Relation of Fasting C-peptide Level and Occurrence of Hypoglycemia at Insulin Initiation among Patients with Immune Mediated Diseases

DISCUSSION

Type 2 diabetes mellitus (T2DM) is a chronic condition associated with insulin insufficiency and insulin resistance at first, followed by a steady reduction in pancreatic beta cells activity.⁸ According to the International Diabetes Federation (IDF) figures on worldwide diabetes prevalence, 415 million individuals had diabetes in 2015, with the number expected to rise to 642 million by 2040.⁹ Diabetes mellitus comes ninth among the leading causes of death in the world, with one in every eleven adults suffering from the disease, with 90 percent of them suffering from type 2 diabetes (T2DM). T2DM is influenced by lifestyle variables such as age, pregnancy, and obesity, but it also has a substantial genetic component; it refers to those who have insulin resistance and are usually deficient in relative (rather than absolute) insulin. These people do not require insulin medication to survive, at least at first and often throughout their lives.¹⁰ Preproinsulin is generated in the endoplasmic reticulum in response to high blood glucose levels in the -cells of the pancreatic islets of Langerhans, and it is broken by microsomal enzymes to yield proinsulin. Proinsulin is transported in vesicles from the rough endoplasmic reticulum to the Golgi apparatus in pancreatic -cells, where it is packaged into clathrin-coated secretory granules and processed by a cascade of proconvertases and carboxypeptidases.¹¹ Plasma C-peptide is typically secreted in an equimolar pattern relative to insulin activity, making it a straightforward indicator for its endogenous production, besides, C-peptide assessment can stage T2DM course and subtypes classifications.² Recent data also support a favorable link between elevated plasma C-peptide concentrations and cardiovascular disorder risks, as well as inverse correlations between diabetic retinopathy progression and high C-peptide levels.⁴ Low FCP levels (0.40 nmol/L) in T2DM, on the other hand, suggest advanced insulin insufficiency and predict an unpleasant glycemic response after secretagogues of insulin, including the glucagon-like peptide-1 stimulators.⁵ Contemporary DM clinical practices recommendations propose a selected and sequential approach to medicines, with HbA1c readings and the existence of concomitant cardiovascular disease being the most important factors. C-peptide is not used in clinical practice to determine treatment modalities/strategies or to forecast the risk of hypoglycemia in the future.¹³ Our research found that 60 patients with type 2 diabetes mellitus had a high or low amount of plasma fasting c-peptide. The average age was 54.10 10.90 years. The participants in the study were 33 men and 27 women, with a mean height of 157.32 8.03, a mean weight of 59.25 9.50, a median diabetes duration of 4.0 years, and 27 patients with diabetes in their family.FCP plasma concentrations during insulin commencement can give useful inputs for selecting targeted treatment plans to attain an ideal glycemic goal while avoiding or minimizing the risk of hypoglycemia, according to the current findings. Clinicians will be better able to decide on insulin initiation and titration schemes according to the major defect, whether it is insulin deficit or insulin resistance if FCP levels are known.

The insulin-sensitive person may benefit from a careful and delayed introduction and titration of basal insulin, eventually necessitating prandial supplementation, whereas the insulin-resistant person will benefit from a more aggressive and forced basal insulin titration.

When comparing Hypoglycemia, overall, Hypoglycemia, nocturnal, Hypoglycemia, severe, and Fasting blood sugar levels, there was a highly statistically significant difference between the studied groups for Hypoglycemia, overall, Hypoglycemia, nocturnal, Hypoglycemia, severe, and fasting blood sugar levels. At baseline, there was no statistically significant difference between the study groups in terms of fasting blood sugar, but after 24 weeks, there was a statistically significant negative correlation between fasting C-peptide (nmol/L) and overall hypoglycemia, nocturnal hypoglycemia, and severe hypoglycemia.

During 6 months of basal insulin administration, an FCP value over 2nmol/L was correlated to about 10% hypoglycemic risk.¹⁴ Despite an equal reduction in HbA1c in both groups, the lowest FCP group's final basal insulin dose was the lowest, indicating that this group was extremely insulin sensitive and insulin deficient.

In this study, it was discovered that patients with diabetes for an average of 3 to 5 years had a non-statistically significant change between baseline and 24 weeks.

This was in contrast to the findings of Leighton et al.¹⁵ , who found a similar decrease in fasting C-peptide levels with diabetes duration and concluded that the progressive decline in C-peptide levels will contribute to increased blood glucose fluctuations, which in turn will contribute to the development of various vascular complications.¹⁵ They went on to say that, regardless of HbA1c levels, fasting C-peptide estimates can predict the overall fate of diabetic patients in the future.¹⁶ After 24 weeks of follow-up, the relationship between Fasting C-peptide (nmol/L) and overall hypoglycemia, nocturnal hypoglycemia, and severe hypoglycemia was shown to be negative.Low C-peptide levels can be considered to be merely a marker of b-cell function, with low levels indicating b-cell failure. Low C-peptide levels are linked to a higher risk of microvascular problems, implying a lack of ability to self-regulate glycaemia, which predisposes to microvascular disease.Patients with greater C-peptide levels, on the other hand, had a slew of risk factors, including hypertension, low HDL cholesterol, hypertriglyceridemia, and obesity, all of which could be linked to insulin resistance and, perhaps, C-peptide resistance. As a result, despite having diabetes for a shorter period, the two C-peptide groups had the same rate of cardiovascular problems.

C-peptide has been shown to have therapeutic effects on arteries by decreasing smooth muscle cell proliferation and migration, as well as anti-inflammatory activities in endothelial cells, in previous studies.¹⁷ C-peptide deposition in diabetic patients' arteriosclerotic lesions, chemotactic action against monocytes and CD4C lymphocytes, and activation of vascular smooth muscle cell proliferation have all been revealed by other kinds of literature.¹⁸

CONCLUSION

According to our study, there was a negative correlation between fasting c- peptide levels and the occurrence of hypoglycemia in diabetic patients with immune-mediated disease who started insulin therapy. Low fasting plasma C-peptide is associated with an increase in the risk of hypoglycemia, which requires a low initial insulin dose.