Does NSF make my blood sugar go up?

I have heard this question before, so thought I would quickly address it.

Blood sugar could go up because 1) too much sugar intake, 2) less absorption of sugar into cells, 3) less utilization of sugar.

NSF is almost always associated with kidney disease. Kidney disease is a common side effect of diabetes. Many people with NSF have diabetes, or a tendency toward it. So if sugars are going up, it is important to ascertain you do not have diabetes. Diabetes is caused by an inability of cells to take up sugar (glucose). This could be because the insulin necessary to make this happen is not present or not effective. Diabetics also have an impaired ability to make glycogen (see below).

Too much sugar intake? Your body is good at regulating sugar. When too much is present it will be made into glycogen and stored in the liver. Following meals, people ordinarily have an elevation of blood sugar, and depending when the reading (level) was obtained, this might be normal.

Less utilization of sugar: again, if you are not using it, sugar tends to be made into glycogen for later use.

Another effect worthy of discussion: some medications can cause your blood sugar to go up. Commonly used ones include corticosteroids (prednisone), beta-blockers (for hypertension), and thiazide diuretics.

What is fibrosis?

Collagen is a protein made by animals and is the most abundant protein in mammals (1). It forms the structure, and provides the substance of skin, bone, and other connective tissues in humans. Collagen in human skin is chiefly of two types (Type I and Type III). Other types of collagen dominate in other organs and tissues. Collagen forms long strands or fibers, but is also capable of forming more elaborate shapes in different tissue types. Collagen production is normal and necessary for life. In human skin, collagen is chiefly formed by cells called "fibroblasts"(2).

If, for whatever reason, too much collagen is formed, the process is called "fibrosis"(3). One extreme version of fibrosis is "scarring" which occurs when fibrosis is extensive enough to obliterate the normal tissue architecture.

Fibrosis is can occur in many situations. In a myocardial infarction (heart attack) heart muscle cells will die due to the loss of available oxygen. To insure the integrity of the organ, collagen will form a scar. This is a trade off for the body. The heart can continue to function (saving the patient's life) yet will not function as well as it did originally.

In the event of traumatic injury to the skin, fibroblasts will create collagen to close the wound, knitting it together. Following surgery, an incision is sewn together, and the fibroblasts will "knit" together the edges of the cut. This occurs quickly. After a biopsy, stitches can usually be removed in a few days. The hole is closed, yet the fibroblasts continue to create new collagen to patch up the damage. After the structure is restored, fibroblasts and other cells will work to "remodel" the collagen, making it stronger, and insuring a closer semblance to the original tissue. This remodeling may occur over many weeks.

In the weeks following a large incision, the healing wound is red and tender around the stitches. This is because new blood vessels have formed and blood and inflammatory cells have made their way from these vessels into the surrounding tissues. These inflammatory cells coordinate the clean up of debris and the destruction of bacteria. They also summon local fibroblasts to migrate to the wound to create new collagen. Lastly, they send signals through the blood to recruit immature fibroblasts to come from the bone marrow. These immature fibroblast stem cells are called "fibrocytes." As they traverse the blood vessels to arrive at the site of injury they resemble white blood cells. They are called "circulating fibrocytes" (CFs). Once they arrive at the site of injury, they emerge from blood vessels into the tissues and transform from immature CFs to mature cells resembling fibroblasts.

CFs are present in everybody's blood at a low level. In some instances they may temporarily increase in number depending on the needs of the body. CFs can be identified in the blood by a combination of markers that "fingerprint" the cell. One of these is procollagen I (an immature form of Collagen type I). Another is a CD34. CD34 is a marker that identifies many types of "immature" cells, as well as the lining of blood vessels. The combination of CD34 and procollagen I in the same cell is unique to CFs (4).

The arrival of many CFs at the site of tissue injury leads to the production of abundant collagen. The incision scar will get very hard. Once the stitches are removed, the scar is raised and very firm. Over time, however, remodeling of this scar takes place, the amount of new collagen tapers off, and the scar flattens out and becomes flesh colored or slightly white.

There are many disorders that result in fibrosis. As with a heart attack, fibrosis may be the last point on a long journey that insures the continued function of an organism. Severe inflammation, such as one might see in pneumonia, can lead to lung fibrosis. Coal miner's lung, and asbestosis are examples of lung fibrosis that follow inhalation of small particles that cause continued, ongoing lung injury.

