. Mostly, type 2 diabetics produce insulin, just an insufficient amount to regulate glucose levels, or their cells have become resistant to insulin because of lifestyle issues. There is almost no relationship between type 1 and type 2 diabetes, except they share the same symptoms of high blood sugar.
COVID-19 and diabetes study
Cardiologist James C Lo and colleagues published the study in Cell Metabolism on 2 November 2021. They studied the blood glucose level of 3854 COVID-19 patients. The results were:
- 49.7% of all COVID-19 patients had hyperglycemia (blood glucose > 170 mg/dL, 120 would be “normal”)
- 91.1% of intubated COVID-19 patients presented with hyperglycemia.
- 72.8% of COVID-19 patients who had died had hyperglycemia.
- Hyperglycemia was associated with a 15X increased risk of intubation and a 3.6X increased risk of death.
- The median length of hospital stay was more than 2-fold longer for patients with hyperglycemia at 10 days compared to 5 days for those without hyperglycemia.
To be clear, these results don’t establish causality — they don’t know if the high blood glucose levels cause the bad outcomes from COVID-19, or if COVID-19 causes hyperglycemia.
High blood glucose levels have been reported in the past with individuals who have acute respiratory distress syndrome (ARDS) caused by injuries or infections other than COVID-19. So it’s not surprising to see diabetes linked to those who have COVID-19, which causes ARDS.
But why?
Some studies had suggested that the coronavirus infected the beta cells in the pancreas that makes insulin. However, Lo’s group found that COVID-19 patients with high blood sugar still made C-peptide, a small protein manufactured in the pancreas that links the chains of insulin together so that it can function. Generally, a normal C-peptide level means that the beta cells are producing insulin.
So, what is causing hyperglycemia but still producing normal amounts of insulin (usually a sign of type 2 diabetes)?
The researchers hypothesize that fat cells infected with the coronavirus send the wrong message to other cells ultimately leading to diabetes. Lo’s team determined that COVID-19 patients had low levels of adiponectin, a hormone produced by fat cells that signal other cells to absorb glucose. Without it, blood sugar isn’t absorbed by the cells, leading to hyperglycemia.
Fat cells do more than just store fat — they are an intimate part of regulating blood sugar. And there is more evidence from a German research team that shows that the SARS-CoV-2 virus, which causes COVID-19, can infect and replicate in human fat cells. The German researchers uncovered evidence that coronavirus infection also affects fat cells’ ability to metabolize some lipids, leading people with COVID-19 to develop high levels of triglycerides in their blood, which is more evidence that the fat cells are not working properly in some COVID-19 patients.
All of this research suggests that COVID-19 patients’ high blood sugar levels result from insulin resistance — a condition in which cells ignore insulin’s message to take in glucose — brought on by a paucity of fat hormones rather than by an inability to produce insulin.
As of right now, all of this research “hints” that COVID-19 may lead to diabetes, but we still don’t know if hyperglycemia is a pre-existing condition that leads to more severe COVID-19 outcomes, or COVID-19 causes diabetes. Research on this area is moving quickly, so this is preliminary. However, that’s how science works — slowly building evidence (or not) over time.
Stay tuned. And this should provide more reasons to get fully vaccinated.
Citations
- Reiterer M, Rajan M, Gómez-Banoy N, Lau JD, Gomez-Escobar LG, Ma L, Gilani A, Alvarez-Mulett S, Sholle ET, Chandar V, Bram Y, Hoffman K, Bhardwaj P, Piloco P, Rubio-Navarro A, Uhl S, Carrau L, Houhgton S, Redmond D, Shukla AP, Goyal P, Brown KA, tenOever BR, Alonso LC, Schwartz RE, Schenck EJ, Safford MM, Lo JC. Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2. Cell Metab. 2021 Nov 2;33(11):2174-2188.e5. doi: 10.1016/j.cmet.2021.09.009. Epub 2021 Sep 16. Erratum in: Cell Metab. 2021 Dec 7;33(12):2484. PMID: 34599884; PMCID: PMC8443335.
- Zickler M, Stanelle-Bertram S, Ehret S, Heinrich F, Lange P, Schaumburg B, Kouassi NM, Beck S, Jaeckstein MY, Mann O, Krasemann S, Schroeder M, Jarczak D, Nierhaus A, Kluge S, Peschka M, Schlüter H, Renné T, Pueschel K, Kloetgen A, Scheja L, Ondruschka B, Heeren J, Gabriel G. Replication of SARS-CoV-2 in adipose tissue determines organ and systemic lipid metabolism in hamsters and humans. Cell Metab. 2022 Jan 4;34(1):1-2. doi: 10.1016/j.cmet.2021.12.002. Epub 2021 Dec 10. PMID: 34895500; PMCID: PMC8663969.
