Insulin resistance induced by de novo pathway-generated C16-ceramide is associated with type 2 diabetes in an obese population.

BACKGROUND: Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. METHODS: The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n = 20), obese-non-diabetic (n = 66), and obese-diabetic (n = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. RESULTS: C16-ceramide (P = 0.023), C16-dihydro-ceramide (P < 0.005), C18-dihydro-ceramide (P = 0.009) and C24-ceramide (P = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels (P = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 (P < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. CONCLUSIONS: The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.

Role of water soluble contrast agents in assigning patients to a non-operative course in adhesive small bowel obstruction.

OBJECTIVES: Adhesive small bowel obstruction (SBO) is a common surgical emergency. It is estimated that at least 60% of SBO are due to post-operative adhesions. Water soluble contrast agents (gastrografin) have been used to identify patients who might be treated non-operatively. This study aims to determine the role of gastrografin in adhesive intestinal obstruction patients. METHODS: In this prospective study, 27 patients admitted between 1(st) August 2004 and 1(st) July 2006 with clinical signs suggestive of postoperative adhesive SBO met the inclusion criteria. After intravenous hydration, nasogastric tube insertion and complete suctioning of the gastric fluid, 100 ml of gastrograsfin was given and plain abdominal radiography was taken 6 hours and 24 hours if the contrast is not seen in the colon. Those in whom the contrast reached the colon in 24 hours were considered to have partial SBO and started oral intake. If gastrografin failed to reach the colon in 24 hours and the patient did not improve in the following 24 hours, laparotomy was performed. RESULTS: Conservative treatment was successful in 31 cases (91%) and 3 (9%) required operation. Patients treated conservatively had short hospital stay (mean=4 days) and tolerated oral feeding with no morbidity or mortality. CONCLUSION: Oral gastrografin helps in the management of patients with postoperative adhesive SBO.