Comparison of clinical characteristics, microvascular complications and inflammatory markers in type 2 diabetic patients under insulin versus metformin treatment: A cross-sectional study at Karbala Diabetic Center, Iraq

Abstract

Type 2 diabetes mellitus (T2DM) is a major global health issue associated with chronic inflammation, which contributes to both disease progression and its complications, including cardiovascular and microvascular disorders. Key inflammatory markers such as tumor necrosis factor-alpha, interleukin-6 (IL-6), E-selectin, and P-selectin are elevated in T2DM patients and are implicated in the development of these complications. Understanding how treatments such as insulin and metformin affect these markers is crucial for improving therapeutic strategies in T2DM. This study investigated the effects of insulin and metformin on these inflammatory markers in T2DM patients. This was a cross-sectional study involving patients with diabetes on insulin (group A), metformin only (group B), and healthy controls (group C). Participants were enrolled from the Diabetic Center in Karbala, Iraq and underwent clinical assessments including ophthalmologic examinations. Fasting blood glucose, HbA1c and lipids levels were assessed. The levels of inflammatory markers (IL-6 and TNF-α), and adhesion molecules (sE-selectin and sP-selectin) were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The study included 522 patients with diabetes: 356 receiving insulin (group A), 70 receiving metformin (group B) and 96 healthy controls (group C). T2DM patients treated with insulin exhibited significantly more microvascular complications than those treated with metformin. Higher rates of retinopathy (64.3% vs 11.4%) and neuropathy (69.9% vs 11.4%) were observed in the insulin group, whereas the incidence of nephropathy did not differ significantly (14.6% vs 11.4%). Inflammatory markers were lower in the insulin group: TNF-α levels were 3-fold lower and IL-6 levels were 8-fold lower. Conversely, sE-selectin levels were 1.5-fold higher in the insulin group, and sP-selectin levels were 1.4-fold higher in the metformin group. This study highlights distinct differences in inflammatory markers and systemic complications between T2DM patients treated with insulin and those treated with metformin alone. Further research is needed to explore the mechanisms underlying these observations and optimize treatment strategies for T2DM patients.

Figure 1.

Distribution of subjects and microvascular complications among diabetic patients.

Figure 2.

(A) Overall and (B) detailed Microvascular complications in T2D patients that take insulin (n = 356) and T2D patients that take metformin (n = 70). Statistical significance is indicated by (ns P ≥ .05, ***P < .001).

Figure 3.

Levels of inflammatory markers and circulating endothelial adhesion molecules in T2D patients treated with insulin (n = 356) versus those treated with metformin (n = 70). Data are expressed as median (25th–75th percentile). Statistical significance is indicated by (****P < .0001).