Background:Insulin resistance (IR) is considered as initial stage of diseases continuum from development of prediabetes to eventual progression to type 2 diabetes mellitus (T2DM). Individuals with prediabetes have also elevated leptin levels, so this adipocytokine along with IR can be considered as predictive laboratory markers of higher risk of T2DM. It is not yet clear whether presence of individual or multiple SLE-related and/or known traditional risk factors of T2DM (such as unhealthy diet, physical inactivity, family history of diabetes, or being overweight) can precipitate the development of IR.Objectives:To analyze the relationship between IR and increasing leptin levels rates. To identify the presence and evaluate the potential role of traditional and disease-related risk factors for IR in SLE patients without T2DM or hyperglycemia.Methods:A total of 49 SLE pts (46 women, 3 men, 40 [33;48] years old) without established DM and with normal fasting glucose levels (<6,1 mmol/l) were enrolled in the study. Median disease duration was 3,0[0,7;8,0] years, SLEDAI-2K was 5[2;8]. SLE pts were treated with glucocorticoids (GC) (84%), hydroxychloroquine (78%), immunosuppressive drugs (20%) and biological agents (10%). Insulin levels were measured using electrochemiluminescence assay Elecsys (Roche Diagnostics), serum leptin concentrations were estimated using ELISA (DBS-Diagnostics Biochem Canada Inc.). IR was defined as Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) ≥2,77. Leptin levels were considered elevated at values ≥11,1 ng/ml for women, ≥5.6 ng/ml for men. Eight traditional T2DM risk factors from the FINDRISK (Finnish Type 2 Diabetes Risk Assessment Form) questionnaire (older age, being overweight, abdominal obesity, family history of diabetes, sedentary lifestyle, lack of regular dietary fiber intake, taking antihypertensive medications as a surrogate marker of high blood pressure, documented episodes of hyperglycemia) were evaluated. This study used 5 risk categories for developing T2DM proposed by FINDRISK questionnaire: low, slightly elevated, moderate, high or very high.Results:Median HOMA-IR levels were 1,7 [1,2;2,5]. HOMA-IR correlated with leptin levels (r=0,7, p<0,001), body mass index (BMI) (r=0,6, p<0,001), waist circumference (WC) (r=0,5, p<0,001), T2DM risk categories by FINDRISK (r=0,3, p=0,03), SLEDAI-2K (r= -0,4, p<0,01), and duration of GCs therapy (r=0,3, p=0,03). Current GC use had no influence on HOMA-IR in SLE. IR was detected in 10 (20%) SLE pts. The traditional T2DM risk factors profiles were similar in pts with (Group 1) or without IR (Group 2) except for higher anthropometric parameters in group 1 (for BMI 27,2[24,8;32,2]kg/m2 vs 23,7[20,6;26,7]kg/m2, p<0,01; for WC: 93[86;102]cm vs 83[76;93]cm, p=0,02). Leptin levels were also higher in SLE pts with IR compared to pts without IR (74,2[30,4;112,7]ng/ml vs 25,0[6,7;42,4]ng/ml, p<0,01). Increased leptin levels were found in 35 (71%) pts, more often in pts with IR (100 vs 64%, p=0,04).Conclusion:IR was found in 20% of SLE pts without T2DM having normal serum fasting glucose concentration. Emergence of IR was commonly preceded by increased leptin levels. IR values were closely associated with accumulation of adipose tissue facilitated by long-term GCs use and disease activity decrease. Contribution of other traditional risk factors of T2DM seemed insignificant.Disclosure of Interests:None declared
Maturity-onset diabetes of the young type 5 a MULTISYSTEMIC disease: a CASE report of a novel mutation in the HNF1B gene and literature review
