Short- and Long-Term Effects of Weight Loss on the Complement Component C3 After Laparoscopic Gastric Bypass in Obese Patients.

BACKGROUND: The C3 complement component (C3c) is increasingly recognized as a cardiometabolic risk factor, but how it is affected after weight loss through gastric bypass is a question yet to be answered. METHODS: A total of 66 obese patients underwent laparoscopic gastric bypass. Anthropometric parameters, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), glucose, insulin, HOMA-IR, liver enzymes, high-sensitivity C-reactive protein (hsCRP), and C3c levels were evaluated at baseline and at 1 and 5 years post-surgery. RESULTS: All anthropometric and biochemical parameters improved significantly after surgery, although a deterioration was detected with respect to the percentage of excess of weight loss, insulin, TC, LDLc, and lactate dehydrogenase 5 years post-surgery. Despite this, a remission rate of 84 % was observed in the presence of metabolic syndrome after 5 years follow-up. hsCRP and C3c were reduced significantly after surgery and maintained throughout the experimental period. In addition, C3c was correlated with BMI and insulin at all time points. The multivariate regression model, in which C3c was a dependent variable, revealed that aspartate aminotransferase and BMI were independent variables at baseline, alkaline phosphatase and insulin were independent at 1 year post-surgery, and insulin, BMI, and TC were independent at 5 years post-surgery. CONCLUSIONS: C3c may be a marker of the chronic inflammatory process underlying insulin resistance. Its association with BMI and liver enzymes supports a major role in metabolic activity, although future research is needed to clarify the nature of the molecular mechanisms involved and the physiological significance of these findings.

Insulin-Induced Normoglycemia Reduces Islet Number Needed to Achieve Normoglycemia after Allogeneic Islet Transplantation in Diabetic Mice.

The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. The aim of this study was to examine whether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Swiss mice were used as donors and recipients. Diabetes was induced by IP administration of streptozotocin (180 mg/kg BW). Diabetic mice were transplanted with 300 (n = 16), 400 (n = 16), or 500 (n = 16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 4 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic mice were given an IP glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student's t-test or ANOVA was used. Only insulin-treated mice achieved normoglycemia by the end of the study (37.5% of animals transplanted with 400 islets and 50% transplanted with 300 or 500 islets). At the end of the study, normoglycemic mice transplanted with 300 allogeneic islets showed better glycosylated hemoglobin (HbA1C) than did normoglycemic mice transplanted with 500 islets (300 islets: 2.7 ± 0.2%; 500 islets: 3.6 ± 0.2%; p < 0.05). After the IPGTT, insulin-treated mice transplanted with 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplanted with 300 or 400 islets showed normal glucose tolerance. Insulin treatment reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1C and IPGTT results suggest that transplanting smaller numbers of allogeneic islets improves ß-cell function; some studies suggest that this may be due to lower immunogenicity, hypoxia, and inflammation.

Insulin-induced normoglycemia reduces islet number needed to achieve normoglycemia after allogeneic islet transplantation in diabetic mice.

The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. The aim of this study was to examine whether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Swiss mice were used as donors and recipients. Diabetes was induced by i.p. administration of streptozotocin (180 mg/kg BW). Diabetic mice were transplanted with 300 (n = 16), 400 (n = 16), or 500 (n = 16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 4 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic mice were given an i.p. glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student's t-test or ANOVA was used. Only insulin-treated mice achieved normoglycemia by the end of the study (37.5% of animals transplanted with 400 islets and 50% transplanted with 300 or 500 islets). At the end of the study, normoglycemic mice transplanted with 300 allogeneic islets showed better glycosylated hemoglobin (HbA1C) than did normoglycemic mice transplanted with 500 islets (300 islets: 2.7 +/- 0.2%; 500 islets: 3.6 +/- 0.2%; p < 0.05). After the IPGTT, insulin-treated mice transplanted with 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplanted with 300 or 400 islets showed normal glucose tolerance. Insulin treatment reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1C and IPGTT results suggest that transplanting smaller numbers of allogeneic islets improves beta-cell function; some studies suggest that this may be due to lower immunogenicity, hypoxia, and inflammation.