Diabetes, one of the deadliest lifestyle disorders of the 21^st century, affects around 60 million Indians and the numbers are steadily increasing. Recently, a team of researchers led by Navin Kumar, Indian Institute of Technology (IIT) Ropar, and Sanjay Kumar Bhadada, Post-Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, has developed a fast, reliable, and cost-effective early diagnostic protocol to estimate tissue damage in Type 2 diabetic patients.

Type‑2 diabetes, the most prevalent form of diabetes in adults, often causes glucose accumulation in tissues and organs, which leads to tissue damage. This can result in secondary complications such as compromised function of organs like heart, kidney, skin, bones, and joints. 

Sadly, the tissue damage usually gets detected only in the later stages when the prognosis of affected tissues is very poor. For example, in severely affected diabetics, the prevalence of foot sepsis is high and in the majority of such cases, amputation becomes necessary. The new diagnostic method developed by Kumar and Bhadada’s team can aid in the timely prevention of organ damage before it becomes irreversible.

Maintenance of tissue integrity in normal individuals depends upon two factors — clearing of damaged tissue and repair. Unwanted proteins are removed to make space for the new ones, just like our household junk needs to be disposed of regularly for a clean house. 

In diabetic patients, high glucose levels lead to unwanted modification (called glycation) of many essential proteins like hemoglobin (Hb), a protein that carries oxygen in the blood, making them bulkier and tougher for the cell to clear off. Just like what would happen if we leave garbage to sit and rot in our houses, these modified proteins accumulate and make it difficult for the cell to perform its normal functions, resulting in damage to tissues. 

The amount of glycated Hb in the blood is commonly used as a diagnostic tool to detect diabetes. The higher the glycation, the more severe the diabetes. However, this method does not tell us about the extent of tissue damage in diabetic patients. 

The authors decided to look for non-invasive markers for tissue damage. They came across keratin, a protein abundant in our hair, skin, and fingernails, which also gets modified (glycated) due to high blood glucose levels. ​“Non-invasive ways are always preferred over invasive methods,” says Bhadada, explaining their rationale for choosing fingernails to test for markers.

To estimate whether glycated keratin can be used as a marker for tissue damage, the researchers tested clipped nails of diabetic and healthy subjects for differences in nail surface morphology and roughness, tissue density, mineral content, material properties, disulfide bond content, and protein composition. Since tissue damage due to type 2 diabetes is a long-term complication, and early detection can help avoid irreparable organ damage, these studies were carried out in aged subjects. 

The study revealed that glycation of keratin in fingernails is indeed an indicator of fingernail quality in the aged diabetic population. The extent of keratin glycation was proportional to the anatomical changes, reduction in calcium content, and other mineral content in the fingernails. In diabetic patients, nail plate quality was significantly lower than controls, and glycation was higher.

Unlike detecting glycated Hb that requires blood extraction, this technique is non-invasive as it simply involves clipping the patients’ fingernails, making it cheaper and safer for clinical set-ups. 

When asked about the future prospects of this research, V Mohan, Founder-Director & Chief Diabetologist, Madras Diabetic Research Foundation (MDRF), who was not involved in this study, suggested that once follow-up studies are carried out to confirm its clinical utility, this technique could become an index of longer-term control of diabetes. 

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