In our study, there was significant difference in all the independent and dependant variables in terms of FBG and PPG with lipid profile and serum nitric oxide level.
A Turkish study compared the basal serum levels of nitric oxide in type 2 diabetes mellitus patients with different stages of diabetic retinopathy and compared them with the levels in non-diabetics using Griess reaction. The patients with type 2 diabetes had significantly higher levels of serum NOx than the non-diabetics.[20
] A Turkish study on micro- and normo-albuminuric type 2 diabetics and healthy controls found that serum and urine NO levels were higher in both micro-albuminurics and normo-albuminurics than controls in early diabetes.[21
] A Japanese study showed that plasma NOx
levels were significantly higher in diabetics than in controls, when measured by high-performance liquid chromatography with the Griess method.[22
] In a Karachi study, a nonsignificant increase was observed in the levels of nitric oxide metabolites in diabetic patients as compared to non-diabetics, but diabetic patients with hypertension showed significantly higher levels as compared to controls, but the levels were not significantly different in patients with and without hypertension.[23
] In an Iranian study, NOx
was measured in adults using the Griess reaction, which was significantly higher in subjects with type 2 diabetes, supporting the existing hypothesis that NO overproduction affects insulin's metabolic actions.[24
Brussels study was conducted to correlate the serum level of NO in patients with acute coronary syndromes in relation to the presence or absence of diabetes mellitus. Before any therapeutic intervention, arterial blood samples were withdrawn to assess the serum NO metabolites level by the Griess reaction. Compared with the control group, patients with acute ischemic syndromes had a significantly lower level of serum NO metabolites, without any significant difference between diabetic and non-diabetic patients.[25
A study at Karachi aimed to find the correlation between glycosylated hemoglobin (HbA1c) and NO anomalies in coexisting diabetes and hypertension found that FBG and HbA1c levels were significantly high, whereas serum NO level was significantly low in diabetic normotensive and diabetic hypertensive patients as compared to controls. A significant negative correlation was found between serum nitric oxide and serum glucose and HbA1c levels in diabetic hypertensive patients, suggesting that HbA1c can critically contribute to anomalies of NO metabolism or vice versa.[26
] Researchers in Taiwan assessed the NO levels in aqueous humor and plasma using the chemiluminescence assay and observed no significant differences between any of the diabetic subgroups in the plasma NO levels.[27
Prospective studies have established that reduction in NO bioavailability is a predictor of dyslipidemia as it is an endogenous anti-atherosclerotic molecule. By the dysfunction of the endothelial L
-arginine–nitric oxide pathway, several cardiovascular risk factors impart their deleterious effects on the vascular wall, including hypercholesterolemia.[28
Researchers at Harbin Medical University, China, observed that the changes in the NO level and other markers of oxidative stress in patients with type 2 diabetes mellitus did not significantly correlate with the changes in plasma lipid profile.[31
In the West Glasgow Hospitals, the researchers observed that the subjects with type 2 diabetes displayed decreased NO production which was related to confounding factors such as age, body mass index, and lipid profile.[32
] Researchers have reported that subjects with diabetes have an unfavorable lipid profile and altered plasma levels of oxidative stress markers like nitric oxide, and the NO levels were lower than in control subjects.[33
] In the study conducted at the Lady Hardinge Medical College, India, on the effect of glipizide, metformin and rosiglitazone on nontraditional cardiovascular risk factors in newly diagnosed patients with type 2 diabetes mellitus, NO levels were increased in all the study groups, though not significantly.[37
To the horizon of our knowledge, this was the pioneering study in this part of India. Moreover, due to ethnic origin and geographical variation in Sikkim, this particular study has been taken up to compare the serum NO level in patients with diabetes and healthy controls and to establish a correlation between serum nitric oxide level and diabetes mellitus. The serum nitric oxide level in the control group significantly differed compared to that in cases.
Limitations of our study include its small sample size and open label design. Selection bias also limits the generalizability of our findings since only the subjects from our diabetic clinic were sampled. Our finding further goes to say that we may have to do a study in primary cases of diabetes, conduct a comparative study among different ethnic groups in Sikkim, use more sensitive methods and probably study the NOS gene expression and polymorphism in the Sikkimese population before we can establish the role of nitric oxide assay in diabetics.
To sum up, serum NO was observed to be lower in diabetic participants, which needs to be further established by prospective population-based studies. This profile for diabetic patient in our hinterland matched with some of the observations of our global peers, while other researchers noted higher levels of NO in diabetics. These wide levels of variations point to the need of the standardization of method of assessment of NO with a robust multicentric study across regions.