Comparative study of Dapagliflozin versus Glimepiride effect on insulin regulated aminopeptidase (IRAP) and interleukin-34 (IL-34) in patient with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is one of the most common diseases, that managed by several medications such as Glimepiride and Dapagliflozin. This study aims to compare the effects of Dapagliflozin versus Glimepiride on glycemic control, insulin resistance, and biomarkers as (extracellular domain of insulin regulated aminopeptidase) IRAPe, (interleukin-34) IL-34, and (N-terminal pro b-type natriuretic peptide) NT-proBNP. This study included 60 type 2 diabetic patients, who are randomized to receive either Glimepiride 4 mg/day (group 1) or Dapagliflozin 10 mg/day (group 2). Blood samples were collected at baseline and after 3 months of treatment for biochemical analysis. Additionally, HOMA-IR is calculated. After 3 months of receiving the intervention, there is no significant difference between the effects of Glimepiride and Dapagliflozin on FBG, PPBG, HbA1C%, fasting insulin, and HOMA-IR. The difference between both groups is significant for IL-34 (p = 0.002) and non-significant for IRAPe (p = 0.12) and NT-Pro BNP (p = 0.68). Both Glimepiride and Dapagliflozin significantly improve glycemic control, and HOMA-IR with no significant difference between them. Both drugs significantly improved the level of NT-proBNP. Dapagliflozin has a borderline significant effect on IRAPe but not IL-34, and Glimepiride has significant effect on IL-34 but not IRAPe. Clinical Trial Registration: This trial was registered on clinicaltrial.gov (NCT04240171).

Circulating IRAPe, Irisin, and IL-34 in Relation to Insulin Resistance in Patients With Type 2 Diabetes.

PURPOSE: This study aimed to evaluate the role of the extracellular part of insulin-regulated aminopeptidase (IRAPe), interleukin (IL)-34, irisin, and visfatin in the development of insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM). METHODS: This observational parallel-group study was conducted in 60 subjects without T2DM who served as a control group and 60 patients with newly diagnosed T2DM. The 2 groups were matched for age, sex ratio, and body mass index. Anthropometric parameters; fasting blood glucose; fasting plasma insulin; Homeostatic Model Assessment for IR (HOMA-IR) index; glycated hemoglobin (HbA1c); and circulating levels of IL-34, visfatin, irisin, and IRAPe were assessed. RESULTS: The group with T2DM showed significantly higher IL-34 and visfatin levels and significantly lower irisin and IRAPe levels as compared to the healthy control group. IL-34 and visfatin were significantly positively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. On the other hand, irisin and IRAPe were significantly negatively correlated with fasting blood glucose, fasting plasma insulin, HOMA-IR, and HbA1c. IL-34 was positively associated with visfatin, while negatively associated with both irisin and IRAPe. IMPLICATIONS: IL-34, visfatin, irisin, and IRAPe may play a vital role in T2DM and in diabetes-associated IR. Additionally, IRAPe may represent a useful and direct marker for use in the detection of IR in the diabetic population. ClinicalTrials.gov identifier: NCT04107259.

Circulating IL-6, clusterin and irisin in obese subjects with different grades of obesity: association with insulin resistance and sexual dimorphism.

OBJECTIVE: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. METHODS: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. RESULTS: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. CONCLUSION: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.

Circulating IL-6, clusterin and irisin in obese subjects with different grades of obesity: association with insulin resistance and sexual dimorphism

ABSTRACT Objective: There are discrepancies about the relationship of IL-6, clusterin and irisin with obesity and obesity associated insulin resistance and also about their sexual dimorphism. This study aimed at evaluating the circulating levels of IL-6, clusterin and irisin in obese subjects of both sexes who had different grades of obesity and examining their sexual dimorphism and their association with insulin resistance. Subjects and methods: This study included 176 non-diabetic subjects of both sexes who were classified according to their sex into two groups; the male and the female groups. The male group (88 men) was classified according to BMI into; group 1 (22 lean men), group 2 (22 class I obese men), group 3 (22 class II obese men) and group 4 (22 class III obese men). The female group (88 women) was classified according to BMI exactly as the male group. Metabolic parameters, IL-6, clusterin, and irisin levels were measured. Data were analyzed by ANOVA test, post hoc Tukey's test and independent t-test. Pearson correlation was used to assess the association between variables. Results: In obese subjects of both sexes, circulating IL-6, clusterin and irisin levels were significantly elevated and positively correlated with HOMA-IR. Obese males showed significantly higher HOMA-IR, IL-6, clusterin and irisin levels than obese females. Conclusion: Obesity in both sexes, especially in males was associated with high levels of IL-6, clusterin and irisin and worsened the metabolic pattern. Circulating IL-6, clusterin and irisin may represent possible therapeutic targets for insulin resistance in obese subjects.