Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at one year following TPIAT in a cohort of children. <p>Research Design and Methods: This was a review of 43 pediatric patients followed after TPIAT for one year or longer. Primary outcome was insulin use at one year, categorized as: insulin independent, low (< 0.5 u/kg/day) or high insulin (≥ 0.5 u/kg/day) requirement. </p> <p>Results: At one year after TPIAT, 12/41 (29%) patients were insulin independent, 21/41 (51%) had low and 8/41 (20%) had high insulin requirement. Insulin independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; p=0.03). Patients with insulin independence had higher transplanted IEQ/kg (p=0.03) and lower body surface area (p=0.02), compared to those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (p=0.03). Higher peak C-peptide measured by stimulated mixed meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at one year (p=0.006 and 0.03, respectively). </p> <p>Conclusions: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ/kg transplanted and lower body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement. </p>

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at one year following TPIAT in a cohort of children. <p>Research Design and Methods: This was a review of 43 pediatric patients followed after TPIAT for one year or longer. Primary outcome was insulin use at one year, categorized as: insulin independent, low (< 0.5 u/kg/day) or high insulin (≥ 0.5 u/kg/day) requirement. </p> <p>Results: At one year after TPIAT, 12/41 (29%) patients were insulin independent, 21/41 (51%) had low and 8/41 (20%) had high insulin requirement. Insulin independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; p=0.03). Patients with insulin independence had higher transplanted IEQ/kg (p=0.03) and lower body surface area (p=0.02), compared to those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (p=0.03). Higher peak C-peptide measured by stimulated mixed meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at one year (p=0.006 and 0.03, respectively). </p> <p>Conclusions: We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ/kg transplanted and lower body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement. </p>

Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation

OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (&lt;0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.

Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2

Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress. The transcription factor nuclear erythroid factor 2-like 2 (NRF2) is a central regulator of antioxidant and cytoprotective responses. Thus, we hypothesized that NRF2 may play a role in glucocorticoid-induced metabolic disease and osteoporosis. To this end, WT and Nrf2 knockout (Nrf2KO) mice of both genders were treated with 2 mg/kg dexamethasone or vehicle 3 times per week for 13 weeks. Dexamethasone treatment led to less weight gain during the treatment period without affecting food consumption, as well as to lower glucose levels and high insulin levels compared to vehicle-treated mice. Dexamethasone also reduced cortical bone volume and density. All these effects of dexamethasone were similar between male and female mice, as well as between WT and Nrf2KO mice. Hepatic NRF2 signaling and gluconeogenic gene expression were not affected by dexamethasone. A 2-day dexamethasone treatment was also sufficient to increase insulin levels without affecting body weight and glucose levels. Hence, dexamethasone induces hyperinsulinemia, which potentially leads to decreased glucose levels, as well as osteoporosis, both independently of NRF2.

Adult-onset Focal Nesidioblastosis with Nodular Formation Mimicking Insulinoma

Nesidioblastosis is defined as the neoformation of the islets of Langerhans from the pancreatic ductal epithelium and is recognized as the most common cause of hyperinsulinemic hypoglycemia in infants. We herein report an extremely rare case of adult-onset focal nesidioblastosis with the unusual feature of hyperplastic nodular formation. A 55-year-old woman was admitted to our hospital for a tumor detected in the body of the pancreas by magnetic resonance imaging screening. Laboratory examinations showed a high insulin level in the blood. Contrast-enhanced computed tomography and the selective arterial calcium injection test suggested the presence of multiple insulinomas in the body and tail of the pancreas, and, thus, the patient underwent distal pancreatectomy. A histopathological examination of the tumor in the body of the pancreas showed the nodular hyperplasia of islet-like cell clusters. In addition, many small intralobular ductules and islet cells appeared to be budding from the proliferating ductal epithelium, forming “ductuloinsular complexes”. No other abnormal lesion was detected in the remainder of the pancreas. The histopathological diagnosis was focal nesidioblastosis. The patient has remained free of the recurrence of hypoglycemic episodes for more than 31 months. The present case of rare adult-onset focal nesidioblastosis with hyperplastic nodular formation was preoperatively identified as an apparent pancreatic tumor mimicking insulinoma. Nesidioblastosis and insulinoma need to be considered in cases of hyperinsulinemic hypoglycemia, even in adult patients.

Case Study of Polycystic Ovary Syndrome -An Overview

Introduction: Polycystic ovarian syndrome (PCOS) is also known as polycystic ovarian disorder (POD). The disease is mainly metabolic (hyper androgenic) one. It usually affects women between the ages of 18 and 44. PCOS has no clear origin, although it seems to work at home. It is related to the effects of high levels of hormones in the body, such as high insulin levels. PCOS affects more than a million people in India each year. PCOS affects one in five Indian women (20%). Left untreated, the disease can lead to serious health problems. Conclusion: There is no permanent treatment for it since it is an irreversible syndrome/disease. The best way to improve health conditions is to change one's lifestyle and take drugs. One of the most effective methods is to make a healthy food/bad food chart and stick to it with exercise and medicine on a daily basis.

Microtubules and Gαo-signaling modulate the preferential secretion of young insulin secretory granules in islet β cells via independent pathways

For sustainable function, each pancreatic islet β cell maintains thousands of insulin secretory granules (SGs) at all times. Glucose stimulation induces the secretion of a small portion of these SGs and simultaneously boosts SG biosynthesis to sustain this stock. The failure of these processes, often induced by sustained high-insulin output, results in type 2 diabetes. Intriguingly, young insulin SGs are more likely secreted during glucose-stimulated insulin secretion (GSIS) for unknown reasons, while older SGs tend to lose releasability and be degraded. Here, we examine the roles of microtubule (MT) and Gαo-signaling in regulating the preferential secretion of young versus old SGs. We show that both MT-destabilization and Gαo inactivation results in more SGs localization near plasma membrane (PM) despite higher levels of GSIS and reduced SG biosynthesis. Intriguingly, MT-destabilization or Gαo-inactivation results in higher secretion probabilities of older SGs, while combining both having additive effects on boosting GSIS. Lastly, Gαo inactivation does not detectably destabilize the β-cell MT network. These findings suggest that Gαo and MT can modulate the preferential release of younger insulin SGs via largely parallel pathways.

Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [¹⁸F]fluorodeoxyglucose and [¹⁵O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.