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The receptor for advanced glycation end products (RAGE) is a cell surface receptor of immunoglobulin superfamily and is highly expressed in the lung tissue. 1 The lung tissue is directly exposed to cigarette smoke in smokers, and the cigarette smoke has been shown to elevate RAGE expression in cultured cells and in the lung tissues of animals. 2 Some of the diseases prevalent among cigarette smokers, particularly atherosclerotic cardiovascular diseases and cancer, have also been shown to be linked with RAGE signalling. 3 A soluble form of RAGE (sRAGE), which is a splice variant of full-length RAGE or a shedding/cleavage product of membrane-bound RAGE, has been found circulating in the plasma. The sRAGE has been considered to be protective against diseases originating from RAGE activation since sRAGE can bind and sequester RAGE ligands, and thereby, can reduce RAGE activation. 3 On the contrary, a pro-inflammatory role of sRAGE has also been described. 4,5 We therefore asked in the present study, whether sRAGE level is altered in cigarette smokers and is associated with smoking habit in non-diabetic healthy subjects.A total of 98 non-diabetic, otherwise healthy, male subjects were recruited from the employees of the Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, after giving written consent. The study was conducted according to the Declaration of Helsinki and was approved by the institutional ethical review committee. A fasting blood sample and medical history including detail history of cigarette smoking were collected. Subjects who reported AbstractThis study was designed to explore the relationship between serum levels of soluble receptor for advanced glycation end products (sRAGE) and cigarette smoking in non-diabetic healthy subjects. A total of 98 non-diabetic, otherwise healthy male subjects were recruited. A fasting blood sample and medical history including detail history of cigarette smoking was collected. The serum sRAGE levels were found significantly higher (p=0.002) in cigarette smokers (1475±422 pg/ml, n=45) compared with non-smokers (1165±350 pg/ml, n=53). Moreover, among the cigarette smokers, serum sRAGE levels were found significantly correlated with number of cigarettes smoked per day (r=0.60, p<0.001). In bivariate analysis in the total population, sRAGE positively correlated with smoking habit (r=0.37, p=0.002) and negatively correlated with systolic (r=-0.32, p=0.01) and diastolic blood pressure (r=-0.36, p=0.003). However, in stepwise multivariate linear regression model, sRAGE showed a significant independent association with smoking habit (b=0.32, p=0.007, R 2 =0.23).In conclusion, this study for the first time shows a significant elevation of serum sRAGE in cigarette smokers compared with non-smokers, a strong correlation between sRAGE and number of cigarettes smoked per day and an independent association of sRAGE with smoking habit in non-diabetic healthy subjects.

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This study examined whether circulating levels of soluble receptor for advanced glycation end products (sRAGE) alter in prediabetes and correlate with insulin resistance (IR) and beta cell function in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Subjects without previous history of diabetes were recruited and grouped as control, prediabetes, and newly diagnosed T2DM. The control subjects (n = 40) and people with prediabetes (n = 52) and diabetes (n = 66) were similar in terms of age, sex, BMI, systolic and diastolic BP, and fasting insulin level. HOMA-IR was found significantly higher in people with diabetes than control subjects (p < 0.001) and people with prediabetes (p = 0.005); and HOMA-%B was found significantly deteriorated in people with diabetes (p < 0.001) compared to control subjects and people with prediabetes. However, serum sRAGE levels did not show any significant alteration in people with prediabetes compared to control subjects. Moreover, univariate and multivariate analyses did not identify any significant correlation and statistical association of sRAGE with HOMA-IR and HOMA-%B in people with prediabetes and newly diagnosed T2DM. Our data suggest that serum sRAGE levels do not alter in people with prediabetes compared to control subjects and do not correlate or associate with IR and beta cell function during development of T2DM.

BackgroundAegle marmelos is a popular fruit plant in the Indian subcontinent, various parts of which are traditionally used against various illnesses including diabetes mellitus (DM). However, the underlying mechanisms of the antidiabetic effects of the plant are not clear, especially in type 2 DM. The present study was undertaken to investigate the effect of aqueous extracts of A. marmelos fruits (AMFE) and leaves (AMLE) on glycemic, lipidemic, insulinemic, insulin resistance and β-cell functional status of type 2 diabetic model rats. Methods An interventional study was designed using 20 type 2 diabetic rats. Type 2 DM was induced in Long Evans rats by a single intra-peritoneal injection of streptozotocin (90 mg/kg body weight) to 48 h old pups. Three months after induction of diabetes, the rats were divided into three independent groups: water-treated control group (n=6), AMLE-treated group (n=7) and AMFE-treated group (n=7). The rats were fed with extracts or water for 21 consecutive days and blood samples were collected at days 0 and 21 after an overnight fast. Data were expressed as mean±SD and analyzed by paired t-test or ANOVA as appropriate. Results There were significantly lower blood glucose values in AMLE and AMFE groups at Endpoint compared to Baseline (mmol/l, mean±SD, Baseline vs. Endpoint, 7.04±1.0 vs. 6.06±0.92; p=0.032 and 7.04±0.97 vs. 5.87±0.93; p=0.047). There were also significantly lower serum insulin levels in AMLE and AMFE groups at Endpoint compared to Baseline (µIU/mL, mean±SD, Baseline vs. Endpoint, 14.02±5.48 vs. 7.57±2.90; p=0.026 and 11.54±4.83 vs. 6.58±4.36; p=0.008). Insulin resistance (HOMA-IR) was significantly improved both in AMLE and AMFE groups at Endpoint compared to Baseline (mean±SD, Baseline vs. Endpoint, 4.22±1.68 vs. 2.05±0.90; p=0.021 and 3.69±1.79 vs. 1.69±1.61; p=0.013). However, β-cell function or lipid profile did not show any significant alteration at Endpoint compared to Baseline in AMLE and AMFE groups. Conclusions Aqueous extracts of A. marmelos leaf and fruit have hypoglycemic property which seem to be mediated by lowering of insulin resistance. These findings highlight the therapeutic potential of the extracts of A. marmelos in human type 2 DM and provides strong impetus for further studies.