WHAT ARE CRP LEVELS AND ITS CONNECTION WITH DIABETES?

ABSTRACT

Inflammation is a very common response of the body to some pathology that is going on inside the body. Ancients have characterized inflammation by the cardinal features such as redness (rubor), swelling (tumour), heat (calor; only applicable to the body’ extremities), pain (dolor) and loss of function (functio laesa).All these symptoms are easily seen if the inflammation is external but many a times the inflammation is internal and has almost no external signs. For that matter modern technological interventions have come up with certain investigations that confirm bodily inflammations.C- Reactive protein test is an effective laboratory marker for systemic inflammation. This test has deep connections with metabolic disorders such as diabetes. This article discusses the significance of this investigation and its impact over the management of severe diseases such as diabetes.

INTRODUCTION

This test is a measurement of the presence of C- reactive protein which is made in the liver and thereby transported in the bloodstream. Its moleculeis an annular (ring-shaped) pentameric protein that is found in the plasma of blood, whose circulating concentrations have seen an immediate rise in response to an inflammation. This protein finds an immediate rise in the acute phase of an illness (causing inflammation).The origin of this protein is hepatic that increases following the secretion of interleukin 6 by T cells and macrophages. In normal physiology its role is to bind lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of pathogens) in order to activate the complement system.

CRP synthesis in the liver is in response to factors released by the macrophages and adipocytes (fat cells). It is a member of the pentraxin family of proteins (located on chromosome1). It is neither related to C- peptide (insulin) or Protein C (for blood coagulation). C-reactive protein was also the first pattern recognition receptor (PRR) to be identified.

NOMENCLATURE AND HISTORY

C – reactive protein is called so because it was first found in a patient (with acute inflammation) in whose body this protein reacted with Capsular polysaccharide of pneumococcus.

Earlier the presence of this protein was thought to be of foreign origin (some pathogen etc) but later it was discovered as a native protein for its origin from the liver.

INFLAMMATION

The massing of leukocytes, majorly neutrophils and monocytes, in sites of inflammation constitutes the prime defensive feature of inflammatory response. Phagocytic cells engulf foreign intruders along with the enzyme rich granules that destroy or at least weaken the invaders. “Leukocytes”is thus thought to constitute the third leg of tripod on which the inflammatory process stands.The other two being “Hemodynamic” and “Permeability changes”. These cells go into the precise flow of injury via the sequence of events such as – “margination and pavement”, “emigration”, “chemotaxis” and “phagocytosis”. For this process of inflammation to take place there are many inflammatory mediators involved with the same such as-Vasoactive amines (Histamine and serotonin), Plasma proteases (such as bradykinin and kallikrein), The complement system(C3 andC5 fragments),The coagulation fibrinolytic system(fibrin degradation products), Prostaglandins, Neutrophil products, Lymphocyte factors, SRS (Slow reacting substance) etc. Morphological types of inflammatory reactions based on location includes abscesses, Ulcers, Membranous inflammation and Catarrhal inflammation. Following this when the inflamed site begins to heal it undergoes Necrosis, Labile and stable cells proliferation, granulation of tissues and the wound ultimately healing.

This entire process activates Tissue Necrosis Factor alpha, Interleukin 6 which is involved with the formation of C – reactive protein.

CAUSES

The elevated levels of this test are a result of inflammatory conditions such as

• Inflammatory Bowel Disease
• Rheumatoid arthritis
• Osteomyelitis
• Bacterial, fungal infections
• Cardiovascular disease
• Diabetes
• Tuberculosis
• Pneumonia
• Cancer

SIGN AND SYMPTOMS

Increased values of CRP brings sign and symptoms as that of infections such as

• Exhaustion
• Muscle stiffness, soreness, and weakness
• Low-grade fever
• Chills and pains
• Headache
• Nausea, indigestion, anorexia
• Insomnia
• Unexplained weight loss

Those who have very high CRP levels are most likely to get an acute bacterial infection.