Skin fibrosis can also occur from many potential causes. In some disorders, the deposition of so much excess collagen can make the skin so stiff that joints cannot properly function. It is, as if, the skin has become as hard as a plaster or fiberglass cast. The joints may be normal, but if they cannot function due to this excess of collagen, in time they may become frozen in position.

Skin fibrosis due to diseases such as scleroderma (which means "hard skin"), morphea, scleromyxedema, and nephrogenic systemic fibrosis (NSF) all share an excess of skin collagen. Under the microscope, a pathologist may see excess fibroblasts and collagen, or they may simply see the collagen (without the fibroblasts). Pathologists describe the process as "fibrosis" when the fibroblasts are still visible, and "sclerosis" when only collagen is visible, and the fibroblasts have largely disappeared. This cannot be determined by clinical examination alone, and examining doctors such as dermatologists and rheumatologists may use the terms "fibrosis" and "sclerosis" synonymously. To a pathologist, they are very different, and serve the purpose of differentiating between several disorders.

To a pathologist, fibrosis is increased collagen and increased numbers of fibroblasts.

Why does a Registry exist for NSF?

What is a Registry?

In the case of the NSF Registry, it is a collection of glass microscope slides and documentation collected to support or refute a diagnosis of NSF. Each individual in the registry has a file that contains paper, electronic, and/or photographic documentation of their case. In addition, there are corresponding glass microscope slides and sometimes tissue blocks.

How does one get into the Registry?

Glass microscope slides and supporting records are sent to my attention at Yale University. I review the materials. If the glass slides are suggestive of a diagnosis of NSF, the supporting documentation is carefully reviewed for clinical information that can help exclude other disorders that resemble NSF. If the clinical and pathological information both support a diagnosis of NSF, and if no other more likely diagnosis can be made, the case is diagnosed as NSF or compatible with NSF and assigned a Registry number.

What happens once a case becomes part of the Registry?

When a case is diagnosed as NSF, an invitation is made to the patient to formally become a Registry member. This entails a pre-arranged telephone conversation during which the details of the case will be evaluated by an experienced interviewer. Additional supporting information will be sought, and the patient will be verbally consented to participate in the Registry. Exchange of detailed protected health information cannot occur until this verbal consent is obtained. A written consent is sent by mail, and once this is returned, any additional missing parts of the story will be sought from physicians and hospital records.

What do you do with the data/records?

These are stored under lock and key. Important data elements are placed in a protected computer database. The database allows data from many patients to be examined simultaneously. For instance, if the US FDA asks our Registry to provide a breakdown of the genders and ages of patients with NSF, we are able to do so. These large scale datasets allow patterns to emerge, and have been instrumental in answering questions such as:

1. Which contrast agents are more likely to trigger NSF?

2. Are peritoneal dialysis patients at a greater risk for NSF than hemodialysis patients?

3. Are children at a greater risk for NSF?

4. Does a higher cumulative dose of gadolinium lead to a higher risk?

So why is this important?

Most clinicians will never see a case of NSF. NSF is a rare disease, and our work has made it even rarer. A clinician cannot rely on his/her experience in diagnosing a case of NSF if they have never seen it. Similarly, pathologists may not be familiar with the disease. The Registry allowed hundreds of records to be compared, and for the common symptoms, signs, lab values, and pathology findings to be identified. Using this information, a clear diagnostic definition was formulated and published. The definition was meant to identify as many cases of NSF as possible while also excluding persons with other diseases that resemble NSF. This definition creates a high degree of certainty that information that comes from the pure population of NSF patients in the database is unpolluted by other disorders. This "clean" information can be used to generate new hypotheses about the disease and to suggest therapies and preventive strategies.

Why isn't every case of NSF in the Registry?

1. NSF is not a disease that has mandatory reporting, like HIV and some other infectious diseases. Entry into the Registry is voluntary.
2. Physicians may not know about the Registry, and will not automatically seek to have a second opinion rendered.
3. Patients may not know they have the option to have their pathology slides sent to me for a second opinion. In most cases, insurance will cover the cost of this second opinion.
4. Many cases diagnosed as NSF elsewhere do not reach the level of diagnostic certainty to be included in the Registry database.
5. In some cases attorneys involved in litigation on their clients' behalf do not want the diagnosis of NSF "confused" by a second opinion. In many cases, however, attorneys seek to have cases of NSF reviewed for possible Registry inclusion.

Ultimately, it is a personal choice of the patient, who has complete control over their own tissue specimens and medical records.

How do I find out more about the International NSF Registry?

Contact us through our website (http://www.icnsfr.org)