Signs of acute infection include

• Pyrexia( fever)
• Tachycardia
• Excessive sweating, chills
• Persistent vomiting, retching
• Diarrhea
• Rash or hives formation
• Parched lips, mouth, and skin
• Dizziness or lightheadedness
• A severe headache, body pain
• Severe stiffness or soreness
• Loss of consciousness
• Difficulty breathing

REFERENCE RANGE

• (For a Standard CRP test) Normal reading – less than 10 milligram per liter (mg/L). If this test result shows a CRP level greater than 10 mg/L then it indeed is a sign of serious infection, trauma or chronic disease, which requires further investigations.
• For High-sensitivity C-reactive protein (hs-CRP) test – This test is more sensitive and more expensive than the standard C – reactive protein test. This test is more effective to evaluate the risk of developing coronary artery disease (in which the arteries of the heart get narrowed) and heart attack.

hs-CRP test levels indicate

1. Lower risk.  hs-CRP level of less than 2.0 milligram per liter (mg/L).
2. Higher risk.  hs-CRP level greater than 2.0 mg/L.

INTERPRETATION OF CRP RESULTS

• Conditions like pregnancy or intake of oral contraceptive pills may increase the levels of CRP.
• Chronic inflammatory conditions such as autoimmune disorders may show an increase in CRP levels and mask any other pathology.
• Minor infections or injuries may increase CRP levels temporarily and conceal other severe metabolic conditions like diabetes or cardiovascular ailments.
• Patients taking NSAIDs may falsely be shown unrisen levels of CRP.

When there is a stimulus, the CRP level has an ability to increase 10,000-fold from less than 50 μg/L to more than 500 mg/L. Its concentration can increase to 5 mg/L by 6 hours and peak at 48 hours.  Its production rate increases with inflammation, infection, trauma, necrosis, malignancy, and allergic reactions. Inflammatory mediators that can increase CRP are tissue necrosis factor alpha etc. In acute inflammation, CRP can increase as much as 50 to 100 mg/L (within 4 to 6 hours)- in mild to moderate inflammation. It can double (every 8 hours) and reaches its peak (in 36 to 50 hours) following injury or inflammation. CRP between 100 and 500 mg/L is highly predictive of inflammation due to bacterial infection. Once inflammation subsides, CRP level falls quickly. This is because of its relatively short half-life.

DIABETES AND CRP

It is seen that there indeed is a central role of inflammation involved with the pathogenesis of atherosclerosis and diabetes. This concept is also otherwise, that is in apparently healthy subjects, increased levels of CRP predicts the risk of developing type 2 diabetes. Evidence suggests that inflammatory and metabolic factors associated along with diabetes, like high glucose, adipokines, modified lipoproteins and free fatty acids may trigger CRP production by smooth muscle cells,endothelial cells and monocytes/macrophages.  Data suggests that local CRP concentration in diabetic atherosclerotic plaques could be higher than in nondiabetic ones.

The obese condition increases the deposition of adipose tissue, which further releases cytokines (that regulates the formation of CRP) that is Tissue necrosis Factor alpha and Interleukins that are somewhere involved with impairing lipid and glucose metabolism thereby leading Diabetes. Patients with diabetes are more prone to cardiovascular ailments. Patients with cardiovascular ailments (such as hypertension etc) along with diabetes are in more of an inflammatory state and hence have more chances of increased CRP.

CONCLUSION

Diabetes is a metabolic syndrome in which along with increased glycosylated levels the findings like CRP too could be found high. Or patients with higher CRP levels for the longer durations are inclined to be cardiovascular or diabetic patients in the near future. Hence stricter lifestyle modifications, along with the holistic practises such as Yoga,Meditation, Exercise should be followed. The increased findings of this test are indicative of some pathological inflammation going on inside the body. It shows that the body is in its immunocompromised state. Hence, the body should be given immune boosting measures to combat the pathologies.